Pharmacology Book by N Murgesh

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Insta - Study_Pharmacy_29
Telegram - Study Pharmacy
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A CONCISE TEXT BOOK OF
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CHARMACOLOGY
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66 8363
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Mandeepb
Dr. N. MURUGESH
B.Sc., M.B.B.S., M.Sc[Medl)., Ph.D., D.F.,F.I.C.S
Professor
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INSTITUTE OF PHARMACOLOGY
@phar Madurai Medical College,

MADURAI 625 020.
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SATHYA PUBLISHERS
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ARAVIND GARDENS, BALAJI NIVAB
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No.1, SOwBAGYA NAGAR 3rd STRE

Opp. SITALAKSHMI MILLS
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TIRUNAGAR
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MADURAl 625 006

Phone: 0452-2482638, Cell 98421-66994
E-mail: sathvapublishers@yahoo.com
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Copyrights reserved .
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First Edition. Preface to the Sixth Edition|
1984
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Second Edition: 1987
uwas released1
Third Edition 1990 Ever since the first edition of this book
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Fourth Edition 1995 twenty years back there has been a tremendous response
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Fifth Edition :1999 paramedical
from students, teachers as also medical and
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Sixth Edition 2004 in their

personnel.. They have found it to be very useful
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Reprint: 2006
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purpose for
Reprint: 2007 academic and professional fields. Thus, the
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Reprint: 2008
which this book was written is amply fulflled.
new
This sixth edition has incorporated almost all the
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have
This book cannot be reproduced in full or in part any
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drugs and recent informations. Many of the chapters
fomm deleted. Care has
without the written permission of the author. been reuwritten and older drugs have been
book such
been taken to preserve the original qualities of this
@pharmae as simplicity of language, neatness of presentation

clarity of contents.
and
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Though this book has been wrtten for Pharmacy
Nursing and
students, it is followed by Medical, Dental,
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Rs. 100/
informative
Veterinary students as well who find it extremely
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and useful.
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Weth fervent hopesof sincerly fulflling the needs of my
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edition. I do hope
dear students, I present this revised sixth
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to gain your appreciation and encouragement

as ever.
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Dr.N. MURUGESH
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Typeset : uru Systems Madurai
& Graphics, B.Sc., M.B.B. S.,M.Sc(Med), Ph.D,
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Madurai
-3.- Press Madurai June 16, 2004
Printed by Vivekananda C.F.F.ILC.s.
: 0452 256111, 98431 61111
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Section V:
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cONTENTTS
Drugs acting on autonomic nervous system
Section I: General Pharmacology
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27. General considerations 72
1
1. Introductior Cholinergic drugs 76
28.
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2. Absorption of drugs Cholinergic blocking drugs 82
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29.
3. Routes of drug administration 85
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30. Sympathomimetic drugs
Distribution of drugs 91
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4 31. Sympathetic blocking drugs

5. Biotransformation of drugs 96
Drugs acting on autonomic gangila
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11 32.
6. Excretion of drugs Neuromuscular blocking agents 99
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12 33.
7. Mechanisnms of drug action
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13 Section VI: Drugs acting on eye
8. Factors modifying drug effects
Drug toxicty 6 104
9. 34. Mydriatics, miotics and drugs used in glaucoma
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10. Methods cf prolonging drug action 18
Section VI : Drugs acting on respiratory system
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11. Drug asseys 19
35. Drugs used in brónchial asthma 109
Section II :
111
Drugs acting on the central nervous system 36. Nasal decogestants
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37. Drugs used in the treatment of cough 112
12.
13.
14.
Alcohols
General anaesthetics
Hypnotics and sedatives
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21
23
30
Section VII: Autacoids
38. Histamine and antihistamines
d 116
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15. Drugs effective in convulsive disorders 34 39. 5-Hydroxytryptamine and its antagonists;
37 Angiotensin and kinins 121
16. Opioid analgesics
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17. Anaigesic antipyretics 44 VII : Cardiovascular drugs
Section
18. Antipsychotic drugs 51
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54 40. Digitalis and related cardiac glycosides 125
19. Anti-anxiety drugs
129
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20. Antidepressant drugs 56 41. Antiarrhythmic drugs
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58 42. Antihypertensive agents 133

21. Psychotogenic drugs
43. Vasodilators and anti-anginal drugs 139
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22. Central nervous system stimulants 59
44. Drugs used in atherosclerosis 142
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23. Centrally acting muscle relaxants 62

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24. Drugs used in parkinsonism 63 Section IX :
25. Drug dependence and abuse of drugs 66
Drugs acting on blood and blood forming organs
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m : Local anaesthetics
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Section 144
45. Drugs affecting coagulation of blood
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26. Cocaine, procaine and other local anaesthetics 68 46. Fibrinolytic agents and anti platelet drugs 149
47. Drugs effective in iron deficiency anemia 152
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48. Drugs effective in megaloblastic anemia 156
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71. Sulfonamides, nitrofurans and other synthetiC
49. Blood substitutes and plasma expanders 158 antimicrobial agents 228
72. Penicillins and other antibiotics mainly effective
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Section X: Drugs acting on kidney
against Gram-positive organisms 232
50. Diuretics 162 73. Aminoglycosides and other antibiotics effective
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51. Antidiuretics 167 mainly against Gram-negative organisms 240
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74. Cephalosporins, Tetracyclines and other Antibiotics
Section XI : Hormones and hormone antagonists
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effective against both gram positive and gram

negative organismss 242
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75. Antifungal antibiotics 24
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53. Anterior pituitary hormones 170

76. Chemotherapy of tuberculosis 249
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54. Gonadotropins 173
Adrenocortical steroids 175 77. Chemotherapy of leprosy 254
55.
180 78. Chemotherapy of urinary tract infections 255
56. Androgens and anabolic steroids
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57 Estrogens and progestins 183 79. Chemotherapy of sexually transmitted diseases 257
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58. Oral contraceptives and ovulation inducing drugs 185 80. Chemotherapy of viral infections 259
189 81. Disinfectants and antiseptics 261
59. Thyroid and antithyroid drugs
194 82. Chemotherapy of malaria 263
60. Parathyroid hormone and calcitonin
61. Insulin and glucagon 195 83. Chemotherapy of amoebiasis 268
62.
Section
Oral antidiabetic drugs
XII : Drugs acting
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on the gastrointestinal
199 84. Chemotherapy of miscellaneous
protozoal infections
85. Anthelmintic drugs
272
275
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tract 86. Chemotherapy of cancer 281
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63. Appetizers, digestants, carminatives, appetite Section XV : Miscellaneous
suppressants and sialogogues 202
87. Heavy metal antagonists 288
205
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64. Emetics, anti-emetics and anti-diarhoeals
88. Drugs used in the treatment of gout 290
65 Purgatives 210
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66. Ano-rectal preparations 214
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67. Antacids 215

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68. Antiulcer drugs 217
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Section XII : Drugs acting on the uterus

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69. Oxytocics and uterine relaxants 220

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Section XIV: Chemotherapy
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Section
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GENERAL PHARMACOLOGY
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INTRODUCTION
1.
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Note on dosage and other informations

I. Pharmacology: Pharmacology is a science that deals with
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drugs. It includes a detailed study of the history, properties,
physiological effects, mechanism of action, absorption, distribution,
The author and publishers of this book have taken
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metabolism, excretion and uses of a diug.
great care o provide necessary information about the drug
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II. Drug: A drug is defined as any substance which is used to
and their dose. However, it is likely that there may be humar:
Cure, diagnose or prevent a disease.
eror or changes might have occured due to ever advanciny
therapeutic approaches and modem development. So the III. Main divisions of Pharmacology: The subject matter of
Phamacology includes the following main divisions.
information contained herein may not be accurate arn
1. Materia Medica which deals with sources, description and
complete. Also, this book has been written mainly with the preparationof drugs. It is an old branch of Phanmacology.
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intention of providing basic infomation for Pinarmacy
2. Pharmacodynamics which deals with biochemical and
students bt not medical practitioners. So, the readers are physiological effects of drugs and also their mechanism of action.
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requested 1o confim the infomation with. other sources or (What the drug does to the body).
manufacturers recommendation for dosage and use related 3. Pharmacokinetics which deals with the absorption, distribution,
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information. Emors or any variation that may arise in dosage, netabolism and excretion of drugs. (What the body does to the drug).
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information or usage will not bind the author, publisher or is concerned with the use of a drug for
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4. Therapeutics which
any other party who has been invoved in the preparation or curing diseases and relieving their symptoms.
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which is the scientific study of drugs
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publication of this work. 5. Clinical Pharmacology

efficacy and safety of a drug is studied in patients and
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in man. The
healthy volunteers.
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6. Chemotherapy which deals with the effects of drugs

on
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micro-organisms and parasiles which occur in a living organism.
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also includes the treatment of cancer.

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Telegram - Study Pharmacy 2
5.Pinocytosis: Proteins and macromolecules
are transported by this
which deals with poisonous effects of drugs, where ceils er gulf tiuids or
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7. Toxicology
process. It is sinmilar to phagocytosis
detection of poisoning and its treatment. macromolecules from the surroundings.
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V. Drug Standards : The govenments nost of the countries The absorption of a
have established legal standards for all important drugs. These Factors modifying drug absorption:
factors:
drug can be influenced by the following
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standards are published in Pharmacopocia which is an official code
liquids are well absorbed
containing a list of established drugs along with their standards. The Physical state : Drugs in the form of
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absorbed through lung
following are some well known Pharmacopoeias: than solids. Gases are quickly
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absorption
Smaller the particle size, better is the
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1. The Indian Pharmacopoeia (l.P) 2.Particie size :
drug is slowly absorbed

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size is large, the

2. The British Pharmacopoeia (B.P) of a drug: If the particle
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3. The United States Pharmacopocia (U.S.P) and hence the action is delayed.
al sorbed. Also
3.Solubility An easily soluble irug is quickly
than solids.
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quickly absorbed
2. ABSORPTION OF DRUGS drugs in the fom of solutions are
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4Concentration: Concentrated fornms of drugs are quickly
Introduction: drug can enter into circulation and reach the site
A absorbed than dilute solutions.
of action only after absorption. The absorption of a drug involves
its
Greater the area of absorbing
passage across cell membrane. As a rule, lipid insoluble and water 5.Area of absorbing surface: For exanple, lungs and
insoluble drugs are not absorbed from the gut. surface, quicker is the absorption of a drug.
from where drugs can be
peritoneal cavity are large surface areas
cell membrane: Drugs can pass
Passage of drugs across quickly absorbed.
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through cell membrane by two processes. They are: blood flow to the
6.Circulation to site of absorption: Increased
b. Specialised transport increase the absorption of a drug. This can be
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a. Passive transfer area of absorption can
heat. asoconstrictors
1. Simple diffusion 1. Active transport achieved by massage or local application of
2. Filtration 2. Facilitated diffusion decrease blood flow and so decrease the
absorption of a drug.
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3. Pinocytosis
important factor which
7.Route of administration: This is a very
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1. Simple diffusion: It is a bidirectional process. Polar
determines drug absorption. Some drugs are absnbed only on
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water-soluble and non-polar lipid - soluble substances can be and they fail to gct absorbed on orai
parenteral administration
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carefully choose thhe
administration e.g. insulin. So it is necessary
transported by this process. to
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2. Filtration Only water soluble substances can be transported by route of administration of a drug.
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this process. It involves passage through pores present in the cell defined as the quantity of. tiie drug that
is
Bioavailability: It is
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membrane. circulation afte non-vascular

absorbed and reaçhes systemic
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3.Active transport: It is a selective process wlhich requires energy. administration. The bioavailabilityis100%% af er intravenous
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administration. Bioavailability is
Also it requires a carrier and so is called ascarrier transport. injection. But it is less after oral
2. Dosage fonn 3.
affected by factors like 1. Physical properties
4.Facilitated diffusion: lt is very similar to carrier transport, but
Physiological factors.
it does not require energy.
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3. ROUTES OF DRUG So inactivation of tlhe drug
in
intestinal juice removes these coatings. the drug
ADMINISTRATION a desired concentration of is
the stomach is avoided. Thus
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released in the intestine.
Route of administration is an important factor which
preparations (Timesules,
Introduction: Sustained release or time release
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containing various
influences the: absorption of a drug. The interval between Spansules): These are oral preparations
at difterent time intervals
releasing
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administration and onset of action is determined by the route of coatings. Each coating dissolves prolonged periods.
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is released slowly for

administration Biological lag is the interval between administration the active drug. So the drug
administration other than oral
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of a drug and development of response. Parenteral routes: Routes of
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(enteral) route are termed as

parenteral.
Classification of routes: The routes of drug administration can
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be classified as: Advamages of parenteral route :
1. Absorption is rapid and quick.

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Oral or Enteral route can be given.
2. Accurate dose of the drug
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2. Pa.enteral route Injection in an active form.
3. The drug enters into circulation
Inhalation
Transcutaneous 4. It is useful in emergency.
5. It is ueful in case of an
unconscious palient.
Transmucosal
Le cal application
3.
Drug delivery systems
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Disadvantages of parenteral route
1. Pain may be produced by
2. Abscess and
inflammation
injection dt
at the site of injection.
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Oral or Enteral route : It is the most commonly used route for
3. Sterile procedures are required
for injection.
drug administi atiofi.
an expensive route.
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Atvantages of oral route:
4. It is
5. Self nmedication is not possible.
1. convenient and economical route.
It is a safe,
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a. Injection
2. Self medication is possible. layers of skin e.g.
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1. Intradermal: The drug is injected in the
3. Withdrewal of the drug is possible.
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B.C.G. vaçcine.
Disadvantages of oral route: can be injected by
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. 2. Subcutaneous: Non-irritant substances alone
Onset cf drug action is slow. even and slow and hence the
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absorption is
this,route. The rate of
Drugs vhich are bitter in taste cannot be administered.
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2. effect is prolonged.
administered.
3. Drugs 1roducing nausea and vomiting cannot be is njcted deep into muscle tissue.
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3. Intramnuscular: The drug

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The drg may be inactivated by gastric

enzymes. onset of action is rapid
The rate of absorption is uiniform and
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4.
This ro te is not possible in an unconscious patient. into a vein.
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5.
4. Intravenous A drug is directly injected
These are oral preparations
Enteric coated pills and tablets
with c2lluiose acetate or gluten. These coatings cannot be Advantages
coated in an active form.
destroyed by the acid juice of the stomach. Only the alkaline i. The drug enters into circulation
ii. Desired blood concentration
can be obtained.
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The force of repulsion between
for negatively charged compounds.
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ii. Quick and immediate effect is produced. the tissues.
similar charges drives the drug deep into
iv. lt is useful in case of emergeney.
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ii) Inunction: It is rubbing_the.drug
on.the skin. he drug gets
V. It is useful in an unconscióiis patient. eifects.g. nitroglycerin: omtment for
absorbed and produces systemic
Disadvantages:
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angina.
i. Drugs which precipitate blood constituents cannot be not require a syr:nge. So it IS
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administered. iii) Jet injection: This method does
with a micro-fine orifiee, the
painless. Using a gun like instrument
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ii. Untoward reactions, if occur are immediate. high velocity jet (dermo, et). The dng
drug solution is projected as a
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ii. Withdrawal of the drug is not possible. skin and gets deposited
solution passes through superficial_layers of
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5. Intra-arterial: In this route, a drug is injected into an artery. subcutaneous..tissue. This method is use ful for mass
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The effect of drug can be localised in a particular organ ,or tissue
a in the
inoculation.
by choosing the appropriate artery. Anticancer drugs are sometimes It
a transdenaidug delivery system.
iv) Adhesive units: It is
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administered by this route. unit. It delivers the drug slowly.
available in the fonn of adlhesive
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6. Intraperitoncal : n this route, a drug is injected into the etfect. e.g. scop0jan ine for motion
So it produces prolonged systemic
peritoneal cavity. By this route, fluids like glucose and saline can be
sickness.
given to children. Sublingual
It is further ciassified as i)
7. Bone - nmarrow: Bone marrow injection is very similar to d. Transmucosal route:
intravenous injection. This route is useful when veins are not ii) Trans-nasal ii) Trans-rectal.
available due to circulatory collapse or thrombosis. In adults, the i) Sublingual route: A tablet
containing the drug is put under the
and
sternum is chosen and in children, tibia or femur is chosen for in the nmouth e.g. nitroglycerine
tongue and allowed to dissolve
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injection. 1soprenaline.
Gases, volatile liquids, aerosols or vapours can be
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b. inhalation Advantages of sublingual route:
administered by this route.
1. Rapid onset of action.
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Advantages the tablet.
2. Temination of the effect by spitting
1. Immediate absorption of the drug.
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is avoiled.
Inactivation of the drug in the stamoch
Localisation of the effect in diseases of the respiratory tract.
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2. systemic circilation without

The drug enters directly into
4.
Disadvantages
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inactivation in the liver.
snuff or
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1. Poor ability to regulate the dose. It is useful for drugs in the fon of
ii. Trans-nasal route: the mucous
Local irritation of the respiratory tract may increase its
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2. readily absorbed throu:gh
drug is
secretions. nasal spray. The pituitary powder.
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membrane of nose. e.g. posterior

3. Difliculty in the method of administration. rectum
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Drugs can be absorbed thrc ugh the
C. Transacutaneous route:
It is further classified as i) lontophoresis ii. Trans-rectal route: bronchospasm,
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e.g. aminophylline for

ii) Inunction iii) Jet injection iv) Adhesive units. for producing systemic effects. 1.
Advantages of rectal route are:
diazepam for status epilepticus. tenminally ill
i) Iontophoresis: In this metlhod, a drug is driven deep into the skin 2. It is useful in old ad
gastric iritation is avoided.
by neans of a galvanic current e.g. salicylates. Anode iontophoresis patients.
is used for positively charged drugs and cathode iontophoresis is used
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non-ionised
circulation. It pemits the entry of only lipid-soluble and
e. New drug delivery systems:
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forms of drugs.
Occusert: t placed directly under the eyelid. It can release
is the
get stored at different areas of
i.
drugs like pil«carpine for prolonged periods. Storage depots: A drug can areas can produce
drug from these
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body. Slow release of the
ii. Progestase:t: lt is an intrauterine contraceptive. device. The following are major storage sites where
drugs
prolonged effects.
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produces cont:olled release of progesterone within the uterus fora
can be stored.
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year. and
1. Plasnma proteins like
albumin e.g. phenylbutazone
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It is an inactive drug which after administration is
ii. Prodrug: sulfonamides.
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metabolised into an active drug. For exanmple, l-dopa is an inactive

2. Connective tissues like
bone e.g. heavy metals and
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conpound. A fter administration, it is metabolised to the active drug
tetracyclines.
dopamine whiuh is etfective in parkinsonism.
3. Cells like liver cells
e.g. quinacrine an antimalarial drug.
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Local application: Drugs in the form of powder, paste, lotion, drops thiopental, a
is highly lipid-soluble e.g.
and ointment can be applied locally for action at the site of application. 4. Fat, if the drug
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lipid-soluble barbiturate.
Drugs can be applicd on mucous membranes of nose, conjunctiva,
vagina, urethr and rectum. The following are some preparations
BIOTRANSFORMATION OF DRUGGS
which are meint for local application: 5.
bougie for urethra
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1.
drug in a living organism is known
a
2. pessary for vagina Introduction: Alteration of
By this process, a drug may either be
3. supposi ory for vagina and rectum. as "biotransfomation'.
more active compound.
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a
Inactivated or converted 1nto
4. enemat: for rectum. sometimes Drug metabolism or
called
Biotransforniation is
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DISTRIBUTION OF DRUGS Detoxication".
4. By means of biotransfornmation,
the duration of action of a drug
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is decreased. Hence, the
toxicity is also decreased.
Introduction: After a drug is absorbed, it is distributed to various
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body tissues and luids. Drugs which easily pass through cell reactions which bring about
Methods of biotransformation: The
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membrane aciieve wide distribution. Drugs which do not pass biotransfomation of drugs can be classified as:
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through cell n embrane are limited in their distribution.
a. Non-synthetic reactions
(Phase I reactions)
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Entry into (entral Nervous System: Entry of drugs into (Phase lI reactions)
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- brain barrier. It is a
b.Synthetic reactions.
central nervous system limited
is by blood
Non-synthetic reactions lead either to
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hypothetical barrier which exists betwcen plasma and extracellular a. Non-synthetic reactions: These reactions are further
activation or inactivation of a drug.
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surface of brai 2. This barrier is constituted by glial cells and capillary
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endothelum in the brain. Only lipid - soluble, non-ionised drugs classified as:
in the liver. A typical
readily pass through this barrier. 1. Oxidation: Oxidation occurs mainly
alcohol.
Entry into fvetal circulation: Entry of drugs into example is the oxidation of ethyl
circulation is restricted by hlood placental barrier. It is also a Alcohol Acetaldehyde
foetal Ethyl alcohol
hypothetica barrier which exists between maternal and dehydrogenase
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Telegram - Study Pharmacy 10 11
Females have less ability to nmetabolise diugs.
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Aldchyde 4. Sex
Acetaldelhyde Acetyl CoA due to thhe presence of
dehydrogenase 5. Species: Rabbits metabolise atropine
i:. toxic to humans
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atropinase. Humans lack this enzyme. So atropine
2. Reduction: It is a less common proces Drugs like prontosil.and
chloralhydrate are metabolised by reduction. but non-toxic to rabbits.
metabolising nzymes can be
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3. Hydrolysis: This is brought about by enzymes called 'esterases 6. Genetic: Deficiencies in drug
produces hemolysis in gen :tic deficiency of
inheritd e.g. primaquine
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which produce cleavage of the ester linkage e.g Acetylcholine is dehydrogenase (G 6-PD).
the enzynne Glucose-6-phosplhate
ha
hydrolysed by 'cholinestierase' and converted into eholine and acetic

7. Body temperature: Increase in
body temperatuure increases drug
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acid.
in body temperature has the opposite
metabolism, where as decrease
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b. Synthetic reactions: Synthetic reactions also called s

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'conjugation reactions' lead only to inactivation of a drug. The effect.
following are the various synthetic reactions:
EXCRETION OF DRUGS
6.
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1. Glucuronide formation e.g. Morphine
y
y
2. Sultate fomation- e.g. Plhenols action.
Introduction: Excretion of drug decreases its curation of
a
3. Acetylation- e.g. Sulfanilanmide Drugs may te excreted in an
This in tum decreases the toxicity. can
4. Methylation- e.g. Adrenaline and Noradrenaline routes through whiclh drugs
active or inactive form. The various
5. Glycine conjugation e.g. Salicylic acid be eliminated are
eliminated through tihe kidney by:
Sites of biotransfomation Biotransfomation of drugs 1. Kidneys: Drugs may be
the drugs are eliminated
occurs primarily in the liver. Other nminor sites of biotransformation Passive glomerular filtration-most of
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are kidney, plasma, placenta. and testis. In the li'ver, drug metabolising by this mechanism.
enzymes are present in microsomes. So these enzymes are called as 11. active tubular secretion e.g. penicillin.
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hepatic microsomal drug metabolising enzymes. salicylates and repacrine.
ii. passive tubular diffusion e.g.
In case of renal damage, excretion of
drugs is decreased and
Factors modilying biotransformation: Biotransfonnation ofa drug
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may be modified by the following factors: so the toxicity is increased.
alcohol and
Ph
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Ph
2. Lungs Drugs like volatile generai anuesthetics,
1. Inhibitors: Drug metabolising enzymes can be inhibited by
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certain other drugs. e.g. cimetidine, onmeprazole, ciprofloxacin. Such paraldehyde are excreted through lungs.
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: Heavy, metals like arsenic and
mercury are excreted
drugs decrease the metabolism of a drug. This in tum increases the 3. Skin
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duration of action. through skin.

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in
4. Intestine: Purgatives like
senna and cascar: are absorbed
2. Stimulators: The activity of drug metabolising enzymes can be
ac
large intesine.
increased by cèrtain drugs e.g phenobarbitsne and rifampicin. They small intestine and later get excreted in
cy
cy
cy
increasc the imetabolism of drugs ke phenytoin and warfarin.
and fhenolpthalein are
Drugs like diphenyllhydantoin
5. Bile: into The se drugs may be
y
small intestine through bile.

3. Age Metabolism of drugs is,poor in young children because of excreted
liver and again excreted into smal
poor development of drug metabolising enzymes e.g. lack of absorbed again, carmied to the
bile. This process called as 'enterohepatic
glucuronyl transferase for the inactivation of chloramphenicolin the intestine through
action of sucl: drugs.
new bom (this produces grey baby syndrome). circulation' prolongs the duration of
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Ph
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h
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***
13
Telegram - Study Pharmacy 12 3:0smosis Magnesium sulphate produces a purgative
effect due
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to osmosis.
Milk: Milk is more acidic than plasnma and hence basic drugs like paraffin produces a smooth coaling
6. 4. Demulcent effect: Liquid
is responsible for its purgative
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pethidine are liminated through it. over the lumen of the intestine. This
7. Saliva: Drugs like iodides and metallic salts are excreted through effect.
its
anticoagulant drug produces
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saliva. Lead is eliminated through saliva and its deposition produces 5. Electrical charge: Heparin, an
Ph
Ph
Ph
black lining of teeth. effect because of negative charge.
active isotopes used for the treatment of
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6. Radio-activity: Radio
MECHANISMS OF DRUG ACTION emitting ionising radiations.
7.
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cancer produce their effect by
r
properties
drug may produce its effect by a number of b. Action through chemical
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Introduction: A
Hydrochloric acid is eífective in the
mechanisns like combining with enzymes, cell membrane or other 1. Acidity and alkalinity:
bicarbonate acts as an antacid
components of' a cell. treatment of hypochlorhydria. Sodium
c
c
acid of the stomach.
t is the hypothetical component of the cell with which by neutralising hydrochloric
Receptor:
y
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combine
inside agents like dimercaprol (B.A.L.)
a drug interact s. The receptor may be on the cell membrane or 2. Chelation: Chelating and form water soluble complexes. This
the cell. It m:iy be a protein or enzyme. with metals like arsenic
the metal through urine.
Agonist isa drug which combines with the receptor and initiates helps in the easy elinmination of
by i:ihibiting cell wal
a phanmacological action. C. Action on celi surface: Penicillin acts
Antagor ist is a drug which combines with the receptor and synthesis of micro- organisms.
and
Some drugs enter into cells
blocks it without producing a pharmacological action. d. Action inside the cell: structures. Anticancer
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intracellular
produce their effect by acting on
Sites of drug action: inhibiting nucleic acid synthesis inside
drugs produce their effect by
Drugs rnay produce localised effects on certain cells, tissues.
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1.
the cell.
organs tC., or generalised effects on most cells of the body. Drugs can produce their effect by
e. Action through enzymes:
Drugs iay act: examples, anticholinesterases like
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. e tracellularly e-g. osmotic diuretics.
modifying enzyme activities. For acetylclholinesterase. This
neostigmine act by inhibiting the enzyme
Ph
Ph
Ph
ii. 01 the cell surface- e.g. penicillin. and increases.its dration of
prevents the inactivation of acetylcholine
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ii. intracellularly -e.g. anticancer drugs. action.

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3. Drugs an produce their effect by physical or chemical
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EFFECTS
FACTORS MODIFYING DRUG
properti:s.
8.
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4. Drugs cn act by modifying enzynme activities.
ac
one individual
Introduction : .The response to a drug varies from
Extracellular effects:
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are the factors which are
responsible for
to the other. "The following
y
a. Action through physical properties variation in drug effects.

reasons
1. Physical m:iss: Agar agar produces a purgative effect because of 1. Age: Children are hyper
reactive to certain dnugs. The
development of enzymes
swelling in pre sence of water which increases its size. are immaturity of renal functions
or poor
acts as an antacid by
2. Adsorption: Magnesium trisilicate
adsorbing hyd ochloric acid in the stomach.
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ud
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Ph
Ph
Ph
h
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15
14
inactivation. So a lesser dose must be given for children dehydrogenase (G-6-PD). Pharmacogenetics is
a scienc e which deals
needed for responses
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than for adults. The dese for children can be calculated by niaking with genetic variations in drug
are excretei slowly. So
use of the following forulae. 10. Cumulation: Drugs like digitalis
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in the sody so as to
Age repeated administration leads to accumulation
a. Young's Fomula: Age + 12 X Aduit dose produce toxcity. This phenonmenon
is called as 'cumuiation'.
y
to nornal therapeutic
11. Tolerance: It is the unusual isresistance
x
Age to procuce an effect.
Ph
Ph
Ph
b. Dilling's Formula Adult dose a large dose required
dose of a drug. So
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Tolerance can be classified into:

2. Body weight: Body weight has a definite influence on the parenteral
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a drug i. True tolerance: It can be produced on both oral and
concentration of the drug at the site of action. So the dose of it is called as
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administration of a drug. When it occurs by nature,

lean or obese individuals.
must be suitably adjusted in case of in rabbits. This can
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natural tolerance e.g. tolerance for atropine Acquired
Sex : Women are more susceptible to the effects of certain drugs exposure to thhe dru;.
3. Occur even without previous
more excitation in women than in men. dministraton e.g. tolerance for
e.g. morphine produces tolerance is produced on repeated
c
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The rate of absorption of a drug the euphoriant effect of morphine.
y
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4. Route of administration
:
tolerance. It occurs on
differs with the. route of administration. The dose also varies with the ii. Tachyphylaxis : It is an acute type of
dose .of a drug is less than short intervals. For examnple,
route of administration e.g. intravenous repeated administration of the drug at
subcutaneous dose. tyramine produces decreased rise in blood pressur> on repeated
is due to depletion of
5. Time of administration This factor has a definite effect on administration. This decreased response
nerves
drug absorption and hence on its effect For example, drugs wlhich noradrenaline stores from sympathetic
gastric iritation) should b taken
Drug interaction: The effects of a drug
produce nausea and vomiting (due to may te modified by
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2.
after food. But anthelmintics should be taken in empty stomaçh. administration of anoth»r drug. The
the prior or simultaneous
Body. temperature and acid-base status combinations can be classified as
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6. Physiological factors effects produced by drug
e.g. salicylates lower
are some factors which modify drug effects, i. Additive effect
fever but not in normal individuals.
body temperature only in
y
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ii. Synergism
Psychological factors: The effect of-a drug may be modified
Ph
Ph
Ph
7. Antagonism
it is necessary to ii.
by psychogenie resonse of the patient. Sometimes pharmacolog ical response
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is a dummy i. Additive effect: Here, the total

please the patient by psychological means. Placebo which the individual effects
produced by two drugs is equal to the sum of
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medication (having the sanme colour, smell etc. as the actual
aminophylline in brc nchial asthma.
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for this purpose. e.g. the effects of ephedrine and

medication) is used
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produced by two crugs is greater
a drug may be modified in ii. Synergism: The total effect
8. Pathological state: The effect of ammonium chloride synergises
than the sum of individual effects e.g.
ac
pathologica conditions e.g. hyperthyroid individuals require large

a
the effect of mercurial diuretics.
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dose of nmorphine. the same physiological system
y
ii. Antagonism: Two drugs act on

9. Genetic factors: The effects of a drug may vary due to genetic effects. Antagonism can be cle ssified as:
and produce opposite
factors like inherited enzyme deficiencies e.g. primaquine produces
Glucose-6- phosphate a. Chemial antagonism
hemolysis in individuals with a deficiency of
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Ph
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Insta - Study_Pharmacy_29 17
16
Competitive
b. reversible antagonism
or
1. Intolerance: defined as the inability of an individual
It is
disorders like
to
enzyme
occur due metabolic
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to
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tolerate a drug. may
It
Non-competetive antagenism reactions.
c.
deficiency (idiosyncracy) or due to allergic
d. Physiolo:gical antagonism toxic effects of a drug
ud
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mostly due to the
occurs as a result of chemical 2. Blood dyscrasias: It is
a. Chemical artagonism: This chloranmphenicol. It occurs in the fom of
e.g. BAL in arsenic poisoning. on bone marrow e.g.
interaction between two drugs anemia and hemolytic anemia.
y
leukopenia, agranulocytosis, aplastic
b. Competitive or reversible antagonism:
This occurs due to
are concentrated in the liver. Hence
Ph
Ph
Ph
the same receptor. The drug 3. Hepatotoxicity: Most drugs
competition be:ween two drugs for form of toxicity. Most of the
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concentration at the receptor produces its effect e.g. damage of this organ is a common
having a greater lhepato toxic.
halogenated hydrocarbons are
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receptors.
antagonism of :icetylcholine by atropine at muscarinic danmage to
Drugs like sulphonamides produce
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to inactivation of 4. Nephrotoxicity
C:Non-compettive antagonism: This occurs due albuminuria and hematuria.
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antagonist e.g. antagonism of acetylcholine by the kidney in the form of crystalluria,
the receptor by' the
decamethonium at the neuromuscular junction. 5. Behavioural toxicity: At
times, drugs may alter the normal
excitation and mania at
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d. Physiologicil antagonism : Here, the
drug and its antagonist act behaviour e.g. atropine produces euphoria,
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produce an opposite effect e.g. adrenaline in toxic dose.
at different rec«ptors to
can
histamine anap 1ylaXIs. 6. Drug induced diseases At times, drugs by themselves
(iatrogenic discases) e.g. parkinsonism
produce certain diseases
9. DRUG TOXICITY caused by chlorpromazine.
aggravate an already
in addition to 7. Unmasking of a disease: Dugs can
Introduction: Dugs can produce toxic effects existing disease or unmask a latent
disease e.g. isoniazid can unmask
esfects. With
pharmacologicil actions. No drug is free from toxic
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may be serious latent epilepsy.
nmay be minor whereas tliey
some drugs, to cic effects administration, reserpine
8. Endocrine disturbances: On prolonged
with certain otiier diugs.
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to feminisation in males
lethal can produce endocrine disturbances leading
: It is defined as the ratio of median females.
Therapeutic index and reduction in fertility in
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dose to mediar effective dose. Corticosteroids like hydrocortisone
9. Electrolyte disturbances:
LDs0
Ph
Ph
Ph
edenma.
Therapeutic index ED 50 may produce sodium retention and
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applied locally can

Median lethal dose or LDso is the dose which kills
half the 10. Skin reactions: Drugs taken systemically or different forms like
ar
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produce skin rashes. The rashes are of
population of ihe animals tested. may produce
exfoliative dermatitis and ur! caria. The same drug
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which produces the

Median effective dose or EDso is the dose
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different types of rashes in different people.
population tested.
desired respon e in half the animal has been found to be directly
ac
11. Carcinogenesis No drug:

The the:apeutic index provides an idea about the safety of the is known to be carcinogenic in
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carcinogenic in humans. Oestrogen
therapeutic index, safer is the drug. Penicillin has
drug. Higher tie
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digitalis is low. experimental animals.

a high therapeutic index and that of administered to pregnant
various toxicities produced 12. Teratogenic effects : Drugs when
Drug toxicities: The following are the women are likely to produce foetal abnormalities e.g. thalidomide
by drugs:
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18
produces 'phocomelia' characterised by sealed cxtremities in infants
by imipramine. Decreased inactivation increases
thhe durtion of action
of a drug.
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when adnministered to pregnant women. penicillin is
ii. Decreasing renal elimination: Tubular secretion of
13. Addiction: This term has now been replaced by "Drug the duration of action o penicillin is
decreased by probenecid. So
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lependence' which involves both psychic and physical dependence
increased.
for a drug. It is a state of periodic or chronic intoxication produced
Suramin, a dru used in
y
by repeated drug administration. iv. Increasing protein binding: So it has a prolonged effect.
trypanosonmiasis is highly protein bound.
Ph
Ph
Ph
The characteristics of addiction are: pla»ma proteins.
Long acting sulfonamides are also highly bound to
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i. an overpowering desire to take the drug.
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ii. á tendency to increase the dose.
11. DRUG ASSAYS
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iii. development of psychic and physical dependence.

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iv. detrimental effect on the individual and society. an active
Assay: It is defined as the estimation' of potency of
quantily of the preparation. Assay methods can
METHODS OF PROLONGING
in
principle. unit
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10. be classified as 1. Chemical 2. Biological 3. Im nunological.
y
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DRUG ACTION
Chemical assay : Here, chemical methods are used for estinmating
the concentration of the active principle. Techniques like colorimetry.

Introduction The action of a drug can be prolonged by: i.
:
spectrophotometry and fiuorometry are used in chemic:l assays.
decreasing absorption ii. decreasing inactivation ii. decreasing renal
It is the estimation of the biological a tivity
in unit
elimination iv, increasing protein binding. An increase in the Bioassay:
like micio- organisms,
duration of action decreases the frequency of administration. quantity of the preparation. Biological systems
a drug can be decreased isolated tissues orintact animals are employed in bioas say.
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i. Decreasing absorption: Absorption of
by: Indications-for bioassay
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. Taking the drug in full stomach or in enteric coated fonms. 1. When the chemical composition is not known.
2. Decreasing the solubility e.g penicillin with procaine. insensitive.
2. When chemical assay methods are not available or
y
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3. Use of vasoconstrictors e.g. adrenaline with local anacsthetics.
3. When the quantity is too small.
Ph
Ph
Ph
4. Administration of oily suspension e.g. adernaline in oil same
4. When drugs have different chemical composit:on but
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injection.
phamacological action.
5. Combination of the drug with protein e.g. insulin with
ar
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protanine. Standard: A substance with known concentration is called as
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standard. In bioassay, the concentration of test sample is estimated

Esterification of the drug e.g. esters of oestrogen with benzoic
ma
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6.
by comparing with the standard.
acid.
ac
7. lmplantation of drug pellets e.g. desoxycorticosterone acetate

Methods of Bioassay:
cy
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cy
(DOCA) pellets. is
assay:A constant dose of the test sample
y
Inactivation of drugs by microsomal 1. Matching

ii. Decreasing inactivation: bracketed between varying doses of standard. This is done, till the
enzymes of liver can be decreased by certain compounds. For the stancard.
inhibited test sample matches with a particular dose of
example, the enzyme mono amine oxidase (MAO) can be
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Ph
Ph
Ph
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20
Interpolation:
2. Here, a log dose response curve is plotted by 21
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using a minir um of 4 submaximal
concentrations of the standard.
The concentration of the test is read from the graph.
Section l
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3. Four point assay: Itincorporates the principles of interpolation
it is the nmost accurate method.
and matching So
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4. Immunoassay: This makes use of
immunological methods.
DRUGS ACTING ON THE
Ph
Ph
Ph
Radio-immunoassay is the one which is widely used especially for
CENTRAL NERVOUS SYSTEM
ha
insulin
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rma
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12. ALcOHOLS
c
c
y
y
-
Alcohols are hydrocarbons. They may contain one or more

hydroxyl (OH) groups. Ethyl alcohol is the commonly used alcohol.
ETHYL ALCOHOL
@pharmae Ethyl alcohol is the nmain constituent of al kinds of alcoholic

beverages. It is generally obtained by fermentation of sugar by yeast.
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Pharmacological actions
External: Externally alcohol is:
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1.
1.astringent since it precipitates proteins.
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i. refrigerent since it produces cooling effect on the skin.
ii. rubifacient since it dilates cutaneous blood vessels.
Ph
Ph
Ph
iv. detergent since it dissolves sebaceous secretions.
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v. antiseptic since it destroys micro-organisns.

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2. Gastrointestinal tract: Alcohol increases gastric acid secretion
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and also produçes a carinative effect.

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Produces fatty liver on clhronic administration.
ac
3. Liver:
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4. Central nervous system : Alcohol produces initial exitation
(characterised by incoherent speech and gait) due to depression of
y
higher inhibitory centres. This is followed by progressive dépression,

drowsiness, sleep and unconsciousness as the dose is increased.
5. Cardiovascular system: Moderate dose of alcohol produces
cutaneous vasodilatation. This produces a fecling of flushing and
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23
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DISULFIRAM (TETRAETHYL THIURAM DISULFIDIE,
wamth. concentrated fonm of alcohol produces slight rise in blood
A
ANTABUSE:
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pressure and increase in heart rate due to reflex action.
aloholism. It
6. Respiration Moderate doses produce slight stimulation It is a drug used for the treatment of chronic
So
doses produce respiratory depression which may be acts by inhibiting the enzyme aldehyde -dehydorgenase.
y
wiereas large
fatal. acetaldehyde is not converted into Acetyl CoA. This leads to the
Ph
Ph
Ph
7. Kidney: Output of urine is increased due to depression of A.D.H. accumulation of acetaldehyde which produces nausea and
ha
once daily for

production. vomiting. It is administered at a dose of 500 mg.
ar
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Sexual function: Alcohol produces an aphrodisiac action a week and later 250 mg. daily as maintenance dose.
r
8.
(erection of sexual organ) due to loss of inhibitory control. Also, it and metailic
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Adverse reactions: Drowsiness, headache, cramps
provokes the sensation but takes away the performance.
taste in the mouth.
9. Food value: Alcohol gives rise to energy due to its rapid
c
c
utilisation. But it is not a true food becuase the energy produced is CITRATED CALCIUM CARBIMIDE (C.C.C) is ar other drug
y
y
not sufticient even for basal metabolism. which acts similar to disulfiram. It is a mixture of calcium
absorbed in the carbimide (1 part) and.citric acid (2 parts).
Absorption, fate and excretion: Alcohol is
It is metabolised in the METHYL ALCOHOL (METHANOL): It is knowr as wood
stomach (25%) and sunall intestine (75%).
liver as follows:
Ethy! alcohoi
Alcohol
dehydrogenase
Acetaldehyde nae alcohol since it is prepared by destructive distillation
is unsuitable for drinking since it produces poisonous
Formaldehyde, a metabolic product of methyl alconhol
of wood. It
effects.
danmages
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methyl
Aldehyde optic nerve leading to blindness. In case of poisoning with
Acetaldehyde Acetyl CoA
ethyl alcohol is given. Ethyl alcohol is metabolised
dchydrogenase alcohol,
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Acetyi CoA is fiuther metabolised to carbondioxide and water. preferentially over methyl alcohol. So methyl alcohol is excreted
Alcohol is eliminated mostly through kidneys and lungs. unchanged.
y
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acidosis)
Acute alcoholism: The symptoms of acute alcoliolism are In addition to this, sodium bicarbonate (to counteract
Ph
Ph
Ph
Also, fomepezole
incoherence, incoordination, fall in body temperature and blood and folinic. acid may also be administered.
ha
pressure and respiratory depression. Treatment consists of siomach (4-methylpyrazole) can be given. It is a specific inlhibitor of alcoho!
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wash, oxygen inhalation, maintenance of warmth and injection of dehydrogenase.
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analeptics.
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GENERAL ANAESTHETICS
Chronic alcoholism: The manifestations of chronic alcoholism zre 13.
atropic changes in gastrointestinal tract, degenerative changes in the
ac
liver and nerves. Also addiction and wilhdrawal symptoms may General anaesthetics are agents which produc: a reversible
cy
cy
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loss of consciousness, so as to enable surgical
operations to be
y
develop.
carried out.
anaesthetics
Classification of general anaesthetics: The gene al
can be classified as:
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Ph
Ph
Ph
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2. It irritates mucous membranes and produces cough.
1. Innalation anaestlietics
It increases secretions of respiratory tract.
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3.
a. Volatile liquids Ether
Halothane 4. Produces nausea and vomiting during recovery.
y
Enflurane 5. Recovery is slow.
fluorinated volatile anaesthetic. It is a
Ph
Ph
Ph
Isoflurane B. HALOTHANE: It is a
Desflurane fruity odour. It
ha
heavy, colourless liquid with a characteristic sweet,

Sevoflurane nubber elenments of
attacks nmetals like steel and brass and also
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Nitrous oxide anaesthetic equipmet.
r
b. Gases
halothane.
Malignant hyperthermia is an an important toxicity of
ma
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L. Intravenous anaesthetics Thiopentone
sarcoplastic reticulunm. It
(Non-volatile Propofol It is due to the release of calcium from the
dantrolene (a directly acting nmuscle
anaesthetics) Etomídate is treated by the administration of
c
c
Benzodiazepines relaxant).
y
y
Ketamine
Advantages:
anaesthetic, It does not irritate respiratory passage.
Stages of anaesthesia: While administering a general I. It is non-inflammable.
the depth of anaesthesia which is related to recovery are quick.
it is necess.iry to control 2. Induction and
the following
dose. The progress of anaesthesia may be divided into 3. It does not produce bronclhospasm and coughing.. But it
four stages nmaking use of various signs and
1. Stag: of analgesia
symptoms:
Ild produces bronchodilatation. So it is preferred in asthimatic
patients.
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field
2. Stage of delirium or excitement 4. It induces controlled hypotension. So it produces bioodless
for safe plastic surgery.
Stage of surgical anaesthesia
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3.
.
Disadvantages
4. Stage of respiratory paralysis
1. Muscle relaxation is not adequate
y
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vOLATILE LIQUIDS 2. Respiratory depression at 2% concentration.
Ph
Ph
Ph
a 3. Cardiovascular depression and hypotension.
ETHER (DIETHYL ETHER): It is colourless and volatile liquid.
ha
with a pun gent odour. It is highly inflammable and explosive.

It is 4. Arhythmias due to sensitisation of myocardium to adrenaline.
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quickly ab:orbed and eliminated through lungs. 5. Delayed recovery of mental function.
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6. Increase in intracranial pressure due to cerebral vasodilatation.

Advntage:
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ma
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7. Hepatic damage due to allergy or idiosyncrasy.
1. It is a safe anaesthetic.
ac
2. It produces satisfactory muscle relaxation. C. ENFLURANE

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3. It dues rot produce liver or kidney danmage. It is a nonirritating, non inflammable liquid with a mild odour.
y
1.
It does not affect uterine contractility. It undergoes less metabolism than halothane, so toxicity is
less.
4. 2.
5. It can be administered without complicated apparatus. 3. Faster induction and recovery than halothane.
-
Disudvanges: 4. Risk of epilepsy like seizures during induction or recovery.
1. Induction is slow and unpleasant. 5. Contraindications patients with epilepsy or brain lesions.
St
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ud
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y
y
Ph
Ph
Ph
h
y
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oxygen of nitrous oxide
D. ISOFLURANCE. It does not decompose in the body. So the
respiration. It is excreted unchanged
. is not available for tissue
ud
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ud
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It is an isomer of enflurane. But it is nore potent and more
nmay be eliminated through
volatile. through the lungs. A small quantity
It is more stable and non inflammable skin.
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2.
3. It does not sensitise the myocardium to adrenaline. Advantages:
Ph
Ph
Ph
4. Muscle relaxation is good. 1. Induction and recovery are quick.
ha
5. Hepatotoxicity is rare. 2. No irritation to mucous membranes.
ar
ar
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Caution is needed in patienls with coronary artery disease surgery
6. produce analgesia which can be used for minor
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3. It can
(CAD) since it produces coronary steal phenomenon. It is or tooth extraction.
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ma
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accompanied by hypotension and increase in heart rate.
4. It is non-toxic to liver and kidney.
E. DESFLURANE: Disadvantages
c
c
It is highly volatile and less soluble in blood and tissues. So potent anaesthetic
y
y
1. 1. It is not a
induction and recovery are quick. 2. Muscle relaxation is not adequate.
2. Its pungent odour may cause iiTitation leadng to coughing and 3. Special apparatus is required for its use.
laryngospasm. excitation during indu:tion.
3. it does not produce arhythmia or seizures
4 No liver or kidney toxicity.

5.
maebO
Suitable as an anaesthetic for outpatient surgery and the patient
4. It produces cuphoria and
INTRAVENOUS ANAESTHETICS
(Non-volatile general anaesthetics)
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can be discharged within few hours.
is produced within
These are quickly acting drugs. Anaesthesia
F. SEVOFLURANE are inostly used as
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intravenous administration. They
20 seconds on
newer poly fluorinated anaesthetic. is induced, it is maintained by an
1. It is a inducing agents. Once anaesthesia
Less potent and less soluble than isoflurane. inhalational agent. The intravenous anaesthetics arc thiopentone,
y
y
2.
3. It is not pungent, so anaesthesia is pleasent. propofol, etonidate, midazolam and ketamine.
Ph
Ph
Ph
Recovery is smootl, Orientation and motor functions recover yltra short acting barbiturate. The
A. THIOPENTONE: It is an
-
4.
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rapid, redistribution. in intravenous

quickly. ultra-short action is due to
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anaesthesia within 15 to 20 seconds. It enters
5. It does not produce seizures or arrhythmia. injection, it produces
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to muscles and fat. So

6. No toxicity to kidney or liver. the brain inmediately and redistributed
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consciousness retums in 10-15 minutes.
ac
GASEOUS ANAESTHETICS
Advantages.
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NITROUS oXIDE: It is also callied as laughing gas. It is an 1. Non- explosive.
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inorganic gas which is colourless and swect in taste. It is heavier 2. Easy to administer.
than air. It is non-inflammable but supports combustion. Induction is rapid and pleasant.
It is insoluble in blood and it does not combine with 4. No irritation of mucous menbranes.
are less.
hemoglobin. It is carried in blood in the form of physical solution. 5. Excitement, nausea and vomiting
St
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ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
Telegram - Study Pharmacy D. BENZODIAZEPINES:
28 preanaesthetic medication ii) induction ii)
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They are used for i)
of, anaesthesia. They do not
6. Quiet respiration maintenance and iv) supplementation
Also, they do not produce
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No sensi isation of myocardium to adrenaline. depress respiration, heart or B.P.
7.
They have a central. muscle
post-operative nausea or vomiting,
8. Recovery is quick. adequate muscle relaxation is produced by a
relaxant effect. But
y
No post anaesthetic complications. and midazolam are the
9.
neuromuscular blocking drug. Diazepam
Ph
Ph
Ph
anaesthesia.
benzodiazepines frequently used for
ha
Disadvantages.
a) DIAZEPAM:
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activity.
1. Poor analgesic and weak muscle relaxant It is used at a dose of 0.2-0.5
mg/kg. lt is administered by slow
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2. Apnoea, cough, hiccup and laryngospasm may

occur during
undiluted injection in a i.v. drip.
This technique avoids burning
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ma
ma
ma
inductior. thrombophlebitis. Diazepam is used for
sensation in the vein and also
less sensitive
3. Depressin of respiratory centre which becomes i) induction and maintenance of
anaesthesia.
c
c
to CO2 .
ii) endoscopy, cardiac

catheterisation and angiographics.
Depression of vasomotor centre and myocardium.
y
y
4.
5. Injection close to a nerve may produce palsy. b) MIDAZOLAM: diazepam.
and It is 3 tinmes more potent, also
fáster and slhorter acting than
6. Injection into an aretery may lead to pain, necrosis it is prefered over diazepam.
gangrene. It is water soluble and non-initant. So
is a non-barbiturate
general
oh.arnma
It
B. KETAMINE (KETALAR).:
B. PROPOFCL (a)r anaesthetic. It produces dissociative
anaesthesia
It
characterised
produces only
by
poor
1. It is an oily liquid used as 1% emulsion. superficial sleep and complete analgesia.
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2. It is usel for i.v. induction and short duration anaesthesia. muscle relaxation.
for
3. Induction occurs in 30 seconds and anaesthesia many last Advantages
ud
ud
ud
u
10 minu es. There is no hangover.
1. It is useful only for short procedures like dressing of burns and
Along with fentanyl, it is used for total i.v. anaesthesia.
4. bronchoscopy.
y
y
5. It has a specific antiemetic action. 2. It does not affect respiration.
Ph
Ph
Ph
6. Post oerativenausea and vomiting is less. Disadvantages.
ha
7. Because of short action, it is suitable for out patient

surgery.
Delirium and hallucinations are
produced during induction and
1.
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ar
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recovery.
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C. ETOMIDATE: are increased.

2. Blood pressure and heart rate
(5-10
ma
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1. It is an i.v. ananaesthetic with' a brief duration of action 3. laryngospasm and salivation.
It produces
ac
min)
4. Muscle relaxation is poor.
quickly nietabolised and has a large margin of safety.
cy
cy
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2. It is
NEUROLEPTANALGESIA
Less resipiratory and cardiovascular depression.
y
3.
Disadvantages which induce apathy and
4.
Neuroleptics (antipsychotics) are drugs and uncaring
a) involuntary movements during induction. mental detachment. So the patient is mildly sedated
use.
b adrencortical suppression on prolonged
c) poor nalgesic effect.
St
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ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
30
surroundings.
about theNeuroleptanalgesia is a iethod of intravenous Qualitatively hypnotics and sedatives produce depression of
central nervous system and the difference between them is mainly
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anaesthesia which combines neuroleptics and opioid analgesics. With
quantitative.
neuroleptanalgesia, the patient is conscious and also co- operative for
ud
ud
ud
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surgery. The combination frequently used for neuroleptanalgesia is Classification of sedative - hypnotics
droperidol (a neuroleptic) and fentanyl (an analgesic).
Phenobarbitone
y
It has antipsychotic effects like chlorpromazine. It Barbiturates
Droperidol Mephobarbitone
calming effect 2.antiemetic effect 3. alpha adrenergic
Ph
Ph
Ph
has 1.
Butobarbitone
blocking eflect 4. cextrapyranidal effect.
ha
Secobarbitone
Fentany: It is a morphine like opioid analgesic. It is 100 times
ar
ar
ar
-
Pentobarbitone
more potent than morphine. Like morphine, it produces depression of
r
Thiopentone
respiratory and cough centers. Tt also produces miosis and vomiting.
ma
ma
ma
ma
Hexobarbitone
These actions are antagonised by naloxone. Methohexitone
c
c
2. Benzodiazepines Diazepanm
PRE-ANAESTHETIC MEDICATION Flurazepam
y
y
Nitrazepam
The term 'pre-anesthetic medication' refers to the use of drugs
prior to the administration of anaesthetics, so as to make anaesthesia Newer non-benzo Zopiclone
safe and agreeable to the patient. Premedication aims at providing diazepines Zolpidem
the following effects
BARBITURATES: Barbiturates are derivatives of baribituric acid
1. Sedation to reduce anxiety of the patient before surgery. This (1malonylurea) which is obtained by the condensation of urea and
can be achieved by sedatives, lhypnotics and tranquilisers. Usually malonic acid.
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morphine and its derivatives and also barbiturates are given.
Barbituric acid itself does not possesshypnotic ativity. But
2. Analgesia aclhieved by morphine and pethidine. hypnotic activity is produced, if the hydrogen atoms at pcsition are
5
ud
ud
ud
u
These
analgesics reduce pain and also decrease the amount of general replaced by alkyl or aryl groups.
anaesthetic requred.
y
y
3. Inhibition of parasympathetic activity so as to decrease HHQ:Oc
Ph
Ph
Ph
N
bronchial and salivary secretion induced by drugs like ether.
ha
4.Antiemetic effect to prevent post-operative nausea and vomiting. O=C O=C2

ar
ar
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Phenothiazines like promethazine are used.
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N HOjoc
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ma
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H
14. HYPNOTICS AND SEDATIVES Urea Malonic acid Barbituric acid
ac
cy
cy
cy
Hypnotics are drugs which produce sleep resembling natural Classification of barbiturates:
y
sleep. Phenobarbitone
1. Long acting
Sedatives are drugs whiclh reduce excitement without Mephobarbitone
producing sleep.
St
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ud
ud
ud
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y
y
Ph
Ph
Ph
h
y
y
33
small extent in kidney and brain. Excretion
is through urine both in
St
St
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2. Short actin3 Butobarbitone free fom and as glucuronic acid conjugate.
Secobarbitone
Adverse reactions
ud
ud
ud
u
Pentobarbitone
3. Ultra short acting Thiopentone 1. Intolerance like nausea, headache and diarrhoea,.
Hexobarbitone administered Guring labour.
2. Foetal respiratory depression if
y
Methohexitone to
automatism due to repeatedly taking the drug owing
Ph
Ph
Ph
3. Drug
Pharmacological actions: forgetfulness.
ha
1. Central nervous system: Barbiturates produce all degrees of Tolerance because of increased inactivation
in the liver.
ar
ar
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4.
CNS depression ike mild sedation, hypnosis and general anaesthesia. symptoms.
r
5. Dependence and withdrawal

a. Sleep: Barbiturate-induced sleep resembles natural sleep. But it
ma
ma
ma
ma
decreases the time spent on "rapid-eye-movement sleep' (REM sleep). Therapeutic uses :
Also there s han;yover effect after awakening. 1. Sedation in case of anxiety or tension.
c
c
b. Analgesic effe:t Barbiturates do not relieve pain without
:
Hypnosis to relieve insomnia.
y
y
2.
producing unconsciousness. But they enhance the analgesic effect of epilepticus.
3. AnticQnvulsant effect in case of tetanus or status
salicylates and para-amino phenol derivatives. produce basal anacsthesia.
4. Pre-anaesthetic nmedication and to
c. Anaesthetic ef'ect: Thiobarbiturates and some ultra short-acting Potentiation of analgesics. like salicylates.
5.
oxybarbiturates pioduce anaesthesia on intravenous administration. jaundice.
6. In psychiatric practice and in neonatal
d. Anticonvulsant effect: Barbiturates like phenobarbitone which
have a phenyl group at the Sth carbon atom have anticonvulsant effect. are
BENZODIAZEPINES: Diazepam, nitrozepam and flurazepam
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c. Respiration: Respiration is not affected at sedative or hypnotic is the commonly used
the important benzodiazepines. Diazepam
dose. Large dose administered intravenously, may produce death due 1) anxiolytic 2) hypnotic 3) anti-
ud
ud
ud
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drug. The benzodiazepines have
to central respiratory paralysis. benzodiazepines
convulsant and 4) muscle relaxant effects. All the
produce less unconsciousness and
2. Gastrointestinal tract: Intestinal motility is not affected at a have a hypnotic effect. They
y
y
relatively non-toxic.
normal dose, but gastric secretion may be depressed. respiratory depression. So these compounds are
Ph
Ph
Ph
3. Uterus: Force and frequency of uterine contractions are
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depressed at toxic dose. NEWER NON-BENZODIAZEPINES

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sedative. It is a
4. Kidney: No effect at nommal dose, but anaesthetic dose decreases ZOPICLONE: It is a non-benzodiazepine
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shortens sleep latency and increases total

urinary output due o decrease in glomerular filtration and release of ADH. cyclopyrrolone derivative. It
ma
ma
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also there is no hangover.
sleep time. It does not affect REM sleep and
5. Liver: No eflect at nomal dose but anaesthetic dose may produce occur.
ac
Tolerance or rebound insomnia does not

hepatic dysfunction.
cy
cy
cy
It decreases sleep
ZOLPIDEM: It is an imidazopyridine derivative.
y
Absorption, fate and excretion :Barbiturates can be It has a weak anticonvulsant

latency and increases sleep duration.
administered by oral and parenteral routes. They are distributed in or physical dependence 2) low
effect. Advantages: 1) No tolerance
all tissues and bocdy fluids. They cross placental barrier and also are 4) safety with overdosage.
abuse potential 3) no rebound insomnia
excreted in milk. They are chiefly metabolised in the liver and to a
St
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ud
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y
y
Ph
Ph
Ph
h
y
y
34 35
Telegram - Study Pharmacy It is well absorbed after oral administration. T he onset of
It is metabolised
St
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15. DRUGS EFFECTIVE IN action is slow. But the duration of action is long.
ring. The nmeiabolites are
by parahydroxylation of the phenolic
CONVULSIVE DISORDERS
ud
ud
ud
u
enterolhepatic circulation. It is almost completely
subjected to
excreted in urine within 48 hours.
Epilepsy: Epilepsy is a collective tem applied for a group of
y
convulsive disorders. The common features of epilepsy are: Adverse reactions:
Ph
Ph
Ph
. tremors, headache, ins omnia and
loss or disturbance of consciousness. CNS symptoms: Giddiness,
ha
2. characteristic body movements (usually but not always). drowsiness.
ar
ar
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3. autonomic hyperactivity. Gastrointestinal effects: Nausea, vonmiting and anore. ia.
r
The different types of epilepsy are grand mal epilepsy, petit Urticarial, scarlantiform and nmeasles-like rashs.
ma
ma
ma
ma
Rashes
mal epilepsy, psychomotor epilepsy, myoclonic epilepsy etc.
Gums Swelling of gums, bleeding and gingivitis.
Classification of anti-epileptic drugs:
c
c
Foetal hydantoin syndrome: When used in pregnancy, il causes
y
y
1. Hydantoins Phenytoin cleft palate, hair lip and microcephaly in the foetus.
niegaloblastic
2. Barbiturates Phenobarbitone Miscellaneous : Blood dyscrasias, hepatitis, jaundice,
Primidone anemia and lymphadenopathy.
it is gradually
Carbamazepine mg. three times daily by oral route and
3. Iminostilbenes
Ethosuximide
Dose: 00
increased to 500 mg
4. Succinimides
und cardiac
Aliphatic carboxylic acids Sodium valproate Use: Grand mal epilepsy, psychomotor epilepsy
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5.
(Valproic acid) arrhythmias.
is
BARBITURATES :
The most important anticonvulsant harbiturate
ud
ud
ud
u
6. Benzodiazepines Clonazepam
grand mal, focal cortical and
Clobazam phenobarbitone. It is effective in
in petitnal epilepsy
Diazepam psychoniotor epilepsy. It should not be used
y
y
(since it is aggravated). Sudden withdrawal of ph>nobarbitone
7. Newer antiepileptics Lamotrigine it must e gradually
Ph
Ph
Ph
Gabapentine increases the frequency of convulsions. So
ha
substituted by phenytoin.
Vigabatrin
leth:argy.
ar
ar
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Trimethadione The toxicities are drowsiness, depression and
8. Miscellaneous
rm
Phenacemide Dose: 60 to 180 mg. daily in divided dosses.

ma
ma
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Acetazolamide
CARBAMAZEPINE: It is a tricyclic compound. It has a structural
ac
HYDANTOIN DERIVATIVES : Diphenylhydantoin (Phenytoin) is the siilarity to imipramine, an antidepressant drug.

cy
cy
cy
most important derivative. It acts by: 1. It is more effective in temporal lobe epilepsy. It1s also
y
1. nomnalising the lowered threshold for seizures. effective in grand mal epilepsy.
2. It improves the personality, attention and
co entration of
2. reducing sodium concentration in brain cells which leads to
decrease in post-tetanic potentiation (P.T.P.). epileptic patient.
St
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ud
ud
ud
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y
y
Ph
Ph
Ph
h
y
y
36
re:narkably effective
3. It is in trigeminal neuralgia and 37
St
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glassophayngeal neuralgia. changes, tremor
Adverse reactions: Drowsiness, ataxia, personality
But the overall skin eruptions,
4. It is slowiy absorbed on oral administration. vertigo and confusion. Sometimes anemia, leucopenia,
ud
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ud
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bioavailatbility is 90%. cardiovascular and gastrointestinal effects.
Adverse ieactions: emergency control of
DIAZEPAM : It is the drug of choice for
5.
y
i. Anorexia, nausea, vomiting, giddiness and
skin rashes. epilepticus and tetanus. For this purpose, it is
convulsions like status
Ph
Ph
Ph
ii. Diploia and þlurred vision. given intravenously.
ha
blocking
peripheral neuritis LAMOTRIGINE: It is a phenyltriazine compound. It acts by
ii. Agrarulocytosis, obstructive jaundice,
ar
ar
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preventing the release of glutamate. This
sodium channels and
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and aplastic anemia.

presynaptic membrane. It is used as an add-on treatment in
. stabilises
ma
ma
ma
ma
- 100 mg. twice a day as tablets. Gradually
Dose Initial patients resistant to other antiepileptic drugs
increased to 600 to 1,200 mg. per day for temporal lobe ataxia and
diplopia,
epilepsy. Adverse reactions: sleepiness, dizziness,
c
c
Ethosuximide is an important member of this vomiting
y
y
SUNCCINIMIDES :
t 1s ettective on GABAPENTINE: centrally active GABA agonist. It has a high

It is a
group. It is eff:ctive only in petitmal epilepsy. receptors. But it acts by
Adverse effects are anorexia, nausea, lipid. solubility. It does not act on GABA
oral adnministr ation. is well absorbed orally.Jt is excreted
releasing GABA. Gabapentine
vomiting and drowsiness. It is available as capsules and
syTup.
increased by 250 mg. unchanged in urine.
Dose: Initial 250 mg. per day. Gradually
cach week to maximum of 750 to
a
sODIUM VALPORATE: (Valproic acid)

1000 mg. daily.
IIla Adverse reactions : mild sedation, tirednéss and
Use: Partial seizures resistant to other drugs.

dizziness.
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. It ishigtly effective in petit mal epilepsy. It
is ineffective in
VIGABATRIN: It is a GABA transaminase inhibitor.
It acts by
ud
ud
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focal corical epilepsy and temporal lobe epilepsy. increasing synaptic GABA concentration. II is well absorbed orally
2. Mechani: m 1. inhibition of gamma aminobutyrate and excreted unchanged in urine. It is useful in refractory epilepsy
potentiation of post synaptic GABA activity. Adverse effects are weight gain,
y
y
not controlled by other drugs.
1i.
transamiase
adnministration. It is
3. It is conpletely absorbed after oral drowsiness, depression and diplopia.
Ph
Ph
Ph
bound to plasma proteins (95%) Also 90% is
extensively .
to high
PHENACEMIDE: It is an acetylurea derivative. Due
ha
metaboli:sed in the liver. only to psychomotor epilepsy

incidence of toxicity its use is restricted
ar
ar
ar
4. Adverse reactions Nausea, vomiting, hepatic damage,
co-ordination. Spina bifida when used refractory to other drugs.
rm
sedation, ataxia and in

It is used
ACETAZOLAMIDE: It is a carbonic anhydrase inhibitor.
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ma
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in pregn:uncy.
in petitmal epilepsy. It also has a diuretic
effect.
Dose: 60 mg to 1600 mg. per day orally.
ac
5.
cy
cy
cy
CLONAZEPAM: It is a benzodiazepine compound.
It is effective 16. OPIOID ANALGESICS
y
myoclonic seizures. It can be used with phenytoin

in petit mal and causing loss
or phenobarbitone for treating grand mal
epilepsy. It acts by Analgesics are drugs which relieve pain without
increasing the «effect of GABA in CNS. of consciousness.
oprum poppy.
Opiates means products obtained from the
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ud
ud
ud
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y
y
Ph
Ph
Ph
h
y
y
39
MORPHINEL
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Opioid analgesics are the naturally occuring, semi-synthetic
i:e. relief of Opium is ihe nilky
and synthetic drugs which have a morphine like action Source Morphine is a natural opium alkaloid.
:
ud
ud
ud
u
plant, Papaver soI niferum
pain and depress1on of CNS. exudate of unripe capsules of the poppy
can be classified nto:
Narcotic analgesics in an old term for opioid analgesics. The alkaloids of opium
y
Morphine and other opioids act through a. phenanthrene group which
ncludes morphine, codine and
Opioid receptors:
Ph
Ph
Ph
specific receptors present in the CNS and peripheral tissues. The thebaine.
ha
following are the opioid receptors and their functions b. benzylisoquinoline group which ncludes papaveiine, noscapine
ar
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depression, and narcine.
(mu). analgesia (supraspinal), respiratory
r
1.
euphoria, sedation and physical dependence. Pharmacological actiôns:
ma
ma
ma
ma
and
2. k (kappa): analgesia (spinal), dysplhoria and sedation Morplhine relieves severe pain like visceral pain
1.Analgesia: The mechanisnis are
analgesia (spinal and affective component of
c
c
3: 8
(delta) :
pain of trauma.
painful stimulus.
y
y
supraspinal) and emotional behaviour: i. it elevates the threshold for
Opiopeptides: These are endogenous peptides havivg imorphine ii. it alters the emotional _reaction to pain.
like action. The opiopeptides are endorphins, enkephalins
and . produces sleep which also elevates
it
the threshold.
presentin brain, pituitary gland and G.I tract. Morplhine produces eurhoria in
2. Central nervous system
dynorphins. They are :
naloxone, produces dysphhoria.

They are active in small amounts. Their action is blocked by pain, it
presence of pain. But in the absence of
an opioid antagonist.t
Ldllld With an increased dose, it produces sleep
produces depression of respiration
by
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Classification of opioid analgesics: 3. Respiration: Morphine gecre asing tIe
a) directly depressing the
respiratory center b)
carbondioxide.
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1. Natural opium alkaloids respiratory center
sensitivity of
to
This
a) Phenanthrene Morphine produces constriction of pupil (mios:s).
4. Pupil: Morphine have constr cted pupil
Codeine Morplhine addicts
y
y
derivatives effect is blocked by atropine.
Thebaine pupil).
Ph
Ph
Ph
(pin point
Benzylisoquinoline Papaverine : In small doses, morphine
produces vo:niting due
ha
b) 5. Emetic action
derivatives Noscapine
to the stimulation, of.
chemoreceptor trigger zone (C1Z). Tolerance
ar
ar
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use. But a large dose o morphine
2.Semisynthetic derivatives Heroin develops to vomiting. on prolonged
rm
Dihydromorphine .
of opium alkaloids inhibits vomiting
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ma
ma
depressing
Apomorplhine
effect: Mophine suppresses cough by
6.Antitussive
ac
Synthetic substitutes Pethidine the coughcenter.

3:
cy
cy
cy
of opium alkaloids Methadone Morphine produces release of AIH.
This
7. ADH secretion:
y
Butorphanol output.
results in decrease of urinary
Pentazocine
Morphine decreases pernstaltic propulsive
Nalbuphine 8. Gastrointestinal tract: muscles and
produces spasm of intestinal smooth
Buprenorphine movements. It
**
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St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
41
St
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So, the feces get Therapeutic uses
sphincters. also incrcases absorption of water. severe pain.
As an analgesic for the relief of
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dried. All tlese effects lead to constipation. 1.
oddi. For producing sedation and sleep.
9. Biliary tract: Morphine
produces spasm of sphincter of 2.
Atropine antagonises As pre-anaesthctic medication.
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mtrabiliary pressure. 3.
This produce: increase in
left ventricular failure.
4. In the treatment of acute
Ph
Ph
Ph
this effect.
5. For the treatment of
diarrhoea.
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10. Other smoath musdes

As an antitusSive.
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6.
i. Monph:ne increases the tone of detrusor
muscle of urinary
vesical sphincter
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urgency). But
bladde (this produces urinary OTHER OPIOID ANALGESICSs
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is contracted.
decreases its peristalsis. pharmacologica actions of
i. It incr >ases tone of ureter and The following are the important
ction of bronchi is produced at large doses.
c
c
ii. Constri morphine
A
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severe pain.
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11. Cardiovascular system
: Nornmal doseof morphine produces 1. Analgesic effect in case of
produced sphincters.
no effect on heart or circulation. But hypotension may be 2. Spasnmógenic effect on smooth muscles and
at toxic dost. 3. Antitussive effect.
Absorption. fate and excretion: Absorption of

gastrointestinl tract is slow and incomplete. Quick
on subcutancous injection. It is partly bound
glucuronic
to
acid.
morphine from
effect
plasma
is produced
It
proteins. It
is almost
4. Nausea and vomiting.
5. Addiction and tolerance.
6. Miosis (constriction of pupil)
pdf M
may have some or all these
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conjugation with
is metaboliscd by The other opioid analgesics
excreted in urine within 24 hours. morphine.
completely pharmacological actions of
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alkaloid of opium. It has a
Preparatins and dose CODEINE: It is a phenanthrene
it is used for the treatment of
Tncture opium 0.3. to 2 ml. by mouth predominant antitussive effect. So
1. compared to morphine. The
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cough. It is a less potent analgesic when
2. Morphine sulphate 8 to 20 mg. by mouth or effect, nausea and vomiting, miosis
other actions like spasmogenic
Ph
Ph
Ph
by injection by morphine) are less with
3. Morphine hydrochloride and addiction (which are produced
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codeine.
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Adverse reactions alkaloid of opium. It does
PAPAVERINE: It is a benzylisoquinoline
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clouding
1. Centrl effects like dysphoria and mental pharnmacological actions as produced by
not produce any. of the
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Gastrvintestinal symptoms like nausea, voiting and cffect on smooth muscles
2.
morphine. It has a predominant relaxant
ac
constiation. alkaloid of opuim. It

NOSCAPINE: It is also a benzylisoquinoline
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treor, delirium and skin rashes.
3. Intole ance like
a significant antitussive, elfect.
It does not have tlhe other
has
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4. Acute morphine poisoning characterised by respiratory

reduced body temperature, disadvantages of morpline.
depre: sion, pin pont pupl, cyanosis, It is a semisyntlhetic derivative
hypotnsion, shock and coma. HEROIN (DIACETYLMORPHINE):
analgesic than morphine. Because
Depre ssion of foetal respiration. of morphine. It is a more potent
5.
of producing severe addiction.
,
it produces euphoria,
it is capable
6. Tolerince and drug dependence.
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Ph
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OPIOID ANTAGONISTS
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APOMORPHINE: It is also a semisynthetic derivative of morphine.
It is obtained by treating morphine with concentrated hydrochloric antagonise. he effects of
Opioid antagonists are drugs which
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acid. It is an emetic and this effect is produced due to simulation of are class:fied as:
morplhine and other opioid analgesics. These
chemoreceptor trigger zone (CTZ)
Naloxone
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1. Pure antagonists
PETHIDINE: It is a synthetic compound. Pethidine produces:
Ph
Ph
Ph
analgesic effect. Nalorphine
2. Partial agonists
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2. spasnmogenic effect on smnooth muscles and sphincters. Levallorphan
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3. nausea and vomiting. Cyclazocine
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4. sedation and euphoria.

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NALOXONE:
5. respiratory depression.
1. analogue of oxymorphone.
It is N-allyl
These effects are similar to those produced by morphine. But depression produced by
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2. It selectively antagonises respiratoiy
pethidine does not produce miosis and antitussive effect as is produced opioids.
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morphine and other
by morphine. it is potent on parenteral
3. Because.of inactivation in the liver,
Pethidine is satisfactorily absorbed on oral and parenteral administration than on oral administration.
administration. It crosses the placental barrier. It is also secreted in naloxone docs not produce
4. It is a pure antagonist. So by itself,
Adverse reactions:
1.
narmnae
milk. It is metabolised in liver and excreted in urine
local irritation on parenteral administration.

respiratory depressant. analgesic
5. It does not produce withdrawal
withdrawal symptoms of
or
morphiie
euphoriant
synmptoms.
and heron.
e fects.
Buti decreases the
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in opioid poisoning
2. dry mouth, nausea and vomiting. 6. It is used as an antagonist
It is a semisyn:hetic congener
euphoria, dysphoria, weakness and palpitation. NALORPHINE (N-allyl normorphine):
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3.
4. depression of foetal respiration. of morphine.
:
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5. respiratory depression, coma and convulsions. Pharmacological actions:
addiction and tolerance. alone, it pi oduces alnmost
When nalorphine is administered
Ph
Ph
Ph
6.
1.
prociuces analgesic
all the effects.of morphine. Thus nalopline
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Preparations and dose: nausea and

smooth muscles,
eftect, spasmogenic effect on
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1. Pethidine hydrochloride tablets 25 to 100 mg. But it dces not produce
vomiting, antitussive effect and miosis.
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2. Pethidine hydrochloride injection 25 to 100 mg. by sub- addiction.

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cutaneous or intramuscular injection and 25 to 50 mg. by presence of morphine, nalorphine
2. When administered in
intravenous injection. of morphine except antitussive
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antagonises all these effects

METHADONE: It is a synthetic opioid. It has analgesic, respiratory
cy
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effect.
depressant, emetic, antitussive, constipating and biliary actions similar a morphine addi:t, nalorphine
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3. When administered to
to morphine. It is used in the treatment of opioid dependence. produces withdrawal symptoms.
Mechanism: When substituted for morphine, methadone accumulates Absorption of nalorphine from
in tissues. On discontinuation, it is slowly releaed from these sites. Absorption, fate and excretion:
gastrointestinal tract is poor. But it is quickly absorbed after
So the withdrawal symptoms are mild.
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Ph
Ph
Ph
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Telegram - Study Pharmacy NSAID and prostaglandin synthesis.
44
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(analgesic, antipyretic and
in brain. It is The three major actions of NSAID
subcutaneous injection. High concentration is present antiinflammatory) are mediated thfough inhibition of prostaglandin
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metabolised in the liver. (PG) synthesis.
3 to 10 mg. by
Preparation and dose: Nalorphine injection: Phospholipid (of cell membrane)
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subcutaneous r intravenous injection.
Ph
Ph
Ph
Therapeutic uses: Arachidonic acid
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1. Treatme'nt of poisoning due to morphine and related COX-I
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compounds.
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2. Diagnosis of morphine addiction.

COX-2
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Prostaglandins
3. Treatment of morphine addiction.
LEVALLORPHAN: It is an opioid antagonist similar to nalorphine.
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It does not reverse pethidine INFLAMMATION
It is more potent than nalorphine.
.
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arachidonic acid (AA) is
induced respir atory depression. During pain, fever and intflammation,
cell membrane.
CYCLAZOCliNE: It is an opioid antagonist similar to nalorphine.
It liberated from phospholipid fraction of
prevents the converts araclhidonic acid
antagonises tiie euphoriant action of morphine and 2. The enzyme cylooxygenase (COX)
is useful for treating prostaglandins formed are responsible
development of physical dependence. So it to prostaglandins. The
inflammation.
morphine intoxication and morphine addiction. for
enzyme cycloxyganase viz.
pure opioid 3. There are two forns of the
NALTREXONE: It is an orally effective, long acting, cycloxygenase-2. (COX-2).
cycloxygenase-1 (COX-1) and
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antagonist. Advantages: present and it is found in blood vessels,
COX-1 is always - 2 is induced only during
1. well to erated stomach and kidney. But COX
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2. no eup'1oric effect. inflammation.
COX inhibitors and they
3. no phy sical dependence Drugs lik asprin are non-selective -
2. Asprin inhibits COX
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and COX
4. blocks the effect of heroin and other opiates for four
days. inhibit both COX -
1 this enzyme.
ireversibiy by acetylation of
Ph
Ph
Ph
COX -2 selectively e.g. Celecoxib,
ANALGESIC ANTIPYRETICS 5. Certain drugs inhibit
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17. Valdecoxib.
Rofecoxib and
analgesics, NSAID)
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Non-opioid
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Analgesic-antipyretics are, drugs which produce relief of pain Classification of drugs
pain of lesšér
of body temperature. These drugs relieve
ac
and lowering
intensity 1like tooth-ache and muscle pain. But they do not relieve A.Non selective COX inhihitors
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opioid analgesics. Asprin
severe pain like visceral pain which is relieved by 1. Salicylates and
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All these drugs produce congeners Salicylic acid

Also these drugs do not produce addiction.
Sodium salicylate
they àre called as non-steroidal
an anti- inflammatory effect. So Methylsalicylate
anti-intlammatory drugs (NSAID). Since they act without
receptors, they are called as nonopioid
interacting with opioid
analgesics.
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Ph
Ph
Ph
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46 47
Telegram - Study Pharmacy 4. Gastrointestinal tract: Salicylates produce
nausea and vomiting
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2. Para-aminophenol Paracetamol due to a) direct iritation b) stimulation of chemoreceptor
trigger
derivativesl can also cause gastric ulceration and hemorhage.
zone. Salicylates
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3. Pyrazolon derivatives Aminopyrine
5. Antiinflammatory and antitheumatic effect:
Salicylates have powerful
Antipyrine
Phenylbutazone anti-rheunmatic effect. This effect is produced by reducing pain and
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Oxyphenbutazone inflammation of the joints.
Ph
Ph
Ph
Immunological effect: Salicylates inbibit an' igen-antibody
****
4. Miscellaneous Indomethacin 6.
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Ibuprofen reaction and so prevent the release of histamine.
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Mefenamic acid
7. Uricosuric effect: Salicylates promote the excretion ofuric acid.
Piroxicam
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in
This effect is produced by inhibiting the reabsorption of uric acid
Diclofenac
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the proxinmal tubule.
Ketorolac
Nimesulide 8. Cardiovascular system: No effect at normal does. Toxic doses
c
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B. Selective COX-2 inhibitors produce paralysis of vasomotor center.
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Celecoxib 9. Blood: Salicylates lower erythrocytic sedimentation
rate (ESR)
Rofecoxib fever. They also decreas prothrombin
which is highin theumatic
Valdecoxib levelof plasma.
Nemesulido from
Endocrines: Salicylates stimulate the release of alrenaline
mae.
10.
medulla.They also stimulate the releas: of adreno-
aSALICYLATES (Asprin as the prototype) adrenal
corticotrophic homione (ACTH). They interfere with :he binding of
thyroxine with plasma proteins. This free thyroxine depresses
the
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secretion of thyroid stimulating hommone (TSH).
The pharmacological actions mentioned are those of salicylates
uncoupling of oxidative
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in general and those of asprin in particular. 11. Metabolic effects: Salicylates produce
phosphorylation. They produce hyperglycemia and glycosuria. They
1. Analgesic effect: Salicylates are effective only in dull-aching inhibit the synthesis but enhance the breakdown of fatiy acids.
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pain of low intensity, They do not relieve severe pain like visceral Salicylates (especially salicylic ac id and methyl
12. Local actions:
Ph
Ph
Ph
pain. They act by preventing the integration of pain sensation in the
salicylate) have antiseptic, fungistatic. and keratolytic ffects.
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thalamus. But they do not alter the emotional reaction to pain.

are ibsorbed fiom
Absorption, fate and excretion: Salicylates
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2. Antipyretic effect: Salicylates do ot lower
normal body
and small intestine. They are bound to plasna proteins.
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lowered. Mechanism: the stomach

temperature. Only the elevated temperature is brain. They
They are mainly concentrated in the liver, heart, muscle ad
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a) The hypothalamic heat regulating center (thermostat of the body)
conjugation with glycine and glucuronic acid.
a lower are metabolised in liver by
is set for a higher temperature in fever. This is reset for
ac
products are mainly excreted through urine.

b) The salicylates produce sweating The metabolic
temperature by salicylates
cy
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cy
which also lowers body temperature. Adverse reactions:
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3. Respiration: Salicylates stimulate respiration

a) directly by 1. Gastrointestinal disturbances like nausea, vomiting and
are
stimulating the respiratory center b) indirectly through carbondioxide diarrheoa. Also ulceration, perforation and hmorrhage
produced.
(produced by increased oxygen utilisation of skeletal muscles).
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Ph
Ph
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49
in the liver. Oxyphenbutazone is a metabolic product of

Intolerance leading to skin rashes of various types.
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2.
to agranulocytosis, phenylbutazone.
3. Bone marrow depression leading
The adverse reactions of phenylbutazone are:
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thrombocytopenia and aplastic anemia.
4. Fatty in:filtration of liver and kidney. 1. Nausea, vomiting and peptic ulcer.
tinnitus, difficulty in
Salicylsm characterised by headach, Aplastic anemia, agranulocytosis and thrombocytopenia.
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5. 2.
hearing, drowsiness, lethargy and confusion.
Oedema due to sodium and water retention.
Ph
Ph
Ph
3.
Preparations and dose: Hypothyroidism and myxoedema.

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4.
Acetylsalicylic acid powder 0.3 to 1g. by mouth. treatment of gout and rheumatoid arthritis.
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It is used for the
0.3 to 1g. by mouth.
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Aspirin table Dose: 200 to 400 mg. daily in divided doses as tablets.
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Sodium salicvlate as a mixture 0.6 to 2g. by mouth.
oXYPHENBUTAZONE: It a metabolic product of
Methyl salicy late as an ointment.
phenylbutazone. Its actions, toxicities and uses are similar to
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as an ointment.
Salicylic aci phenylbutazone.
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Therapeutic uses: INDOMETHACIN: derivative of indole acetic acid. It has an
It is a
. For lo:al application as a keratolytic,
fungistatic and antiseptic. analgesic, anti-pyretic and anti-inflammatory activity. It is uch effective
It is adninistered at a
2. As an analgesic for light and moderate pain. in the treatment of rheumatoid arthritis and gout.
dose of 50 to 150 mg. daily in divided doses. It is coimonly used for
3. As an antipyretic in case
4. As an anti-rheumatic.
of. fever.
PARACETAMOL: It is a para-amino phenol derivative.

n. It has
medical closure of patent ductus arteriosus (PDA).
Sulindac is a fluorinated derivative of indomethacin.

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salicylates. But it does not have
analgesic and antipyretic effects like 1BUPROFEN (Brufen): It is a synthetic compound having anaigesic
uricosuric effects. Also it does not produce
anti-inflamnatory and and mild anti- inflammatory effect. It produces less gastric irritation
ud
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gastrointesti'nal irritation. Paracetamol is well absorbed on oral
than aspirin.
urine in a
administration. It is metabolised in liver and excreted in
Dose: 0.4 to 0.6 g. three times daily by oral route.
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conjugated orm.
Maximum dose 2.5 g MEFENAMIC ACID: It is derivative of anthranilic acid. It has
a
Ph
Ph
Ph
Dose: 3O to 600 mg. as tablets.
cysteine. toxicities like gastrointestinal
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Paracetanmo overdosage is treated with N-acetyl weak analgesic effect. It produces

pyrazolon derivatives. disturbances, skin rashes and blood dyscrasias.
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AMINOPYRINE and ANTIPYRINE: Both are
inflammatory effects. The lt has an
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They have analgesic, anti-pyretic and anti- PIR OXICAM: It belongs to the group of oxicams.
it does not
analgesic, antipyretic and anti-inflammatory effect. But
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use of these drugs is limited due to their toxicity.
administration.
PHENYLBJTAZONE: Phenylbutazone belongs to the
group of produce gastric irritation. lt is well absorbed on oral
ac
antipyretic activity. it has a prolonged effect. It is used in rheumatoid

arthritis and
analgesic and Also
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pyrazolon derivatives. It has less
is more than that produced by acute gout. Dose: 20 mg. once daily.
But the a:iti-inflanmatory effect
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salicylates. It also has an uricosuric effect. DICLOFENAC: It is an aryl acetic acid derivative. It is an analgesic
It is well absorbed on oral and parenteral
administration. It is antipyretic and anti inflammatory drug. It inhibits prostaglandin
It is completely metabolised synthesis. Also, it has a short antiplatelet action. Since it
accumulates
extensively bound to plasma proteins.
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Ph
Ph
Ph
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50
Telegram - Study Pharmacyhas longer action. It is used in rheumatoid.arthritis 18. ANTIPSYCHOTIC DRUGS
insynovial fluid it a
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and osteoarthritis.
majoi psychosis.
KETOROLAC: I1 is a pyrolo-pyrrole derivative.
Ithas a pontent These drugs are used for the treatment of
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major tranquilizers since tey reduce
antintlammatory activity. Itinhibits They are also cailed as
analgesic and moderate in schizophrenia.
agitation and disturbed behaviour seen
prostaglandin synthesis. Also it inhibits platelet aggregation for short
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periods. It is useful in post-operative pain and acute
musculoskeletal pain.
Classification of drugs:
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Ph
Ph
Selective COX 2 inhibitors .
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Phenothiazines Chlorpromazine
CELECOxIB: It is selective COX-2 inhibitor. It has
a
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Triflupromazine
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antiinflanmmatory, analgesic and antipyretic effects. But ulcerogenic Fluphenazine
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It is metabolised
effect is less. Also it does not have antiplatelet action. Thioridazine
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concentration. It has
in liver. Hepatic impairment increases its plasma Haloperidol
Adverse effects: hypertension oedeima, 2. Butyrophenones
a plasma half life ofll hours. Trifluperidol
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abdominal pain, dyspepsia and mild diarrhoea.
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dysmenorrlhea, dental 3. Thioxanthines Chlorprothixene
Use: Osteoarthritis, rheumatoid arthritis, Thiothixene
and post-operative pain.
ROFECOXIB It is a more potent COX - 2 inhibitor than celecoxib. 4 Indolic derivatives -Molindone
Oxypertine
Like celecoxib, it is
Similar to celocoxib, it has no antiplatelet action. 5. Miscellaneous
useful in ostcoarthritis,
post operative pain. t
rheunmatoid
has a
arthritis,
plasa half
dysnanorrlhea,
life of
effects: hcadache, dizziness, gastrointestinal disturbances,
dental and
17 hrs. Adverse
oedema and
DOOkS Tetrabenazine
Pimozide
Pentluridol
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hypertension. 6. Atypical antipsychotics Clozapine
inhibitor. Its Risperidone
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VALDECOXIB: It is a newer selective COX 2
efficacy is similar to rofecoxib. lt has a plasma half life of 8 to 11 Olanzepine
dysnmenorrhoea
hrs. It is useful in osteoarthritis, rheumatoid arthritis,
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and post operative pain.
- PHENOTHIAZINES: Phenothiazines are three-riged s.nuctures, in
atom.
which two benzene rings are linked by a sulphur and nirogen
a
Ph
Ph
Ph
effect.
NIMESUIIDE: It is a NSAID with less COX-2 inhibiting plienothiazine. The following are
effect. Also it has important
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It has analgesic, antipyretic and antinflanmatory Chlorpronmazine is the

in general md those of
mild antihistaminic and antiplatelet actions.
It can cause the pharmacological actions of phenothiazines
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gastrointestinal disturbances. Advantage : lt can be used in patients chlorpromazine in particular.
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or other NSAID's. Dose 200 to 300 mg daily in

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allergic to asprin
divided doses.
ac
chlorpromazine s given to
1. Central nervous system: When
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PSYCHOPHARMACOLOGICAL AGENTS patients with psychosis, it produces:
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classified into
. emotional quieten:ng
The psychoplharmacological agents are broadly i. psychonmotor slowing
antipsychctics, anti-anxicty agents, anti-depressants and psychotogenic iv. decreased anxiety
chapters. ii. decreased initiative
drugs. Each of these groups are discussed in the succeeding
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Insta - Study_Pharmacy_29 mastndgoluis
Telegram - Study Pharmacy Sol hos tbt
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53
Pheno nazines do inot have an analgesic cffect. But they
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potentiate he analgesic effect of morphine. They do not have 5. Endocrine effects like gynaecomastia, lactation and menstrual
anticonvulsa t effect. disturbances.
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2. Antiemetc action: Chlorpromazine has a powerful antienmetic 6. Intolerance like skin ernptions. photosensitivity, contact
effect. This effect is produced by depressing the chemoreceptor dernatitis and cholestatic jaundice.
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irigger zone CTZ) Preparations and dose:
Ph
Ph
Ph
3. Autonomic nervous system: Chlorpronmazine has an alplha 1. Chlorpromazine tablets and syrup-25 to 1000 mg. by mouth.
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adrenergic biocking cífect. it also blocks the actions of acetylcholine 2. Chlorpromazine injection-25 to 50 mg. by intramuseular
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and 5- hydro xytryptamine. injection.
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4. Cardiovascular system: Chlorpromazine has a hypotensive, Therapeutic uses:

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myocardial depressant and ati-fibrillatory effect. 1.In the treatment of major psychosis."
5. Endocrin2 system: Chlorpromazine produces inhibition of 2.To control aggressiveness in children.
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ovulation, an enorhea and lactation in females. In nmales, it produces 3. As an antiemetic.
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loss of libidc. These effects are produced by blocking the action of 4. In the treatment of hiccough.
dopamine on hypothalamus and piuitary. 5. For pre-anaesthetic medication.
6. Miscellaneous actions:
They are: HALOPERIDOL: I is a buterophenone derivative. It produces more
i.
ii.
Inhibit on of hiccough
local aaesthetic etfect harma sedative and autonomic effects than chlorpromazine., Dose: 1.5 to 4.5
mg. three times a day.
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i1. skeletal musçle relaxant effect PIMOZIDE and PENFLURIDOL: Both these drugs are diphenyi
butyl piperidines. They have a long duration of action. A single dose
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Absorption. fate and excretion: Chlorpromazine is well
is sufficient to treat the patient.
absorbed afte oral and parenteral administration. A high concentration
is found in the lungs, liver and adrenal glands. It is subjected to ATYPICAL ANTIPSYCHOTICS
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enterohepatic circulation. This increases its duration of action. It is
The characteristics of atypical antipsychotics are.
Ph
Ph
Ph
metabolised i 1 the liver. The metabolic products are excreted in urine.
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1. Extrapyramidal effects are less and so margin of safety 1s more.

Adverse reactions
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2. Improve negative symptoms.
CNS Jeets like drowsiness, excitement, psychotic reactions,
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1. 3. Do not elevate serum prolactin level.

contus on and parkimsonism.
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ma
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4. Do not produce catalepsy in animals.
,
2. ANS fects like blurred vision, tachycardia and constipation.
The atypical antipsychotics are clozapine, risperidone and
ac
They cccur due to anticholinergic effects.

olanzepine.
cy
cy
cy
3. Fxtrap ramidal symptoms of parkinsonism like tremor,
y
muscuiar ngidity. (Thioridazme produces least extrapyramidal CLOZAPINE

effects 1. It is an atypical antipsychotic which does not produce
4. Hemopvietic effects like agranulocytosis, thrombocytopenia and extrapyramidal symptoms.
aplasti anemua. a
2. It also has antiadrenergic ( 1), antinuscarinic, antihistaminic
and anti 5-HT effects.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
55
important benzodiazepine compund. Like
St
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Agranulocytosis is a very important adverse effect.
DIAZEPAM: It is an muscle
3. all other benzodiazepines, it has a hypnotic, anxioly' ic,
Use it is a reserve drug in resistant schizophrenia.
ud
ud
ud
u
It is quickly absorted on oral
4. relaxant and anticonvulsant actions.
:
acute panic states 2) anxiety associated

RISPERIDONE: administration. Uses: 1)
y
. with,organic disease 3) status epilepticus.
another atypical antipsychotic.
It is
Ph
Ph
Ph
2. benzisoxazole.
It is a Dose: 2 to 5 mg twice daily.
ha
3. Eftects are similar to clozapine. on oral

S-HT 2. OXAZEPAM: This benzodiazepine is slowly absorbed
ar
ar
ar
4. It blocks adrenergic
(
a1 and a2) , histaminic and a short
administration. Also, penetration in brain is slow. It las
r
receptors.
in short lasting anxiety
duration of action. So it is used mainly
ma
ma
ma
ma
5. It produces less extrapyramidal etfects.
states.
OLANZEPINE:
c
c
it is slowly absorbed orally and
1. It is also an atypical antipsychotic.
3. LORAZEPAM: Like oxazepam,
for short an <iety states.
y
y
also penetration in brain is slow. is preferred
It
2. It is a dibenzodiazepine compound
function. 4. ALPRAZOLAM: It is a recently
introduced antianxie ty drug. In
3. It does not antagonise a2 receptor
symptoms. addition to anxiolytic effect, it has a mood elevating
act on. Also it
4. It does not produce extrapyramidal
It Is an advantag produces less drowsiness.
5. Aiso it does not produce agranulocytosis.
over clozapine.
sedation, nausea and weight gain
Use:anxiety states associated with depression
6. Adverse effects dry mouth,
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Dose: 0.25 to I mg three times daily.
ANTIANXIETY DRUGS
19. antianxiety drug. It does not have
ud
ud
ud
u
5. BUSPIRONE: It is a new
muscle relaxant and anticonvulsant ettects
asS
Antianxiety drugs (anxiolytics) are CNS depressants which sedative, hypnotic, has a slow act.on and the
a calming effect n produced by benzodiazepines. Buspirone
control symptoms of anxiety. They produce
y
y
effect is delayed for even two weeks. Use: mild to modei ate anxiety.
anxiety states.
Ph
Ph
Ph
Dose: 10 to 30 mg daily is divided doses.
ha
Classification of drugs It binds

FLUMAZINIL: It is a benzodiazepine antagonist.
ar
ar
ar
and blocks many of the
Benzodiazepines Diazepam competitively with benzodiazepine receptors
1) to reverse
rm
Oxazepam pharmacological actions of benzodiazepines. Use:

3) hepatic
ma
ma
ma
Lorazepam benzodiazepine anaesthesia 2) in benzodiazepine overdos:
ac
Alprazolanm coma and alcohol intoxication.

cy
cy
cy
2. Azapirones Buspirone
20. ANTI-DEPRESSANT DRUGS
y
BENZODIAZEPiNES
Benzodiazepines are the commonly used antianxiety drugs These are drugs used for the treatment
of inental depression.
anticonvulsan 'mood elerators
They have anxioiytic, hypnotic, muscle relaxant and They are also called as 'psychoanaleptics' or
and addiction liability is very low.
actions. They are less toxic
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St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
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c) Absorption, fate and excretion
: These compounds are
Classification of drugs: well absorbed after oral administration. They are quickly metabolised.
ud
ud
ud
u
1. Mnoanine oxidase inhibitors (MAOI) But thhey produce long lasting effects.
a. Hydra zine derivatives Isocarboxazid
d) Adverse reactions:
y
lproniazid
headache, excitcment and disturbed
Nialamide Behavioural effects
Ph
Ph
Ph
1.
Phenelzine
ha
sleep.
Non-liydrazine Tranylcypromine CNS effects: twitching, ataxia and tremors,
ar
ar
ar
b. 2.
lerivatives dry mouth, constipation and blurred vision.
r
3. ANS effects:
2. Tricy clic compounds Tmipramine
Tyramine is metabolished by the enzyme
ma
ma
ma
ma
Desipramine 4. Hypertensive crisis:
In presence of
Amitriptyline MAO. Food products like cheese contain tyramine.
to accumulation of
MAOI, tyramine is not metabolised. This leads
c
c
Nortriptyline in blood pressure by releasing
tyramine. Tyramine produces rise
y
y
3. Serotonin reuptake Fluoxetine
noradrenaline.
inhibitors Paroxetine
TRICYCLIC COMPOUNDS: Imipramine is the commnonly used
Fluvoxamine
Sertaline drug.
Lithium carbonate by inhibiting, the
4. Lithin:m compounds. a. Mechanism of action:Imipramine acts
produces increase in its concentration
reuptake of noradrenaline. This
MONOAMINE OXIDASE INHIBITORS (MAOI) This contributes for the antidepressant action.
at the receptor sites.
St
St
St
St
S-hydroxy
a) Mechanism of action: Biogenic amines like
are inactivated by the enzyme b. Pharmacological actions:
tryptamine, noradrenaiune and dopamine
ud
ud
ud
u
monoamine xidase (MAO). MAOI inlhibit the enzyne MAQ. This 1. Behaviour: Same as MAOO1.
of these.amines in brain. This produces as
ieads to acc uilation 2. Reserpine reversal Same MAO.
y
y
antidepressaut effect. But toxic
3. Cardiovascular system: No effect at nomal dose.
Ph
Ph
Ph
b) Pharmicological actions doses may produce cardiac arrhythmias.
ha
In case of mental depression, these compounds 4. Autonomic nervous system: Imipramine

produces anticholinergic
1.Behaviou
ar
ar
ar
blurred vision.
elevate the rnood. The patient feels more energetic and fresh. effects like dry mouth, constipation.palpitation and
rm
animals pretreated with MAOL Imipramine is well absorbed

Reserpine reversal: In Absorption, fate and excretion
ma
ma
ma
2. c.
mediated through
reserpine dous not produce drowsiness. Instead, it produces agitation on oral administration. Its actions are
ac
reversal:'. metabolic product.

and excitement. This is called as 'reserpine desmethylimipramine which is a
cy
cy
cy
Cardiovescular system: No effect on heart or circulation at
d. Adverse reactions:
y
3.
normal dose 1. CNS effects: lethargy, headache and drowsiness.
compounds
4. Potentiation of sympathomimetic anmines: These 2. ANS. effects: dry mouth, constipation and
tachycardia.
amines like amphetamine
potentiate the action of sympathomimetic
3. CVS effects: cardiac arhythmias and hypotension.
and tyramine.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
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called as "hallucinogens
4. Allergic reactions: skin rashes and photosensitivity. they produce hallucinations, they are also
are lysergic acid die:hylamide,
Drugs which belong to this group
ud
ud
ud
u
e. Therapeutic uses: Mental depression and noctumal enuresis.
mescaline and cannabis.
which belong
5. SEROTONIN REUPTAKE INHIBITORS: Drugs 1. LYSERGIC ACID DIETHYLAMIDE (LSD):
It is namine
They
y
to this group are luoxetine, fluvoxamine and sertalinec. It produces disintegration
and alkaloid and it is synthesised from ergot.
selectively inhibit HT reuptake. They have less antimuscarinic also produces change in
Ph
Ph
Ph
patterns. It
than tricyclic of inborn and learned behaviour
sedative effects. Also, they are safer impairs judgment and inotivation.
ha
less mood and emotional outbursts.

It
antidepressants. effects like dilatatio of pupil,
Also it produces sympathomimetic
ar
ar
ar
nausea, anxiety, insomnia, headache and sexual tachycardia and hyperglycenia.
r
Adverse etfects
dysfunction.
ma
ma
ma
ma
lt is used as a research tool for producing eperimental
LITHIUM CARBONATE: neurotic disorders.
psychosis and also for the treatment of certain
c
c
It is used in the treatment of manic depressive psychosis It is an alkaloid isolated
from he cactus
2. MESCALINE:
y
y
(MDP). AIso it is used prophylactically in biopolar depression. adinistralion, it produc es anxiety,
Lophophora williamsii. On oral
sympathomimetic effe cts. It also
Mechanism: tremors, colourfül hallucinations and
produces delusions, excitement,
restlessness and change in mood.
1. Interference with Na"/ K* ATPase.
to produce psychosis.
formmation. is used as an experimental tool
2. Interference with AMP
ionositol triphosphate fomation. Cannabis is obtained fron the hemp
with. 3. CANNABIS (Marihuana)
:
3. Interference
indica. Marihuana is any part
Precautions: Lithium has very low therapeutic index. So
it is
plants Cannabis sativa and Caunabis
active principles. Tetrahydro
St
St
St
St
the
necessary. to monitor the plasma levels of lithium coustantly. Overdose of the plant or extract containing
principle of cannabis. The effe:t produced
lithium can be treated by osnmotic diuretics, sodium bicarbonate
and cannabinol is the active
of route of adninistration.
ud
ud
ud
u
by cannabis in man depends on
the dose and
hemodialysis. and cxcite. nent. At a
Normally it produces a dreamy state, euphoria
Adverse effects: hallucinations. Sometimes it
larger dose, it produces pleasant
y
y
diarrlhoca and dryness of mout:. Cannabis
I. Nausea, vomiting and mild diarrhoea. produces nausea, vomiting,
Ph
Ph
Ph
use.
2. Thirst and polyuria. does not have any therapeutic
ha
3. Fine tremors and rarely seizures.

ar
ar
ar
4. CNS effccts like tremors, giddiness ataxia,
1nystagmus and SYSTEV
22. CENTRAL NERVOUS
rm
confusion.
STIMULANTS
ma
ma
ma
5. Teratogenic effects such as foetal goitre and
cardiac
ac
abnormalities.
not have a selective
Stimulants of central nervous system do
cy
cy
cy
is followed by dep:ession. So
|21. PSYCHOTOGENIC DRUGS action. Excessive stimulation of CNS
y
usefiul. Some of these drugs are

these drugs are not thrapeutically
drugs which stimula: e the CNS.
Psychotogenic drugs are those which produce behavioural used as analeptics. Analeptics are
In large doses, they produce
abnormalities resembing psychosis. Since they produce effects like They also stimuiate respiration.
Since
natural psychosis, hey are also called as psychotomimetics. convulsions.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
61
Telegram - Study Pharmacy 60 iv. increase in volumë and acidity of yastric
secretion.
St
St
St
St
.
are well absorbed

Absorption, fate and excretion: Xanthinesmetabolised in liver
Classification of drugs parenteral administration. They are
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u
on oral and
by demethylation and oxidation.
The nmetabolic products are exereted
1. Direct CNS stimulants
Xanthine alkalóids in urine.
y
a. Cortical stimulants
Amphetanine
Adverse reactions:
Ph
Ph
Ph
Methylphenidate
Confusion, insomnia, excitement and delirium.
ha
1.
Pipradrol
Nausea, vomiting, epigastric pain and ulcer.
ar
ar
ar
2.
Medullary stimulants Picrotoxin
Tolerance and habituatioin.
r
3.
Pentylenetetrazol
ma
ma
ma
ma
are useful as antidepressants,
Bemigride Therapeutic uses: The xanthines
Nikethamide anti-asthmatic agents and diuretics.
coronary vasodilators,
Amiphenazole
c
c
PICROTOxIN, PENTYLENETETRAZOL, NIKETHAMIDE
y
y
Spinal stimulants Strychnine
C.
AND BEMIGRIDE
2 Reflex CNS stimulants Lobeline thhe brain stem and medullary
Ammonia All these drugs are stimulants of
center. In arge doses, they
Veratrine centers. They stimulate the respiratory
opisthotonus (i.e., arching of the back
Nicotine produce convulsions leading to
alkaloids are
with extension of legs and flexion of
amis).
CLL
XANTHINE ALKALOIDS: The three xanthine These drugs are mainly used
:
St
St
St
St
in the seeds of Coffea arabica (coffee seeds);
Caffeine, resent 1. as analeptics in the freatment of narcofic
poisoning.
in the leaves of Thea sinensis (tea leaves);
Theophylline. present diagnosis of latent epilepsy.
ud
ud
ud
u
cacao (coco seeds). 2. for the
Theobromine. present in the seeds of Theobrona
DOXAPRAM
Pharmacological actions:
y
y
1. non-specific analeptic.
It is a
Caffeine stimulates cerebral cortex. stimulant.
Central nervous System 2. It is used as post-anesthetic respiratory
:
Ph
Ph
Ph
1.
It induces :lear flow of thoughts and
association of ideas. Motor tachycardia, arrhythmias and
ha
3. Adverse reactions: hypetersion,

fatigue is delayed. But in large doses,
activity is increased and convulsions.
ar
ar
ar
headache, confusion and deliriu. Also caffeine
caffeine produces 1.V. drip.
Dose: 0.5 to 1.5 mg. per kg. as
rm
vagal centers.
produces stmulation of respiratory, vasomotor and
ma
ma
ma
the button shaped
Xanthines produce a direct stimulant STRYCHNINE: It is an alkaloid obtained from
2. Cardiovascular system
:
Stryclmine acts mainly on the spinal
ac
they produce dilatation of coronary seeds of Strychnos mux vomica.

effect on tke myocardium. Also
the entire neuraxis. On oral
cord. But in large doses, it can stimulate
cy
cy
cy
and pulmo:ary blood vessels. convulsions. The convulsions
or parenteral administration, it produces
y
opisthotonus.
Miscellaneous effects: Xanthines produce body and
:
extension of the
3. are characterised by tonic
due to asphyxia. Though
i. relaxation of bronchial smooth muscle. After convulsions, death may occur as a
CNS, it inot used
strychnine increases the general activity of
is
ii. decrase in fatigue of smooth
muscle.
ii. diure tic effect on kidneys.

St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
52 63
The reason
dnug. 1s, the margin between therapeutic and toxic
dose TIZANIDINE:
St
St
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a congener
IS narrow. itnewer centrally acting muscle relaxant. It is
1s a
action. It acts by
Strychnine poisoning can be treated by of clonidine. It has a central a2 agonistic
ud
ud
ud
u
2 parts of powdered
giving universal antidote (which contains 1. Inhibiting the release of excitatory aminoacids.
charcoal, part cach of magnesium oxide and tannic acid). glycine.
1
2. Facilitating the inhibitory transmitter
y
convulsions.
2. giving paraldehyde or diazepam to control 3. Inhibiting polysynaptic reflexes.
Ph
Ph
Ph
reduces muscle tone. Also it decreases the frquency
of
ha
It
CENTRALLY ACTING MUSCLE
23. muscle spasms.
ar
ar
ar
RELAXANTS Drymouth, drowsiness, insominia at night and
r
Side effects :
ma
ma
ma
ma
hallucinations.
relaxation
These drugs act on the CNS and produce uscle of 24 mg pe
them produce sedation. Dose: 2 mg three times daily and a maximum
without loss of consciousness. But most of
c
c
diazepam, baclofen, mephenesin day.
Drugs which belong to this group are
y
y
and methacarbamol. IN PARKINSONISM
24. DRUGS USED
DIAZEPAM:
It is
1. It is used in patients with lesions of spinal cord and
cerebral Parkinsonism is an extrapyramidal motordiso'der.
rigidity tremor and hypokinesia. Secondary
palsy. characterised by
a id dimentia
muscle spasm. manifestations like excessive salivation, changes in mood
2. It is useful in stiffiman syndrome and localised
may also occur.
is a drug of clhoice in spasms caused by
tetanus toxin.
St
St
St
St
3. I
Diazepam should not be used with other drugs for intravenous
Classification of drugs.
4.
ud
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use. A. Drugs affecting brain dopaminergic system
Dopamine precursor Levodopa

BACLOFEN 1.
y
y
spinal cord Decarboxylase inhibitors Carbidopa
1. It is apowerful neuronal depressant. It acts in the
Ph
Ph
Ph
mechanisms. Benzserazide
on presynaptic
ha
Bromocryptine
2. It decreases the release ot excitatory transmitter. S. Dopaminergic agonists
ar
ar
ar
Pergolide
in patients with spinal
It improves bladder and bowel control
rm
3. Lisuride
ma
ma
ma
lesions. Peribedil
reactions drowsiness, blured vision and
4. Adverse
ac
MAO B inhibitor Selegiline

gastrointestinal disturbances. 4.
cy
cy
cy
Amantadine
MEPHENESIN and METHACARBAMOL: These
drugs act by
5. Dopamine facilitator
y
over monosynaptic reflexes. Also

depressing polysynaptic reflexes
arca of brain stem. They produce sedation. They
they act on lateral
spasm.
are effective in the treatment of localised muscle
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
65
Telegram - Study Pharmacy64 CARBIDOPA and BENZSERAZIDE:
Drugs affecting brain cholinergic system
St
St
St
St
B.
the
Trihexyphenidyl They are peripheral decarboxylase inhibitors. They prevent
Central antic holinergics
peripheral décarboxylation of levodopa. So more of levodopa enters
ud
ud
ud
u
Benztropine
Procyclidine the brain for getting converted into dopamine.
y
Promethazine Advantages.
2. Antihistamin ics
The ti/2 of levodopa is increased and so the dose is decreased.
Ph
Ph
Ph
Orphenadrine. 1.
ha
2. Systemic concentration of dopamine is reduced, so nausea and

LEVODOPA (1-dopa)
ar
ar
ar
vomiting is less
precursor of dopamine. It acts by getting converted into
r
It is a 3. Cardiac toxicities are reduced.

it does not cross
dopamine. Dopainine ty itself is not useful since
ma
ma
ma
ma
4. On-off effect is minimised.
blood-brain barrier.
5. Degree of improvement is higher.
Decarboxylase iihibitors like carbidopa and benzseraside are
c
c
peripheral decarboxylation of BROMOCRYPTINE:
given with levodopa. They decrease the
y
y
levodopa. So, more levodopa can enter the brain for getting converted
It is an erget derivative. It is a dopaminergic agonist.
into dopamine. Improvement in parkinsonism occurs within 30 to 60 minutes after
oral administration. The effect lasts for 6 to10 hours. It is
effective
not respond or resistant to levodopa. It inhibits
in patients who do
Actions prolactin release.
Levodopa inmproves all the manitestations of parkinsonism.
1.
Adverse effects, nausea, vomiting, postural hypotension,
hypokinesia. Later tremor is
St
St
St
St
Initially, there is relief from rigidity and insomnia, hallucinations, nasal stuffiness and cardiac arrhythmias.
also relieved.
ud
ud
ud
u
SELEGILINE:
2. Levodopa is inetfective in drug induced parkinsonism.
tachycardia by It is aselective MA0-B inhibitor. It leads to the accumulation
3. The peripherally formed dopamine can cause
of dopamine brain by preventing its breakdown. When used early
in
y
y
in
acting on.beta airenergic receptors.
cases it retards the progression of symptoms.
Ph
Ph
Ph
4. Peripherally foriaed dopamine can act on the CTZ producing.
Commonly it is used with levodopa to prolong its action. The
ha
neusea and vom ting.

clinical benefit of selegiline is short (6 to 24 months) Advantage:
absence
ar
ar
ar
5. Also levodopa inhibits prolactin secretion.
hypertensive crisis (cheese phenomenon) with levodopa or tyramine.
rm
of
Adverse effects.
AMANTADINE: It is an antiviral agent effective in parkinsonism.
ma
ma
ma
1. Nausea and von iting It increases the synthesis and release of dopamine and inhibits
its
ac
Postural hypotersion Also, it has some anticholinergic effects. It is less

2. neuronal uptake.
cy
cy
cy
Cardiac arrhythrias efective than levodopa. Dose: 100 mg twice daily
y
3.
4. Exacerbation of angina Adverse effects: insomnia, confusion, halucinations, dizziness
(due to local
5. Alteration of tas.e sensation and night mares. Also livedo reticularis and ankle edema
response and no response). release of catecholamines which produce vasoconstriction).
6. On off phenomenn (altemative phases of
St
St
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St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
Telegram - Study CENTRAL
PharmacyANTICHOLINERGICS: The central anticholinergics consciousness. The addicts sometines commit criminal acti tmder its
St
St
St
St
benztropine and influence. Cannabis does not lhave any medical use.
used in. parkinsonism are trihexyphenidyl,
procyclidine. They are effective in drug induced parkinsonism. They :
coCAINE Cocaine addicts use cocaine in the form o snuff or
ud
ud
ud
u
effective in reducing rigidity and hypokinesia. injections. Addiction is due to alertness, euphoria and re tuction in
improve tremor but less
fatigue produced by cocaine.
Adverse effects: dry mouth, blurred vision, amnesia,
y
confusion, night mares, hallucination, increased
intraocular pressure OTHER DRUGS OF ADDICTION: A varicty of other irugs like
mescaline, lysergic acid diethylamide (L.S.D.), barbiturates,
Ph
Ph
Ph
and constipation. amphetamine, chloral hydrate, alcohol etc. are capabie of roducing
ha
addiction.
ar
ar
ar
25. DRUG DEPENDENCE AND
r
Drug habituation : Drug babituation is a condition wh: ch occurs

ABUSE OF DRUGS
ma
ma
ma
ma
due to repeated administration of a drug. Its characteristic i are:
1. only a desire (and not a compulsion) to take the dug for its
purposes
The tenn 'drugs abuse' refers to the use of drugs for euphoric effect.
c
c
Drugs like narcotics are
other than approved medical and social use. 2. no tendency to increase the dose.
y
y
leading to addiction.
sometimes used indiscriminately 3. only psychic but no, physical dependence on the dru;.
Drug addiction is a state in which an individual 4. a hamful effect if any, only to the individual and not to the
Drug addiction :
is incapable of maintaining nonmal physical and mental functions society.
without the presence of the drug. The Expert

Committee of W.H.O. The common agents which produce habituation are nic otine and
now replaced the tem addiction' beverages like coffee and tea.
on addiction producing drugs has
dependence'. The characteristics of drug dependence are:
with 'Drug
St
St
St
St
1. an over powering desire to take the drug.
a tendency to obtain the dng by any
means.
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ud
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u
2.
3. a tendency to increase the dose.
physical and psychological dependence on the drug.
y
y
4.
society.
Ph
Ph
Ph
5. hamful effect to the individual and
ha
used to relieve pain. i

OPIUM ALKALOIDS: Morphine is frequently
It produces both psychic and
i
ar
ar
ar
So addiction is comnmon with this drug.
morphine are
physical dependence. The withdrawal synptoms of
rm
Heroin and pethidine are other

ma
ma
ma
restlessness, vomiting, sweating etc.
which produce addiction. Addiction to these drugs
narcotic analgesics
ac
drug. Hypnotics like

is treated by gradually withdrawing the
cy
cy
cy
administered during withdrawal phase..
barbiturates may be
y
psychotherapy can also be given.

Occupational therapy and
cigarettes. It is also
CANNABIS INDICA: It is used in the form of
dreamy state of altered
introduced into sweets and tea. It produces a
St
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St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
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St
Mechanism of action: Local anaesthetics prevent the generation
Section ll and conduction of impulses, This is produced
by blocking voltage
ud
ud
ud
u
permmeability of cell
dependent sodium channels. So they decrease the
stabilizing effect). This.prevents
membrane to sodium (membrane
ANAESTHETICS declines 2)
y
of action potential
LOCAL depolarisation., As aresult
3)
1). rise
nerve conduction fails.
impulse conduction slows
Ph
Ph
Ph
ha
ar
ar
ar
block the
1. Effect on sensation: Initially, the local anaesthetics
r
loss of
sensation of pain and temperature. Later, they produce
ma
ma
ma
ma
OTHER seiusation for touch and pressure. They produce biockade of smaller
COCAINE, PROCAINE AND Recovery occurs
26. nerve fibers initially followed by large nerve fibers.
LOCAL ANAESTHETICS
c
c
in the reverse order.
y
y
anaesthetics produce
agents. which block
conduction of 2. Central nervous system: Local
Local an iesthelics are produce loss of; stimulation of CNS. This manifests as euplhoria, restlessness and
When app;icd locally, they
impuises n neives. tremors. Addiction to cocaine occurs mainly due to its euphoric
the desired area. *****
sensation in effects.
Classification of drugs 3. Cardiovascular system: All local anaesthetics except cocaine
produce vasodilatation and so hypotension. But cocaine vroduces
Injectable vasoconstriction and so a hypertensive effect. All local anaesthetics
A.
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Procaine
1 Low potency
Chlorprocaine produce a depressant effect on the myocardium.
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on smooth muscles
Lignocaine 4. Other actions : They produce relaxant effect
Intei mediate potency
Prilocaine and neuromuscular blockade.
y
y
Mepivancame : Local anacsthctics are not
Absorption, fate and excretion
Ph
Ph
Ph
through
Higi potency
Tetracaine absorbed from unbroken skin. But absorption can occur
ha
3. subcutaneous
Bupivacaine mucous membranes. They are usually administered by
infiltration.. Vasoconstrictors like adrenaline prolong their duration of
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Ropivacaine
plasma
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Dibucaine action, The local anaesthetics are metabolised in the liver and
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Cocaine by hydrolysis.
B.Surface araesthetics
Lignocaine
ac
Tetracaine Adverse reactions

cy
cy
cy
Benzocaine 1. Intolerance like dermatitis, asthmatic attack and anar nylactiC
y
Oxethazine reactions.
2. Cardiovascular symptoms like hypotension and
cardiac arrest.
3. Central effects like euphoria, excitation,

restlessiness, tremors
and convulsions.
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y
y
Ph
Ph
Ph
h
y
y
71
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BUPIVACAINE: It is four times more potent than lignocaine. Also
Therapeutic uses it is long acting. It is used for infiltration, nerve block, epidural and
ud
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1. Surface anaesthesia for pain due to burns,, fissures and ulcers. spinal anaesthesia of long duration. It is cardiotoxic and can pro iuce
2. Infiltration anaesthesia to anaesthetise nerve endings by ventricular tachycardia and cardiac depression.
subcutaneous infiltration.
y
ROPIVACAINE: It is a newer congener of bupivacaine. It is long
3. Nerve hlock anaesthesia where it is injected close to. a specific acting but less cardiotoxic. Continuous epidural adnministration
is ised
Ph
Ph
Ph
nerve. relieve post-operative and labour pain. Ît can also be used for nerve
to
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4. Spinal anaesthesia where it is injected into the subarachnoid block.
ar
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ar
space. BENZOCAINE: It has very low solubility. So it is not absorbed irom
r
5. Syistemic use for antiarrhythmic effect. mucous membrane or abraded skin. Also it produces long lasting
ma
ma
ma
ma
COCAINE: It is a natural alkaloid. It is obtaind from the leaves anaesthesia without systemic toxicity. It is used as lozenge, dusting
of coca tree, Erythroxylon coca. It produces a local anaesthetic effect powder or suppository.
c
c
and CNS stimulant eifect like other local anaesthetics. Unlike
others,
OXETHAZINE: It is a potent local anaesthetic. Its main advantage
y
y
it produces a sympathomimetic effect (due to inhibition of is low degree of ionisation even at very low pH values.
So it can
noradrenaline reuptake) leading to: mucosa at its own low pH. So it is administered
anaesthetise gastric
. dilatation of pupil (mydriasis). with antacids for gastritis, drug induced gastric iritation
and
2. rise itn body temperature. gastroeosophagial reflux.

3. rise of blood pressure
4. rise in blood sugar level. harmaebookspdf
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PROCAINE Procaine is a synthetic compound. It is a derivative
It is not absorbed from
of para amino benzoic acid (P.A.B.A.).
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mucous membrane. So it is not useful for local use. It has a
P.A.B.A., it decreases
vasodilator effect. Since it is a derivative of
suifonamides. So procaine should not be
the antimicrobial activity of
y
y
used with sulfonanides.
Ph
Ph
Ph
LIGNOCANIE: It is an acetanilide derivative. It is the most
ha
comnoniy used drug. It has a quick onset of action. Also it has a

ar
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no
higii degree of pcnetration. It may produce drowsiness but has
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action on blood vessels. It can be used for all purposes including

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topical use. It is used in patients allergic to procaine and other local
ac
anaesthetics.
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TETRACAINE (Amethocaine): It is an ester of PABA. It is more
y
potent. Also it is more toxic due to slow metabolism. On spinal

injection, it produces prolonged effect. It is more suitable for topical
use on cye, nose and throat. But it should not be used
on injured,
inflanmed or vascular surfaces. Rapid absorption from these sites may
produce serious conplications and fatal effects.
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y
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Ph
Ph
Ph
h
y
y
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Preganglionic nerve FOstgangiionicnerve
Section V Effector organ
Ganglion
y
DRUGS ACTING ON AUTONOMIC
Ph
Ph
Ph
a. Parasympathetic system:
ha
NERVOUS SYSTEM . The transmitter in preganglionic parasympathetic nerve is
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acetylcholine (Ach) which is liberated at the ganglion.
r
2. Again, acetylcholine is the transmitter in postgangionic

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parasympathetic nerve. It is liberated at the postganglionic
parasympathetic nerve ending.
c
c
27. GENERAL CONSIDERATIONSS
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The Autonoiaic Nervous System (Visceral, Vegetative or Ach Postganglionic
Preganglionic
Involuntary nervous system) is widely distributed throughout the body. parasympathetic parasympathetic
It controls tissues (.g. smooth muscles, heart and glands) which are nerve nerve Effector organ
not under voluntary control. The autonomic nervous system consists
aebG S Ach
Ganglion
of two divisions:
1. The sympath:tic (CODIldi
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2. The parasymathetic system:
b. Sympathetic
The sympath etic and parasynmpathetic mostly exhibit mutual
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1. Similar to preganglionic parasympathetic nerves, acetylcholine
antagonism. is the transmitter in. preganglionic sympathetic nerves also.
The parasympathetic is mainly concemed with the vegetative But in postganglionic sympathetic nerves, noradrenaline is the
y
y
2.
functions e.g. motility and secretions of gastrointestinal tract. This transmitter. It is liberated at the postganglionic synpathetic
Ph
Ph
Ph
system is essential for the normal existence of the organisim. nerve ending.
ha
The sympat ietic system 1s concemed with preparing the

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organism for energency (fight or flight). Unlike parasympathetic, the Açh Postganglionic
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sympathetic is nöt 2sential for normal existence. Preganglionic

sympathetic sympathetic
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Anatomical considerations: Both the sympathetic and nerve nerve Effector organ
ac
parasympathetic essentially consist of: Noradrenaline

Ganglionn
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1. A pregangiionic nerve.
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2. A ganglion (a collection of nerve cells).

3. A postgangl onic nerve. Cholinergic receptors: The receptors for acetylcholine are present at
4. An effector organ. 1. Both sympathetic and parasympathetic ganglia. These receptors

(and also those present at neuromuscular junction) are called
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Ph
Ph
Ph
h
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their
as nicotinic receptors. The two subtypes of nicotinic
receptors The predominant distribution of beta receptors and
are effects are:
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NN receptors present on ganglia 1. Blood vessels of skeletal
NM receptors present at neuromuscular junction. muscles Dilatation
y
2. Postganglionic parasympathetic
nerve ending. These are 2. Uterus Relaxation
called muscarinic receptors. The three subtypes of muscarinic Dilatation
Ph
Ph
Ph
3. Bronchi
receptors are M1, M2 andM3 4. Intestine Relaxation
ha
exceptional effect)
Nicotinic action: It is the stimulant effect of acetylcholine
on: 5. Heart increase in force and rate (an
ar
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acts
Sympathetic and parasympathetic ganglia ( NN receptors). It
is Noradrenaline acts only on alpha receptors. Isoprenline
r
1.
on both alpha and beta
blocked by pentamethonium or hexamethonium. only on beta receptors. Adrenaline acts
ma
ma
ma
ma
contraction
2. Neuromuscular junction ( NM receptors) producing receptors.
as
of skeletal muscle. It is blocked by d - tubocurarine Alpha receptors are further classified
c
c
of acetylcholine at the smootk muscles.
Muscarinic actions: The effect Alphaj receptors which are preset in yascular
y
y
postganglionic parasympathctic nerve ending is called "muscarinic The effect occurs as constriction.
muscarinic actions of acetylcholine are: presynaptiC drenergic
action The Alpha2 receptors which are present in
. Decrease in heart rate (bradycardia). nerve teminals. They decrease the release of noradrena ine from
2. Increase. in glandular secretions like salivary and
other
adranergic nerve endings.
gastrointestina secretions. Beta receptors are further classified into:
3. Contraction of snmooth muscles like intestine and
bronchi. heart. The efficct occurs
Beta receptors which are present in
actions can be selectively blocked by contraction.
All these muscarinic as an increase in force and rate of
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atropine. Beta2 receptors wlhich are present in
bronchi. The effect occurs
at postganglionic
Adrenergic receptors: The receptors present the
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as relaxation.
sympathetic nerve ending are called 'adrenergic receptors'. The
adrenergic receptors are classified as: sOMATIC NERVOUS SYSTEM
y
y
is excitaory (except
1. Alpha receptors, the action on which action of voluntary
Somatic nervous system controls the
Ph
Ph
Ph
intestine)
muscles. The sonmatic erve (motor nerve)
supphes skeletal muscles.
the action on wlhich is inhibitory (except heart).
ha
2. Beta receptors,
nerve and skeletal muscie is called as
The junction between motor.
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at the neuroinuscular
The predominant distribution of aipha receptors and their neuromysCular juncion. The receptors preset
in a moto: nerve is
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junction are NM receptors. The transmitter

effects are as follows: neuromuscular junction.
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ma
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acetylcholine which is* liberated at the mmuscie and this effect
1. Blood vessels of skin and skeletal
Acetycholine produces contraction of
ac
mucous membranes Constriction

is blocked by d-tubocurarine.
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2. Splecn Contraction
y
3. Pupil Dilatation Ach

4. Nictitating membrane -- Contraction Motor nerve Skeletal muscle
Errector pili muscle
(of hair follicles) Contraction
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Ph
Ph
Ph
h
y
y
77
76
alkaloids| Pilocarpine
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2. Cholinominietic
Arecholine
28. CHOLINERGIC DRUGS
Muscarine
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Cholnergic drugs (lso calied as parasympathomimetics) act on
3. Anticholinesierases
a. Reversible Plhysostigmine
y
organs innervated by postganglionic parasympathetic nerves. They Neostignine
produce an effect similir to the stimulation of parasympathetic
Ph
Ph
Ph
O. lrreversible Di-isopopyl
nervous system.
ha
flurophohate (DFP)
Tetraethyl
ar
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ar
Cholinergic receptors: The receptors for acetylecholine are
Pyrophosphate (TEPP)
r
classified as 1. muscarinis: receptors 2. niçotinic receptors.

*
Octamethyl
ma
ma
ma
ma
1. Muscarinic receptors: They are present at postganglionic Pyrophosphotetramide (OMPA)
parasympathetic nerve e iding. The three subtypes of muscarinic
c
c
receptors are M1, M2 and M3 ESTERS OF CHOLINE
y
y
Mi receptors are fresent in autonomic ganglia, gastric glands ACETYLCHOLINE: It is an ester of choline with acetic acid.
and CNS. Their function: are gastric acid secretion atd GI motility.
M1 receptor blockers are pirenzepine and telenzepine. Pharmacological actions: The actions of acetylcholine are
generally classified into two types. They are:
M2 receptors are fresent in heart. They produce a decrease in
the rate and force of he rt. (hegative ionotropic and cironotropic) 1 Muscarinic action produced o1n organs innervated by
The specific M2 receptor blocker is methoctramine.LCC postganglionic parasynpathetic nerves.. This action is blocked by
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atropine.
M3 receptors are presení in smooth muscles and exocrine
glands. Their functions are i) contraction of smooth muscles ii)
2. Nicotinic action próduced as stimulation of both sympatlhetic
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and parasympathetic ganglia. (NN receptors) This action is blocked by
secretions of exocrine glinds. M3 receptor blocker is darifenacin.
pentamethonium or hexamethonium (which are ganglion blockers).
2. Nicotinic receptors: They are present in The other action is contraction of skeletal muscles (NM receptors) and
y
y
this effect is blocked by d-tubocurarine.
Ph
Ph
Ph
a) both sympatt etic and parasympathetic gangia (NN
Muscarinic actions:
ha
receptors). The effect is stimulation of these ganglia. NN receptors are

blocked by pentamethor.ium or hexamethonium. 1. Heart: The effect of acetylcholine on heart is similar to that
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produced by stimulation of the vagus. It decreases Iheart .rate and nmay
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b) neuromuscular junction (NM receptors). The effect is

ma
ma
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contraction of skeletal muscies. NM receptors are hocked by produce cardiac arrest
2. Blood vessels: Acetylcholine dilates a variety of blood vessels
ac
d-tubocurarine.
(like those of skin, mucous niembranes and coronary arteries) and
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Classification of checlinergic drugs: produces a fall in blood pressure.
y
1. Esters of choline Acetylcholine 3. Smooth muscles: Acetylcholine produces contraction of smooth

Methacholine muscles like those of gastrointestinal tract, bronchi, urinary bladder
Carbachol and ureters.
Bethanechol
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Ph
Ph
Ph
h
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78
Telegram - StudySecretions:
Pharmacy Acetylcholine increases gastric, intestinal, pancreatic
4. 1. PILOCARPINE: It is an alkaloid obtained from South
Anierican
jaborandi. It
microphyllus_ and Pilocarpus
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bronchial, lacrimal and salivary secretions. shrubs, Pilocarpus salivary glands
produces a sustained muscarinic action. Sweat and
But injection of the eye it produces miosis,
5. Eye: nstillation into the eye has no effect. very sensitive to its action. On
ud
ud
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are
accommodation. lt is
acetylcholine in the carotid artery produces: decrease in intraocular tension and spasim of
in intriocular
mainly used for the treatment of glaucoma (increase
miosis (coistriction of the pupil). and eye ointment.
y
i. It available as eye drops
tension). is
spasm of accommodation (vision is fixed for short distance).
1i.
2. ARECHOLINE: It is an alkaloid obtained
from betel nut (Areca
Ph
Ph
Ph
receptors. It has
ii. decrease in iniraocular tension. catechu). It acts on both muscarinic and nicotinic
ha
use except as an anthelmentic in veterinary prictice.

Nicotinic action: This occurs as stimulation of both sympathetic no therapeutic
ar
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from the po.sonous
and parasympathetic ganglia (NN). It can be demonstrated
as rise in 3. MUSCARINE: It is an alkaloid obtained
r
atropine. The Amanita muscaria. It produces an etfect similai to the

blood pressure for acetylcholine.when administered with mushroom,
It as no
ma
ma
ma
ma
nerve.
a very stimulation of postganglionic parasympathetic
other action is contraction of skeletal muscle (NM). However, It is chiefly used as an experimcntal dol
in
skeletal muscles (duue therapeutic use.
large dose.of acetylcholine produces paralysis of Pharmacology.
c
c
to persistent depolarisation).
y
y
inactivated in the ANTICHOLINESTERASE DRUGS
Route of administration: Acetylcholine is
gastrointostinal tract. So it is administercd by intravenous injection. acetylclholine sterase.

**** * Acetylcholine is inactivated by the enzyme
inhibitcrs) act
Uses: Acetylcholine is not used for any therapeutic effect. It used
is Anticholinesterase drugs (also called as cholinesterase
enzyme acetylcholinesterase This produces
only for experimental puuposes. by inhibiting the.
accumulation of acetylcholine at cholinergic sites.
METHACHOLINE: It is an ester of beta methylcholine with acetic
acid. It is cffective onoral administralion. It
produces onlyy
Classification of anticholinesterases
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muscarinIC action. It does not produce nicolinic action
on.autonomic
psuedocholinesterase. So it has a longer
ganglia. It is resistant to 1. Reversible Physostigmine
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duration of action. anticholinesterases Neostigmine
CARBACHOL: It is an ester of choline with carbaic acid. It is Pyriodstignmine
well absorbed after oral adnministration. Similar to acetylcholine,
it
y
y
Edrophonium
actions. But the muscarinic effects
produces muscarinic end nicotinic Ambenonium
Ph
Ph
Ph
It is used for
of carbachol are not effectively blocked by atropine. Demacarium
ha
tire treatment of urinay retention and peripheral vascular diseases. Benzypyrinium

ar
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BETHANECHOL: it is an ester of beta methylcholine with carbamic Diisopropylfluro
oniy a muscarinic action which is effectively 2. Ireversible
rm
acid.. It produces
atropine. t is used for the treatment of urinary anticholinesterases, phosphate (DFP)
ma
ma
ma
antagonised by
retention and paralytic ileus. It is also used for the treatment of (Organophosphorus Tetraethyl
pryrophoshate (TEPP)
ac
abdominal distention following surgery. compounds)

cy
cy
cy
Octamethyl pyro
CHOLINOMIMETIC ALKALOIDDS phosphotetramide (OMPA)
y
Parathion
These are naturaly occurring alkaloids having acetylcholine Malathion
like action.
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y
y
Ph
Ph
Ph
h
y
y
81
80
2 For the diagnosis and treatment of myasthenia gravis.
Acetylcholine is inacti vated by combining
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Mechanism of action:
3. For the treatment of curare and atropine poisoning.
with the enzyme acetylcholinesterase at two sites:
4. For the treatment of post-operative paralytic ileus.
ud
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tlhe quaternary nitrogen
a. an anionic site which combines with
atom of acetylcholin. 5. For the treatment of paroxysmal atrial and supraventricular
group of tahycardia.
b. an esteratic site which combines with the carboxyl
y
acetylcholine. Irreversible Anticholinesterases (Organophosphorus
Ph
Ph
Ph
to
The reversible anticholinesterases have a structural similarity compounds):
ha
acetylcholine. So they coiibine with both anionic and esteratic site

These conmpounds are organic esters of phosphoric acid.
They
ar
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inhibited. This
of acetylcholinesterase. So this enzyme temporarily
is
are highly lipid soluble. So they can be absorbed through all routes
r
prevcints the mactivation o' acetylcholine. lungs. The pharmacological actions of these
including the skin and
ma
ma
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ma
the
The ireversible an icholinesterases combine only with compounds result due to inhibition of cholinesterase. These
esteratic site.
esteraticsit. They prod:ic phosphorylation of. the conmpounds have prolonged action and high toxicity. So
they have
acetylcholinesterase. So
c
c
This produces an ireversisle inhibition of limited therapeutic use.
prevented leading to its
y
is
y
the inactivation of acetylcholine
accumulation Poisoning with organophosphorus compounds
reversible Organophosphorus compounds like parathion and malathion are
Reversible anticholineiterases: All the
d
used as insecticides. So poisoning with these compounds is quite
anticholinesterases except phxsostigmine are synthetic compounds.
common. The syimptoms of poisoning are
Physostigmine is an alkaloid obtained from calabar bean, the seed of
secretions.
Physostigma venenosun.
C
Pharmacological action:s: ln general, the anticholinesterase
1Increased secretions like sweat, saliva and bronchial
2. Gastrointestinal symptoms like anorexia, nausea, vomiting,
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drugs produce 1. a muscornic type of effect.on organs innervated abdominal cramps and diarrhoea.
2. stimulation followed 3. Pupillary effects like miosis and spasm of accommodation.
by postganglionic parasyinpathetic nerves
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by depression of autonomic ganglia and skeletal muscles. 4. Respiratory symptoms like bronchospasm, cough and tightness
1. Eye: On the eye, the antichoiinesterase agents produce .miosis, of the chest.
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spasm ol accomni1ocdation nd decrease in intraocular tension. 5. Central effects like giddiness, anxiety, confusion, convulsions
Ph
Ph
Ph
2. Gastrointestinal tract: The effect of antichoiinesterases on and coma.
ha
in motility organophosphorus
gastrointestinal tract are identical. They produce increase 1reatment of poisoning: Poisoning with
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and also secretions of gasirointestinal tract. compounds can be treated by the administration of atropine and
rm
followed by cholinesterase reactivators. Atropine antagonises only the muscarinic

3. Skeletal muscle: Thes: drugs produce stinulation
symptoms and not skeletal muscle paralysis. But cholinesterase
ma
ma
ma
depression.
reactivators antagonise the later effect also.
ac
4. Secretions: Bronçhial. lacrimal, salivary, gastric and pancreatic

cy
cy
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secretions are ncreased. CHOLINESTERASE REACTIVATORS (OXIMES):
-
y
5. Smooth muscles: Bronchioles and ureters are contracted. 1. Pyridine - 2 aldoxime methiodide (P 2 AM)
2. Diacetylmonoxime (DAM)
Therapeutic uses: The reversible anticholinesterases are used:
. 3. Obidoxime chloride
fFor reducing intraocular tension in glaucoma.
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Ph
Ph
Ph
h
y
y
82
The oximes arc used in t:e treatment of organophosplhorus
do not prevent the release of acetylcholine at cholmeigic nerve
endings. These drugs produce a competitive blockade of muscarinic
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poisoning They act by dephosphorylating the phosphorylated
receptors.
cholinesterase. So the free enzyme can inactivate acetylcholine. The
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OXilnes reverse atso the neuromuscular paralysis
produced by Pharmacological actions:The following ae the
organophosphorus compounds. pharnaçological actions of belladonna alkaloids in general and those
y
of atropine in particular.
CHOLINERGIC BLOCKING DRUGS
Ph
Ph
Ph
29. i. Smooth musdes
.
ha
On the gastrointestinal tract, the effect of atropine cepcnds on

Cholinergic blocking drugs inhibit the action of acetylcholine
ar
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on structures innervated by postganglionic parasympathetic
nerves. functional activity. It does 1not atlect normal peristaltic
r
acetylcholine. So they are moveents. It relieves only hypemmotility. t a so blocks

They block only the muscarinic actions of
ma
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excessive activity produced by cholinergic agents.
also called as antimuscarinic drugs. These drugs are also called
as
blockers or anticholinergic 2. On biliary tract, it produces an antispasmodic actio0n.
parasympatholytics, parasympathetic,
3. On urinary bladder, it decreases the, tone of the lundus but
c
c
drugs. increases the tone of the trigonal. sphincter
y
y
Classification of drugs: On bronchi, it relaxes the smooth muscles.
4.
On uterus, it does not have any significant effect or tone and
5.
1. Belladonna alkaloids Atropine
Scopolanine (hyosine) motility.
Homatropine ii. Secretions: Atropine decreases all secretions under cholinergic

2. Semisynthetic substitutes
Atropine methylnitrate influence. It decreases salivary secretion and also secretion of nese,
ofbelladonna alkaloids Scopolamine methylbromide pharyix and bronchi. Italso inhibits sweat secretion. t also
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decreases the volume and total acidity of gastric secretior. But it
Homatropine methylbromide
does not affect milk secretion which is not under cholinerg e control.
ud
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3. Synthetic substitutes of Methantheline
belladonna alkaloids Propantheline ii. Eye: Atropine produces
Oxyphenonium 1. Mydriasis. (dilatation of pupil).
y
y
Dibutoline
2 Cycloplegia (eye is fixed for distant vision).
Ph
Ph
Ph
Cyclopentolate
3. Increase in intraocular tension.
ha
BELLADONNA ALKALOIDS: These alkaloids are obtained from

ar
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iv. Cardivascular s/sem:
solanacae plants. Atropine is found in Atropa belladonna and Daturu
rm
1. The effect on heart depends on dose. Smaller dose produce

stramonium. Scopolamine is found in Hyoscyamus niger. Atropine
ma
ma
ma
is an ester
central Slowing. Larger doses produce acceleration due to
is an ester of tropic acid with tropine, a base. Scopolamine peripheral" vagal paralysis.
ac
of tropic acid with scopine. Atropine by itself has no effect on blood vessels or blood
cy
cy
cy
pressure. But it counters vasodilatation and hy potension
Mechanism of action: The belladonna alkaloids block. the
y
produced by parasynmpathonmimetic agents. TOxic dose of

muscarinic actions of acetylcholine. They block the effect of
extermally and also that is released on atropine produces cutaneous vasodilatation leading to 'atropine
acetylcholine administered
flush'.
stimulation of postgangiionic parasympathetic nerve. But these drugs
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Ph
Ph
Ph
h
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Telegram - Study Pharmacy B4
85
atropine has no
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v. Central nervous system: Therapeutic dose of
eflect except slight stimulation of medullary vagalnuclei. With toxic substitutes of atropine were synthesised to produce selective effects.
This occurs in the fomm off Unfortunately, no atropine substitute is highly selective in its action.
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dose, it produces centril excitation. can be
restlessness, imitability, nallucinations and deliriuun.
But scopolamine Based on the predomnant actions, these atropine substitutes
sedative effect. classified as:
(hyoscine) produces a
y
alkaloids are Homatropine
Absorption, fate and excretion: Thc belladonna Mydriatics and
Ph
Ph
Ph
administration. Atropine crosses cycloplegics Eucatropine hydrochloride
well absorbed on oral aid parenteral
ha
1s secreted in milk. It is partly excreted Atropine methonitrate

the placental barier and also Antispasniodics
ar
ar
ar
2.
unchanged by kidneys Methoscopolamine bromide
r
Methantheline
ma
ma
ma
ma
Toxicities: The toxici ies of atropine are: Propantheline
. Dry nmouth, difticulty in speech and
swallowing. Oxypheno1nium
c
c
2 Dry skin and inu rease in body teniperature.
y
y
3. Mydriasis and pralysis of accommodation. 30. SYMPATHOMIMETIC DRUGS
4. Urnary urgency and difticulty in micturition.
5. Excitement, restl >ssiiess and motor inco-ordination. Sympathomimetic drugs (adrenergic drugs) are agents which
produce an effect similar to the stimulation of postganglionic
or
Preparations and dose: sympathetie nerves Most of these compounds have an intact
called as
rm substituted amino group. So they are

Atropine sulphat> powder partially
Atropine sulpliat: tablet 0.25 to 2 mg sympathomimetic amines.
St
St
St
St
Atropine sulphate injection Classification of drugs:
Based on the presence or absence of catechol nucleus (ortho
ud
ud
ud
u
belladonna alkaloids are
Therapeutic uses: Atropine and otlher dihydroxy benzene), the sympathomimctic amines can be classified
used for the following purposes: as:
y
y
.In ulcer 1o decrease the secretion of acid.
peptic Adrenaline
1. Catecholamines
of the yastrointestinal tract.
Ph
Ph
Ph
2. In colic Noradrenaline
ha
3. As a biliary aniispasmodic. Dopamine

practice.
As a mydriatic and cycloplegic in ophthalmic isoprenaline
ar
ar
ar
4.
rm
S. In organophosp! orus poisoning. Ephedrine

2. Non-catecholamines
ma
ma
ma
6. As pre-anaestlhe.ic medicatipn. Amphetamine
ac
Methylamphetamine
SYNTHETIC AND SEMISYNTHETIC
SUBSTITUTES OF Hydroxyanmphetamine
cy
cy
cy
ATROPINE Mephentemine
y
Metaramino
The belladonna alkaloids including
atropine do not have a Phenylephrine
In addition to therapeutic effects, they produce
selective action.
Lundesirable effects.. A variety of synthetic and semisynthetic
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
87
St
St
St
St
3. Blood pressure: On intravenous adnministration. adrevaline
CATECHOLAMINES produces biphasic effect on blood pressure. There is an initial rise
ud
ud
ud
u
due to stimulation of alpha receptors (vasoconstriction as ment oned
Catecholamines are compounds which contain catechol nucleus
includes: above). Later, there is a fall due to an etfect on beta receptors
(ortho dilydroxy benzene). This group (vasodilatation as described earlier). If adrenaline is injected after the
y
.Noradrenaline, the sympathetic neurolhumoral transmitter.
administration of ergotoxine (an alpha receptor blocking age:1), it
Ph
Ph
Ph
nmedulla.
2. Adrenaline, the hormone of adrenal produces only a fall in blood pressure. This phenomenon is called as
ha
in central
3. Dopamine, a neurohumora! synipathetic transmitter Dale's vasomotor reversal.
ar
ar
ar
nervous system.
4. Smooth muscles
r
4. Isoprenaline, a synthetic compound.

ma
ma
ma
ma
in the i. Gastrointestinal tract: Adrenaline relaxes the smooth muscles of
ADRENALINE (EPINEPHRINE): Adrenaline is synthesised
conmpound for the synthesis of adrenaline intestine and decreases the motility.
adrenal medulla. The parent
c
c
is phenylalanine and the pathyway of
synthesis is as follows: ii. Bronchi: Adrenaline relaxes the bronchial simooth muscle and
y
y
relieves the spasim.
Phenylalanine
Hydroxylase ii. Uterus: The effect depends on species and presence or ab:ence
fac tors.
of pregnancy. But rat uterus is relaxed irrespective of these
Tyrosine
Hydroxylase iv. Spleen: The spienic capsule is contracted releasing nore
Dihydroxyphenylalanine (DOPA)
Dopa decarboxylase
oharm erythrocytes into circulation.
v. Hair follicie: Adrenaline contracts the pilomotor muscle of the
St
St
St
St
.
Dopamine hair follicle, producing erection of hair.

Dopanine beta oxidase 5. Eye: Adrenaline produces mydriasis and reduction
in uiraccular
ud
ud
ud
u
Noradrenalne tension.
N-methyl transferasec
6. Respiration: Adrenaline produces a weak stimulatior of
y
y
Adrenaine apnca b:fore
respiration. On intravenous administration. it produces
Adrenaline is stored within intracellular particles or granules of stimulation. This is due to stinnulation of baro-receptors and
ciirect
Ph
Ph
Ph
adi enal nmedulla.
ha
central action.
ar
ar
ar
Pharmacological actions: 7. Skeletal muscles: Adrenaline improvCs neuromuscular
transmission. It. also relieves fatigue of skeletal muscles.
rm
a
1. ieart: Adrenaline acts oin beta receptors of heart and produces
ma
ma
ma
2'so
increase in 8. Metabolic effect: Adrenaline increass blood sugar level.
ac
i. rate of contraction (positive ionotropic

effect) increases ftee fatty acid level of plasma.
cy
cy
cy
ii. force of contraction (positive chronotropic
effect) is inactivated in the
Absorption, fate and excretion: Adrenaline
y
ii. cardiac output gastrointestinal tract. So it is administered by injection or-inhattio:n.
2. Blood vessels: Adrenaiine constricts

the blood vessels of skin Adrenaline is metabolised by:
and mucous membranes (due to its eifect on alplha receptors). But it . Catechol orthomethy! transferase (COMIT) which ccverts
to the effect on bcta
ilates the blcod vesscis of skeletal muscles (due adrenaline to metanephrine.
receptors).
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
St
St
2. Monoamine ocidase (MAO) which converts adrenaline to 3. 5. Metabolic effects like hyperglycaemia produced by adrenaline
methoxy-4-ly«lroxy mandelic acid. This product is excreted in are absent with noradrenaline.
ud
ud
ud
u
urine. Noradrenaline is mainly used for elevating blood pressure in
case of shock.
Preparations and dose:
y
1. Adreialine injection 0.2 to 0.5 ml of 1:1000 solution ISOPRENALINE
Ph
Ph
Ph
adninistered ty subcutaneous or intramuscular injection. It is a synthetic compound having a selective beta receptor
ha
2. Adrenaline in oil injection 2mg. every 8 to 16 hours by stimulant effect. It stimulates the myocardium, but produces
ar
ar
ar
intramuscular injectio. peripheral vasodilatation. So it produces a fall in blood pressure and
r
gastrointestinal
3. Adrenaline inlalation tachycardia. It relaxes smooth muscles of bronclii and
ma
ma
ma
ma
tract. Also it releases free fatty acids as produced by adrenaline.
Therapeutic uses:
It is readily absorbed when given parenterally or as an aerosol.
c
c
a. Emergency uses: It is mostly administered as sublingual tablets. It is metabolised
and
y
y
1. syncopil attacks of Stokes-Adams syndrome.
In the climinated by the same route as adrenaline.
2. For resuscitati on of failing heart (intracardiac administration). Isoprenaline is mainly used as a bronchodilator and as a cardiac
3. In allergic disorders, as a physiological antidote to histamine. stimulant in heart block.
4. As a broncho lilator, in bronchial asthma. DOPAMINE: It is a naturally occurring compound and it is a
b. Non emergency
.
uses:
Onar
To prolong the effect of local anaesthetics.
precursor of noradrenaline. It acts on both alpha and beta receptors.
Also it acts on specific dopamine receptors in the mesentric and renal
vascular beds. On intravenous infusion, it stimulates the heart and
St
St
St
St
in shock
To control he norrhage by producing vasoconstriction. produces renal vasodilatation. It raises blood pressure
the treatment
ud
ud
ud
u
without producing cardiac arrhythmias. So it is used in
NORADRENALINE (NOR EPINEPHRINE):
of cardiogenic shock.
It is a chemical mediator liberated by postganglionic
y
y
sympathetic nerves. It is also present in adrenal medulla to the extent NON-CATECHOLAMINES
Ph
Ph
Ph
of 10 to 18%. Unlike adrenaline, it does not have a methyl
These are sympathomimetic amines ad they are devoid of
ha
substtution in the ainino group.

catechol nucleus. They can act:
ar
ar
ar
Noradrenaline acts only on alplha receptors, whereas adrenaline
1. directhy by stimulating alpha and beta adrenergic receptors.
rm
stimulates both alphe and beta receptors. The actions of noradrenlaine

2. indirectly by .releasing noradrenaline and dopamine from
ma
ma
ma
are
. chromatingranules-of sympatheiic nerves.
ac
It constricts blood vessels of skin and mucous membranes. But

it does not dilate blood vessels supplying skeletal muscles like The non-catecholamines are effective on oral administration.
cy
cy
cy
adrenaline. They have prolonged effects because they are resistant to inactivation
y
2. It does not have.cardiac,cffect as produced by adrenaline. by monoamine oxidase. Also they have significant effect on central
3. It has no bro.chodilator effect as seen with adrenaline. nervous system.
4 !trelaxes the plain muscles of intestine, but the action is weaker EPHEDRINE: It is an alkaloidobtained from plants belonging to the
hen compur:d to adrenaline. genus ephedra. It acts directly on both alpha.and beta adrenergic
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
St
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nerve It
receptors and also by rcleasing noradrenaline from sympathetic MEPHENTERMINE: It has a prominent beta receptor eifect.
increases blood pressure by increasing cardiac output.
ud
ud
ud
u
ending.
Tachyphylaxis occurs to the pressor effect. It also dilates coronary,
Actions
cerebral and renal blood vessels.
y
vasoconstriction and
1. It increases blood pressure by peripheral
But repeated administration HYDROXY AMPHETAMINE: It acts on both aljpha nd beta
by ncreasing cardiac output.
Ph
Ph
Ph
decreases the presser response (tachyphylaxis). receptors. It constricts renal blood vessels, but dilates coronary
ha
as
[t also has a relaxant effect on bronçhial and uterine smooth blood vessels. It also increases cardiac output. It is efiective
ar
ar
ar
2.
muscles. decongestant and as a mydriatic.
r
a nasal
3. It also produces CNS stimulant
effect characterised by
ma
ma
ma
ma
activity.
restlessiness, insomnia, anxiety and increased mental SYMPATHETIC BLOCKING DRUGS
accommodation and 31.
4. It produces mydriasis without affecting
c
c
intraocular tensio. Sympathetic blocking agents (adrenergic blockin; agents)
y
y
asthma. It is used as a nasal response
Uses: Ephedrine is useful for bronchial inhibit a) the response to sympathetic nerve stimulation b) the
It is also used
decongestant and also for the treatment of narcolepsy. to adrenaline, noradrenaline and other sympathomimetic anines.
in nocturnal enuresis.
AMPHETAMINE: Amphetamine exists in d, and racemic forns.
l
called as amphetamine. d The sympathetic blocking drugs can be classified as:

dl- amphetamine is commonly
1-amphetamine has Drugs acting on adrenergic receptors.
amplhetamine has more central effects, whereas 1.
St
St
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more cardiovascular effects. 2. Adrenergic neurone blockers.
3. Drugs which interfere with the synthesis and r:lease of
ud
ud
ud
u
Actions: noradrenaline.
Tachyphylaxis
1. produces a moderate rise in_blood pressure.
It
significant effect on cardiac
DRUGS BLOCIKING ADRENERGIC RECEPT(ORS
occurs to this effect. But there is no
y
y
output.
Ph
Ph
Ph
2. It produces CNS stimulant effect
characterised by euphoria, These drugs block the response of effector crgans to
ha
These
insomnia, increased physical and mentäl
activity. endogenous and also exogenous adrenaline and noradrenalin e.
ar
ar
ar
drugs are again classified as:
3. No siguificant bronchodilator effect.
rm
a feeling of fullness.
4. It suppresses appetite by inducing Alpha adrenergic blocking agents:
ma
ma
ma
treatment of narcolepsy,
Uses: Amphetanmine is used for the Both o and a2 blockers Phenoxybenzamine
ac
nocturnal enuresis and obesity. Dibenamine

cy
cy
cy
It is chemically Ergot alkaloids
METHYL AMPHETAMINE (METHEDRINE):
y
ephedrine. In small doses, it produces Tolazoline

related to amphetanmine and Phentolamine
in large doses, it produces a sustained -
CNS stimulant effect. But
it is used as a CNS stinnulant at a a blocker Prazosine
rise in blood pressure. So
a2 blocker Yohimbine
smaller dose and as a pressor agent at large doses.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
93
Telegram - Study Pharmacy92 PRAZOSINE: It selectively blocks alpha receptors. It dilates both
St
St
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St
arteries and veins. So there is a decrease in venous return and cardiac
Beta adrenergic blocking agents output. It is used in Raynaud's syndrome and in benign prostatic
ud
ud
ud
u
Propranolol hypertrophy. Also it is used to treat essential hypertension.
Both Bi and p2 blockers
Sotolol YOHIMBINE: It is an alkaloid obtained from Yohimbene, a West
y
Nodolol African tree. The alpha2 receptor blockade is of a short duration. It
Timolol
Ph
Ph
Ph
is claimed to have an aphrodisiac action.
Atenolol
ha
Bi blockers Therapeutic uses of alpha adrenergic blockers:

Acebutolol
ar
ar
ar
Metaprolol . Peripheral vascular disorders.
r
Butoxamine Treatment of hypertension.

ma
ma
ma
ma
2.
B2blockers
3. Diagnosis and treatment of pheochromocytoma.
ALPHA ADRENERGIC BLOCKING AGENTS Treatment of heamorrhagic and bacteremic shock.
c
c
4.
y
y
PHENOXYBENZAMINE and DiBENAMINE: These drugs belong
to the group of beta haloalkylamines.
They are. structurally similar BETA ADRENERGIC BLOCKING AGENTS
mustards. The alpha receptor blockade is due to positively
to nitrogen
in the body. These compounds These drugs inlibit adrenergic responses medieted through beta
charged cyclic intemediates forned
can also block the ac tions of 5-bydroxytryptanine, acetylcholine and receptors. They have become very important since they are widely
histamine. They alsc exhibit Dale's vasomotor reversal. They do not used in hypertension, angina pectoris and arrhythmias.
But they inhibit cardiac
antagonise cardiac actions of catecholamines.
St
St
St
St
arrhythmias induced by adrenaline. They block the nmydriatic effect Classification:
and pruduce miosis.
of adrenaline 1. Non-selective (B1 + B2)
ud
ud
ud
u
viz. ergotamine,
ERGOT ALKALOIDS: The natural ergot alkaloids a. Without intrinsic Propranolol
dihydrogenated derivatives can
ergosine and ergotox ine and also their sympathomimetic activity Sotolol
y
y
block alpha adrenerrgic receptors. But the duratioin of blockade is Nodolol
Ph
Ph
Ph
produced by haloalkylamines. They also antagonise Timolol
shorter than that
alkaloids antagonise the
ha
the actions of 5-hydroxytryptamine. These

b. With intrinsic Pindolol
produce Dale's vasomotor
pressor effects of adrenaline. So they can
ar
ar
ar
sympathomimetic activity Oxprenolol
also antagonise adrenaline induced cardiac
rm
reversal. They Alprenolol

ma
ma
ma
arrhythmias. Labetalol
c. With additional a
PHENTOLAMINE: These compounds produce:
ac
TOLAZOLINE and blocking activity

.
cy
cy
cy
alpha adrenergic blockade. 2. Cardioselective (B1) Metaprolol
y
Atenolol
2. increase in the force of myocardial contraction.
Acebutolol
3. dilatation of peripheral blood vessels.
Butoxamine
4. increase in salivary, pancreatic and lacrimal secretions. 3. B2 Selective
5. antagonism of the actions of 5-hydrr xytryptamine.

St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
94
Pharmacological actions of ß blockers Therapeutic usesS:
St
St
St
St
1. Heart: No effect on nomal heart. They prevent rise in heart fate 1. Angina pectoris
and cardiac output produced by an increased sympathetic tone. 2. Cardiac arrhythmias
ud
ud
ud
u
is helpful in
Myocardial oxygen requirement is decreased. This 3. Myocardial infarction
angina. 4. Hypertension
y
2. Blood pressure: They reduce blood pressure by acting on the 5. Thyrotoxicosis
Ph
Ph
Ph
heart and decreasing cardiac output. 6. Pheochromocytoma
ha
3. Bronchii: They increase bronchiai, resistance by blocking

ß2 7. Chronic open-angle glaucoma
ar
ar
ar
receptors. This is dangeroùs in asthmatic patients.
r
blockers e.g. ALPHA AND BETA ADRENERGIC

4. Central nervous system: Lipid soluble beta
ma
ma
ma
ma
propranolol cross tlhe blood brain barrier. They have sedative and BLOCKING AGENTs
anticonvulsant effects.
LABETALOL: It is a competitive antagonist of both alpha and beta
c
c
lipolysis
5. Metabolism: Propranolol blocks adrenergically induced adrenergic receptors. On oral administration it decreases i. heart rate
y
y
It also blocks the increase in free fatty acid
and glycogenolysis. 2. cardiac contractility 3. A-V conduction 4. peripheral resistance
produced by adrenaline. 5. blood pressure. It undergoes extensive first pass metabolism.
6. intraocular pressure: On topical application the beta blockers
Adverse reactions:
produce a decrease in intraocular pressure.
Gastrointestinal disturbances, dry mouth and fluid retention.
1.
7. Membrane stabilisation: Beta blockers have a membrane
is Bradycardia and orthostatic hypotension.
2.
stabilising effect which is unrelated to beta blockade. This
3. Nervousness, muscle cramps, depression and sexual
St
St
St
St
responsible for cardiac depressant effect of propranolol
dysfunction.
8. Intrinsic sympathomimetic action: Some beta blockers have l:ypertensive
Therapeutic uses: Mainly for high blood pressure and
ud
ud
ud
u
an intrinsic sympathomimetic effect. e.g. pindolol and
oxprenolol.
emergencies.
These drugs may produce less myocardial depression.
y
y
Absorption, fate and excretion: Most of the beta blockers are ADRENERGIC NEURON BLOCKING AGENTS
Ph
Ph
Ph
completely and rapidly absorbed orally. Also they are rapidly and
act on
Adrenergic neuron blocking agents are drugS W11ch
ha
entirely metabolised in the liver. Because of rapid metabolism only ability a nerve
postganglionic synmpathetic nerves to prevent the of
ar
ar
ar
a fraction of the drug enters into circulation.
impulse to release noradrenaline. These drugs do not affect
rm
Adverse reactions: parasympathetic nervous systeni and ganglionic transmis sion. Also,
ma
ma
ma
Sudden hypotension, bradycardia leading to cardiac asystole. affect the response of effector organs to injected
1. they do not
ac
2. Nausea, vomiting, constipation and bronchospasm. noradrenaline. So their action is selective on postganlionic
the release of
cy
cy
cy
3. Cold extremities and absent pulses. sympathetic nerves where tlhey act by preventing
y
4. allergic reactions, thrombocytopenia and agranulocytosis. noradrenalne.

5. Prolonged use of propranolol may produce fatigue, muscle Drugs which belong to this group are Guanethidine,
cramps, icthargy. iallucinations and menta depression. Guanoxon, Guanachlor, Bethanidine and Debrisoquire sulphatc.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
97
96
GANGLIONIC STIMULATING DRUGS
are called as newer adrenergic neuron
St
St
St
St
Except guanethidine, the i1est
blocking agents. Though the ganglionic stimulating agents have no therapeutic
ud
ud
ud
u
GUANETHIDINE: It is ai adrenergic neuron blocking agent which use, they find use as experinmental tools.
acts by inhibiting the release of noradrenaline at sympathetic nerve
It produces ai initial sympathomimctic effect before Classification of drugs:
y
endings.
depletion of
producing a fall in blood pressure. This is due to the Natural alkaloids Nicotine
Ph
Ph
Ph
noradrenaline from sympathetic nerve endings. The hypotensive
Lobeline
ha
guanethidine is delayed for 2 to 3 days. But once manifested,

effect of Tetramethylammonium(TMA)
Synthetic compounds
ar
ar
ar
it is prolonged for 7 to 10 days.
Dimethylphenylpiperazinium
r
Adverse reactions of guanethidine (DMPP)

ma
ma
ma
ma
1. Postural hypotensio 1.
NICOTINE: Nicotine is an alkaloid obtained from the leaves of
2. Inhibition of ejacultion.
c
c
tobacco plant Nicotiana tabacum. Nicotine produces an initial
Nasal congestion. stimulation of ganglion cells followed by paralysis at large doses.
y
y
4. Nausea, vomiting and diarrhoea. Ganglionic blockade is due to persistent depolarisation and
competitive blockade. Also, it produces an initial stimulation of
Newer adrenergic neuron blocking agents skeletal muscles followed by paralysis. It also produces an initlal
Guanoxon, Guanachlor, Bethanidine and Debrisoquine increase in salivary and bronchial secretions followed by decrease.
These drugs act
sulphate are the drugs wiich belong to this group. Nicotine stimulates the release of adrenaline from adrenal medulla. It
guanethidine. But the hypotensive action
by the same mechanism as also produces and antidiuretic effect due to release of ADH. The
is quick in onset (2 to 3 hours) and of short duration
of these drugs respiratory, vasomotor and vomiting centers of the medulla are
St
St
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St
by these drugs
(less than 24 hours). The adverse effects produced stimulatéd directly. It also produces tremors and convulsions in large
guanethidine. Except bethanidine
are similar to those prod iced by doses. It produces stimulation of central nervous system followed by
ud
ud
ud
u
sulphate, the other drugs have no advantage over
and debrisoquine depression. Death occurs due to respiratory paralysis.
guanethidine.
y
y
Acute nicotine poisoning: The symptoms are:
DRUGS WHICH INTERFERE WITH THE SYNTHESIS
Ph
Ph
Ph
1.Saliv.tion, vomiting; diarhoea and cold sweat.
ha
AND RELEASE OF NORADRENALINE 2. Rapid respiration and rapid pulse.

ar
ar
ar
been 3. Inco-ordination and respiratory failure.
Alpha methyldopa which belongs to this group has
rm
discussed in chapter 42 (Antihypertensive agents) Chronic nicotine poisoning: The symptoms are
ma
ma
ma
Gastrointestinal disturbances like indigestion, dyspepsia, nausea
ac
32. DRUGS ACTING ON AUTONOMIC GANGLIA| and gastric ulcer.

cy
cy
cy
2. Circulatory disorders like palpitation, cardiac. arrhythmias and
y
Drugs can act on sympathetic and parasynmpathetic ganglia myocarditis.

stimulants
producing either stimulauon. or blockade. Ganglionic 3. Neurological disorders like neuritis and amblyopia.
limited theapeutic application. But ganglion blocking
have extremely 4. Bronchial carcinoma which is common in smokers.
agents are effective in the treatment of hypertension.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
hypotension). Also, there is pooling of blood
in veins. This
natural alkaloid obtained from the dried leaves tum decreases cardiac output.
St
St
St
St
LOBELINE: It is a decreases venous return, which in
herb, Lobelia influta. It resembles nicotine in its produces my driasis,
of the
direct central 2. Blockade of parasympathetic ganglia
pharmacological actions. It stimulates respiration by intestina niotility.
ud
ud
ud
u
cycloplegia, decrease in gastric secretion and
the sensitivity of respiratory center to emptying of bladder. They
action and also by increasing There is also interference in the
carbondioxide. In the fornnm of a tincture, it was once used
as secretion.
also decrease sweat
y
bronchial antispasmodic. quaternary amine ganglion
Absorption, fate and excretion: The
Ph
Ph
Ph
gastrointestinal tract. But the
TETRA METHYL AMMONIUM AND DIMETHYL blockers are not absorbed from
ha
are well absorbed orally.

PHENYLPIPERAZINIUM: secondary and tertiary amines
ar
ar
ar
and hey do
compounds. Their The distribution of quaternary amines is limited
r
These are synthetic quaternary ammonium secondary and tertiary amines

But ganglionic stimulation not cross the blood-brain barrier. But
ma
ma
ma
ma
ganglionic actions are similar to nicotine.
drugs are excreted almost
is not followed by paralysis. They are not
satisfactorily absorbed from can cross blood-brain barrier. All these
gastrointestinal tract. unchanged by the kidney.
c
c
Adverse reactions:
y
y
GANGLIONIC BLOCKING AGENTS sympathetic blockade.
1. Postural hypotension and syncope due to
in both sympathetic mouth, constipation, urinary
These are drugs which block transmission 2. Mydriasis, cycloplegia, dry
blockade.
drugs do not affect conduction retention etc. due to parasympathetic
and parasympathetic ganglia. These
postganglionic nerves (both depression, mental confusion and mania
of impulses in the preganglionic or Central effects like
sympathetic and parasympathetic). Also, they do not prevent the produced only by secondary and tertiary amines.
acetylcholine on preganglionic nerve stimulation. But they blocking drugs are rarely used as
release of Therapeutic uses: The ganglion
St
St
St
St
produce ganglionic blockade by occupying
receptor sites on the used to contro
antihypertensive agents. Occasionally they are
ganglion cells. gastrointestinal tract.
excessive secretion and motility of
ud
ud
ud
u
Classification of drugs: BLOCKING AGENTS
33. NEUROMUSCULAR
y
y
Tetraethylammonium
Quaternary aminesS
Ph
Ph
Ph
Pentamethonium of skeletal muscles
Hexamethonium These are drugs which produce relaxation
ha
. nerve impulse at neuroiuscular

Pentolinium by inhibiting the transmission of
ar
ar
ar
Chlorisondamine junction.
rm
Mecamylamine Classification of drugs:

ma
ma
ma
Secondary ainineS
Trimethaphan
A.Nondepolarizing (Competitive) blockérs
ac
Tertiary amines
Pempidine
cy
cy
cy
d Tubocurarine
1. Long acting
Pancuronium
y
the peripheral Pipecuronium
1. Blockade' of. sympathetic ganglia decreases pressure. Fall Doxacurium
sympathetic tone. This produces a fall in blood
in blood pressure is more in the standing
posture (postural
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y
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Ph
Ph
Ph
h
y
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Telegram - Study Pharmacy100 101
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Intermediate acting Vecuronium
4. Respiration: Small dose of d-tubocurarine has no effcct on
Atracurium
respiration. But large doses produce paralysis of respiratory muscles
ud
ud
ud
u
Rocuronium
like diaphragm and intercostal muscles. This can be treated with
3. Short acting Mivacurium artificial respiration.
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B. Depolarizing blockers Succinylcholine 5. Autonomic ganglia: d-Tubocurarine produces ganglionic
Ph
Ph
Ph
Decamethonium blockade after an initial brief stimulation. The ganglionic blockade
ha
can be antagonised by neostigmine.
ar
ar
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d-TUBOCURARINE: It is quaternary amnmonium alkaloid 6.Histamine release: d-Tubocurarine releases histamine from
r
from plants lik: Chondrodendron tomentosum and Strychnos tissues. This leads to bronchospasm and hypotension.
obtained
ma
ma
ma
ma
lethalis.
Absorption, fate and excretion: Being quaternary
Mechanism of action : Amuscle cell at rest has largge ammonium compound, d-tubocurarine is not absorbed from
c
c
the muscle
concentration of intracellular potassium. The exterior of gastrointestinal tract. But it is well absorbed on intramuscular
-
y
y
concentration of sodium. An entry of sodium into the
cell has large
phase. When injection. It does not cross blood brain barier and blood placental
muscle cell is not possible diring the resting barrier. It is metabolised mainly in the liver and excreted in urine.
move into
acetylcholine is liberated by a nerve impulse, sodium ions
produces depolarisation,
and potassium ions out of the cell. This Adverse reactions :
contraction of the muscle. After a muscle
leading to a mechanical 1. Respiratory failure due to paralysis of respiratory muscles,
from the cell and
contraction is over, sodium 1ons are extruded repolarisation and which can be treated by artificial respiration.
potassium ions enter into the cell. This produces
now the imuscle is ready for a second contraction. 2. Hypotension which can be treated by sympathomimetic amines.
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d-Tubocurarine ompetes with acetylcholine for the receptors 3. Bronchospasm and allergic reactions which can be treated by
acetylcholine is prevented from antihistamines.
at neuromuscular junction. So
ud
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is prevented. This
combining with the receptors and so depolarisation Preparations and dose: Tubocurarine injection 6 to 9 mg.
produces muscle relaxation. by intravenous injection.
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Pharmacological actions: Therapeutic uses
Ph
Ph
Ph
d-Tubocurarine initially paralyses smaller
1. Sequence of paralysis :
in anaesthesia to produce muscle relaxation.

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Later, bigger muscles 1. As an adjuv

muscles like those of fingers, toes, eyes and ears.
by intercostal 2. In orthopedic procedures for correction of dislocations.
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like those of limbs, neck and trunk are affected followed
So respiratory
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affected. To prevent trauma in electro shock therapy.

muscles. The diaphragn: is the last muscle to be 3.
occurs the reverse order.
ma
ma
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in
failure occurs as the last event. Recovery 4. To decrease muscle spasm in tetanus and convulsive states.
d-Tubocurarine being a quaternary 5. In the diagnosis of myasthenia gravis.
ac
2. Central nervous system

:
cross the blood brain barrier. So it PANCURONIUM: It is a synthetic neuromuseular blocking agent
cy
cy
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ammonium compound does not
stimulation or depression.
does not produce any central effects like
y
with a steroidal structure. It is 5 times more potent than d

normal dose. But large tubocurarine. It does not release histamine. So it does not produce
3. Cardiovascular system: No effect at
doses produce fall in blood pressure due to ganglionic blockade and flushing or bronchespasm. It can cause rise in BP and tachycardia due
to vagal blockade. It is inexpensive. So it is routinely used as a muscle
histamine release.
relaxant in developing countries.
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y
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Ph
Ph
Ph
h
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103
acetylcholine is not achieved. In a myasthenic patient, stir ulation of
St
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steroidal neuromuscular
PIPECURONIUM: It is another newer a motor nerve produces normal response initially. Later, the response
but long duration of action. It has
blocking agent. It has a slow onset decreases rapidly and fails altogether. So the patient is not able to
ud
ud
ud
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But it can cause transient
hypotensión
minimal cardiovascular effects. maintain voluntary muscle contraction for more than a short period.
and bradycardia. Administration of neostigmine, an anticholinesterase drug improves
y
muscle relaxant. It has the response to motor nerve stimulation and increases the strength of
DOXACURIUM: It is a recent bisquarternary
it is suitable for long
Ph
Ph
Ph
duration of action. So skeletal muscles.
a slow onset but a longer
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duration surgeries. Treatment: Neostigmine was once the dug of choice for the
as atracurium. But it has
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treatment of myasthenia gravis. Since it has a shorter curation of
VECURONIUM: It has similar properties
1) no cardiovascular action, other drugs like pyridostigmine and ambenonium are preferred.
r
action. Advantages
:
a shorter duration of 3) does not liberate Ephedrine is an adjuvant that can be used with these anticholinesterase
ma
ma
ma
ma
vagal blockade
effects 2) no ganglionic or 100
by neostignine. Dose 80 to drugs. Since thymoma is associated with myasthenia gravis,
histanine 4) tóxicity is antagonised
thymectomy also produces improvement.
c
c
micrograms per kg.
competetive neuromuscular DANTROLENE: It is a directly acting muscle relaxant. It has no
y
y
ATRACURIUM: It is a bisquarternary
potent than pancuronium and
also cffect on central nervous system or on neuromuscular junction. It
blocking agent. It is 4 times less inactivated in plasma by directly acts in the skeletal muscles. It acts by inhibiting the release
is short. It is
the duration of action
degredation (Hotmann elimination). of calcium from the sarcoplasmic reticulum. Also it inter feres with
spontaneous non enzyimatic
nondepolarzing excitation contraction coupling.
MIVACURIUM: It is the shortest acting
flushing due to histamine release. Use: 1. Malignant hyperthermia produced by halothane 2.
neuromuscular blocker. It can cause Neurolepti malignant syndrome.
cholinesterases. Prolonged paralysis can
It is metabolised by plasma
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deficiency.
occur in pseudocholinesterase
compound. It
SUCCINYLCHOLNE : It is a quaternary ammonium
ud
ud
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acetylcholine joined
two moiecules of
has a structure resembling persistent. (1.e., prolonged)
together. It acts by producing
occurrence of skeletal muscle paralysis,
y
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depolarisation. Before the Succinylcholine
fasciculation and twitching.
there is brief muscular So it
Ph
Ph
Ph
liver pseudocholinesterase.
is rapidly destroyed by
plasma and 5 minutes.
to
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for 3
lasting only
has a very short action. But large doses
mayy
Succinylcholine does not release histamine.
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ganglionic blockade.
produce. hypotension due to
rm
intravenous
of mg. per kg. by slow
1
adminstered at a dose
ma
ma
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It is
kg if required.
injection foilowed by 0.3 mg per
ac
enzyme
aponea in genetic deficiency of the
Adverse effect: Prolonged
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cy
cy
fresh blood transfusion.
psuedcholinesterase. It is treated by giving
y
weakness and
Myasthenia gravis: It is a disease characterised by
thymoma is
muscie. High incidence of
rapid fatigability of skeletal myasthenia gravis is at
The defect in
another feature of his disease. required concentration of
the neuromuscular junction
where the
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Ph
Ph
Ph
h
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accommodation or cycloplegia). Drugs which paralyse
Section V accommodation are called cycloplegics
ud
ud
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ORUGS ACTING ON THE EYE
Ph
Ph
Ph
- Circular Muscle
ha
ar
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Parasympathetic nerve
rma
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ma
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34. MYDRIATICS, MIOTICS AND DRUGS Pupil
Radial muscle
USED IN GLAUCOMA
c
c
y
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Sympathetic nerve
The iris: The diaineter of the pupil is controlled by two sets of
(which
muscles which supp y the iris. They are radial muscles
(which are arrangec
are arranged radially) and circular muscles
concentrically). The radial muscles are innervated by
postganglionic symsathetic nerves arising from cells in
superior cervical gar glion. Stimulation of these nerves or
the
injection
aebookspdf
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radial muscles. This Fig.1. Mechanism of miosis and mydriasis.
of noradrenaline p1 oduces contraction of
leads to mydriasis (dilatation of the pupil). The circular muscles
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ud
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from cells in the
1. Stimulation of parasympathetic produces contraction of
are innervated by pirasympathetic nerves arising
nerves or injection of
circular muscle causing miosis.
ciliary ganglion. Stimulation of these
y
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acetylcholine produces contraction the circular muscles. This leads 2. Stimulation of synpathetic produces contraction of radial
Ph
Ph
Ph
muscle causing mydriasis.
to miosis (constrict on of the pupil).
ha
The lens: The lens is attached to suspensory ligaments which

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it to the ciiary body. The ciliary body contains smooth The Aqueous humour: The interior of the eye-ball contains
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connect
muscles (ciliary m'iscles which contribute to the mechanism of aqueous humour. Glaucoma (increase in intraocular tension)
ma
ma
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accommodation). (Fig.2) They are innervated by postganglionic occurs due to excessive production of aqueous humour or due to
ac
parasympathetic narves which arise from ciliary ganglion. decreased drainage. The drainage of aqueous humour occurs
cy
cy
cy
Stimulation of this nerve or injection of acetylcholine produces through the canal of Schlemn. (Fig. 2) When the pupil is dilated,
y
contraction of the ciliary muscles. This leads to focussing of

the the ciliary muscles are relaxed. The relaxed ciliary muscles obstruct
Relaxation of the the canal of Schlemn. So the drainage of aqueous humour is
lens for near vision (called as accommodation).
this condition, prevented leading to an increase in intraocular tension. When pupil
ciliary muscles produce flatteting of the lens. In
paralysis of is constricted, the ciliary muscles are contracted. This widens the
the lens is focussed for distant vision (called
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Ph
Ph
Ph
h
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muse le to
accomodation) by blocking the response of ciliary
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be drained leading
cunal of Schlemn. So the aqueous humour can
parasympathetic stimulation. Also they raise intraocular tension
to a decrease in intraocular tension. Schlemn
because the drainage of aqueous humour through the canal of
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Cliary is obstructed.
Suspensory
y
body Miosis can
Miosis (constriction of the pupil) be
:
ligament
Ph
Ph
Ph
produced by:
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1. Cholinergic drugs like pilocarpine, physostigmine and
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Lens 1neostigmine. These drugs act by contracting the circular muscle of
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iris. The eye is set for near vision (spasm of accommodation) and
in turm, reduces
ma
ma
ma
ma
Canal of this is produced by contraction of ciliary muscle. This
LParasympathetic Schlemn aqueous himour
intraocular tension by facilitating the drainage of
through the canal of Schlemn.
c
c
like ergotamine and dibenamine.
y
y
2. Sympathetic blocking drugs
Fig. 2. Mechanism of accomnmodation These drugs act by blocking the mydriatic response to the stimulation
nerves. These drugs do not affect accommodation
. Stimulation of parasympathetic contracts ciliary muscle.
of sympathetic
since the ciliarymuscles are not affected. Also they do noi alter
This makes the lens more convex (so eye is fixed for near intraocular tension,
vision) and widening of the canal of
Schlemn This
in
humour. Glaucoma: Glaucoma is a disease characterised by incre:ise
facilitates the drainage of aqueous nerve diunage
intraocular tension. If it is severe, it can lead to optic
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2. Parasympathetic blockers like atropine produce paralysis and ireversible blindness. Drugs effective glaucoma
can be clasified
of the lens
of ciliary muscle. This produces flaltening as
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fixing the eye for distant vision) and narrowing of the
aqueous Beta adrenergic blockers Timolol
canal of Schlemn. 1his prevents the drainage of
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Betaxolol
humour. Levobunolol
Ph
Ph
Ph
Mydriasis can be
Mydriasis (Dilatation of the pupil): Pilocarpine
ha
2. Miotics
produced by: Physostigmine
ar
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1. Sympathomimetic drugs like
ephedrine, phenylephrine and Dipivefirine
rm
Alpha adrenergic agonists

the radial muscles Apraclonidine
also by cocaine. These drugs act by contracting
ma
ma
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ciliary muscle, they do no Brimonidine
of iris. Since they do not affect the
ac
not raise the. intraocular

paralyse accomodation. Also they do
Carbonic anhydrase Acetazolamide
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cy
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lowered because of constriction of blood
tension. But it may be inhibitors
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vessels in the eye ball.

Prostaglandins Latanoprost
2. Anticholinergic drugs
(parasympathetic blockers) like atropine 5.
Levobunolol
and homatropine. These drugs act by paralysing the circular muscles 1. Beta adrenergic blockers: Timolol, Betaxolol and
cycloplegia (paralysis of effective in glauconma. They act by reducing the
of iris. These drugs produce are the beta blockers
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ud
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Ph
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Ph
h
y
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109
108
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1
No change in pupillary
formation of aqueous humour. Advantages: Section VI
4. Convenience of administration
ud
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size 2. No myopia 3. No head ache
once or twice daily.
miotics used in
Pilocarpine and physostigmine are the
y
2. Miotics:
the ciliary muscle. So the DRUGS ACTING ON
glaucoma. They produce contraction of
Ph
Ph
Ph
drainage of aqueous umour through the canal of schlemn is RESPIRATORY SYSTEM
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facilitated.
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The drugs used are Apraclonidine
3. Alpha adrenergic agonists:
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and Brimonidine. Botl: are congeners of clonidine. They act by

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ma
ma
ma
decreasing aquous humour production.
Acetazolamide belongs to this DRUGS USED IN BRONCHIAL ASTHMA
4.Carbonic anhydras inhibitors: 35.
generation of bicarbonate ion in the
c
c
group. It acts by inhib ting the
y
y
Bronchial asthma is characterised by periodie spasm of
y
ciliary epithelium.
bronchial
used is Latonoprost. It is a PGF2 a bronchial smooth muscles, increased secretion and edema of
5. Prostaglandins: Tie drug remains locked
pigmentation and sometimes blurred mucosa. Because of the spasnm, large volume of air
derivative. It can produce iris leading to
in the alveoli. This decreases tidal air and vital capacity
vision.
dyspnea.
Opharm Classification of drugs : Drugs used for the treatment of

bronchial asthma can be classified as:
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1. Bronchodilators
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ud
ud
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a) Sympathomimetics Adrenaline
Ephedrine
y
y
Isoprenaline
Ph
Ph
Ph
Orciprenaline
ha
Salbutamol
ar
ar
ar
b) Methyl xanthines Theophylline
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c) Anticholinergics Atropine
ma
ma
ma
Ipratropium bromide
ac
2. Mast cell stabilisers Disodium chromoglycate

cy
cy
cy
Ketotifen
y
Corticosteroids Beclomethasone dipropionate

3.
wlhich acts by stimulating beta
1. ADRENALINE: It is a potent drug
acute attack
receptors in the bronchial smooth muscle. It relieves an
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y
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Ph
Ph
Ph
h
y
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110 111
relieves pulmonary congestion by constricting pulmonary injection. Usual route is oral or slow i.v. injection at
a dose of 250 to
and also
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arteries. Prolonged use of adrenaline in bronchial asthma may produce 500 mg.
resistance. Also it produces side effects like ventricular tachycardia 7. DISODIUM CHROMOGLYCATE (CROMOLYN): It is a synthetic
ud
ud
ud
u
and ventricular fibrillation. Adrenaline should not be give in patients compound which acts by preventing mast cell degranulaticn. This
and
with cardiac asthma, hypertension and hyperthyroidism. prevents the release of spasmnogenic substances like histaraine
y
have antihistaminic effects. It alse inhibits
1000 solution administered by serotonin. But does
it not
Dose: 0.2 to 0.5 ml of I in
o oral
the enzyme phosphodiesterase. It is poorly absorbed
Ph
Ph
Ph
subcutaneous injection. except local
administration. It does not produce any adverse effect
ha
2. EPHEDRINE It is a sympathomimetic drug which acts on both irritation.
ar
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alpha and beta adrenergic receptors. It is a weeker bronchodilator. by
20 mg. capsules given by inhalation 3 to 4 times daily
r
Also it produces sleeplessness. This can be prevented by combining Dose:

ma
ma
ma
ma
means of 'spinhaler.
with phenobarbitone.
Jtacts on beta receptors of bronchi. It is
Use: Allergic bronchial asthma and allergic rhinitis.
3. ISOPRENALINE
c
c
administered sublingually at a dose of 10 to 20 mg. It can alsobe 8. KETOTIFEN It has similar actions as disodium chromoglycate.
y
y
adininistered by inlhalation. The only risk of isoprenaline is cardiac It acts by inhibiting airway inflammation induced
by platellet
stimulation. factor (PAF). It also lias an antihistaminic effest. Side
activating
daily.
effects: drowsiness and dry mouth. Dose: to mg twice
I 2
4. ORCIPRENALINE : It is a derivative of isoprenaline which acts
It is a corticosteroid
by stimulating beta receptors. It has a long duration of action and 9. BECLOMETHASONE DIPROPIONATE:
chronic asthma. It is administered as a: aerosol.
produces less cardiac stimulation. It can be administered by oral, which is effective in
it does not produce
parenteral and inhalation routes. It has a topical action in bronchial asthma. So
In chronic asthma it is prefer ed over
any systemic effects.
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5. SALBUTAMOL: It acts similar to orciprenaline by stimulating
glucocorticoids. Sometimes it produces local infections of c ndida in
beta receptors. It has a potent bronchodialator effect by acting on B2 the mouth and throat.
ud
ud
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receptors. But cardiac stimulant effect is less. So it can be used
safely in patients with cardiac diseases. Also it is resistant to
36. NASAL DECONGESTANTS
y
y
inactivation by COMT and hence the duration of action is long. It is
administered by mouth, inhalation and injection.
Ph
Ph
Ph
synmpatlhomimetic drugs
Nasal decongestion can be produced by
to 4 mg. by mouth; 0.6 vasocoistriction
ha
Dose 100 micrograms by inhalation: 2

which act on alpha receptors. These drugs produce
mg. every 4 hours by S.C. or I.M.injection. mucosa.
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and shrinking of the nasal
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6. THEOPHYLLINE It is a relatively weak bronchodilator, It acts Properties of an ideal nasal decongestant

ma
ma
ma
synergistically with beta adrenergic agonists. It is effective when . effcct.
It should produce prompt, prolonged and reliable
adrenaline fails to relieve an acute attack or if the patient is resistant
ac
2. It should not produce nasal irritation.

to adrenaline. It produces a direct relaxant effect on bronchial smooth
cy
cy
cy
Imuscle. Repeated use of theophylline in children may produce 3. It should not damage nasal cilia.
y
dishrbance in leaming and sleep. 4. It should not produce after-congestion.

5. It should not produce tachyphylaxis.
Aminophylline (Theophylline ethylenediamine) s the
commoniy used preparation. It is not administered by s.c or i.m. 6. It should be free from side effects.
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y
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Ph
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h
y
y
113
decongestants do not satisfy all these Classification of drugs.
Most of the nasal
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requirements. 1. Pharyngeal demulcents Syrups
drugs which have a specific
ud
ud
ud
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Linctuses
Drugs used: Only sympathhomimetic
Ephedrine. Lozenges
effect on alpha receptors are used as nasal decongestants.
on alpha receptors. Liquorice
y
because of its effect
produces nasal decongestion are its
and systemic effects Expectorants
But tachyphylaxis, after congestion
Ph
Ph
Ph
solution in normal saline. (Mucokinetics)
disadvantages. It is used as 0.5 percent
ha
only on alpha receptors) are a) Direct expectorants Guaiacol

The other drugs (which act
ar
ar
ar
Guaiphenesin
Pheuylephrine
r
1. Balsum of Tolu
ma
ma
ma
ma
2. Xylometazoline Îhydrochloride Vasaka
3.. Oxymetazoline b) Reflex expectorarts Ammonium chloride
Potassium iodide
c
c
4. Taumine sulphate
y
y
c) Mucolytics Acetyleysteine
5. Taumino heptan
Carbocysteine
combined with
Sometimes the nasal decongestants are Bromohexine
and antibiotics. These preparations
antihistamines, cortico steroids Ambroxol
have doubtful efficacy
DRUGS USED
a)nhar1
an
IN THE TREATMENT OF
Antitussives
(Central cough
Suppressants)
OkSpadf
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St
37. a) Opioids Codeine
COUGH Pholcodeine
ud
ud
ud
u
(Expectorants and antitussives) b) Nonopioids Noscapine
Dextromethorphan
y
y
irritant or obstructive Chlorpheniramine
Cough is a protective reflex by which an c) Antihistamines
occurs by the
Ph
Ph
Ph
froom the respiratory tract. Cough Diphenhydramine
material is expelled
deep inspiration.
ha
Initially, there is a Promethazine

following mechanism
temporarily. This increases the
Following this, the glottis closes They are syrups, linctuses, lozenges and
ar
ar
ar
expiration which opens Pharyngeal demuicents:
forceful mucosa.
liquorice. They produce a smooth coating over the pharyngeal
there is
intrathoracic pressure. Later,
rm
pulmonary air which is forced through saliva. So

the glottis suddenly. Now the or by increasing the flow of
ma
ma
ma
This effect is.produced directly
secretions of the respiratory
the trachea carries wit1 it the obstructing they reduce the afferent impulses arising from the iTitated pharyngeal
ac
tract. mucosa. They are usefül in the symptomatic relief bf dry cough.
cy
cy
cy
are 1. Pharyngeal Expectorants (Mucokiretics): Expectorants are drugs
which
Drugs used ir the treatment of cough
y
Antitussives (central cough This helps in their

demulcents 2. Expectorants and 3. increase respiratory tract secretions or liquify them.
and by different mechanisms.
supprassants). They act at different sites easy expulsion.
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ud
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ud
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y
y
Ph
Ph
Ph
h
y
y
114 115
expectorants: They are guaiacol, Tolu balsm and
vasaka.
Opioid antitussives
Direct
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They act directly and increase bronchial
They are administered orally. 1. CODEINE: It is an opium alkaloid of phenanthrene goup. It is
action.
secretion. Also, thhey increase mucociliary a narcotic antitussive. Its actions are similar but less poient when
ud
ud
ud
u
are emetics which in subemetic doses compared to morphine. It suppreses cough for hours.Ana gesic and
6
Reflex expectorants: These
produce mild irritation of the gastric constipating effects are less. It does not produce tolerance or addiction.
act as expectorants. These drugs
y
This helps to increase the It is administered as syrup of codeine phosphate.Dose, 4 to 8 ml by
mucosa which stimulates gastric reflexes.
produce nausea and
Ph
Ph
Ph
doses, they mouth.
respiratory secretions. In large
ha
expectorants are PHOLCODEINE: Its antitussive potency is similar to.coc.eine. But

vomiting. Drugs used as retlex
ar
ar
ar
ammonium it is longer acting (12 hrs or more). lt has no analgesic or addicting
1. Ammonium salts like ammoniun chloride and
r
property Dose: 10 to 15 mg
bicarbonate.
ma
ma
ma
ma
2. Potassium salts like
potassium iodide. Nonopioid antitussives
and hence produce nausea
All these drugs are potential emetics NOSCAPINE: It is an opium alkaloid of benzylisoquinoline group.
iodide can produce iodism characterised
by
c
c
and vomiting. Potassium It is.equivalent to codeine in antitussive effect. But it has no nalgesic
lacrimation. It can also
y
y
and
y
conjunctival swelling, edema of eyelids effect. Also it has no narcotic or addicting property. So it is grouped
produce goitre and hypothyroidism. as a nonopioid antitussive. Adverse effects: headache and nausea.
decrease the viscosity DEXTROMETHORPHAN: It is a synthetic compound. nly the
Mucolytic agents: These are drugs which
in easy expectoration. The following are d-isomer has antitussive action The I isomer has analgesic action.
of the sputum. This helps It has no constipating or addicting properties. Adverse effects, nausea,
Some mucolytic agents: drowsiness, dizziness and ataxia
of
It acts by opening disulfide bonds
1. ACETYLCYSTEINE: yiscid. It ANTIHISTAMINES: Antihistamines like chorphen iramine,
sputum less
St
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St
makes the
mucoproteins present in sputum.This diphenhydramine and promethazine are used in cough. They relieve
into the respiratory tract.
has to be directly administered cough by their sedative and anticholinergic actions. They do not act
ud
ud
ud
u
It
It acts in the same way as acetylcysteine. on cough centre.Also, they do not have an expectorant action, They
2. CARBOCYSTEINE: and rashes.
administered orally. Side effects: G.I. iritation reduce secretions by anticholinergic effect.
is
y
y
3. BROMOHEXINE: It is
obtained from the plan Adhathoda vasica.
the sputum by dissolving the
Ph
Ph
Ph
it decreases iheiscosity. of are present.
mucopolysaccharide fibres. It is usefül if mucus plugs
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Dose 8 mg thrice daily.

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bronmohexine. Mucolytic actions
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AMBROXOL: It is a metabolite of
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and uses are similar to bromohexine.
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tussal
Antitussives: These drugs act on the CNS. They reduce the
Antitussives are
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impulses by raising the threshold of cough centre.
Antitussives are classified as:
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used only in dry unproductive cough.

1. Opioid antitussives: Codeine
and pholcodeine.
and dextromethorphan.
2. Nonopioid antitussives Noscapine
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Ph
Ph
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116 117
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Section Vi H1 and H2 receptors : Histamine is known to act on two lypes
. actions of
of receptors viz Hi and H2 Hi receptors mediate the
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histamine on smooth muscles aid other systenis except gastric acid
AUTACOIDS secretion. These actions are blocked by conventional antihistamines
y
(Hi receptor antagonists). H2 receptors mediate only gastric
acid
antagonists.
Ph
Ph
Ph
secretion. This effect is blocked by H2 receptor
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: Histamine is absorbed on
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injection. Its absorption is very poor
subcutaneous and intramuscular
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on oral adnministration. It is metabolised by:

HISTAMINE AND ANTIHISTAMINES
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38. 1. methylation by MAO
which ie widely
Histamine is a biogenic amine 2oxidation by diamine oxidase
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HISTAMINE
It is formed by
distributed in plant and animal tissues. are hypotension, flushing, headache,
y
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the reaction being catalysed by histidine Adverse reactions: They
decarboxylation of histidine, fluids, visual disturbances, dyspnoea and diarrhoea.
biological
decarboxylase. Histamire is present in various in
cells. It is also present
platelets, leucocytes, basophils and mast
1
Histamine acid phosplhate 0.5 to mg.
Preparation and dose :
mucosa.
lungs and gastrointestinal by subcutaneous injection.
The effect
phar
of histamine varies with species. In
Uses: Histamine does
for diagnostic purposes
not have any therapeutic use. But it is used
like study of gastric secretion, diagnosis of
1. Blood vessels:
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produces vasoconstriction. In humans,
it
rat and rabbit, histamine leprosy (where the triple response is absent) and pheochromocytoma.
This leads to fluslhing of the face and
produces vasodilatation.
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throbbing headache.
Histamine in relation to allergy and anaphylaxis:
produces fall in blood pressure in When a foreign protein (antigen) is injected into an animal, the
2. Blood pressure: H:stamine
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vasodilatation and venous pooling of reticuloendothelial system responds by fomming specific antibodies.
humans. This effect is cue to
The antibodies circulate and later are absorbed by the tissues. When
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Ph
Ph
blood.
a large dose of the same antigen is injected after few weeks,
it
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intradernnal injection, histamine produces

3. Triple response : Cn combines with the antibodies. This produces an antigen-antibody
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a 'triple response' which consists
of
reaction. This reaction damages the tissue mast cells, leading to the
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i) loca redness (flusl1)due to dilatation of capillaries and venules. liberation of histamine and certain other substances. This produces a
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ii) local arteriolar dilitation
(flare). shock-like state temed anaphylaxis. The effects are similar to those
ac
due to escape of fluid from the capillaries. produced by histamine.

ii) local edema (wheal)
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contraction of smooth Antihistamines: Antihistamines are drugs which. antagonise the
4. Smooth muscles: Histamine produces
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muscles like intestine, bronchioles and

uterus. actions of histanine that is liberated in the body. The conventional
Histamine is a powerful agent in inducing
gastric antihistamines are HI antihistamines. Théy are mainly used in the
5. Secretions on
It has a weak stimulant action symptomatic relief of allergic disorders.
secretion rich in acid and pepsin.
secretions.
salivary, pancreatic and iacrimal Classification of H1 antihistamines:
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y
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Ph
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Ph
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Telegram - Study Pharmacy 118 |19
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4. Local aneasthesia: Most antihistamines posses a local
A. First generation anaesthetic effect. Preparations of antihistamines mean for local
ud
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Low sedative Mepyramine application owe their effect to local anaesthetic effect.
Triprolidine
5. Suppression of motion sickness: The antihistamines suppress
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Cyclizine
motion sickness caused by vestibular disturbances. They aiso prevent
Ph
Ph
Ph
L. Moderately sedative Pheniramine vomiting due to labyrinthine disturbances.
ha
Meclizine
Buclizine 6. Depressant effect on heart: Some antihistamines have a
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Cinnarzine quinidine like effect on the heart. So they are useful in «ontrolling
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fibrillation of the heart.

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3. Highly sedative Diphenlydramine
Promethazine 7. Drying of secretions: Antihistanines produce dryness of
Hydroxyzine mouth. They also produce drying of nasal secretions and hence the
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Terfenadine Ise as 'cold cures'.
y
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B. Second generation
Astemizole
Centrizine Absorption, fate and excretion : Antihistamines are ffectively
Loratadine absorbed after oral and parenteral administration. They aclieve high
Azelastine concentration in the lungs. They are also distributed in spleen, kidney,
Mizolastine brain, liver and muscles. They are metabolised mainly in the liver
and to some extent in the lungs.
Hi Receptor antagonists (H1 antihistamines)
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chemically Adverse reactions
Mechanism of action: The antilhistamines do not
histamine. They do not enhance natural histaminase 1. Gastrointestinal disturbances like nausea, anorexia and
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neutralise
histamine wlhen epigastric pain.
activity. Also they do not prevent the release of
exposed to an allergic substance. They act. by competing with 2. Cardiovascular symptoms like hypotension and palpi ation.
y
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histamine for receptors in the tissues. 3. Blood dyscrasias like agranulocytosis, leucopenia and
Ph
Ph
Ph
hemolytic anaemia.
Pharmacologicai actions:
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4. Dryness of nose, mouth and eyes.

These conventional antihistamines (H
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1. General effects :
all the actions of histamine on skin, 5. Sedation and drowsiness.
receptor antagonists) block
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membranes and plain muscles. They do not antagonise 6. Allergy ? Antihistamines can themselves produce this.
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mucous
histamine induced gastric secretion. This is blocked by H2
receptor
Therapeutic uses:
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antagonists.
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varying extent.
1. For the symptomatic relief of allergic disorders like urticaria,
2. Sedation: Antihistamines produce sedation of
y
hay fever and rhinitis.

So skilled work is not advisable after taking antihistamines.
2. To prevent allergic reáctions in blood transfusion.
the antihistamines
3. Autonomic nervous system: Most of 3. In the management of vomiting due to motion sickness.
exhibit anticholinergic effects. As a result, they produce dryness of
antihistainines exhibit an adrenergic blocking effect. 4. In common cold, to inhibit nasal discharge.
nmoth. Some
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Ph
Ph
Ph
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121
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HI receptors act by releasing intracellular Ca"
SECOND GENERATION ANTIHISTAMINES
receptors act by releasing intracellular cyclic AMP.
ud
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1980.They lhave one H2
These are Hi antihistamines marketed after
or more of the following properties
H3 receptors are presynaptic auto receptors. They produce auto
inhibitory control on the synthesis and release of histamine in
y
1. Higher selectivity for Hi receptors. the brain.
Ph
Ph
Ph
2. No antichclinergic effects.
Betahistine is a partial agonist of Hi and H2 receptors, but it
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3. No CNS depressant effect. is a weak antagonist of H3 receptor.

histamine
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Additional anti-allergic mechanism other than
4.
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blockade.
39. 5-HYDROXYTRYPTAMINE AND ITS
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Advantages
1. No impairnent of psychomotor
performance. ANTAGONSTS; ANGIOTENSIN AND
c
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2. No sleepiress. KININS
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3. No potent.ation of alcohol or
benzodiazepines.
selective. It has a rapid onset 5-HYDROxYTRYPTAMINE (SEROTONIN)
1.TERFENADINE: It is highly Hi
duration of action (12 to 24 hrs). It is useful
to 2 hrs) and moderate Occurrence 5-Hydroxytryptamine (5-HT) also called as serotonin
It can produce polymorphic ventricular tachycardia.
for short term ust:. is widely distributed in plants, animal tissues, mast cells and platelets.
onset
ASTEMIZOLE: Actions similar to terfenadine. But it has slow The highest concentration is present in pineal gland of mammals.
perennial rhinitis. Like terfenadine, it can
2 to 5 days). It s useful in Venoms of wasps and bees also contain 5- HT. It is also present in
St
St
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produce ventricular tachycardia. fruits like bananas, pineapples, tomatoes and plums.
has
CETRIZINE: I: is a carboxylated metabolite of hydroxyzine. It Synthesis: 5-HT is synthesised from the amino acid tryptophan.
ud
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receptors. Penetration into brain is
good affinity for peripheral Hi The pathway of synthesis is as follows
produce arrhythmias. Indications upper respiratory
poor. It does noi Tryptophan
dermatitis.
y
y
allergies, pollincsis, urticaria and
Tryptophan-5-hydroxylase
LORATIDINE: It is a long acting, selective peripheral Hi antagonist.
Ph
Ph
Ph
it is. faster acting than 5-hydroxytryptophan
It does not produce CNS depression, Also,
ha
It does not produce cardiac arrhythmias. Use: urticaria and

astemizole. S-hydroxytryptophan decarboxylase
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atopic dermatitis.
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5-hydroxytryptamine.
Fomotidine
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Ranitidine and
H2 Receptor antagonists: Cimetidine, Pharmacological actions
which belong to this group. These drugs specifically
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are the dugs

block histamine induced gastric acid secretion. These drugs have been 1. Blood vessels: 5-HT produces constriction of renal, meningeal
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discussed in che pter 68. and pulmonary blood vessels. But blood vessels of skeletal muscle,
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skin and coronaries are dilated.

H3 Receptors: These are histamine receptors present in the brain.
it is synthesised 2. Heart 5-HT acts directly on heart producing an increase in the
Histamine does not cross blood brain barier. But
and released locally in tlhe brain. In fact, there are three types force and rate of contraction. But these effects are not demonstrable
stored
and H3. because of reflex actions.
of histamine receptors in brain namely Hi, H2
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y
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Ph
Ph
Ph
h
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3.Blood pressure: A triphasic response is produced which Antagonists of 5-Hydroxytryptamine
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consists of: A number of compounds antagonise the effects of -HT at
i) A short lasting fall (due to reflex bradycardia). This is various sites. They are lysergic acid diethylamide (LSD), -bromo
followed by
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LSD and dihydroergotamine. The following are the important 5-HT
ii) A rise in blood pressure (due to vasoconstriction). This is antagonists.
Ph
Ph
Ph
followed by
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vasodilatation in 1. METHYSERGIDE: It is a congener of LSD. It blocks the actions

iii) A sustained ,fall in blood pressure (due to
of 5-HT on smooth mvscles without any effect on brain. It coes not
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skeletal muscles).
possess vasoconstrictor activity but antagonises the vasodilater effect
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4. Smooth muscles 5-HT increases the tone and motility of

:
of 5-HT. It is used in the prophylaxis of migraine.

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gastrointestinal tract and facilitates the peristaltic reflex. It also
produces bronchoconstriction in most species of animals. 2. CYPROHEPTADINE: It has a structural resemblaice to
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present in midbrain and phenothiazines. It is a powerful antagonist of 5-HT. It also has
5. Central nervous system: 5-HT is
antihistaminic effect which is helpful in the treatment of pruritus.
y
y
hypothalamus in significant amounts. 5-HT does not cross
5-hydroxytryptophan, a precursor of 5-HT, Cyproheptadine also has anticonvulsant and atropine-like effects.
blood-brain barrier.. But
can cross this barrier. Angiotensin and Kinins
6. Miscellaneous effects They are1 ANGIOTENSIN Angiotensin is a polypeptide derived fiom an
i) Facilitation of ganglionic transmission and release of inactive precursor called angiotensinogen present in plasma.
adrenaline from adrenal medulla. Angiotensinogen is converted to angiotensin by renin an enzyme
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ii) An antidiuretic activity. present in kidney.
gastric juice.
ii) Decrease in volume, acidity and pepsin content of Angiotensin produces powerful vasoconstriction. t is 4) times
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inactivated on oral
is more potent a vasoconstrictor than noradrenaline. it also stimulates
Absorption, fate and excretion: 5-HT
administration. It is absorbed on parenteral administration. It is the plain muscles of intestine and uterus. t has an antidiureti effcct
y
y
metabolised by the enzyme monoamine oxidase (MAO) and is and this occurs due to decreased renal blood flow. Angioten in has
It is recommended as a substi: ute to
Ph
Ph
Ph
5-hydroxy indole acetic acid (5-HIAA). a limited therapeutic use.
excreted as
noradrenaline for its pressor effects.
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Physiological role: 5-HT is involved in a number of

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KININS Kinins are polypeptides released from alpha gobulin
physiological functions. They are
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neurones fraction of plasma. This fraction is temed as kallidino:yen or

5-HT is a, chemical transmitter in tryptaminergic
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1.
bradykininogen. Kallikreins (which are enzymes present in plasma)
present in brain. convert kallidinogen (or bradykininogen) into kinins.
ac
2. Disturbances in the metabolism of 5-HT in brain produces

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psychiatric disorders like schizophrenia. The two important kinins are kallidin and bradykinin. The
y
3. It acts as a local hormmone in gastrointestinal mucosa

and kinins are potent vasodilators. They are 10 times more potert than
induces peristalsis. histamine in the vasodilator effect. They produce an ionotropic and
chronotropic effect on heart. Also they release adrenaline from
4. Carcinoid tumours of the gastrointestinal tract secrete excessive
amount of 5-HT. This produces intemittent flushing, adrenal medulla. They produce contraction of smooth musces like
tachycardia, hypotension, asthnia, colic, diarrhoea etc. intestine, uterus and bronchi.
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Section Vill
The physiological role of kinins is not certain. They are. said
to be mediators of intlammatòry and anaphylactic
reactions. They
ud
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have also been implicated as neurohumoral transmitters.
Slow reacting substances (S. R. S.) CARDIOVASCULAR DRUGS
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These compounds are of unknown structure. They are formed
Ph
Ph
Ph
in the body by the action of phospholipases. Phospholipases are
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enzymes present in body fluids and snake venom. These substances
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produce vasodilatatio1. They produce a slow contraction of smooth
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muscles like intestine. bronchi and uterus. These substances are said
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to be mediators of anaphylactic shock. 40. DIGITALIS AND RELATED CARDIAC
GLYCOSIDES
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The term Cardiac glycosides refers to a group of chemically
related drugs which have specific action on the heart. They are used
for the treatment of congestive heart failure.
@pharm Sources of cardiac glycosides:The cardiac glycosides are

obtained from a number of plants. They are
. Digitalis which has two species, namely D.lanata and
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D.purpurea. They contain the cardiac glycosides digitoxin and
gitoxin.
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2. Strophanthus, which has two species viz: S. gratus containing
G-strophanthin and S.kombe containing K- strophanthin.
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3. Squill, a liliaceous plant which contains proscillaridin.
Ph
Ph
Ph
4. Certain other plants like Thevetia nerifolia, Neriunm oleander
ha
and Convallaria majalis also contain cardiac glycosides.

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The one animal source is Bufo vulgaris, a toad which contains
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the cardiac glycoside bufotoxin.

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Chemistry of cardiac gdycosides : The cardiac glycosides
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contain sugar portion and a non-sugar portion. The non-sugar portion

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is called as aglycone or genin. The aglycone has a steroid structure
y
with a lactone ring attached to the 17th carbon atom. The aglycone,
especially the lactone ring is responsible for the pharmacological
action. The sugar portion helps in the permeability and fixation of
the cardiac glycosides on the myocardium.
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Ph
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126 127
Telegram - Study Pharmacy 7. Venous pressure: Digitalis decreases the increased venous
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Actions of Digitalis pressure seen in congestive heait failure. This is produced due to
increased cardiac output and decreased plasma volune produced by
a) Cardiac actions
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diuresis.
the force of systolic
1. Cardiac contractility: Digitalis increases
contraction of the heart muscle. Also it decreases the duration of 8. Blood pressure: The effect depends on the iaitial state of
y
contracts powerfully leading circulation. If it is low, it is returned to nommal and it is not raised
systole. So in a linmited time, the heart
Ph
Ph
Ph
beyond normal.
to complete ventricular emptying.
ha
Digitalis raises oxygen consumption of heart to

nomal. It does 9. Coronary circulation: No effect on coronary flow.
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muscle but improves energy Improvement in coronary flow occurs secondary to improved cardiac
not increase energy production by cardiac
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digitalised heart can do more work with less. output.

utilisation. So the
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heart.
energy. This improves the efficiency of 10. Effect on ions :
the heart rate increases as a

2. Heart rate: In heart failure,
c
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because the ventricle i) Sodiun: With a failing heart, sodium ions are. etained in the
compensation for the reduced output. It is also body They are mobilised and eliminated by digitalisation. Digitalis
y
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lowered threshold).
y
auricular stimuli (due to
is excited even by weak
mechanisms also inhibits sodium reabsorption in the renal tubules.
Digitalis reduces heart rate by the following
i) Ventricles do not respond to weak
auricular stimuli. i) Calcium: Digitalis increases the force of cntractionby
muscle is prolonged. increasing_the amaunt of-calcium liberated in the ardiac tissue.
ii) Refractory period of ventricular Digitalis acts synergistically with calcium. The toxicty of digitalis
tissue, which reduces the passage of
ii) Depression of conducting is enhanced by excess of calcium ions. Excessive calcium leads to
auricular impulses. cardiac arest in systole.
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Small doses of digitalis produce
3. Vagal and extravagal effects:
vagal stimulation. In large doses, it is due to ii) Potassium: Therapeutic doses of digitalis enha ce potassiunm
cardiac slowing duc to
ud
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uptake. Toxic doses lead to its depletion from the heart. Digitalis
prolongation of refractory peiod.
toxicity can be induced by loss of potassium produc ed by potent
depresses the.conduction system
4. Conduction system: Digitalis diureties.
y
y
increased and the conduction
directly. Also, the refractory period is
increase in P-R interval in
Ph
Ph
Ph
rate is slowed. This is shown as. an b) Extracardiac actions
ha
electro-cardiograin (E.C.G.) 1. Kidney: The first prominent manifestation of the effect of

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5. Cardiac size : Digitalis
decreases the size of.both normal and digitalis in edema is diuresis. This is due to:
returns the size of enlarged heart
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failing heart. In heart failure, digitalis 1) Decrease in.venous pressure which shifts the edema fluid into
In normal heart, digitalis
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cardiac output.
to normal. This increases circulation.
output is decreased.
decreases the size and hence cardiac
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ii) Direct renal action, inhibiting the reabsorption of sodium.

output in normal
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6. Cardiacoutput: Digitalis decreases cardiac 2. Gastrointestinal tract: In toxic doses, digitalis procluces nausea,
size. In failjng heart,
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heart and this effect is due to reduction_in vomiting and diarrhoea. The emetic effect is due to i) direct irritation
cardiac output. This effect is produced due to return
digitalis increases
force of contraction and complete of gastrointestinal tract i) stinmulation of chemoreceptor trigger zone
of heart to normal size, increased (CTZ).
cardiac emptying.
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Ph
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129
128
Preparations and dose :
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Digitalis adequately
: Is
1: Digitoxin is available as_tablets and injections. The initral
dose
Subcutaneous or intramuscular injection
absorbed from the intestine. for oral, intravenous and intramuscular administration is-1.to
ud
ud
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irritation, swelling and abcess.
is unreliable and it may pr»duce local daily.
plasnma albumin. High concentration is found 1.5mg. The maintenance dose is Q.1to 0.15, mg.
In blood, it is bound to 2. Digoxin is available as tablets and injections. The initial oral
though the kidney. So it is
y
in the heart. It is eliminated very 'slowly for maintenance, it is administered at
dose is to 2.5 mg. and
likely to produce cumulative toxicity. The initial intravenous and
Ph
Ph
Ph
0.125 to 0.75 mg. daily.
intramusculardose is 1 to 2 mg. and the maintenance doseis
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Adverse reactions 0.125 to 0.75 mg. daily.
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duces nausea, vomiting and
Gastrointestinal tract Digitalis
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1.
anc parenteral administration. This is due to Therapeutic uses:
diarhoea both on oral
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gastrointestinal tract b) an indirect efifect by
1. For the treatment of congestive heart failure.
a) a direct irritation of and
(CTZ). 2. To control arrhythmias, like atrial flutter, atrial fibrillation
stimulation of chemoreceptor trigger zone
paroxysnal atrial tachycardia.
c
c
Digitalis produçes all types of
cardiac
2. Cardiac toxicity OUABAIN (STROPHANTHIN-G) It is a pure crystalline glycoside
y
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:
tachycardia, atrial fluter, atrial fibrillation,

arhythmias like atrial fibrillation. obtained from the plant, Strophanthus gratus. It is poorly absorbed
and ventricular
ventricular tachycardia, ventricular flutter from gastrointestinal tract. So it is administered by parenteral route
due to disturbed inmpulse formation
These cardiac arhythmias öccur like intravenous injection. The pharmacological actions of
ouabain
or disturbed impulse conduction. are very similar to those of digitalis. But the actions is quick and of
increases the coagulability of blood. a short duration. So it is useful in emergency.
3. Blood coagulation: Ligitalis
thromboembolic complications.
So it is likely to produce AMRINONE It is a bipyridine derivative. It is a non-glycoside. It
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is a non-adrenergic positive ionotropic agent. The ionotropic
effect
shortening of Q-T interval,
4. E.C.G. changes: They are is additive to that of digitalis. It is useful in patients resistant to
the T wave.
lengthening of P-R interval and inversion of
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digitalis. Thrombocytopenia is a.common adverse effect.
vision and
5. Vision :Digitalis prociuces visual defects like blurred
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colour defects. |41. ANTIARRHYTHMIC DRUGS
fatigue, drowsiness
Ph
Ph
Ph
6. Neurological symnptonis: They are headache,
Antiarrhythmic drugs are used to corect cardiac arrhythmias.
ha
and mental symptoms.

Cardiac arrhythmias occur as a result of defective impulse fomation
ar
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Mode of administration Digitals is slowly eliminated. So it is
: or defective impulse conduction.
rm
likely to produce cunulative

poisoning. Before digitalis -is
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administered, it is necessary to know whether the patient has received Classification of drugs:
ac
digitalis earlier. 1. Myocardi-l depressants Quinidine

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effect at smaller Procainamide
Unlike other drugs which produce a smaller
y
dose, digitalis must be present at Disopyramide

dose and a larger effect at a lager amount is Lignocaine
etfect. This saturating
a 'saturating' amount to produce
its
(digitalising dose). This is followed Phenytoin
achieved by an initial large dose
(maintenance dose).
by smaller daily doses
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Ph
Ph
Ph
h
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130 131
Telegram - Study Pharmacy 2. If cardiac output is low, quinidine returns it to norm:il. No
Sympåthetic biockers Propranolol
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2. change is produced, if it is normal.
3. Calcium channel blockers Verapamil 3. Quinidine produces a relaxant effect on skeletal muscles. It
ud
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4. Miscellaneous Potassium also has antimalarial, antipyretic and oxytocic actions.
Amiodorone
bur
Absorption, fate and excretion : Quinidine is slowly after
y
Aprindine
coinpletely absorbed from gastrointestinal tract and also
Ph
Ph
Ph
QUINIDINE : It is an isomer of quinine. It is a natural alkaloid
intramuscular injection. In plasma, it is partly bound to alburin (60
ha
occuring in cinchona bark. percent). It is metabolised in the liver by hydroxylation. These
ar
ar
ar
metabolites are excreted in urine along with unchanged quinictine.
Phar acological actions
r
Cardiac effects: These effects occur due to vagolytic (atropine like

Adverse reactions :
ma
ma
ma
ma
effects) and myocardial depressant actions. local
1. Gastrointestinal: Nausea, vomiting and diarrhoea due 10
1. Depolarisation: Quinidine slows the rate of
depolarisation. This
iritant effects.
c
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is produced by depressing the enty of sodium into the cell. So
y
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light-headedness,
quinidine prolongs the depolarisation repolarisation cycle. So the 2. Cinchonism Characterised by giddiness,
rate at which cardiac contractions occur is dcecreased. tinnitus, impaired hearing and blurred vision.
2. Impulse formation: Quinidine, by a direct effect, depresses or Convulsions due to an effect on central rervous
3. Cerebral:
slows the production of impulses from the sinoauricular node or pace- system.
maker.
1
3. Excitability: Quinidine decreases the excitability of the cardiac
4. Hypotension: This is produced on intravenous administration.
muscle. So the threshold of an impulse to initiate cardiac activity

is like ventricular extrasystoles, ven ricular
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5. Cardiac: Arhythmias
increased. So a weak impulse becomes ineffective. tachycardia and ventricular fibrillation.
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4. Refractory period: Quinidine prolongs repolarisatior of the
potassiunm efflux Preparations and dose:
cardiac tissue. This is produced by depressing
during repolarisation. This increases the refractory period. During 1. Quinidine sulphate tablets and capsules-200 to 400 mg every
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6 hours.
refractory period, the heart does not respond to weak and premature
Ph
Ph
Ph
stimuli. This brings down the rate of heart. 2. Quinidine gluconate injection-200 mg. by intramuscular or slow
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intravenous injection.
5. Conduction velocity: Quinidine slows the rate of conduction
in
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the heart muscle. This along with decreased excitability and increased paro:ysnmal
Therapeutic uses : Cardiac arhythmias like
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refractory period brings down the rate of heart. ventricular tachycardia and atrial fibrillation.
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6. Cardiac contractility: Cardiac contractility is decreased by
PROCAINAMIDE Procaine, a local anaesthetic has been shwn to
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decreasing the entry of calcium into cardiac muscle cells. suppressventricular arrhythmias. But its disadvantages are: I. It is
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Extracardiac effects ineffective on oral administration. 2. Its action is short due tu rapid
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1. Quinidine produces a fall in blood pressure on oral or inactivation by esterases in plasma 3. It produces central excitation.
parenternal administration. This is due to decreased But procainamide, a derivative of procaine is devoid of all these
sympathetic activity and direct dilatation of arteries. disadvantages retaining only the antiarrhythmic effect.
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132
The antiarhythmic effect is exactly 133
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atropine like anticholinergic
similar to that of quinidire. It also has an PHENYTOIN SODIUM (DIPHENYLHYDANTOIN): It is an
quinidine. effect is due to decrease in
anticonvulsant drug. The antiarrhythmic
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effect similar to
and completely sodium and potassium. It is used in
Absorption, fate and excretion: It is rapidly permeablity of cardic muscle to
arrhythmias.
and intramuscular injection. ventricular arrhythmias, especially in digitalis induced
absorbed after oral aclministration
y
is less. It is eliminated in urine, mostly
Binding with plasma proteins PROPRANOLOLIt is a beta adrenergic blocking drug. It acts as
Ph
Ph
Ph
in an unmetabolised fonn. antiarrhythmic drug by virtue of its membrane stabilising and
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an
conduction
Adverse reactions: antiadrenergic effects. It depresses automaticity and A-V
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refractory period. It is useful in
diarrhoea. velocity. Also it prolongs the
Gastrointestinal symptoms like nausea, vomiting and
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1.
ventricular arhythmias, particularly those induced by digitalis.
administration.
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2. Hypotension on intravenous
psychosis. VERAPAMIL It interferes with slow channel calcium influx. Lack
3. Mental symptoms like
contraction of the
quinidine. of calcium decreases 1) initiation of impulses 2)
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4. Cardiac toxicities similar to in AV nodal tachycardia and Wolf Parkinson
myocardium. It is useful
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Preparations and dose vertigo
white syndrome. Adverse reactions are hypotenion, asystole,
- every 4 to 6
1. Procainamide hydrochlorice tablet 0.25 to 0.5 g and constipation.
hours 10 mg. thrice daily by oral route.
injection - 0.25 to 0.5 g. every 4 Dose:
2. Procainamide hyirochloride
to 6 hours by intramuscular
injection acts by depressing automaticity, conduction
POTASSIUM:It
Primarily in paroxysmal ventricular or artial velocity and prolonging refractory period. But toxic doses produce
Therapeutic uses:
tachycardia, as a substitute to quinidine. intraventricular block.
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It i1as a membrane stabilising and
anticholinergic
DISOPYRAMIDE AMIODARONE: It is structurally related to thyroxine. It has an
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period. Also it increases
effect. It prolongs the effective refractory antiadrenergic effect. It acts by prolonging effective refractory period
the duration of action potential. and duration of action potential. It is the drug of choice in refractory
ventricular and supraventricular tachycardia. Adverse reactions:
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urinary retention,
Adverse reactions: Dry mouth, constipation,
nausea, anorexia, corneal opacities and hallucinations.
Ph
Ph
Ph
mental depression and impotence.
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Ventricular and supraventricular tachycardia. APRINDINE: electrophysiological effects similar to quinidine.

It has
Use:
It is useful in refractory supraventricular tachycardia.
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100 to 150 mg. four times daily
upto a maximum of 1600
Dose:
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mg. daily by oral route.

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LIGNOCAINE (LIDOCAINE, XYLOCAINE): It
is a local anaesthetic. 42. ANTIHYPERTENSIVE AGENTS
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effects. It depresses automaticity and

It possesses more venricular
Hypertension is a disease characterised by abnormallv high
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ventricular tissue. Also it shortens
diastolic depolarisatior: in
blood pressure. Hypertension is classified as:
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ventricular arrhythmias.
ventricular action potential. So it is useful in
It produces an immediate effect but the
duration of action is short. 1. Primary (essential or idiopathic) hypertension for which the
drowsiness, muscle twitching, confusion and exact cause is not known.
Adverse reactions are
convulsions. 2. Secondary hypertension which may be due to renal, endocrine
or vascular lesions.
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Ph
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irespective of the cause, hypertension is hannful. It may lead ACE inhibitors
to degenerative changes in cerebral, coronary, renal and retinal tissues.
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Antihypertensive drugs are lhelpful in the treatment of hypertension. CAPTOPRIL:
Classification of antihypertensive drugs: It acts by inhibiting angiotensin converting enzyme (ACE). 1 his
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prevents the conversion of angiotensin I to angiotensin I. Ii is
ACE inhibitors Captopril effective in all types of hypertension. But marked effect occurs in
Ph
Ph
Ph
I.
Enalapril renovascular hypertension. Diuretics potentiate the effect of captopril.
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Lisinopril
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Ramipril Adverse reactions: 1) renal damage 2) hyperkalemia 3)
inpairment of immune response 4) loss of taste sensation 5)
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Angiotensin antagonist Losartan

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2. neutropenia and proteinuria.
Calcium channel blockers Nifedipine
J.
Felodipine Does: 25 mg. thrice daily as tablets.
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Amlodipine
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ENALAPRIL:
Verapamil
Diltiazem It is an ACE inhibitor like captopril. It is more potent. Als) it
Chlorothiazide has a slower but longer effects. It acts by getting converted into
4. Diuretics
Frusemide enalaprilic acid. It can produce urticaria and angioneurotic oedema.
Spironolactone
Triamterene
Amiloride
ari Angiotensin antagonist
LOSARTAN: It is a competitive antagonist of angiotensin il lt
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. B adrenergic blockers Propranolol blocks all the actions of angiotensin I like 1.vasoconstriction 2.
central and peripheral sympathetic stimulation 3. release of aldosterone
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Metoprolo!
Atenolol and adrenaline. The antihypertensive effect of losartan lasts for 24
hours. It does not alter heart rate or cardiovascular reflexes. It is vell
y
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O. d-adrenergic blockers Prazocin absorbed orally. It undergoes first pass metabolism in the liver.
Terazocin
Ph
Ph
Ph
Phentolamine Adverse reactions: hypotension, hyperkalennia,. fetal toxicty,
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weakness and dizziness.

7.Centralsympatholytics Clonidine
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Methyldopa Calcium channel blockers: The contractility of cardiac nd
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vascular smooth muscle is dependent on extracellular calcium

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8. Vasoilators
Hydraiazine concentration. The calcium channel blockers interfere with the entry
i) Arteriolar
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This
Minoxidil of calcium into myocardial and vascular. smooth muscle.
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Diazoxide decreases the availability of intracellular calcium. The three chann els
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of calcium transport are:

Sodtum nitroprusside
teradoL and verulac 1. Voltage dependent channel: It opens and closes in response to
a voltage gradient. Calcium channel blockers close this gate. Tis
* inhibits the entry of extracellular calcium
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Ph
Ph
Ph
h
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136 137
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2. Receptor operated channel: This activated by alpha
is FRUSEMIDE: It is a high ceiling diuretic. It is a strong diuretic. But
is also blocked by it has a weaker antihypertensive effect than thiazides. Fall in BP is
adrenergic agonists or angictensin. This channel
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due to reduction in plasma volume and cardiac output. It has a short
calcium channel blockers.
duration of action of only 4 to 6 hours.
exchange: It is important only for the action
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3. Sodium channel
B-Adrenergic blockers: Drugs which belong to this group are
of cardiac glycosides.
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Ph
propranolol, metopralol and atenolol.
Important actions of calcium channel blockers are:
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Mechanism: The B-adrenergic blockers produce an
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1. Negative ionotropic effect which decreases cardiac contractility. antihypertensive effect by the following mechanisms:
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2. Antiarrhythmic effect.
decrease in_cardiac output by an action on the heart.
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1.
3. Dilatation of coronary arteries.
2. decreased renin.release. from the, kidney.
4 Relaxation of periphe:al blood vessels
3. Central action by reducing sympathetic outflow.
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5. Antianginal effect.
The B-adrenergic blockers can be used alone or with other
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NIFEDIPINE: It is a dihy dropyridine derivative. It is a calcium antihypertensive drugs.
channel blocker used for the treatment of hYpertension and angina
pectoris. The essential action arteriolar dilatation. This decreases a-Adrenergic blockers: Drugs which belong to this group are
in B.P.It also has mild prazosin, terazocin and phentolamine.
total peripheral resistance leading to fall
natriuretic action without significant diuresis. PRAZOSIN: It is a selective competitive antagonist of a -receptors.
Adverse reactions: palpitation, flushing, ankle edema, hypotension, a -receptor blockade leads to i) peripheral vasodilatation i) decrease
headache, drowsiness and n:usea. in peripheral xascular resistance ii) fall in B.P. It does not produce
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reflex tachycardia. Also, it does not produce poštural hypotension.
Dose: 5 to 20 mg oral 2 o3 times daily.
There is no alternation of renal function. Prazosin is useful in mild
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FELODIPINE: It differs fronh nifedipine in that it has i) selective to moderate hypertension.
distribution in vascular tissue ii) larger tissue distribution ii) longer Adverse reactions : giddiness, drowsiness, tiredness, weakness,
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half life. An extended relea e preparation is available for once daily nausea, diarrlioea, fluid retention and nervousness.
Ph
Ph
Ph
administration. Dose: 50 to 10 mg once daily.
TERAZOCIN: It is a congener of prazosin with longer action. It has
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AMLODIPINE: It is also a dihydropyridine calcium channel blocker. similar properties as prazosin.

Its advantages are: i) it is slowly but completely absorbed on
oral
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administration. ii) carly viisodilator side effects like flushing and
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Central sympatholytics
5
palpitation can be avoided ii) oral bioavailability is high. Dose: to
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CLONIDINE It is an imidazoline derivative.
10 mg once daily.
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Pharmacological actions: On intravenous administration,

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Diuretics a
clonidine produces short hypertensive effect. This is followed by
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CHLOROTHIAZIDE AND IrS ANALOGUES: These drugs are prolonged hypotension and bradycardia. It acts mainly by central and
effective in the treatment of mild to moderate hypertension, Also they minor peripheral mechanisms. Clonidine stimulates alpha adrenergic
potentiate the effect of other antihypertensive. drugs. They act
by receptors in the vasomotor centre. This blocks the release of
reabsorpiion in the renal tubules. This decreases noradrenaline from nerve terminals. This leads to lowering of blood
decreasing sodium
plasma volume and cardiac utput. pressure and bradycardia.
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Ph
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is less when_given alone. tachycardia and increased cardiac output. It also acts by depressing
The hypotensive effect of clonidine the vasomotor centre.
diuretics. Tolerance develops for
So it is combined with
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use. It decreases insulin Adverse reactions Headache, nausea, weaknesS, palpitation,
antihypertensive effect on prolonged
the level of growth hormone. flushing and tachycardia. Also neuropathy which is reversed by
secretion but increases
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vertigo, impotence, pyridoxine. It also produces priopism (painful erection)
Adverse reactions: Dry mouth, constipation,
Ph
Ph
Ph
DIAZOXIDE: Diazoxide is chemicaly related to chlorothazide.
drowsiness and depression.
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But it is not a diuretic. In fact, it produces retention of sodiun and

To start with, 0.1mg once or twice daily. Maximum 0.3
Dose water. It has a powerful hypotensive effect which is due to direct
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mg thrice daily, orally. arteriolar dilatation. It produces an immediate effect which lasts for
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Antihypertensive agent 2) Prophylactic in 12 hours. It also has a potent hyperglycemic effect

Therapeutic uses: 1)
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migraine 3) for glaucoma. sODIUM NTROPRUSSIDE: It. decreases peripheral resistance byy
(ALDOMET, EMDOPA): It is an alpha acting on both arteriolar and venous smooth muscle. It produces a
ALPHA METHYLDOPA
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rapid but short action. So, for continuous effect it is administered as
methyl analogue of dopa.
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OOn and intravenous I.V. drip.
Pharmacological actions: oral
latency.
occurs after a short Uses: 1) Emergency treatment of hypertension 2) Controlled
administration, the hypotensive effect
in hypertensive than in norinotensive hypotension during surgery 3) Acute myocardial infarction.
Fall in blood pressure is more
The hypotensive effect is
individuals.' Postural hypotension is less.
increased by combining with
thiazides. 43. VASODILATORS AND ANTI-ANGINAL
metabolised into alpha methyl DRUGS
Mechanism : Methyldopa gets
alpha adrenergic receptors
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noradrenaljne. This metabolite stimulates
in the vasomotor centre. So
the action is similar to clonidine. Also Angina pectoris: Angina pectoris is a referred pain that results
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renin from the kidney.
it acts by inhibiting the release of from anoxia of the cardiac muscle. Myocardial anoxia may be caised
by a number of factors. They are
Adverse reactions
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1. Occlusion of coronary vessels due to thrombosis or spasni of
mental depression.
1. Sedation, headache, weakness and the vessels (ischaemic anoxia).
Ph
Ph
Ph
2. Changes in sleep rhythm
and night-mares.
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2. Aneamic conditions (Aneamic anoxiaj

3. Lactation in females.
Oxygen demand of the myocardium not met by increase in
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.Redentio ot soduT andd waAer. coronary blood flow (Functional anoxia).
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Oral-0.5 to 3g. per day in

divided doses. IN - 250 to 500 Insufficiency in coronary circulation imposes strain on health
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Dose
function of the heart. This leads to anginal or substernal p:in
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nig.
hich radiates down the left shoulder and arm.
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Vasodilators
denvative. It is an
HYDRALAZINE: ydralazine is a hydrazine
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this effect and

is no correlation between
inhibitor of MAO. But there
hypotensive action.
beta adrenergic
Ithas an agonistic effect onaccompanied by
Mechanism of action:
produces vasodilatation
receptors. Because of this, it
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Ph
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141
Telegram - Study Pharmacy 3. Erythrityl tetranitrate tablets-5 to 10 mg. sublingually.
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140
4. Pentaerythritol tetranitrate- 10 to 30 mg. oraly
Classification of anti-anginal drugs Beta adrenergic blockers: Beta adrenergic blocking drugs like
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propranolol have an anti-anginal effect. These drugs act by preventing
(Coronary vasodilators) the response of heart to sympathetic nerve stimulation. So the effect
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Amyl nitrite
1. Nitrites and nitrates of adrenaline on cardiac rate and force of contraction is prevented.
Glyceryl trinitrate
Ph
Ph
Ph
Propranolol is prophylactic in the treatment of angina.
Erythrityl tetranitrate
ha
Pentaerythritol tetranitrate Calcium channel blockers: Contractility of cardiac and
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Isosorbide dinitrate vascular muscle depends on extracellular calcium concentration.
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Propranolol Calcium channel blockers interfere with calcium entry into myocardhal
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2. Beta adrenergic blockers and vascular smooth muscle. This decreases_ the availability of
Verapamil
3. Calcium channel biockers intracellular calcium. The antianginal effect of calcium channel
Nifidepine
blockers is due to: 1) improvement in coronary blood flow 2) decrease
c
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Diltiazem
in systemic vascular resistance and blood pressure-this decreases
y
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openers Nicorandil oxygen demand of heart.
4. Potassium channel
NITRITES AND NITRATES VERAPAMIL: It is a synthetic papaverine derivative. t produces
coronary vasodilatation and antiarrhythmic effect. Jt is well absorbed
Pharmacological actions: from gut. But it undergoes first pass hepatic metabolism.
effect
compounds produce direct relaxant
1. Blood vessels: These no involvement of Contraindications: 1) With beta blockers and digitalis 2) severc
apillaries. There is
on arteries, veins and congestive heart failure 3) cardiogenic shock.
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equally
nerves or recaptors. All blood vessels are not
autonomic coronory, cerebral and Dose: 40 to 80 mg. 3 to 4 times daily as tablets.
affected. Vasodilatation is marked in
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increased. But decrease in blood
is
cutaneous vessels. Bloocl flow NIFEDIPINE: It is a dihydropyridine derivative. It is used in variant
pressure is minimal. angina refractory to nitrate. It is a potent inhibitor of platellet
y
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relaxtion of
and nitrates produce aggregation.
2. Smooth muscles: Ntrites ureter and uterus.
tract,
Ph
Ph
Ph
biliary
smooth muscles like inte stine, Adverse reactions: Headache, tachycardia, fatigue, orthostatic
blood vessels. So intraocular
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dilate intraocular hypotension and gingival hyperplasia.

3. Eye These drugs
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pressure may be increased. Dose: 5 mg. 3 times daily by mouth. Gradually increased upto 20
haemoglobin to
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4. Methemoglobin
formation : Nitrites convert mg. 3 times daily.
cyanides to form
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with
methemoglobin. Methe moglobin combines treatment of Nicardipine, Felodipine and Nimodipine have similar actions as
So nitrites are useful in
non-toxic cyanmethemoglobin."
ac
nefedipine.
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cyanide poisoning. DILTIAZEM: It is a less potent vasodilator than nifedipine. The
flushing of the face and
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Adverse reactions: lleadache, negative ionotropic effect is moderate. It can produce brädycardia.
hypotension leading to dizziness or
fainting
So it can be combined with beta adrenergic blockers.
Preparations and dose: Dose: 30 to 60 mg. 3 or 4 times daily.
ml by inhalation.
1. Amyl nitrite pearls-0.1 to 0.3
trinitrate tablets-0.2 to 0.6. mg. sublingually.
2. Glyceryl
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Ph
Ph
Ph
h
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143
Telegram - Study Pharmacy 142 glucuronide. Adverse reactions are nausea, diarrhoea, alierg and fluid
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Potassium channel openers retention. Dose: 1.5 to 2g. daily.
It activates ATP
NICORANDIL: It is a novel antianginal drug. 2. GEMFIBROZIL: It is a congener of clofibrate. It acts by lowering
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This produces hyperpolarisation of
sensitive potassium channels. It produces
triglyceride level. It can potentiate the action of oral anticoagulants.
muscle leading to vasodilatation. Adverse reactions are gastriontestinal upset, nmuscular pain, leucopenia
vascular smooth
coronary blood flow.
y
arteriolar and venular dilatation. It increases and cosinophilia. Dose : 600 mg. twice a day before meals.
Ph
Ph
Ph
headache, dizziness, nausea 3. CHOLESTYRAMINE RESIN: It is an insoluble chlorile salt of
Adverse reactions: flushing, palpitation,
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an anion exchange resin. It binds to bile salts (cholates) in the

and vomiting.
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intestine and forms an insoluble complex. This is excreted in feces
Dose: 5 to 20 mg. twice daily. So cholate is not reabsorbed. So there is an increase in cholate
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synthesis from plasma cholesterol. This decreases cholestrol level

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44. DRUGS USED IN ATHEROSCLEROSIS| of plasma. Adverse reactions are nausea, vomiting and constipation.
|
Dose 15 g per day by mouth.

c
c
vessels. in
Atherosclerosis is a disease which affects blood Colistipol is another drug with similar actions.
y
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narrowing of blood vessels like cerebral and
atherosclerosis, there is DEXTROTHYROXINE: It acts by: i) increasing the turnover of
with increased level
coronory arteries. Atherosclerosis is associated cholesterol i) promoting the fecal excretion of cholestero and its
triglycerides. A drug used
of plasma lipids, namely cholesterol and plasnma level of either
metabolites. Adverse reactions are angina, palpitation, tremor,
atherosclerosis lowers the
in the treatment of insomnia and diarrhoca. It is contraindicated in cardiac, hep atic and
of these lipids or both.
Classification of drugs
pharm renal diseases.
Dose: to 2 mg. daily and increased by
1 1
to 2 mg. eaci month
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upto 6 mg. per day.
Drugs lowering triglyceride Clofibrate
1. 5. PROBUCOL: It reduces serum cholesterol level wi thout a
Gemfibrozil
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reduction in triglyceride level. Liver cholesterol is not edueed.
Cholestyranmine Adverse reactions: headache, dizziness, parasthesia and eosinophilia.
2. Drugs lowering cholesterol
Dextrothyroxine
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y
Dose: 500 mg. thrice daily.
Probucol NICOTINIC ACID: It lowers plasma cholesterol and triglyceride
Ph
Ph
Ph
Nicotinic acid levels but at high doses. It acts by reducing the hepatic syntnesis of
Drugs lowering triglyceride
ha
3.
and cholesterol very low density lipoproteins (VLDL). Adverse reactions: Pruritus,
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LOLIPID): Chemically, it is ethyl flushing, GI disturbances, hyperglycemia and hyperurecemia. Dose
1. CLOFIBRATE (ATROMID S,
rm
2 to 8g. per day orally in divided doses.

isobutyric acid. It lowers plasma level of cholesterol
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chlorophenoxy
triglyceride is maximum. It acts
and triglycerides. But lowering of
ac
by:
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inhibiting the synthesis of cholestçrol in liver.
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i)
from liver to plasma.
ii) inhibiting the transfer of triglycerides
tract. In
Clofibrate is well absorbed fiom gastrointestinal
is bound .to albumin. It is eliminated in urine as
plasma, it
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Ph
Ph
Ph
h
y
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144 145
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Classification of coagulants
Section IX
1. Vitamin K
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Ki (from plants) Phytonadione
DRUGS ACTING ON BLOOD

K2 (from bacteria) Menaquinone
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k3 (Synthetic) Menadione
ORGANS
AND BLOOD FORMING
Ph
Ph
Ph
2. Miscellaneous Fibrinogern
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Antihaemophylic globulin
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Tissue extract
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Adrenochrome
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ma
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Rutin
AFFECTING
45. DRUGS
c
c
1. VITAMIN K: It is a fat soluble vitamin. It is not a single entity.
COAGULATION OF BLOOD
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y
Naturally it occurs in the form of two distinct substances, vitanmin Ki
and K2. Vitamin K3 (menadione) is a lipid soluble synthetic
involves the biosynthesis of prothrombin
The mechanism of clotting compound. Vitamin K is necessary for the
Mechanism of clotting:
and factors VII, IX and X. Vitamin K is produced by bacterial flora'
following sequence of reactions:
of human intestine and it is absorbed in presence of bile salts. It can
Tissues pharm
Thromboplastin
also be absorbed on parenteral administration.
Uses.
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Piatelets
Calcium 1. Hypoprothrombinemia due to hepatocellular disease,
obstructive jaundice and chronic diarrhoea.
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Prothrombin - Thrombin
2. For treating toxicity of oral anticoagulants and salicylates.
Fibrin (Clot) It is obtained from human plasma.. It is used to
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2. FIBRINOGEN:
Fibrinoge in hemoplhilia and also in the deficiency of
control bleeding
Ph
Ph
Ph
antihaemophilic globulin (AHG)
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damage of platelets and

Thromboplastin is liberated due to Dose: 0.Sg as I.V. infusion.
to thrombin.
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it converts prothrombin
tissues. In presence of calcium, formed enmeshes
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to fibrin. The fibrin 3. ANTIHAEMOPHYLIC GLOBULIN: It is highly effective in

Thrombin activates fibrinogen clot. It
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cellular elenments and forms a controlling bleeding. It is prepared from pooled human plasma.
red blood cells and other
is used in haemophilia and AHG deficiency.
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cOAGULANTS 4. TISSUE EXTRACT: It acts by activating plateilet ageregation.

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cy
cy
It can be used to control intermal haemorrhages.
y
coagulation. They
are agents which promote 5. ADRENOCHROME: It reduces capillary fragility. It prevets
Coagulants: These
states. bleeding from raw surfaces and microvessels. e.g. epistaxis,
are used in haemorrha:zic
hematuria and retinal hemomhage.
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y
y
Ph
Ph
Ph
h
y
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Insta - Study_Pharmacy_29 146 147
Telegram - StudyRUTIN:
Pharmacy
6. plant glycoside.
It is a It is used to reduce capillary In vitro anticoagulants: These compounds are chela ing agents
with vitamin C which facilitates its action. ike citrates, fluorides and E.D.T.A. Ethylene diamine tetra acetic
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bleeding. It is used
to acid). They act by removing calcium ions. These compounds are
substances used
Local haemostatics (Styptics): These are used in' vitro to preserve blood (so as to make it st:itable for
ud
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effective on oozing surfaces
stop bleeding from local sites. They are transfusion).
like tooth sockets and open wounds. They should never be injected.
In vivo aniticoagulants (slow acting anticoagulan:s)
y
It is applied
1.THROMBIN: It is obtained from bovine plasma.
a freshly prepared solution. Coumarin derivatives: Dicoumarol
Ph
Ph
Ph
on bleeding surfaces as a dry powder or as
Cyclocounmarol
ha
It is used in skin grafting.

plasma. It is used as sheets Phenprocouman
ar
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2. FIBRIN: It is obtained from human Ethyl biscoumacetate
or foam for covering bleeding surfaces.
r
is moistened with saline or DICOUMAROL (BISHYDROXYCOUMARIN): Dicoumarel was

ma
ma
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ma
3. GEL FOAM: It is spongy gelatin. lt
packing wounds. Sine it is completely earlier isolated from spoilt sweet clover hay. In cattle it produced
thrombin solution and used for
after suturing a sweet clover disease which is characterised by severe bleecing. It is
absorbed within 2 months, it can be left in place
c
c
effective orally.
y
y
wound.
4. RUSSELS VIPOR VENOM:
It enhances coagulation by Mechanism of Action: Dicoumarol acts by inhibiting the
stimulating thrombokinase. It is used to stop external

bleeding in synthesis of prothrombin and factors VIl, IX and X in the liver. For
haemophilics. the synthesis of prothrombin, vitamin K is necessary. Dicoumarol
gauze soaked in percent1 acts as a competitive.antagonist of vitamin K. The anti:ougulant
5. VASOcONSTRICTORS: Cotton effect of dicoumarol is antagonised by vitamin K.
bleeding.
adrenaline can stop epistaxis or similar
gums and Absorption, fate and excretion: Dicounmarol is effectiv: on oral
6. ASTRINGENTS: Tannic acid can be used for bleeding
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and intravenous administration. In blood it is bound to albumin.
bleeding piles. High concentration is present in liver. It crosses placental bamier and
Anticoagulants
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clotting. also is secreted on milk. It is eliminated in urine, motly in a
Anticoagulants are agents which inhibit the process of metabolised from.
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Classification of anticoagulants: Adverse reactions: Haemorrhage is the major toxicity.his may
occur as haematuria, bloody stools, bleeding of gums etc These
Ph
Ph
Ph
1. In vitro anticoagulants Citrates
effects can be treated by large doses of vitamin K.
ha
Oxalates
Fluorides Dose: 300 mg, on the first day. 200 mg. on the second day and 50
ar
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E.D.T.A. to 100mg. on subsequent days by oral route.
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Coumarin derivatives
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ma
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vivo anticoagulants INDANEDIONES Phenindione
2. In
Indanedione derivativs Diphenadione
(Oral anticoagulants)
ac
Warfarin Anisindione
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Herparin Chlorphenindione
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3. Both in vitro and in

vivo anticoagulants The indanediones are effective on oral and pairenteral
(parenteral anticoagulants) administration. They act by inhibiting prothrombin synth«sis like
**
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Ph
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Ph
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148 149
duration of action.
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dicoumarol. They have a rapid onset and short Absorption,fate and excretion: Heparin is ineffective orally.
hepatitis and skin
Toxicities of indanediones are haemorrhage, It is well absorbed after subcutaneous injection. On intravenous
ud
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reactions. injection, it produces immediate anticoagulant effect. Heparin
It is well soluble
WARFARIN: It was originally used as a rat poison. should not be used intramuscularly because it produces hematoma.
y
all routes. it acts by the
samme
and so can be administer ed by coronary Heparin does not cross placental barrier. Also it is not secreted
bronchodilator and
Ph
Ph
Ph
mechanism as dicoumarc l. It has a in milk. It is metabolised in the liver by an enzyme called
toxicity and it can
vasodilator effect. Haemorrhage is the important
ha
toxicities are alopecia, urticaria heparinase. It is eliminated in urine both in an inactive and a
by controlled by vitanmin K. Other
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metabolised form.
and dermatitis.
r
Adverse reactions:
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ma
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Both in vitro and in vivo anticoagulants 1. Danger of bleeding due to over dosage.
(Fast acting anticoagulants) Allergic and anaphylactic reactions.
c
c
Alopecia on prolonged use.
y
y
3.
HEPARIN
Preparations and dose: Heparin is available as sodium or
liver. It is also obtained calcium heparin. I.V. bolus - 5000 to 10,000 units, every 4 to 6
Source: Heparin was first extracted from
tissues, it is present in hours; Subcutaneous injection -25000 units every 12 to 24 hours.
from lungs and intestinal mucosa. In these
from niast cells during anaphylactic
mast cells. Heparin is released
Substitutes of heparin (Heparinoids): These are sulfated
shock. (CO polysaccharides. Their anticoagulant activity is dependent on the
It consists of
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emistry: Heparin is a mucopolysaccharide. degree of esterification with sulphuric acid. These compounds are
molecules esterified with sulphuric
mine and hexuronic acid is very high. This dextran sulphate, paritol and treburon.
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"he content of esterified sulphuric acid
in the stronge st acid present in the

body. ARVIN (ANCORD): It is an enzyme obtained from Malayan pit
1) degrading
viper venom. It produces an anticoagnlant effect by
y
y
al actions fibrinogen 2) converting fibrinogen to fibrin. Arvin is used
Ph
Ph
Ph
tion Heparn prevents clotting both in vivo and intravenously as an alternate to heparin.
ha
the
hibit prothrombin synthesis. It acts by
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bin HI (heparin co-factor). This

46. FIBRINOLYTIC AGENTS AND
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im coagulation factors.
2.
ac
conversion of prothrombin to ANTI PLATELET DRUGS

[elouaiepd
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like
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3. Both synthesis sd conversion of fibrinogen FIBRINOLYTICS (THROMBOLYTICS)

VIva
pares lears the turbidity of lipemic Fibrinolysis: The process of fibrinolysis (dissolution of clot) occurs
on of the enzyme lipoprotein lipase. as follows. Plasminogen is the ina "ive precursor present in plasma.
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Insta - Study_Pharmacy_29 *

150
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present in blood ANTIFIBRINOLYTICS
It isconverted to plasmin by an activator substance
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breakdown clots. These drugs inhibit fibrinolysis and therefore prevet the
and tissues. Plasmin can
Plasminogen > Plasmin > Clot dissolution. dissolution of clot. They act by inhibiting plasminogen activaion.
y
act EPSILON AMINO-CAPROIC ACID (EACA): It is structurally
Fibrinolytic agents: All fibrinolytic agents currently in use
Ph
Ph
Ph
plasminogen activators. They produce lysis related to lysine. It blocks plasminogen activation by competitive
directly or indirectly as
ha
So they are curative rather than blockade. Thus it reduces fibrinolytic activity. Dose: Initial-5g.
of an already formed clot.
1) intra arterially close to a oral or I.V. followed by g. every one hour till bleeding stops.
ar
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1
prophylactic. They can be injected

for a genaralised effect It is used to control haemorhage like: 1) abruptio placenae 2)
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thrombus for a localised effect 2) intravenously

bleeding is high with intravenous
ma
ma
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in multiple thrombi. Incidence of post-partum haemorrhage 3) traumatic and surgical bleedings
easily than arterial
injection. In general, venous thrombi are lysed TRANEXAMIC ACID: It is a synthetic inhibitor of fibrinolys is. It
thrombi. Also recent thrombi respond better.
c
c
is 10 times more potent than EACA. It binds to lysine binding
y
y
Indications: Fibrinolytic agents are used in: site on plasminogen. Thus it prevents the combination of
plasminogen with fibrin. Dose: g. orally or I.V., to 4 tines a
1 3
1. Myocardial infraction.
2. Pulmonary embolism day.
3. Deep vein thrombosis APROTININ: It is a polypeptide protease inhibitor. It is isolated
4. Peripheral arterial occlusion. from bovine tissues. It inhibits kallikrein, trypsin and fibrinoiysin.
STREPTOKINASE: It is afibrinolytic agent obtained fiom
activator leading Sclerosing agents: These are irritating substances used to
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haemolytic streptococci. It acts as a plasminogen obliterate varicose veins. They are also used for closure of hurmial
1) it is inactivated by antibodies to
to fibrinolysis. Disadvantages: rings and for fibrosing haemorrhoids. The preparations used are:
ud
ud
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body 2) it is antigenic and so produces
Streptococci present in the
dangerous . Phenol 5% in vegetable oil.
hypersensitivity reactions 3) local irritation and
haemorrhage 4) produces fever. 2. Preparations containing salts of fatty acid (like sodium linolcate
y
y
or ethanolamine oleate).
It is used in decp vein thrombosis at a
dose of 2,50,000 units
Ph
Ph
Ph
It is followed by 100,000 units every hour
for
ANTI PALATELET DRUGS
ha
I.V. in 30 minutes.
24 to 72 hours.
ar
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is mitiated by
UROKINASE: It,is an enzyme prepared from human urine.
It is Functions of platelets: Intravascular thrombosis
rm
kidney cells Unlike platelet adhesion and aggregation. Platelets stick to the damaged
from cultured human
ma
ma
ma
now prepared (aggregation)
does' not they stick to each other
streptokinase, it is 1) non-antigenic 2) non-pyrogenic 3) vessel wall (adhesion). Then
ac
and release adenosine diphosphate (ADP) and thromboxane

A2
roduce allergic reactions. But it is expensive.
cy
cy
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and also fibrin fornmation
It is a natural (TXA2). This promotes further aggregation
OE PLASMINOGEN ACTIVATOR: (clot). Antiplatelet drugs inhibit platelet aggregation. So the are
y
It is prepared by recombinant DNA techrnology. It

like
bound to fibrin clot. Systemic useful in the prevention and treatment of thrombosis in conditions
effect on piasminogen myocardial ischemia 3) cerebral ischemia.
minimised. So it is safer 1) myocardial infraction 2)
asmirogen and so bleeding is
Prostacyclin (PGI2) synthesised in the biood vessels is a natural
nase. inhibitor of platelet aggregation.
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y
y
Ph
Ph
Ph
h
y
y
152
153
the body is about
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the release of ADP from
platelets. Also Iron metabolism: The nomal iron content of
1. ASPRIN: Asprin inhioits
1
hemoglobin The remaining g. is

prostaglandins and thromboxane A2. All 3g. Of this 2 g. is present in
it inhibits the synthesis of
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distributed in two pools. They are:
aggregation.
these mechanisms inhibit platelet bone marrow. This
By inactivating A mobile pool stored in liver, spleen and
It is an uricosuric agent. occurs.
2. SULFINPYRAZONE:
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iron can be mobilised whenever demand
the synthesis of prostaglandins
inhibits
the enzyme cyclo-oxygenase,
it
throughout the body in all
A fixed pool which is distributed
Ph
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Ph
2.
and thromboxane A2. tissue cells. This iron is essential for cellular respiration and
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thromboxane
It has no effect on the levels of it cannot be mobilised.
3. DIPYRIDAMOLE:
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phosphodiesterase which inturn
A2 or PGl2. It acts b
inhibiting requirements are as follows:
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This inhibits platelet aggregation. Iron requirement: The daily iron

increases cyclic AMI
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ma
ma
ma
Dipyridamole is also a coronary vasodilator. 5 to 10 mg. for a normal male adult.
It is a new synthetic
inhibitor of platelet 10 to 15 mg. for women upto menopausal age.
4. TICLOPIDINE:
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c
cyclo-oxygenase or cyclic AMP. It lactation.
aggregation. It has no effect on 15 to 20 mg. for women during pregnancy and
y
y
and release reaction.
inhibits platelet deposition, aggregation duodenum,
Iron absorption: The active site of iron absorption is the
sphincter. The mucous menmbrane
IN especially the region below the pyloric
47. DRUGS EFFECTIVE regulatory mechanism for iron absorption.
of gastrointestional tract has a
IRON DEFICIENCY ANEMIA In nomal individuals, only the amount
of iron that is required by the
dose of iron if given
body is absorbed. In healthy individuals, greater
as "microcytic anemic individuals,
Irondeficiency anemia is also called does not raise hemoglobin level beyond normal. In
cells are small
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the red blood hemoglobin level to
hypochromic anemia". in this condition, synthesis of only the amount of iron required to bring back the
hemoglobin. For the iron absorption is
sized and they contain less nornmal is absorbed. This regulatory mechanism of
of anenia
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nec:ssary The deficiency in this type mechanism operates hrough a protein
hennoglobin, iron is
absorption called "mucosal block". This
due to incomplete of
is due to inadequate iron in food or called apoferritin.
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iron.
Mechanism of iron transfer: Iron can be absorbed only in
Ph
Ph
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containing moiety, present in ferric from. The stomach
Hemoglobin: Hemoglobin has an iron with the protein ferrous fom. But in food, it is
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l:eme) which is combined colloidal ferric iron into monomolecular ferric

(metalloporphyrin or initially converts the
pyTole rings. Porphyrin and to ferrous iron.
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four
globin. Porphyrin cousists of does not iron. Later, it is reduced by the stomach
and so their defciency
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globin are synthesised in the body for iron. So the The ferrous fom of iron is absorbed
in the small intestine. In
depends on food intake
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ma
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occur. But the body form is converted to ferric form.
the intestinal mucosa, the ferrous
deficiency of iron produces anemia. apoferritin and converts it to
ac
The ferric form then combines with

muscosal cells.
Iron defciency may occur due to: ferritin. The ferric fom is transported
through the
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cy
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Causes for iron deiiciency: cells, the ferric iron is reduced
Again at the blood stream end of the
y
1. Excessive loss as in chronic haemorrhage.

to ferrous fom.
2. Dietery deficieny. There, it is again
and pregnancy. The ferrous iron enters the blood stream.
3. Increased demard as in puberty converted to ferric form. The ferric iron binds
to the specific iron
4. Defective absorytion as in
chronic diarrhoea.
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Ph
Ph
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binding protein in blood called as trausfferrin and circulates along c)Intravenous iron:
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with it. 1. Saccharated iron oxide-100 to 200 mg. of iron.
Mucosal block" mechanism operates through apoferritin. 2. Iron-dex tran complex-30 to 100 mg of iron.
Apoferritin is a protein of molecular weight 4,60,000. The presence
y
of iron in the mucosal cells stimulates the production of apoferritin.
Ph
Ph
Ph
The absorption of iron is controiled by the availability of apoferitin. 48. DRUGS EFFECTIVE IN
ha
If apoferritin is saturated, no iron is absorbed. So apoferritin

MEGALOBLASTIC ANEMIA
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regulates iron absorption.
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Excretion: The unabsorbed iron is eliminated through stools. Only Megaloblastic anemia is also called as "Maurocytic
ma
ma
ma
ma
negligible quantity of iron is eliminated through urine, bile and sweat. hyperchromic anemia". In this type of anemia, there is defect
Parenteral iron administration: Iron is adequately absorbed in the maturation of red blood cells. In this case, immature and
c
c
from the oral route. But parenteral iron is indicated in special large-sized red blood cells (called megaloblasts) are released into
y
y
Circumstances like: circulation. But the hemoglobin formation is not defectivc. This
Bi12 and
1. Anemia due to malabsorption. type of anemia occurs due to the deficiency of vitamin
2. Genuine intolerance for oral iron. folic acid.
3. Cases of haematemesis where oral iron is contraindicated.
4. Unreliable patients who do not take oral iron regularly.
5. Women in late stage of pregnancy.
n Both vitamin Bi2 and folic acidare necessary for
nucleoprotien synthesis. Their deficiency leads of defective DNA
(deoxyribonucleic acid) synthesis. This in turn affects rapidly
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Adverse reactions: multiplying cells in the buccal cavity, tongue, gastrointestinal tract,
vagina, ovary, testes etc.
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1. Astringent effect on oral administration.
2. Pain, irritation and tenderness on intramuscular injection. VITAMIN B12 (CYANOcoBALAMIN)
y
y
3. Shock or cardiac arrest on intravenous administration. Vitamin B12 belongs to the group of cobalamins. It contains
4. Hemosiderosis (accumulation of iron in internal organs).
Ph
Ph
Ph
a cyanide group attached to the cobalt atom.
ha
The antidotes for iron are desferrioxamine and D.T.P.A. synthesised byy
(Diethylenetriamine penta acetic acid). Source and occurrence: Vitamin BI2 is
ar
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micro-organisms of the colon. But it is not absorbed there and so it
rm
Preparations and dose: is eliminated in feces. Comercially it is obtained from Strepiomyces

ma
ma
ma
as a by-product of streptomycin. It is nmostly present in
a) Oral iron: griesius,
non-vegetarian foods like liver, kidney, fish and c8g
ac
1.Excicated ferrous sulphate-600 mg. daily.

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1
Requirement: The requirement of vitamin Bi2 is about

2. Ferrous gluconate-900 mg. daily.
y
3. Ferrous fumarate-600 mg. daily. microgram per day. The recommended daily intake is:
2 micrograms for normal adults.
b) Intramuscular iron:
1. Dextran-iron combination-50 to 250 mg. of iron.
3 micrograms for women during pregnancy and lactaticn.
2. Iron-sorbitol-citric acid complex-75 to 100 mg. of iron. 0.3 micrograms for children.
St
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y
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Ph
Ph
Ph
h
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156
157
FOLIC ACID (PTEROYLMONOGLUTAMIC
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ACID)
Absorption, distribution and excretion: In food, vitamin B12 is
present in a metabolically in ictive and bound form. It released
is by Chemistry and occurrence: Chemically folic acid molecule
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cooking. Vitamin B12 isabsorbed only in presence of intrinsic consists of pteridine, para amino benzoic acid and glutamic acid. The.
factor. Intrinsic factor is mucopeptide secreted by the gastric rich sources of folic acid are vegetarian foods like cabbages and
y
mucosa. It acts a carrier fo" vitamin B2. greens. However, small quantities are found in eggs, meat, fish and
dairy products. Cooking destroys folic acid.
Ph
Ph
Ph
Vitamin B12 is stored in the liver to the extent of 99 percent.
ha
It is excreted in
Some quantity is present in the spleen and kidneys. Absorption, distribution and excretion : In food, folic acid is
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bile but it is reabsorbed ty enterohepatic circulation. The daily present in a conjugated fom. Usually it occurs as triglutamic acid
r
urinary excretion of vitamin Bi2 is negligible. The total body content and heptaglutamic acid conjugate. It is broken down by enzymes
ma
ma
ma
ma
So
is about 5 ng. Of this onl about 0.1 microgram is eliminated. known as conjugases present in the gastrointestinal tract. In the
occur except after 5 or 6 years absence of conjugases, folic acid is not absorbed. It is absorbed
the deficiency of vitamin Bi2 does not
of prolonged malnutrition. mainly in the proximal portion of small intestine.
c
c
y
y
B12 is necessary for the following Folic acid circulates in blood as N-methyl tetralhydrofolate. It
Metabolic actions: Vitanin is distributed in all tissues. But high concentration is found in liver.
metabolic actions:
It is excreted mainly through urine.
1.
2.
3.
In methyl group traiusfer reaction, which is required for the
conversion of homocysteine to metlhionine.
For the biosynthesis »f DNA.
For the synthesis of nyelin.
Requirement:
100 micrograms for children.
200 micrograms for adults.
Spdf
The requirement of folic acid is:
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4. To maintain sulphydyl (SH) group containing enzymes in the 300 to 400 micrograms for women during pregnancy and
reduced state. lactation.
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ud
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5. For growth promoting effect in birds and animals. Metabolic actions: Folic acid is necessary for the following
metabolic actions:
y
y
1. Biosynthesis of purines and pyrimidines.
Ph
Ph
Ph
1. Cyanocobalamin injection 50 to 100 micrograms weekly by
ha
intramuscular injection followed by 50 to 100 micrograms 2. Interconversion of amino. acids (like serine to glycine and
every 2 to 3 weeks. homocysteine to methionine).
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ar
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Hydrox"cobalamin injection-the dose is the same as 3. Incorporation of formate into purine ring.
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2.
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ma
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cyanocobalamin. All these reactions are needed for nucleic acid synthesis.
ac
Therapeutic uses: Preparation and dose : Folic acid tablet-5 to 20 mg. daily.
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cy
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1. Megaloblastic anemia due to vitamin Bi2 deficiency. Therapeutic uses:
y
2. Anemia due to deficient intake, defective absorption and 1. Megaloblastic anemia due to nutritional deficiency.
defective. utilisation f vitamin B12.
2. Megaloblastic anemia of pregnancy and infancy.
3. Parenteral vitanmin B12 is used for the treatnient of permecious 3. Some cases of agranulocytosis.
anemia (which is due to defective intrinsic factor)
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y
y
Ph
Ph
Ph
h
y
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FOLINIC ACID (CTROVORUM FACTOR): at a constant temperature of 2 to 6°C. Storage below 2°C dannages
RBCs. It should be used within 21 days.
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In the body,
Folinic acid is the formyl derivative of folic acid.
acid. Folinic acid is required for Advantages
folic acid is converted to folinic
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synthesis. It is used in the treatment of toxicity due to folic Complete restoration of physiological deficiency inciuding
thymine
It is effective in megaloblastic provision .for oxygen transport.
acid antagonists like methotrexate.
y
anemia even at a dose of 50 micrograms. Disadvantages
Ph
Ph
Ph
1. Difficulty in procurenment.
49. BL0OD SUBSTITUTES AND
ha
2. Need for typing and cross matching.

PLASMA EXPANDERS
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3. Transmission of diseases like syphilis, malaria and AiDS
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4. Danger of untoward reactions (like pyrogenic, hemolytic and

ma
ma
ma
ma
Shock : Shock is defined as a state of acute circulatory failure sensitisation reactions).
accompanied by defective perfusion of tissues. It is produced
by a
PLASMA : It is available as citrated liquid plasma or pow dered
decrease in circulating
number of factors. But the important one is
c
c
plasma. It is prepared by mixing equal parts of citrated bloocd from
fluid volume. This may be produced by:
y
y
different persons and then separating by centrifugation. Strict aseptic
. loss of blood due to haenmorrhage. conditions must be observed in the preparation. Plasma thus prepared
2. loss of plasma into the tissues or the outside.
does not contain coagulation components. But these componens can
restored by the be supplied fom fresh frozen plasma. Plasma is used in oliyemic
The circulating fluid volume can be
fluids and plasnma substitutes. These. agents shock, especially in burms.
administration of various
HUMAN ALBUMIN: It is a plasma protein. It is obtained from
are thus useful in the treatment of shock.
are human blood by fractionation. It has a nmolecular weight of about
agents
Agents wlhich restore fluid volume These
:
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60,000. Albumin expands the volume of plasma. It is non-1oxic.
classified as Also it does not interfere with coagulation. It is used:
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. Blood products Whole blood 1. As a plasma expander in shock.
Plasma 2. To raise serum protein level in hypoproteinemia.
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Plasma proteins 3. To reduce edema.
Ph
Ph
Ph
2. Colloidal plasma Dextran
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substitutes Polyvinylpyrolidone cOLLOIDAL PLASMA SUBSTITUTES

Gelatin
ar
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These are cheaper substitutes of plasma. They are usefil in
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Fluid plasma Normal saline conditions where plasma is indicated. They have only an osn iotic
ma
ma
ma
substitutes Dextrose solution effect. This helps to maintain an adequate circulating blood volume.
But they do not fulfil nutritive, hematological and other functiors of
ac
BLOOD PRODUCTS
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cy
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plasma.
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donors is DEXTRAN: It is an inert polysaccharide. It is produced by the

WHOLE BLOOD: Whole blood obtained from human
disodium action of bacteria (Leuconostoc mesenteroides) on sucrose. t is
preserved with A.C.D. solution (containing 2.5 g. of
dextrose in 120 ml). It is stored available as Dextran 40,000 and Dextran 75,000. It acts by expan ling
monohydrogen citrate and 3.9 g. of
St
St
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St
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y
y
Ph
Ph
Ph
h
y
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160
161
DEXTROSE : It is used as an infusion at a
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concentration of 5
effect. It is stored in liver, spleen
the blood volume by an o'motic
percent. It is useful in renal failure. Also it
hours. is a nutrient. The
cells. It is effective for 12 to 24
and other reticulo endothel al
disadvantages are similar to normal saline.
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ud
ud
u
manifestations and prolongation of
Toxicities of dextran are ailergic Use of vasodilators in shock: Vasodilators like phentolanmine
bleeding time. and sodium nitroprusside increase blood flow
to vital organs. So they
y
are also useful in the treatment of shock.
Advantages
Ph
Ph
Ph
filtration or autoçlavin8 Use of corticosteroids in shock
1. Dextran can be easi y sterilised by Massive doses of
ha
as long as 10 years. dexamethasone is useful in the treatment of shock.

2. It can be stored eas:ly for It is supposed to
ar
ar
ar
route. stimulate the myocardium and to increase tissue
in saline by intravenous perfusion.
500 ml. of percent solution
6
r
Dose:
ma
ma
ma
ma
In shock, as a substitute
for blood products.
Use:
It is a synthetic plastic
POLIVINYL PYRROLIDONE (PVP):
c
c
It has a molecular weight of 35,000 to
material, soluble in water.
y
y
dextran. It is stored in skin, skeletal
40,000. It is less potent than drugs and
systeim. It binds to various
muscle and reticuloendothelial by these drugs.
toxicities produced
toxins. So it has been usei to treat Also it interferes with
haebookspdf
erythrocytes.
It produces agglutination of
antibody' production.
produces reticulum cell sarcoma
PVP is relatively nN-tOxic. It administered
produced on humans. It is
St
St
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in rats. No such effect s physiological saline.
in buffered
intravenously as a 40 percent solution
ud
ud
ud
u
protein obtained from animal
GELATIN: It is a solulble denatured
weight of about 35,000. It acts as a
collagen. It has a molecular coagulation,
It does not interfere with
y
y
plasma expander like dextran. toxicites are flushing,
matching. Occasional
blood grouping and cross
Ph
Ph
Ph
spasm and hypotension. Dose : S00 ml. of
rigors, broncho
ha
urticaria,
6 percent solution by
intravenous route.
ar
ar
ar
rm
FLUID PLASMA
SUBSTITUTES
ma
ma
ma
It is 0.9 percent sodium
chloride solution. It
ac
NORMAL SALINE dehydration.

chloride and water in case of
cy
cy
cy
can replace loss of sodium vasopressor agents e.g.
for administering
y
It is used as a vehicle repidly and so it

from blood
noradrenaline as a drip. It is removed quantities may
administration of large
has a short effect. Ripid febrile reaction due to
It may produce
produce pulmonary edeina.
tlhe presence of pyrogens.
St
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ud
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y
Ph
Ph
Ph
h
y
y
162 163
Telegram - Study Pharmacy Based on potency
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Section X
Weak diuretics Osmotic diuretics
ud
ud
ud
u
Xanthine derivative
KIDNEY Carbonic anhydrase
DRUGS ACTING ON THE
y
1nhibitrs
Moderately potent Thiazides
Ph
Ph
Ph
- diuretics
ha
Very potent diuretics Frusemide
ar
ar
ar
(High ceiling diuretics) Buinetanide
r
DIURETICS Ethyacrynic acid

ma
ma
ma
ma
50. 4. Potassium retaining Triamterene
*
tlhe flow of urine. These

diuretics Amiloride
Diuretics are drugs which increas
c
c
edema. Also they are useful Spironolactone
drugs are mainly used for the relief of XANTHINES: The xanthines are caffeine, theophylline and
y
y
products through urine.
for the elimination of toxic theobromine. All these xanthines produce diuretic effect. But the
effect is marked with theophylline. Theophylline is also used as
Classification of diuretics theophylline ethylenediamine (aminophyiline)
Based on mechanism of action: The mechanisms of diuretic action of xanthines are:
T Xanthines
1.Promotorsof glomerular 1, The number of functioning glomeruli is
increased.
blood flow 2. The afferent vessels are dilated more than the efferent vessels.
St
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St
Inhibitors of tubular Thiazides This increases glomerular blood flow and filtration pre ssure.
L.
reabsorption Acetazolamide
ud
ud
ud
u
3. The glomerular filtration is increased and tubular reabsorption
Spironolactone is decreased.
3. Antagonists of
aldosterone THIAZIDE DIURETICS: Thiazides are moderately potent diuretics.
y
y
Mannitol They are derivatives of the parent compound, benzothiaciazine.
Osmotic diuretics
Ph
Ph
Ph
4.
Glycerol Chlorothiazide was the first compound that was extensively sudied.
ha
Isosorbide Other drugs f this group are hydrochlorothiazide,

ar
ar
ar
. Potassium retaining
Triamterene hydroflumethiazide, bendroflumethiazide, polythiazide and
rm
Amiloride chlorthalidone.
diuretics
ma
ma
ma
. Loop of Henle diuretics
Frusemide Pharmacological actions
ac
Ethacrynic acid
Diuretic effect
cy
cy
cy
y
1. The thiazides act directly on the renal tubule. They p event

the reabsorption of sodium and chloride. The raie of
glomerular filtration is not affected. The diuretic effect is not
modified by acidosis or alkalosis.
St
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ud
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y
y
Ph
Ph
Ph
h
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y
Telegram - Study Pharmacy164
week inhibition of carbonic
anhydrase.
These drugs produce a 165
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2.
reabsorption. So
3. There is marked
inhibitory effect on sodium
is made available in the
distal tubule. Therapeutic uses: For the treatment of sodium retention and
a large amount of sodium
ud
ud
ud
u
exchanges with potassium. This leads edema.
The excessive sodium
to more potassium loss.
y
ACETAZOLAMIDE(A CARBONIC ANHYDRASE INHIBITOR):
sodium produces hyponatramia.
4. Excessive loss of
Ph
Ph
Ph
hypokalemia
Excessive loss of potassium produces Diuretic effect: Acetazolamide acts by inhibiting the enzyme
ha
hypochloremia. carbonic anhydrase. This enzyme catalyses the following reaction:

Excessive loss of chloride produces
ar
ar
ar
alkalosis.
So tlhiazides prodice
hypokalemic hypochloremic
r
Carbonic
H20+COz H2CO3
Hypotensive effect
ma
ma
ma
ma
ii) anhydrase
effect. This is due to
Thiazides produce a mild hypotensive H2CO3 H + HCO
c
c
. an effect on sodium
metabolism.
y
y
Due to inhibition of carbonic anhydrase, hydrogen ions are not
y
vessels.
2. a direct effect on blood available for exchange with sodium. So, sodium is not reabsorbed
ii) Metabolic effect and eliminated. Along with it water is also eliminated. Diuresis
On prolonged use, thiazides
1.
produce.. hyperglycemia and produced by acetazolamide is accompanied by loss of bicarbonate and
glycosuria. This is due to inhibition of insulin release. potassium.
2. Thiazides decrea:se the
excretion of uric acid. This increases Acetazolanmide decreases the synthesis of aqueous
Other effects
plasma.
uric acid concentration of humour. So it decreases intraocular tension. It also has an antithyroid
St
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thiazides decrease urine volume.
3. In diabetes insipidus, and anticonvulsant effect.
Absorption, fate and excretion:

The thiazides are well
ud
ud
ud
u
Absorption, fate and excretion: Acetazolanmide is well absorbed
nistration. By oral route, the diuretic effect
absorbed on_oral adni on oral administration. It is eliminated by kidney within 24 hours, in
concentration is present in the kidney. an active rorm.
starts within an hour. High
y
y
Elimination is through kidney by tubular
They cross placental barier.
Ph
Ph
Ph
Adverse reactions: Metabolic acidosis, hypokalemia, skin rashes
secretion.
ha
and blood dyscarsias.

Adverse reactions
ar
ar
ar
Dose: 025 to 0.5 nmg. in a single dose as tablets.
Hypokalemic hypochloremic alkalosis.
rm
1.
loss. Ethozolamide and methazolamide are compounds which have
Muscle weakness due to fluid
ma
ma
ma
2.
thrombocytopenia. similar effects as acetazolamide.
3. Blood dyscrasia:: like
ac
reactions. SPIRONOLACTONE (ALDACTONE): It is a steroid, hav.ng a

cy
cy
cy
4. Rarely allergic
structural similarity to aldosterone. It is an aldosterone antagonist. It
y

acts by competetively antagonising the effect of aldosterone on distal
Chlorothiazide tablet - 500 to 1000 mg. by mouth.
tubules. It decreases the elimination of potassium. Spironolactone is
Hydrochlorothia zide as tablets - 25 to 200 mg. by mouth ineffective in edema not associated with rise in aldosterone
Hydroflunmethiazide concentration. The diuretic effect of spironolactone develops slowly.
So it is combined with other diuretics like thiazides.
St
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St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
166 167
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are nausea, vomiting, Absorbtion, fate and excretion:
Adverse reactions of spironolactone Frusemide is rapidly absorbed
Dose 25 mg. two to four on oral adnministration. It is excreted unchanged within 4 hours. It
ud
ud
ud
u
drowsiness, hirsutism and gynecomastia.
has a quick but shorter duration of action. On intravenous
times a day by nnouth.
mannitol and glycerol belong administration the diuretic effect starts in 2 minutes. The effect is
OSMOTIC DIURETICS: Isosorbide,
y
concentration of these complete in 2 to 3 hours.
to this group. By increasing the plasma
Ph
Ph
Ph
glomeruiar filtrate _can be Adverse reactions
substances, their concentration in tlie
ha
activity, these substances oppose the

increased. Due to osmotic produces Muscle weakness and cramps due to electrolyte loss.
1.
ar
ar
ar
filtrate. This
reabsorption of water. from the glomerular than 2.Cardiac arrest on intravenous adiinistration.
r
elinmination of water
diuresis. These substances produce more and 3. Skin rashes, nausea, and diarhoea.
intracranial
ma
ma
ma
ma
treating increased
sodium. Mannitol is used for
4. Liver and bone marrow changes.
intraocular tension.
diuretic. It is a Dose: 40 mg. daily orally.
c
c
TRIAMTERENE: t is a potassium vetaining
by the oral route.
y
y
only
y
adninistered ETHACRYNIC ACID: It is a very powerful diuretic with an effcct
non-steroidal compound which is
so it is used along with other drugs. similar to that of frusemide. Like frusemide, it acts on tie
It is not powerful diuretic and But
clhloride and bicarbonate.
It inhibits the reabsorption of sodiun ascending loop of Henle. On oral administration, the diure ic
due to inhibition of its
itdecreases the renal exeretion of potassium effect starts in a few minutes and is complete in 1 to 2 hours. It
secretion the distal neplron.
in produces hypochloremic hypokalemic alkalosis like frusemide.
hyperkalenmia, vomiting, diarrhoea, skin
Adverse reactions are The adverse reactions are
rashes and dryness of mouth. Dose
: 100 to 200 mg. by oral route.
St
St
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St
1.
Muscle weakness and lethargy due to electrolyte loss.
It is a week diuretic 'and so
it is not usually recommended.
2.Anorexia, nausea, vomiting and diarrhoea.
diuretic like
is also a potassiun retaining
ud
ud
ud
u
AMiLORIDE : It 3. Skin rashes.
than trianterene. Also,
triamteme. But is 10 times more po:eni decreases calcium 4. Vertigo, tinnitus and deafness.
than triamterene. It
duration of action is longer
y
y
also be given with
excretion, butincreases wic acid excretion. It can
51. ANTIDIURETICS
Ph
Ph
Ph
nausea, diarrhoea and
thiazides or frusemmde. Adverse veactions:
ha
headache. Dose 10 to 201mg daily.

Antidiuretics are drugs which decrease urine output. Th:
ar
ar
ar
diuretic being
FRUSEMIDE (FURosEMIDE, LASIX): t is potent
a
following are some agents, which have specific antidiuretic effect.
rm
similarity to thiazides.
eifcctive orally. it has a structural ANTIDIURETIC HORMONE (ADH) The antidiuretic hormone is
ma
ma
ma
adninisiration, fiuseimide produces a
Effect on kidney: On oral released fronm the posterior lobe of pituitary along with oxytocin.
starts in hur arnd is complete
ac
quick and intense diuresis. The effect It also has a vasopressor effect. So it is also called as vasopressin.
cy
cy
cy
n o hours. The degree of dehydration and circulating blood volume influenc
y
reabsoption of sodium in the proximal

It acts by inhibiting the the secretion of ADH. But chlorpromazine and alcohol depress it
chloride is more than
tubule and ascending loop of Henle. Loss of release.
potassium excretion.But there is nc
hat of sodiuim. A!so it enhaces
So it produces inypochieremic hypokalcmic ADH acts by increasing water reabsurption in the distal tubules
oss of bicarbonate.
and in the loop of Henie. This decreases the amount of water in
alkalosis.
St
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ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
168
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is used
excretion of electrolytes. ADH Section XI
urine. It does not affect the
ud
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u
in the treatment of
diabetes insipidus.
effect in
diuretics have an antidiuretic
THIAZIDES: The thiazide diabetes
nephrogenic HORMONES AND
y
diabetes insipidus. 7hey are effective in
supposed
is not known. They
are
HORMONE ANTAGONISTS
Ph
Ph
Ph
insipidus. The exact niechanism filtration and by producing
the rate of glomerular
ha
to act by decreasing urine.

produces a decrease in the volume of
negative sodium balance This
ar
ar
ar
antidiuretic effect are
drugs which have an
r
Other Drugs Other

:
carbamazepine.
ma
ma
ma
ma
chlorpropamide, clofibrate and
GENERAL CONSIDERATIONS
52.
c
c
The endocrine system consists of ductless glands. They
y
y
without
synthesise hormones and secrete them directly into circulation
the intervention of a duct.
Hormones: Homone (derived from the Greek word Hormona

special
which means to urge in') is defined as a substance secreted by
@pharm cells and transported to a site distant from its origin where
its action. A hormone can act on another endocrine gland or on
it produces
a
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tissue. It only alters the rate of natural function of them by producing
them.
stimulation or depression. But no new functions are endowed to
ud
ud
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They require a latent period
The hormones act in trace amounts.
before their effect is produced. They act only on particular sensitive
y
y
tissues.
Chemical nature of hormones : Homones generally

Ph
Ph
Ph
fall into
ha
the following chemical classes:

ar
ar
ar
1. Aminoacids and their derivatives e.g. adrenaline, noradrenaline
rm
and thyroxine.
Steroids e.g. adrenal cortical and gonadal hormones.
ma
ma
ma
2.
Polypeptides and proteins e.g. anterior pituitary hormones and
ac
3.
insulin.
cy
cy
cy
: Hormones are directly relcascd into
y
Regulation and release

venous blood. Their secretions are mostly regulated by the anterior
lobe of pituitary which secretes a variety of hormones e.g.
thyroid
hormone (TSH). These hormones act on target glands,
stimulating
stimulating them to release more hormones. For example, TSH of
St
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St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
St
St
5. Luteinizing hormone (LH)
anterior pituitary stimulates the thyroid gland. This stinmulation
releases thyroid hormone. The thyroid hommone in turm acts back on 6. Luteotrophic hormone (LTH)
ud
ud
ud
u
the pituitary and inhibits further release of TSH. This mechanisnm of The hormones of posterior pituitary are oxytucin and
mutual regulation existing between two glands is called feed back vasopressin.
y
system. GROWTH HORMONE (sOMATOTROPHIC HORMONE, STH): Growth
Ph
Ph
Ph
Amodified type of feed back system involves a blood hormone (GH) is synthesised in eosinophil cells of anterior pituitary.
ha
constituent e.g. glucose (but not a trophic hormone). The secretion Its structure varies considerably from one species to another. Human
of insulin fron pancreas is regulated by the concentration of glucose
ar
ar
ar
growth homone has a molecular weight of about 25,000. It has a
in blood. A increase in blood glucose level stinulates the release of
r
growth promoting effect and other metabolic effects required for

insulin. A decrease in blood glucose level produces an opposite
ma
ma
ma
ma
growth. t acts directly on tissues and not through a target endocrine
effect. .
gland. In this aspect, it is unique among the anterior pituitary
bormones.
c
c
Transport and metabolism: ln blood, the hormones circulate
y
y
partly bound to plasma proteins and partly in a free form. The protein Pharmacological actions
bound from is inactive, but can be released slowly producing 1.GH proniotes growth of every tissue and organ in tiie body.
prolonged effects. The free form is the active fom. This free form The effects are due to retention of nitrogen, water and minerals
is inactivated in the liver, the target endocrine glands or in the tissues but not fat. In children, it promotes linear bone gr>wth by
with
where they act. Inactivation occurs mostly by conjugation acting on the epiphyseal cartilage. This action on eriphyseal
sulfuric acid or glucuronic acid. Occasionally a hormone can be
. cartilage is not a direct one. It is through somatomedir fonmed
converted to a more active compound (e.g. testosterone to by its action on the liver.
St
St
St
St
dihydrotestosterone). The hommones are excreted through urine 2. GH stimulates protein mthesis. It also oduces rete ntion of
mostly in a conjugated for and to a little extent in a free fom. nitrogen, phosphate and potassium.
ud
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u
3. It mobilises fat from adipose tissue which is used for protein
|53. ANTERIOR PITUITARY HORMONES synthesis.
y
y
4. It produces hyperglycemia.
The pituitary gland is situated in a hollow
Ph
Ph
Ph
The pituitary gland: Regulation of secretion: Hypoglycemia, stress of any kind and
called the Sella turcica, at the base of the skull. It is composed of
ha
adenohypoplhysis (or vasopressin stimulate the release of GH. The reiease of GH is

two parts which are fused together. They are
ar
ar
ar
lobe). These two regulatcd by growth hormone-releasing factor (GH-RF) and growth
anterior lobe) and neurohypophysis (or posterior
rm
hormone release inhibiting horinone (GH-RIH) produced by the

parts have separate embryological origin and function.
ma
ma
ma
hypothalanmus.
cells
The anterior lobe of pituitary contains three types of
ac
namely chromophobe, eosinophil and basophil. The hormones of Disorders of GH production

cy
cy
cy
anterior lobe of pituitary are 1. Excessive production before puberty produces giyantism
:
y
(excessive growth). After fusion of epiphyseal plates of long

I. Growth hormone (GH)
bones, it produces acromegaly.
2. Thyrotrophic hormone (TSH) 2. Decreased productien produces dwarfism.
3. Adrenocorticotrophie homone (ACTH)
Therapeutic uses: Only hypopituitary dwarfism.
4. Follicle-stimulating hormone (FSH)
St
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y
y
Ph
Ph
Ph
h
y
y
Telegram - Study Pharmacy Regulation of secretion: Secretion of ACTH is regulated by
172 corticotrophin releasing factor (CRF) produced by the hypothalamus.
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Increase in circulating cortisol level depresses the release of ACTH.
THYROTROPHIC HORMONE(THYROID STIMULATING HORMONE,
ud
ud
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u
Decrease in cortisol level produces the opposite effect. This again is
TSH a negative feedback control.
glycoprotein (molecular weight about 28,000) formed in
It is a
y
Therapeutic uses: ACTH is used in the replacement of its
the basophil cells of acenohypophysis. TSH regulates the synthesis
endogenous deficiency. But it is conveneint to use adrenocortical
Ph
Ph
Ph
accumuiation
and release of thyroid hormone. It also stimulates the
steroids than ACTH. ACTH is occasionally used in the treatment of
ha
acids by the cells of the thyroid.

of iodine, glucose anci amino
thyriod gland. allergic and inflammatory disorders (which are favourably treated by
ar
the
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ar
Hypophysectomy produces atrophy of
of hypophysectomy. glucocorticoids). Aso ACTH is used in the treatment of infantile
r
Administration of TSH reverses the effect

spasm.
ma
ma
ma
ma
Regulation of secreti on: The release of TSH isregulated by a
con rol. TSH stimulates the release of thyroid GONADOTROPINS: Follicle-stinmulating hormone (FSH),
negative feedback
in turm acts on luteinizing hormone (LH) and luteotrophic homone (LTH) regulate
c
c
homone from the thyroid gland. Thyroid hormone
the functions of gonads. These hormones have been discussed
y
y
the pituitary and inhibiis further release of TSH.
separately in the next chapter.
is associated with
Disorders of TSH secretion: Thyrotoxicosis
excessive secretion of SH. produces
It deposition of adipose tissue
behind the eye leading
goitre.
to exophthalmus i.e., protrusion of the eyes.
Decreased production cf TSH leads to hypothyroidism manifesting
ldl
as
ae
54. GONADOTROPINS
f
The anterior pituitary hormones regulating ovarian and
testicular functions are known as gonadotropins. The anterior
St
St
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St
Therapeutic uses: TSH is not used for replacement of endogenous
pituitary hormones which have gonadotropic activity are
deficiency since it is less satisfactory than thyroid hormone.
follicle-stimulating hormone (FSH), luteinizing homone (LH) and
ud
ud
ud
u
ADRENOcORTICOTROPHIC HORMONE luteotrophic hormone (LTH). In addition to these homones, human
placenta produces chorionic gonadotrophin (HCG) and it has also been
y
y
(cORTICOTROPHIN, ACTH):
discussed below.
ACTH is a polyyeptide with a molecular weight of about 4,000.
Ph
Ph
Ph
FOLLICLE-STIMULATING HORMONE (FSH): FSH is glycoprotein a
Human ACTH contains 39 amino acids. It is rapidly destroyed
by
ha
it is ineffective orally. But it can be (molecular weight of about 29,000) secreted by basophilic staining
proteolytic enzymes. So
ar
ar
ar
intramuscular or intravenous injection. cells of the adenohypophysis. In the female, FSH is responsible for
administered by
rm
the stimulation of growth and secretion of oestrogen by the graffian

ma
ma
ma
Physiological and phamacological effects: After hypophysectomy, follicle. In the male, FSH stimulates testicular growth and
zona
the adrenal glands are veduced in size. This is due to atrophy of
ac
spermatogenesis.
fasciculeta of adrenal cortex. Consequently there is a decrease
in
cy
cy
cy
Administration of ACTH restores the The release of FSH is controlled by FSH releasing factor. This
adrenocortical secretion.
y
functions of zona fasciculata and increases adrenocortical secretion. factor is produced by the median eminence of the hypothalamus. The
In intact animals, ACTH induces a rapid increase in the blood
level secretion of FSH is also influenced by the level of oestrogen and
adrenal hypertrophy. progesterone.
of corticosteroids and iater produces narked
a
It also has a melanocyte-stimulating activity. It

is because, ACTH
has structural
a similarity to melanocyte-stimulating hormone (MSH).
St
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St
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ud
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y
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Ph
Ph
Ph
h
y
y
174
Telegram - StudyLUTEINIZING
Pharmacy HORMONE (LH), (INTERSTITIAL animals, it evokes follicular growth and induces ovulation in females.
St
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HCG stimulates the interstitial cells of the testes to secrete androgen.
CELL-STIMULATING HORMONE or ICSH):
Therapeutic uses:
LH has a structure similar to those of FSH and TSH. LH
is
ud
ud
ud
u
secretion is 1. For induction of ovulation, HCG can be used with FSH.
produced in nomal menstruating women, but the rate of
is high in the first half of the cycle. But 2. To promote the descent of testes in cryptorchisnm (failure of
not constant.. The secretion
y
testes to descend into scrotum).
there is peak in secretion during ovulation.
a
Ph
Ph
Ph
3. For delayed puberty in boys.
LH is responsible for the stimulation of the interstitial cells of
ha
testosterone. HUMAN PITUITARY GONDADOTROPIN (HPG): It is a crude

the testes (Leydig cells) which leads to the production of
ar
ar
ar
preparation obtained from hunman pituitary glands. It has strong
In the female, it stimulates:
FSH-like and a weak LH like activity. It stimulates fol icular growth
r
1. The interstitial cells in the ovary leading to the production of and production of oestrogen in amenorrlieic women.
ma
ma
ma
ma
some androgens. Uses.
2. The production of oestrogen by the follicle.
c
c
I. In patients with low urinary gonadotropins and oestrogens.
3. The production of oestrogen by the cells of the corpus luteum..
y
y
2. With HCG in the treatment of infertility.
LUTEOTROPHIC HORMONE
HUMAN MENOPAUSAL URINARY GONADOTROPIN (HMG)
(LTH, LACTOGENIC HORMONE, PROLACTIN):
It is present in the urine of menopausal women. Its actions are
LTH is secreted by acidophilic staining cells of the similar to HPG. When used with HCG in amenorrheic v'omen, it can
adenohypophysis. It is a polypeptide with a molecular weight of induce ovulation.
about 17,300. LTH stimulates milk production in mammals
(luteotropic action) in
and
rats.
CL
maintains the functions of corpus luteum ADRENOCORTICAL STEROIDS
55.
St
St
St
St
like
Secretion of LTH is stimulated by oestrogens, tranquilisers
dopamine. Its secretion is inhibited by ergot
ud
ud
ud
u
phenothiazines and The adrenal glands, one lying above each kidnev, consist of
derivatives. Bromoergocryptine, a semisynthetic ergot alkaloid two separate parts. They are inner medulla and outer cortex. The
receptors in
inhibits LTH secretion. It acts by stimulating dopamine medulla produces adrenaline and noradrenaline.
y
y
and abnormal lactation.
the pituitary. It suppresses normal The cortex has three distinct laryers of cells. They are
Ph
Ph
Ph
HUMAN CHORIONIC GONADOTROPIN (HC6): This homone I. An outer layer caliled Zona glomerulosa.
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growth hormone like and prolactin like activities. It is produced

has 2. A middle layer called Zona fasciculata.
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It is produced by trophoblast
in large amount throughout pregnancy. 3. An inmer layer called Zona reticularis.
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of the placenta shortly after implantation of the blastocyst. The level

of pregnancy, it The zona glomerulosa secretes mineralocorticoids which
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is maintained until parturition. At the termination
infuence water and mineral metabolism. The zona fasciculata
disappears slowly from circulation.
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secretes glucocorticoids which influence carbohydrate metabolism.

the corpus luteum and prolongs the
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Functions: HCG preserves The zone reticularis secretes androgenic (or sex) steroids
cycle. This is associated with an
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secretory phase of the menstrual

Chemistry and synthesis: The adrenocortical hor nones are
It is capable of inducing
increased urinary excretion of pregnanediol. steroids. Al these hormones have a basic structure, namely
in the endometrium even in the absence of
decidual reaction cyclopentanophenanthrene ring. All these homones are synthesised
(pseudopregnancy). When administred to imnmature
conception
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Ph
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from acetate via cholesterol. These hormones are not stored in the leads to water retention and edema. This may produce rise in blood
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as and when they are
adrenal cortex. They are secreted into blood pressure.
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formed.
adrenocortical steroids 5. Calcium metabolism : Glucocorticoids increase calcium
Regulation of secretion The secretion of excretion, Also, absorption of calcium from the gut is decreased. They
are regulated by varia tions in the blood level of ACTH. These
y
also stimulate breakdown of the protein nmatrix of bone. All these
any nervous influence. But the secretion of
secretions are not under effects lead to osteoporosis.
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Ph
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mineralocorticoid) is not influenced by ACTH. It is
aldosterone (a
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under the influence of angiotensin. 6. Hematological actions: Ghucocorticoids decrease the
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production of eosinophils and lymphocytes. But they stimulate
Hyporfunction of the
Disorders of adrenocortical function: erythropoiesis and the production of polynmorphonuclear leucocytés.
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occur due to
This may
adrenal cortex produces Addison 's disease.
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disease is characterised by loss of 7. Muscles: Muscles weakness seen in Addson's disease is
infection of the gland. Addison's
gustrointestinal disturbances and pigmentation of corrected by glucocorticoids.
weight, hypotension,
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the skin. 8. G.I. tract: Glucocorticoids.stimulate the secretion of pepsin
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syndrome
Hyperfunction produces Cushing's syndrome. This and hydrochloric acid of gastric juice.
deposition of fat on the face and back,
is characterised by
may occur 9. Anti-inflammatory effect: Glucocorticoids inhibit
hyperglycemia and hypertension. Primary aldosteronism
leading to an excessive inflammatory response caused by bacterial, chemical or
due to hyperfunctioning of zona glomerulosa
aldosterone secretion. The symptoms are muscle weakness and immunological factors. The anti- inflanmatory effect is due to a
deranged mineral metabolism. decreasein capillay pemeability and stabilisation of lysosome
membrane.
GLUCOCORTICOIDS: The glucocorticoids are hydrocortisone
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Hydrocortisone is the
(cortisol), cortisone und corticosterone. 10. Anti-allergic effect: The glucocorticoids suppress aliergic
important glucocorticoid secreted in man. reactions such as asthma. They also reduce the formation of
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antibodies and cause shrinkage of lymphatic tissue.
11. CNS Glucocorticoids have an effect on psyche. Large doses
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glucocorticoids promote
1. Carbohydrate me:abolism The :
can produce elevation of mood, euphoria and restlessnes.

glucose from non-carbohydrate
gluconeogenesis (fonnation of
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But utilisation of 12. Miscellaneous They have an uricosuric and non-specific
sources) and deposition of glycogen in the liver.
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antipyretic effects.
glucose is inhibited.
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the break down
Protein metabolism: Glucocorticoids increase Adverse reactions
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:
2.
gluconeogenesis.
support
of protein. The aminoacids so produced
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1. Cushing's syndrome characterised by rounding of face.
the mobilisation of
3. Fat metabolism : Glucocorticoids increase 2. Sodium retention and edema.
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On prolonged administration, they

fat from pheripheral fat depots. Muscular weakness due to potassium loss.
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3.
fat in the body. There is loss of fat from
produce a redistributicn of
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4. Gain in weight due to fluid retention and fat deposition.

extremities and it is deposited in the neck, face etc. 5. Glycosuria and aggravation of diabetes.
Hydrocortisone
4. Electrolyte and water metabolism: 6. Hypertension and congestive cardiac failure.
retention and potassium excretion. Sodium retention 7. Androgenic effects like hirsutism and amenorrhea.
increases sodium
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Ph
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178 179
Psychologicai effects
8. like euphoria and excitation. synthetic glucocorticoids are prednisone, prednisolone, trianicinolonc.
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fracture of bones. paramethasone, dexamethasone and betamethasone.
9. Osteoporosis and spontaneous
haemorrahage. The phamacological actions and toxicities of these conpounds
10. Peptic ulcer, perforation and
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are similar to those of natural glucocorticoids. But these compounds
infections.
11. Increased susceptibility to do not have a mineralocorticoid action.
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Preparations and dose : Advantages of synthetic glucocorticoids are
to 400 mg. daily.
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1. Cortisone acetate tablets-50 1.Effectiveness in smaller doses.
200 mg. daily by intramuscular
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2. Cortisone injection-50 to 2. Easy diffusion into the tissues.
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injection. 3. Possibility to prepare esters suitable for topical appiication and
mg. 4 times a day by mouth initially
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3. Hydrocortisone-10 to, 20 injection into tissues.

and then adjusted as required.
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topical Preparations and dose
to 2.5 per cent solution for
4. Hydrocortisone acetate-0.5 1. Prednisone tablet 10
to 100 mg. daily in divided doses.
or ophthalmic use.
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2. Prednisolone tablet 10 to 100 mg. daily in dividei doses.
Therapeutic uses :
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3. Methylpredinsolone tablet 10 to 80 mg. daily in div.ded doses.
insufficiency as in Addison's
1. Substitution therapy in adrenal 4. Triamcinolone tablet - 2 to 24 mg. daily in divided doses.
disease. 5. Paramethasone acetate tablet 2 to 4 mg. daily.
rheumatic
like rheumatoid arthritis and
2. Mesenchymal diseases
fever.
3. Anti-inflammatory
effect as in case of gout.
4. Allergic diseases like

asthma.
mae MINERALocORTICOIDS
The natural mineralocorticoids are aldosterone and
desoxycorticosterone. The action of these two compounds are almost
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and
5. Skin diseases like
exfoliative dermatitis, contract dermatitis similar. But aldosterone is thirty times more potent than
desoxycorticosterone. Fludrocortisone is a synthetic mineralo-
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psoriasis.
involving inflammatory and exudative corticoid. It is commonly used for salt-retaining effect.
6. Diseases of the eye
Pharmacological actions Both aldosterone and desoycorticos-
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phases.
like auto-immune haemolytic
anemia, terone induce reabsorption of sodium by the renal tubules. But they
7. Haemopoietic diseases
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thrombocytopenic purpura and agranulocytosis. increase urinary loss of potassium. They induce sodium reabsorption in
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lymplhoid leukemia and the sweat and salivary glands also.

8. Neoplastic diseases like myeloma,
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Hodgkin's disease. Excessive levels of aldosterone (as produced by tumours) leads
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colitis.
9. Gastrointestinal diseases like ulcerative to hypematremia, hypokalemia, increased plasma volme and
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viral hepatitis. hypertention. In case of aldosterone deficiency (as seen in addison's
10. Hepatic diseases like acute
disease), there is hyperkalemia, decrease in blood volme and
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SYNTHETIC GLUCOCORTICOIDSs collapse.

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(i.e., hydrocortisone, cortisone and
The natural glucocorticoids Uses: Only in the management of Addisons's disease.
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The most important of them

corticosterone) have undesirable effects. less
The synthetic glucocorticoids have Aldosterone antagonists: Amphenone B interferes with
are salt and water retention. anti-inflammatory effect. The
more aldosterone synthesis. But there are conpounds which conyete with
salt and water retaining effect and
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this type.
Progcsterone has a mild effect of Physiological actions: Androgen is formed in the foetal testes
aldosterone binding site s. antagonist and
is a potent aldosterone
But spironolctone (Aldactone) under the influence of maternal gonadotropin.. This causes descent of
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detail in chapter 49. the testes. Later, no androgen is fommed until puberty. At puberty,
it has been discussed i
the hypophysial cells stimulate the Leydig cells to produce androgen.
Adrenocortical antagonists
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adrenocortical steroids This leads to the development of testes and secondary sex characters.
AMPHENONE B It inhibits the synthesis of
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The adverse
has an antithyroid effect. In adult male, the effects of androgens are
including aldosterone. It also
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gastrointestinal disturbances, liver

1. Induction of spermatogenesis, growth of prostate and seminal
reactions are CNS depression,
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symptoms. vescicles.
damage and neurological
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It inhibits he synthesis
of hydrocortisone and 2. Changes in skin like appearance of pubic hair, axillary hair and
METYRAPONE
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synthesis of aldosterone. This beard hair.
corticosterone. It also inhibits the adrenocortical steroids
the synthesis of 3. Growth promoting effect on body tissues including penile and
leads to diuresis. Inlhioition of turn stimulates the
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ACTH. This in scrotal growth.
induces the liberation of 11-dehydrocortisone
desoxycorticosterone and
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production of 11- 4. Growth of larynx and thickening of vocal cord such that the
retention and nullifies the
(mineralocorticoids). This produces sodium voice becomes low pitched
reactions are dizziness and gastrointestinal
diuretic effect. Adverse 5. Skeletal growth and epiphyseal closure.
disturbances. 6. Psychological and behavioural changes.
in the pathway
AMINOGLUTETHIM:DE : It blocks the early steps
airenocortical steroids (blocks the conversion of Control of secretion :
The production of testosteone is controlled
of the synthesis of it inhibits the
synthesis of by the pituitary release of LH. This in tum is controlled by luteinzing
cholesterol to pregenolone).So steroid secretion
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in reducing hormone releasing factor (LHRF) produced in the hypothalamus.
adrenocortical steroids. It may be useful is a common
adrenocortical malignancy. Lethargy
in patients with Adverse reactions:
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side effect. 1.Enlargement of clitoris, deepening of voice, baldness, hirsutism,
ANDROGENS AND acne and masculinization in females.
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56. 2. Early closure of epiphysis and blockade of its growth:
ANABOLIC STEROIDS
Ph
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Ph
3. Suppression of spermatogenesis and degeneration of
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the testes is carried out

by cells seminiferous tubules produced at large doses.
The endocrin activity of
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occur in groups in 4. Retention of sodium and edema.
Leydig cells. They
known as interstitial cells or
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seminiferous tubules. The

ues between the
the connective tiss Preparatons and dose
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androgens. The most
hormones secreted ty these cells are known as 1. Testostrone propionate 5 to 25 mg. by intramuscular injection
Testosterone is also present in the
ac
important androgen is testosterone. dehydroepiandrosterone every I to 3 days

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Androstenidione and
ovaries and adrenals. small amounts.) They Testosterone phenylpropinonate 50 to 100 ng. by
2.
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in man (produced in
are the other androyens testes. intramuscular injection every 7 to 14 days.
are produced largely in
adrenals rather than in the
3. Testostrone cypionate - Dose as for phenylpropionate.
4. Testosterone enanthate - 200 mg. by intramusculiar injection
every 2 to 4 weaks.
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Ph
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182
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and 5 2. To promote growth in hypogonadal children and pituitary
25 to 50 mg. daily in males
Methyl testosterone tablet
-
5. dwarfs.
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to 20 mg. for females. 3. Carcinoma of the breast in females.
daily.
6. Mestcrolone tablet - 25 to 100 mg.
ANTI-ANDROGENS: These are compounds wlhich anta;:onise or
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Therapeutic uses: inhibit the actions of androgens. Cyproterone acetaie is an
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'cilmacteric'.
1. Hypogonadism, cryptorchism and male anti-androgen. It acts by inhibiting the action of androgens at the
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breast cancer and dysmenorrhea. target organs. Also it has progestational effect. It is used to decrease
2. Breast engorgement,
excessive sexual drive. Dose : 50 to 100 mg. per day by n1outh.
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3. As an anabolic steroid.
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ANABOLIC STEROIDs 57. ESTROGENS AND PROGESTINS
anabolic effect, it also has
Though testosterone has an Estrogens and progestins are hormmones produced mainly in the
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an
steroids were synthesised in
androgenic effect. The anabolic less ovary. The mass of the ovary contains ovarian follicles. The follicles
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and
with more anabolic effects
attempt to produce compounds are about 40,000 in number. They are formed during foctal li.e. Only
anabolic steroids can be classified as
androgenic effects. The about 400 of them develop into ova during adult life. The rest get
Nandrolone degenerated. But, all the follicles are lost at menopause. Cvulation
1. Derivatives of occurs due to the rupture of ovarian follicles. This is stimulated by
testosterone phenylpropionate
Nandrolone decanoate LH of anterior pituitary. After discharging the ovum, the rest of the
Oxymethalone follicles in the ovary form the Corpus luteum. Estrogens are produced
Derivatives of by the developing follicle. Progestins are produced by the corpus
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2. Oxandralon
methyltestosterone luteum.
Oxyimesterone
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a ESTROGENS: The estrogens are produced mainly in the ovary.
Pharmacological actions :
Small amounts are produced by the placenta, adrenals and te stes.
anabolic steroids promote protein
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The
1. Protein anabolism: in muscle mass and body Classification of estrogens:
anabolism. This manifests as increase
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weight. 1
Natural estrogens Estradiol
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glucocorticoids are
The catabolic effect of Estrone
2. Anticatabolic effect:
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balance is produced. Estriol
counteracted and a positive nitrogen
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decrease in bone
Miscelianeous: Progestational activity and Semisyntlhetic.estrogens Ethinyl estradiol
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3.
resorption which prevents osteeoporosis. Synthetic estrogens Stilbesterol
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Mestranol
Adverse reactions
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pregnancy. Hexoesterol
Virilization of foetus when given 1n
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1.
Chlorotrianesene
2. Cholestatic jaundice and liver damage.
3 Sodium and water retention on prolonged use. Actions
Therapeutie uses :
1. Growth and development of vagina, uterus, fallopian t ube and
. also secondary sex characters.
In chronic illness, io accelerate rebuilding of tissues.
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gland. Derivatives of 19-nor Norethisterone
Growth of ducts in the mamary
3.
2. testosterone Norethynodrel
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3. Growth of axillary
and pubic hair. Norgestrel
hip and
fat and accumulation around Lynesterol
4. Distribution of body fenmale body contour.
breasts. This produces typical
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endometrial lining. Physiological functions of progesterone
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5. Development of
like retention of sodium, nitrogen
and fluid Maturation and secretory changes of endometrium.
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1.
6. Metabolic changes
2. Development of alveolar system of breast.
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in tissues.
implantation of fertilised
3. Preparation of the endometrium for
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Adverse reactionss: ovum.

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anorexia.
1. Nausea, vomiting, diarrhoea and 4. Metabolic changes like increase in body
temperature.
dizziness
2. General malaise and Actions of synthetic progestins
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to edenma and breast
Sodium and vater retention leading
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engorgement. a) Progesterone derivatives
1. Production of a secretory endometrium and
maintenance of
4. Development of endometrial carcinoma.
pregnancy.
Therapeutic uses: 2. Antagonism of aldosterone induced sodium retention.
2.
1. To control menopausal
In atrophic vazinitis.
symptoms.
harm 3. No androgenic or estrogenic effects.
b) Others
di
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3. In postpartum breast
engorgement. 1. Decidual changes in the endometrial stroma.
menorrhagia. 2. No support of pregnancy.
Amenorrhea, dysmenorhea and
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4.
3. Inhibition of gonadotropins
in ovarian dwarfism.
5. Substitution therapy Minimal estrogenic, androgenic. or anabolic activity.
4.
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6. Aene and hirsutism Therapeutic uses of progestins
is the natural progestin. It is
secreted
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PROGESTINS: P1ogesterone and testes. 1. Treatment of threatened and habitual abortion.
placenta, adrenals
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lso synthesised by
by the ovary. It is 2. To relieve pre-menstrual tension.
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Classification of progestins : 3. Treatment of dysfunctional uterine bleeding.
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4. To induce menstruation in amenorrhea.

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Progestrone and its Progesterone
Hydroxy progesterone 5. As oral contraceptives.
derivatives
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caproate
AND
58. ORAL CONTRACEPTIVES
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Medroxy progesterone
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acetate OVULATION INDUCING DRUGS

Chlormadinone acetate
Ethisterone Contraceptives are drugs which prevent conception. Since they
Derivatives of
control fertility, they are also called as antifertility agents.
L.
estosterone Dimethisterone
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2. Sequential method: Estrogen alone is given from the Sth to 20th
isthe key
Physiology of human reproduction: Ovulation day. From the 21st to 25th day, estrogen progestin combin:ition is
the 14th (+2
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event in human reproductive cycle. It usually occurs on
the graffian follicles mature given.
day) of a 28 day cyclc. During this cycle,
pituitary. Ovulation In combination method, FSH rise and LH peak is supressed.
under the influence of FSH released from anterior 1.
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occurs wlhen the rupture of the follicle is stimulated by LH released So follicular growth is not initiated. This prevents ovlaltion.
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from anterjor pituitary. A peak of LH coincides with ovulation. 2. In sequential. nethod, the estrogen suppresses FSH se cretion
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fertilised by the but stimulates LH secretion. This unusual rise f LH

The ovum enters the fallopian tube and gets
suppresses the. early FSH rise. So growth of tollicle is not
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ovum gets converted into blastocyst. This
sperm. The fertilised
initiated and ovulation is prevented.
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by 21st to 23rd day of

reaches the uterine cavity and gets implanted
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completed by 35th day. Pharmacological actions
the cycle. The implantation is
Control of fertility by drugs: Drugs can control fertility by the 1. Endometrial changes: These changes vary with the prepa ations.
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following mechanisims With sequential agents, there is no variation fronm normal. But
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i)
1. By inhibiting spermatogenesis in males. during the last 5 days, progestatianal effect on the ghndular
2. By inhibiting ovulation in females. tissues is seen.
to inhibit sperm
3. By modifying the cervical mucus so as i) With combined agents, there is stromal deciduation towards the
penetration. end of the cycle.
4. By slowing the rate of egg transport.
5. By preventing the maturation of ovum. harm 2. Ovarian changes: Both combined and sequential agents ciepress
ovarian function. There is minimum follicular develo»ment.
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6. By interfering with implantation. Morphological changes seen in evulating women is absent.
there is high level of
Oral contraceptives : During pregnancy, 3. Miscellancous efects:
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prevent ovulation. So ovulation can be
ovarian hormones and they i) Hyperglycemia, glycosuria and hypertension.
administration of either estrogen or progesterone.
prevented by the
ii) Increase in thyroxine binding globulin. This increases protein
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prevented. The oral
When ovulation is prevented, pregnancy can be bound iodine (PBI) of plasnia.
contraceptives contain estrogens or progestins (or both).
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ii) increase in transcortin (cortisol binding protein).
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Types of preparations:
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are Adverse reactions:
The types of preparations of oral contraceptives
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1. Combination of estrogens and progéstins. 1. Anorexia, nausea and vomiting due to estrogen content.
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by estrogen-progestin Fluid retention, breast engorgement and weight gain.
2. Sequential use of estrogens followed 2.
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combination. 3. Breakthrough bleeding and mid-cycle spotting.

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3. Progestins alone. 4. Hypertension.
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Estrogen-progestin combination 5. Carcinogencity.
Method of administration Progentins alone as contraceptüves Smail doses of preestins

estrogen-progestin combination can be administered alone can act as contraceptives. The progestins used for
1. Combination method: toThe25th day of a 28 day cycle. this purpose are chlormadinone acetate and levonorgestrel.
administrated from the 5th
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fertilised
oestrogen antagonist. It interferes with implantation of
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less reliable. These remains nomal.
Progestins alore as contraceptives are ovum. Menstural cycle
estrogen is undesirable. menstural cycle and ovarian
drugs are suitable in yatients for whom Adverse effects: nausea, lengthening of
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orally at a
CHLORMADINONE ACETATE: This drug when given hypertrophy.
contraceptive. It does not non-steroidal compound obtained from cotton
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dose of 0.5 mg. daily acts as an effective GOSSYPOL: It is a
endometrium and cervical orally. It inhibits
suppress lactation. It acts by making the seed. It is a male contraceptive effective
Ph
Ph
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spenm penetrability. It does does not produce genetic damage or
mucus thick and tou;gh. This reduces spernatogenesis in men. It
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effects nausea, headache and

not suppress LH pezik. Adverse hormonal disturbance.
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loss of libido
breakthrough bleeding. Adverse effects: gastrointestinal disturbances, fatigue,
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It is
LEVONORGESTRE. a 19-nortestosterone compound.
It is and hypokalemic paralysis.
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micrograms continuously
effective when given at a dose of 50 to 75 Ovaulation inducing drugs
It by 1) reducing spernm penetrability 2) inhibiting
by mouth. acts
CLOMIPHENE CITRATE: It is chemically related to the estrogen,
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bleeding intervals.
luteal function. It produces iregular and short It is effective
chlorotrianesene. It is effective on oral administration.
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injectable progestational ovulation in women with ovulatory failure.
Injectable contraceptives: The in inducing
progesterone acetate (DMPA, depot of estrogen
preparations are depot-medroxy Mechanism of action: It blocks the inhibitory influence
They are highly
Provera) and norethisterone enanthate (NET-EN). on the hypothalamus. This increases the production of gonadotropins
reversible effects.
effective, long acting and produce (FSH and LH) and thus induces ovulation.
It is the long enlargement and cyst
ACETATE) Adverse reactions : Hot flushes, ovarian
:
DMPA (DEPOT MEDROXY PROGESTERONE
progesteron acetate. "It blurred vision.
acting intramuscular preparation of medroxy formation, restlessness and
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pituitary LH. This leads to suppression of ovulation. Treatment of infertility due to anovulation.
acts by inhibiting Therapeutic uses :
fallopian tubes and cervical
It also has an effect on endometrium,
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lactation. Adverse effects are disruption Dose:50 mg. daily for 5 days.
mucus. It does not suppress
cycle, bleeding irregularities and prolonged It induces
of normal menstrual CYCLOFENIL: It has a structure similar to clomiphene.
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y
amenorrhoea. for 5 to 10 days by
ovulation at a dose of 500 to 800 mg. per day
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peripheral antiestrogenic effects.
Dose: 150 mg by J.M. injection every 90 days. mouth. It does not have
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by a similar
NET-EN (NORETHIS TERONE ENANTHATE): It acts THYROID AND ANTITHYROID DRUGS
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short duration of action. It causes 59.
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mechanism as DMPA. It has a

disturbances similar to DMPA. Dose: 200 mg. in an oily
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menstrual
6 months and every THYROID HORMONES
suspension by I.M. injection every 60 days for
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thyroxine and tri

60 to 84 days later. The thyroid gland synthesises two hornones:
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given characterstics of thyroid hormmones is their
MEFEPRISTONE : It is a progesterone antagonist. When iodothyronine. The striking
y
pregnancy (within 10 days of missed high concentration of iodine. Both these compounds can be
orally, it terminates very early
bleeding. considered as derivatives of tyrosine.
period). Adverse ef ects: nausea, fatigue and heavy
was This occurs in four stages:
CENTCHROMAN: It is a nonsteroidal oral contraceptive. It Synthesis of thyroid hormone :
Lucknow. It is an
developed by Central Drug Research Institute,
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190
Telegram - Study lodide
Pharmacy
1. removedis from the circulating plasma and concentrated Effect of triodothyronine and thyroxine:
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in thyroid gland. The overall effects of both these homones is similur. But the
enzyme
2. lodide is oxidised to elemental iodine by the action of triiodothyronine is quick. Also it is effective in small doses.
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peroxidase. But thyroxine has a long duration of action.
3. lodine combines with tyrosine to form monoiodotyrosine
(MIT)
and diiodotyrosine (DIT). Disorders of thyroid function
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thyroxine
4. Two molecules of DIT couple to fom Hypothyroidism.
Ph
Ph
Ph
(tetraiodothyronine). One molecule each of DIT and MIT
ha
1. Cretinism: This is due to intra-uterine thyroid deficiency. It

couple to form triiodothyronine.
manifests as mental retardation.
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in the
Storage and release : The thyroid hormones are stored
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2. Myxedema: This is due to thyroid deficiency appering after

released due to
thyroid gland as thyroglobulin. These hormones are
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birth. This produces retardation of physical growth.
(TSH) on thyrogolbulin.
the action of thyroid stimulating hormone
per day. 3. Endemic goitre: This type of hypothyroidism occurs due to
About 80 micrograns of thyroid homones are secreted deficiency of iodine in food. So there is decreased production of
c
c
These honnones circulate in blood partly in a protein
bound fom and
thyroid hormones. This leads to increased production of "TSH. The
y
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iodine (PBI) represents the iodide
partly in a free form. Protein bound stiulant effect of TSH on the thyroid glands leads to its hy pertrophy.
triodothyronine. Increase in PBI reflects an increased
in thyroxine and
function of the thyroid gland. Hyperthyroidism
is Exophthalamic goitre (Grave's disease): This is due to excess of
Regulation of secretion: The secretion of thyróid honmones TSH production. This occurs as protrusion of the ey:s due to
controlled by thyroid stimulating hormone (TSH) secreted by anterior
is depressed. deposition of fat behind the orbits.
pituitary. In the absence of TSH, the thyroid function
thyroid homones increases.
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But in presence of TSH, the secretion of Preparations and dose:
on TSH, please refer chapter 52. (Anterior
For more infomation 1. Thyroid L.P-30 to 240 mg. daily.
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pituitary homones). 2. Thyroxine sodium LP.-0.05 to 0.5 mg. daily.
Physiological and pharmacological actions: Thyroid 3. Thyroglobulin-100 to 150 mg. daily.
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metabolism. These 4. Liothyronine sodium-0.005 to 0.1 mg. daily.
hormones produce major effects on growth and
are:
Ph
Ph
Ph
effects
most
Therapeutic uses
ha
1. Increase. in oxygen co1nsumption and heat production in 1. In hypothyroid states like cretinism and myxedema
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tissues. 2. In the treatment of non-toxic goitres.
Increase in basal metabolic rate (BMR).
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2. 3. In the treatment of obesity.

Intra-uterine and extra-uterine growth as also tissue
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3. 4. To lower cholesterol content of blood.
differentiation.
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4. Anabolic effects like promotion of growth and protein ANTITHYROID DRUGS

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synthesis.
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5. Increase in the absorption and utilisation of glucose. Antithyroid drugs are those which are used in the tretment of
6. Increase in the rate of cholesterol syntlhesis in the liver.
hyperthyroidism. These drugs control the over production cf thyroid
homones.
7. Myelination of central nervous system.
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Ph
Ph
Ph
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192 193
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IONIC INHIBITORS :
Classification of drugs :
Mechanism of action: These drugs competetively inhibit the
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Propylthiouracil
1. Thiourea derivatives trapping of iodide by the thyroid gland This effect can be countered
Methiamazole
by an excess of iodide ions.
Carbimazole
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Preparations and dose: Potassium perchlorate tablets 600 to 800
Potassium thiocyanate
Ph
Ph
Ph
2. Ionic inhibitors mg. initially followed by 200 to 400 mg. for maintenance.
Potassium perchlorate
ha
Sodium iodide Iodides
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3. Iodides
Potassium iodide Mechanism of action: The! dides act by decreasing the response
r
Lugol's iodine of thyroid gland to TSH. Iodides shut off the release of preformed
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1311 thyroid hormones. This effect is called as 'thyroid constipation.'
Radioactive iodine
4. Actions
c
c
THIOUREADERIVATIVES: 1.The secretion of thyroid hormones is decreased.
y
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compounds act by
Mechanism of action: The thiourea 2. There is a fall in basal metabolic rate (BMR).
inhibition
iodide to iodine (due to 3. The gland becomes less vascular and fim.
1. Inhibiting the oxidation of
of peroxidase). residues of
4. The acinar cells become small in size and colloid content
2. Inhibiting the
incorporation of iodine into tyrosyl increases.
thyroglobulin Adverse reactions: lodism characterised by skin rashes,
are well lacrimation and increased salivary secretion.
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These drugs
Absorption, fate and excretion: administration. Only a
30) minutes after oral Proparations and dose
absorbed within 20 to unchanged.
The rest is excreted
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fraction is metabolised in the body. milk.
1. Sodium iodide 6 to 10 mg. daily.
and also are secreted in
They cross placental bar:ier 2. Potassium iodide 6 to 10 mg. daily.
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3. Lugol's iodine
Adverse reactions: (containing 5% iodine
Ph
Ph
Ph
arthralgia.
1. Drug fever, skin 1ashes and and 10% potassium
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2. Leucopenia,
agra ulocytosis and thrombocytopenia. ic lide) 0.3 mi. daily.
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3. Hypothyroidism and
goitre. Use: In the preoperative preparation of the patient for thyroid
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surgery. The gland becomes fim and less vascular. So it is easy to

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operate.
in divided doses.
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1. Propylthiouracil tablets 300 to 600 mg. daily RADIOACTIVE IODINE: 1 is the isotope of iodine that is
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cy
Methimazole and 5 to 20 mg. daily. commonly used. It has a half-life of 8 days. Like normal iodine,
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2. Carbimazole tablets f
is trapped in the thyroid gland. It is incorporated. into thyroid
Therapeutic uses hormones and stored in the colloid. It emits beta and gamma rays.
1. Treatment of hyperthyroidism. The beta rays destroy the overactive thyroid tissue and inhibit their
surgery. replication.
for thyroid
2. In the preparatio 1 of patients
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Ph
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194
Telegram - Study Pharmacy Disorders of parathyroid function.
I.
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Advantages Hyperparathyroidism produces osteitis fibros. In this
hospitalisation. Also it is
requires no condition, there is decalcification of bone leadir g to loss of
Radioactive iodine surgery. strength and fibrous appearance.
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cannot undergo
useful in patients who a dose of 5 to
10
Solution of Na 'I at 2. Hypoparathyroidism produces hypocalcemia wh ch leads to
Preparation and dose tetany.
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microcuries by mouth. count,
decrease in leucocyte CALCITIONIN: Calcitionin is a polypeptide containing 32 amino
Febrile reactions,
Ph
Ph
Ph
hypothyroidism.
Adverse reactions
:
thyroid and acids. It is secreted by 1) the C cells of thyroid in mar mals 2) the
damage to foetal
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neoplastic changes in the thyroid, cells of ultimobranchial bodies in lower vertebrates.
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AND
PARATHYROID HORMONE Actions Calcitionin lowers the plasma levc! of calcium This effect
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60. is produced by blocking PTH induced bone resorption. It also

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CALCITIONIN increases the excretion of calcium in urine. Calcitionin is secreted in
Parathyroid response to increase in calcium level of plasma.
(PARATHORMONE, PTH):
c
c
PARATHYROID HORMONE the parathyroid glands. It Uses Hypercalcemic state associated with hyperparithyroidism,
by the chief cells of
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is secreted the plasma, it is
hormone amino acids. In vitamin D intoxication and Paget's disease.
containing 84 fraction and
is a polypeptide They are an
inactive larger
two fractions.
separated into 61. INSULIN AND GLUCAGON
fraction.
an active smaller calciun of plasma
and
PTH increases the ionic the following
Actions: produced by INSULIN: Insulin is the hormone secreted in the pancreas by the beta
extracellular fluid. This effect is
cells of islets of Langerhans. Insulin lowers blood sugar level.
mechanisms: There is Diabetes nmellitus occurs in the absence of insulin secreticn.
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calcium resent in the bone.
1. Mobilisation of from bone into the Chemistry: Insulin is a polypeptide and it has a moleciular weight
and phosphorus
resorption of calcium
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extracellular fluid of about 6000. It contains 51 amino acids arranged in two chains
the renal tubule. viz. A chain containing 21 amino acids and B chain containing 30
Increased reabsorption of calcium by
2. from the gut. amino acids. These two chains are linked by disulfide bridges.
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absorption of calcium
3. Increased PTH is not under
The secretion of
Ph
Ph
Ph
secretion: Synthesis, storage and release: In the pancreas, insulin is
Regulation of calcium level
fall in plasma
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hormmonal influence. A calcium level

synthesised by beta cells of islets of Langerhans. Initially it is
neurogeinc or
PTH. A rise in plasma synthesised as a single chain polypetide called proinsulin. Proinsulin
ar
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stimulates the secretion of is 1/8th as active as insulin. It is later cleaved into A anl B chains
PTH.
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inhibits the secretion of enzymes. So it

hydrolysed by proteolytic which are connected. by disulfide bridges.
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Administration: PTH is subcutaneous injection.
is administered by Insulin is stored. in the granules of beta cells. It is 1eleased in
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orally. It
is ineffective and anaphylactic
reaction.
response to a rise in blood glucose level. The release of insulin i
Only hypercalcemia
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Adverse reactions: controlled by the concentration of glucose in blood.
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Therapeutic uses: parathyroid deficiency. Transport, fate and excretion: Insulin circulates ir plasma
hypocalcenmia due to
1. Control of pseudo-hypoparathyroidism. partly in a protein bound form and partly in a free form. it is taken
2. In the diagnosis of
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Ph
Ph
Ph
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taken
muscle. No insulin is
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up mostly by the
liver, kidney and skeletal 4. It also promotes the conversion of glucose to fat in adipose
and brain.
up by red blood cells tissue.
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testes and
tissues like liver, kiduey,
Insulin is de:zraded by glutathione-insulin transhydrogenase Administration: Insulin is destroyed by gastrointestinal enzymes.
by
placenta. It is metabolised the two chains. The
individual So it is ineffective on oral administration. It is given by parenteral
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enzyme separates
(unsulinase). This route like subcutaneous injection.
proteolytic enzymes.
Ph
Ph
Ph
chains are degraded by
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Adverse reactions:
Action of insulin: two enzymes:
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insulin increases the activity of 1. Hypogycemia which may lead to coma and convulsions.
a) Liver: In the liver,
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increases glucose uptake. 2. Allergy characterised by itching, redness and swelling at the
!. Gucokinase wlich
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glycogen deposition. site of injection.
2. Glycogen
syathetase which increases
enzymes: 3. Lipodystrophy due to atrophy of subcutaneous tissue at the site
It decreases the activity
of two other
c
c
inhibition of which decreases of frequent injection.
. Phosphoryla se and cyclic
AMP,
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glycogen). 4. Presbiopia due to alteration in the physical properties of lens.
glycogenolysis (breakdown of
gluconeogenesis (fresh synthesis of 5. Obesity leading to increase in body weight.
concerned with
2. Enzymes sources).
non-carbohydrate
glucose frorn Therapeutic uses:
As a result, he
of glucose is deceased.
deposited as glyccgen.
breakdown of liver glycogen
But, glucose is
and fresh synthesis
mobilised to the liver and
permeability, uptake and

1.
3.
Treatment of diabetes mellitus.
ndf
Treatment of diabetes due to pancreatic diseases.
In
schizophernia where insulin induced coma is useful (insulin
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Insulin increases the
b) Adipose tissue: cell. Increased glucose
utilisation leads shock therapy).
utilisation of glucose in the fat glycerophosphate and fatty acid. 4. For improving appetite and increasing body weight.
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glycerol, alpha
to the synthesis of form triglyceride (storage fom
combine to
The later two conpounds lipogenesis (synthesis of fat). But it Preparations of insulin: Insulin is well soluble. It is rapidly
induces
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of fat). Thus insulin absorbed and rapidly eliminated. So it has a short duration action.
lipoiysis (break-down of fat).
prevents The addition of substances like protamine or zinc decreases the
Ph
Ph
Ph
Insulin stimulates the uptake
of glucose by the
solubility of insulin. These preparations are slowly absorbed and
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c) Skeletal muscle: into the cell and its

the entry of aminoacid
muscle cell. It stimulates it prevents the hence have a long duration of action. The common preparations
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(anabolic effect). But
incorporation int» protein of insulin can be classified as:
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(anti- lipolytic effect).

breakdowm of fat in the muscles
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blood
Mechanism of hypoglycemic action: Insulin lowers Short acting Plain insulin
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mechanisms: Insulin zinc suspension (semilente.)

glucose level by the following
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prevents glycogen Globin zinc insulin
glycogen synthesis but Intermediate acting.
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1. Insulin promotes
Isophane insulin
breakdown in the liver.
gluconeogenesis. Insulin zine suspension(lente)
2. It also prevents in the skeletal
promotes
It the uptake and utilisation of glucose Long acting Protamine zinc insulin
3.
Insulin zinc suspension (ultralente)
muscles. eu
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Ph
Ph
Ph
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198
Administration: It is destroyed by proteolytic enymes of
siable
purer fom of neutral and
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gastrointestinal tract. . So it is administered by parenteral route.
Newer insulins: These are they are less antigenic and
preparations free from proinsulin. Also insulin. But these Preparation and dose: Glucagon hydrochloride-1 mg. by
allergic to beef
so can be used in patients
y
preparations are: subeutaneous or intravenous injection.
preparations are expensive. The
Ph
Ph
Ph
insulin in clear, neutral solution. Therapeutic uses: It is mainly used in the treatment of insulin
1. Nuso: It is bovine
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induced hypoglycemia
monocompetent porcine
It is a clear, neutral solution of
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2. Actrapid:
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insulin. 62. ORAL ANTIDIABETIc DRUGS

bovine insulin.
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3.Rapitard: cloudy mixture of actrapid and
It is a
It is non-
highly purified porcine insulin. Insulin is ineffective orally and so it has to be injec ted. But
4. Monotard: It contains
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the oral antidiabetic drugs (oral hypoglycemic agents) lovwer blood
antigenic. glucose level on oral administration.
y
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E. coli cultures by
It is obtained from
5. Humiln insulin
:
recombinant DNA techniques. Classification of «irugs:

The following are the newer
Newer insulin deiivery devices: 1Sulfonylureas
have the advantages of easy and
insulin delivery devices. They a) First generation Tolbutamide
accurate administration.
1. Insulin syringes harmn b) Second generation
Chlorpropamide
Glibenclamide
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2. Jet injectors Glipizide
Glyclazide
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3. Pen devices
Glymepiride
4. Insulin pumps.
2. Biguanides Phenformin
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S. Implantable pumps
Metformin
External artificial pancreas
Ph
Ph
Ph
6.
SULFONYLUREAS: These compounds are chemically related to
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containing 29 amino acids and has

GLUCAGON: It is a polypeptide sulfonamides: They have the following basic structure:
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the alpha cells of the
3485. It is secreted by
a molecular weight of
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Ri SO2 NH -
CO NH - R2
islets of Langerhans
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Actions: amino acid

A fall in blood glucose
level and a rise in plasma 1. These drugs lower blood sugar level on oral and parenteral
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1.
glucagon. administration.
level stimulates the release of
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a result, there is a rise in

blood
It produces glycogenolysis. As 2. They lower blood sugar level in some of the diabetic and in
2.
glucose level. all non-diabetic individuals.
presence of glucocorticoids They are effective only in presence of functional pancreas.
3. It stinulates gluconeogenesis. The 3.
is necessary for this effecl. 4. They produce increase in body weight like insulin.
in peripheral tissues.
4. it also stimulates lipolysis
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y
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Ph
Ph
Ph
h
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following 4. They increase fibrinolytic activity of plasma.
Sulfonylureas act by the
Mechanism of action: Mechanism of action:
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mechanisns: The presence of exogenous or endogenous insulin is necessary
release of insulin from the beta
1.
1. Stimulation of th: synthesis and for the action of biguanides. But insulin release from pancreas
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cells of islets of Langerhans. is not stimulated.
2. Increase in the rumber
of beta cells. Peripheral utilisation of glucose is stimulated.
Ph
Ph
Ph
2.
glycogenolysis and gluconeogenesis.
Absorption of glucose form intestine is inhibited.
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3. Inhibition of 3.
insulin degradation.
4. Decrease in the rate of
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Absorption, fate and excretion: Biguanides are wcll absorbed
Sulfonylureas are rapidly
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from gastrointestinal tract. Maximum activity occurs in 4 hours. They

They are partly bound to plasma
tract.
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absorbed from gastrointestinal urine. are eliminated through urine within 24 hours.
liver and excreted in
proteins. They are metabolised in
Adverse reactions:
c
c
Adverse reactions potentiated by phenylbutazone
1.Unpleasant, bitter or metallic taste.
y
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1. Hypoglycemia ind this effect is 2. Abdominal discomfort, anorexia and nausea.
and salicylates. 3. Lethargy and muscle weakness.
2. Allergic reactio1s
leading to skin rashes.
thrombocytopenia. 4. Decrease in body weight
like leucopenia and
df
3. Bone marrow changes
4. Hypothyroidism and
goitre.
sedative-hypnotics. ma Preparations and dose:
1. Phenfomin tablets-25 to 150 mg. daily,
5. Potentiation of barbiturates and other
2. Metformin tablets-500 to 2000 mg. daily.
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. Tolbutamide tablets-0.5 to lg. daily. Therapeutic uses:
tablets-250 to 500 mg. daiiy
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1. Obese mild diabetics.
2. Chlorpropamid»
diabetes, 2. Non-diabetic obese patients
of maturity onset
Therapeutic uses: In the treatmentinsipidus. 3. In patients allergic to sulfonylureas.
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diabetes
insulin tesistant diabetes and
following general chemical a Glucosidase inhibitors
Ph
Ph
Ph
BIGUANIDES: Biguanides have the
It is an a-glucosidase inhibitor. By reversibly binding
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ACARBOSE:
structure: it. prevents the absorption of glucose. This effect
with this enzyme,
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NH NH occurs in the brush border of small intenstine. It can be used with
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RI N -C- NH-C-NH2 insulin, sulfonylureas or biguanides.

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MEGLITOL: It is another a-glucosidase inhibitor. It acts by similar
ac
R2
mechanism as acarbose.
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in a diabetic individual
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Biguanides lower blood sugar level only

1.
individual.
but not in a normal
potentiate the hypoglycemic action.. of insulin and
2. They
sulfonylureas.
in adipose tissue.
3. They inhibit lipogenesis
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Ph
Ph
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Classification of digestants:
Section XII
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1. Enzymes Papsii
Rennin
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Pancreatin
Ph
Ph
Ph
DRUGS ACTING ON THE 2. Choleretics Bile salts
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Bile acids
GASTROINTESTINAL TRACT
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Caerulein
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Florantyrone
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1. PEPSIN: It is a proteolytic enzyme secreted by the stomach. It
c
c
is effective in case of defective secretion of pepsin. But such a
condition does not usually occur.
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63. APPETIZERS, DIGESTANTS, 2. RENNIN: It is a milk curdling enzyme obtained from glandular
CARMINATIVES, APPETITE layer of calf stomach. It has sinilar use as pepsin.
SUPPRESSANTS AND SIALOGOGUES
Appetizers (Stomachics): These are drugs used for the

ae 3. PANCREATIN: It contains the enzymes amylase, trypsin and
lipase It is prepared from fresh hog's pancreas. It is used for
replacement in pancreatic deficiency.
4.CHOLERETICS: Choleretics are drugs which increase the output
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The appetizers induce
treatment of anorexia (loss of appetite). of bile by the liver. Bile is necessary for the emulsiication and
secretion. The agents used in the
appetite by increasing gastric absorption of fat and fat soluble vitamins. Bile salts increase the flow
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treatment of anorexia are: and concentration of bile. The preparations used for this purpose are:
taste buds and this produces i) Ox bile extract tablet-300 mg. by mouth.
1.Bitters: These agents stimulate the
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Chirata, quassia, aristolochia and i) Dehydrocholic acid tablet-500mg. thrice daily.
reflex secretion of gastric juice.
Ph
Ph
Ph
gentian are the commonly used
bitters. ii) Sodium dehydrocholate injection(25% solution)-3 to 5 ml. by
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secretion by a direct action and intravenous injection.

2.Alcohol: Alcohol induces gastric
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Caerulein, a polypeptide and florantyrone a syntheti: compound
also by reflex stimulation of taste buds.
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also have choleretic action.

miscellaneous compounds
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3.Miscellaneóus compounds: The Carminatives: These are drugs which help in the expulsion of gases
which induce appetite are:
ac
producing
from the stomach and intestine. They are used in the treatment of
gastric secretion by
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i) Ins n which increases flatulence and also in colics.
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hypoglycemia.
ii) Histamine which produces direct
stimulationof gastric glands.
therapeutic application.
But these drugs have no
enhance the process of
Digestants: Digestants are drugs which
digestion.
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Ph
Ph
Ph
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Telegram - Study Pharmacy204 Bulk anorexiants:
205
Methylcellulose is a non-digestible material. It
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absorbs water from the stomach and swells up. This produces a
Classification of carminatives: feeling of fullness.
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1. Condiments and spices Cardamom
Ginger Miscellaneous drugs: Biguanides. phenteramine resin,
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Asafoetida phenindimetrazine and mazindol have an anorexiant effect. The
Coriander anorexiant effect of biguanides is marked. They produce a
Ph
Ph
Ph
Tincture cardamom_ Co. significant weight loss.
Tinctures of volatile oils
ha
Z.
Tincture zingiberis
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Dimethylpolysiloxane Sialogogues: Sialogogues are drugs which increase salivary
Miscellaneous
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3. secretion. The secretion of saliva and gastric juice occur by a comnon

carminatives except
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Mechanism of action: Most of the mechanism. So stomachics can also act as sialogogues. Sialogogues
(methyl-polysiloxane) are aromatic volatile oils. These compounds
are used in dry mouth caused by fevér and also to control side effects
increased gastrointestinal
produce mild irritation which leads to of antiparkinsonism drugs. Ganglionic stimulants like nicotine and
c
c
This helps in the expulsion of
motility and relaxation of sphincters. cholinergic drugs like pilocarpine and physostigmine are capable of
y
y
gases. inducing salivary secretion. Flavoured sweets and lemon drops also
a
Dimethylpolysiloxane (a silicone derivative) acts as increase salivary flow.
escape of gases from the
defoaming agent. This action produces
Anti-sialogogues: These are drugs which reduce salivary secretion.
gastrointestinal tract.
Drugs which decrease salivary secretion are
Anorexiants are drugs
Appetite suppressants (Anorexiants): treatment of 1 Anticholinergics like atropine.
which suppress appet:te. These drugs are used for the
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2. Local astringents like alum and tannic acid.
obesity.
3. Ganglion blockers like hexamethonium and pentolinium.
Classification of anorexiants:
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4. Antihistamines like promethazine and chlorcyclizine.
1. Amphetamin>s Dextroamphetamine
Fenfluramine
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Methylcellulose 64. EMETICS, ANTI-EMETICS AND
Ph
Ph
Ph
Bulk anorexiants
ANTIDIARRHOEALSs
ha
Miscellaneous compoundsS Phenteramine resin

Phenindimetrazin
ar
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ar
Mazindol Mechanism of vomiting: Vomiting often starts with nausea in
rm
Biguanides which case. there is increased secretion of saliva, bronchial fluid, and
ma
ma
ma
sweat. Vomiting is a complicated, co-ordinated act which is
ac
AMPHETAMINES: Dextroamphetamine produces anorexiant effect controlled by vomiting centre (present in the reticular formation of
cy
cy
cy
It produces CNS stimulation and
due to stimulation of hypothalamus. the medulla oblangata). Voniting centre is sensitised by another
effects. The dose of
y
tolerance. But fenfi uramine has no central centre in the medulla called the chemoreceptor trigger zone (CTZ).
dextroamphetamine is 2.5 to 5 mg. and that of fenfluramine is 20 to CTZ has neuronal connections with the vomiting centre. Stimulation
100 mg. daily. of CTZ cannot produce vomiting in the absence of vomiting centre.
But direct stimulation of vomiting centre can induce vomiting.
St
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ud
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y
y
Ph
Ph
Ph
h
y
y
Emetics: Emetics drugs which produce vomiting.
arc Classification of anti-emetics:
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1. Anticholinergics Hyoscine
Classification of emetics: Dicyclomine
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ud
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Stimulants of CTZ Apomorphine Cyclizine
1. Antihistamines
Morphine Meclozine
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Hydergine
3. Neuroleptics Chlorpromazine
Ph
Ph
Ph
2. Iritants of Mustard Prochlorperazin:
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gastrointestinal mucosa Copper sulphate

4. Prokinetics Metoclopramide
Sodium chloride
ar
ar
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Domperidone
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3. Both by stimulation of CTZ Digitalis Cisapride

ma
ma
ma
ma
and irritation of Emetine
5 HT3 antagonists Ondansetron
gastrointestinal mucosa Granisetron
c
c
1. APOMORPHINE: It is obtained by treating morphine with
y
y
concentrated hydrochloric acid. It acts by stimulating CTZ.
ANTICHOLINERGICS: Anticholinergics like hyoscine act by i) a
Vomiting induced by apomorphine is blocked by chiorpromazine
sadative action ii) blocking afferent impulses to vomiting centre.
(which depresses CTZ). Apomorphine produces vomiting within
15
2 to 8 mg. by Hyoscine is used in motion sickness.
minutes after subcutaneous injection. Dose:
subcutaneous injection. ANTIHISTAMINES: They act by an effect on vomiting centre and
It liberates a by producing sedation. They are safer and preferred for long tem
2. MUSTARD: Mustard is a household remedy. to
irritation. use. They are effective in motion sickness and vomiting due
St
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volatile oil in the gastrointestinal tract which produces
labyrinthine disorders.
Dose: 1
teaspoonful with water.
NEUROLEPTICS: They are phenothiazines. They act by depressing
ud
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irritation of
3. COPPER SULPHATE: It produces vomiting due to
effect. Dose: 200 nml. CTZ. So they antagonise vomiting produced by drugs whi:h stimulate
gastrointestinal tract. It also has an astringent
CTZ. But they have a short duration of action. They are 1ot effective
y
y
within 15 minutes, a
of 0.15% solution. If vomiting does not occur in motion sickness.
also fails, a stomach wash should
Ph
Ph
Ph
second dose can be given. If this
be given to prevent the poisonous effect. PROKINETICS: These are drugs which promote gastrointestinal
ha
motility and quicknen gastric emptying. Metoclopromide,

ar
ar
ar
due
4. HYPERTONIC SODIUM CHLORIDE: It produces irritation Domperidone and Cisapride belong to this group.
rm
stomach wall. This produces reflex emesis.

to dehydration of the
Metoclopramide: It is chemically related to procaina nide. The
ma
ma
ma
5. DIGITALIS AND EMETINE: These drugs act by direct irritation
antiemetic action is due. to both central and peripheral e fects. The
ac
of gastrointestinal mucosa and stimulation of CTZ. Since they are

central action is due to blockade of dopaminergic recejtors. The
cy
cy
cy
too toxic they are noi used as emetiCs. peripheral action is due to increased gastric emptying and increased
y
peristaltic movements.
Anti-emetics:
Anti-emetics are dnugs which prevent or control vomiting. Dose: 5 to 10 mg. thrice daily.
St
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y
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Ph
Ph
Ph
h
y
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209
208
1. LIGHT KAOLIN (CHINA CLAY): It is an insoluble colloidal
St
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of
Uses: In post-operative vomiting, vomiting during induction powder. It has an adsorbent and demulcent effect.
anaesthesia and in hiccough.
ud
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action 2. PECTIN: It is a carbohydrate product extracted from the inner
Domperidone: It is al:o a prokinetic agent. Tlhe prokinetic portion of citrus fruits. It acts by producing a mechanical coating
Prokinetic effect is due to blockade of
is not blocked by atropne.
y
upper G.1.T Penetration into blood brain in the gastrointestinal tract.
dopaminergic receptors in the
sidee effects.
barrier is poor.So it doe: not produce extrapyramidal
Ph
Ph
Ph
3. CRETA PREPARATA (PREPARED CHALK): It is a naive form
ha
It acts
Cisapride: It is a prok inetic with no antiemetic properties. of calcium carbonate. It acts by producing a protective coating
5 -HT
in the gut wall. Also it acts as a
ar
ar
ar
by releasing acetylcholie over the gastrointestinal tract.
CTZ. Also it does not
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GI tract. It has no effect on

antagonist in the
Gastroesophagial reflex 4. ACTIVATED CHARCOAL: Charcoal obtained from vegetable
produce extrapyramidal side effects. Use:
ma
ma
ma
ma
disease and impaired gastric motility. material can be activated by heating in steam at a very high
temperature. It acts as an adsorbent. It is used as an
c
c
5-HT3 ANTAGONISTTS anti-diarrhoeal and also in the treatment of poisoning. Universal
y
y
-antagonist. It is administered
Ondansetron: It is a si:lective 5 HT3 antidote (used for alkaloidal poisoning) contains 2 parts of
intravenously. It is used to
orally (8 mg three times daily) and also charcoal, I part of magnesium oxide and 1 part of tannic acid.
chemotherapy or radiotherapy.
control vomiting inducec: by
It Astringents: Astringents are agents which precipitate superficial
Granisetron: It is 10 o 15 times more potent than ondansetron. proteins and form a protective layer. This prevents irritation of the
is more effective in repeat cycle chemotherapy.
gastrointestinal tract. Tannic acid acts as an astringent. It precipitates
Anti-diarrhoeals: These are drugs used in the treatment of proteins in the fom of protein tannate. It is administered as tincture
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diarThoea. catechu. It acts by releasing tannic acid. Bismuth salts also have an
astringent effect.
ud
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Classification of anti-diarrhoeals:
Light kaolin
Miscellaneous drugs:
y
y
Protectives and
adsorbents Pectin .Opiates in the form of tincture opium or codeine have good
Ph
Ph
Ph
Creta preparata anti-diarrhoeal effect.
ha
Activated charcoal 2. Belladonna alkaloids in the form of tincture belladonna or as

ar
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Tannic acid atropine sulphate.
2. Astringents
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Bismuth salts 3. Loperamide .s a derivative of haloperidol. It has a structural

ma
ma
ma
Opium alkaloids resemblance to pethidine. It acts by combining with intestinal
3. Miscellaneous opiate receptors. Dose: 2 to 4 mg. Repeated if necessary upto
ac
Belladonna alkaloids
16 mg. per day.
cy
cy
cy
Loperamide
4. Diphenoxylate is a pethidine substitute. Dose: 5 mg. along with
y
producing
1) by
Protectives and adsorbents: These agents act 0.25 mg. of atropine (Lomotil) 3 to 4 times a day.
coating on the gastrointestinal mucosa which prevents
a protective 5. Lactobacillus acidophyllus acts by altering the intestinal pH.
bacteria
irritation 2) by adsorbing noxious substances (like gases, This inhibits the growth of intestinal pathogens.
diarrhoea.
and bacterial toxins) responsible for
St
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Ph
Ph
Ph
h
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211
Telegram - Study Pharmacy 210 Irritant Purgatives
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65. PURGATIVES ANTHRAQUINONES
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promote defecation and
Purgatives (cathartics) are drugs which Anthraquinone is present as an inactive glycoside in he leaves
1.
used in the treatient of constipation. of Senna and Cascara sagrada. The active anthrac uinone is
they are
y
liberated in the small intestine. They are absorbed anl excreted
Classification of purgatives: in the large intestine, where they act by stimnulation.
Ph
Ph
Ph
can be classified as:
Based on intensity of action, purgatives 2. The purgative effect occurs in 6 to 8 hours alter oral ingestion.
ha
1. Laxatives when the action

is mild. Stools are semisolid in nature and gripping is low.
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2. Drastics wlhen the action is severe. 3. They are excreted in milk. So they can produce diarrhoea in
r
Based on the mechanism of

action, they can be classified as: breast-fed infants.
ma
ma
ma
ma
4. Adverse effects are excessive purgation, dehydration and
1. Stimulant or irritant purgatives weakness.
c
c
Anthraquinones Senna
a) CASTOR OIL:
Cascara sagrada
y
y
Jalap 1. It is a fixed oil obtained from castor seeds (Ricimus communis).
b) Resinous compounds
Colocynth Chemicaly it is a triglyceride of ricinoleic acid.
2 Castor oil is a bland, non-irritant oil when applied extemally.
arr
Irritant oils Castor oil
C)
- On internal administration, it is hydrolysed in the int stine by
Plhenolpthalein pancreatic lipase. This liberates ricinoleic acid which is an
d) Miscellaneous
Calomel iritant and so produces a purgative effect.
Bisacodyl
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3. Castor oil acts on the small intestine. The purgative effect
Magnesium sulphate occurs within 2 to 3 hours. It produces copious liquid stools
2. Osmotic purgatives
Magnesium citrate
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with fluid loss.
Milk of nmagnesia Castor oil interferes with the absorption of various nutrients.
Sodium potassium tartrate
y
y
5. Castor oil is contra-indicated in iactating mothers (si nce it is
Lactulose excreted in milk), menstruation and in pregnancy.
Ph
Ph
Ph
Methyl cellulose 6. Dose: 4 to 16 ml.
Bulk purgatives
ha
3.
Agar agar
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ar
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Plantago seeds Resinous Purgatives:
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Bran These purgatives include jalap, colocynth and podoyhyllum.

ma
ma
ma
Lubricant purgatives Liquid paraffin They liberate the active ingradient in the small intestine wich acts
4.
ac
Dioctyl sodium sulfosuccinate by irritation. Stools formed are watery in nature. Toxic ties are
dehydration, prostration and collapse.
cy
cy
cy
y
PHENOLPTHALEIN:
. Phenolpthalein acts on the large intestine. Its effect manifests
in 6 to 8 urs.
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Ph
Ph
Ph
h
y
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212
213
administercd phenolpthalein is
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2. Aboul 15 percent of orally It is subjected to
absorbed ard it is excreted in bile. Preparations and dose:
it produces a long lasting
So
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cnterohepatic circ:alation. 1. Magnesium sulphate-2 to 16 g
stools fonmed are soft and semisolid in
purgative effect. The 2. Milk of magnesia-15 ml.
nature.
y
3. Light or heavy magnesium carbonate-2 to 4 g.
Adversc reactions: 4. Solutioni of magnesium citrate-200 ml.
Ph
Ph
Ph
purgation.
Fluid loss due to xcessive 5. Sodium sulfate-2 to 16 g.
ha
1.
Colic, palpitation nd collapse. 6. Sodium potassium tartrate-8 to 16 g.
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2.
Pink or purple co oured skin eruptions.
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3. LACTULOSE: It is a synthetic disaccharide. It is not absorbed in

feces (the patient should be the gastrointestinal tract. So it produces an osmotic effect which leads
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4. Reddish colouration of urine and
informed of this). to purgation.
it bed tüme
c
c
Dose: 50 to 300 mg. Bulk purgatives
y
y
converted into soluble
y
CHLORIDE): It 1s 1.These purgatives include various natural or synthetic
CALOMEL (MERCUROUS of the gut. This
the epithelial cells polysacharides and cellulose derivatives. These substances are
fonm which is taken uj by (alomel is an unreliable
1.1creased peristalsis. neither absorbed nor digested on oral administration. They
produces irritation and So the use of another
it is not eliminated. absorb water and swell. This increases the bulk of intestine
purgative. Sometimcs calomel.
to eliminate
purgative may be neces ary to
which initiates peristaltic reflexes necessary for defecation.
is structurallyrelated 2 These agents produce a mild purgative effect. The purgative
BISACODYL (DULCOLAX): It oral and rectal route. It
through effect is delayed and occurs in 12 to 24 hours.
phenolpthalein. It is administered is not known.
and the mechanism of action
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acts on the large intestine available as 5 mg. enteric coated
3. These purgatives are not absorbed. So they do not produce
c.
Itis relatively not-tox
It is any systemic toxicity. Sometimes they may produce. intestinal
suppositories.
capsules and as 10 mg. rectal
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obstruction.
purgatives) 4. Preparations and dose:
Osmotic purgatives (Saline
oral route are not absorbed.
y
y
1. Certain salts, when administered by i) Agar 4g.
osmotic effect whiclh leads to retention of
So they produce an
Ph
Ph
Ph
tract. Also they draw fluid
from ii) Isapgol (dried seeds of Plantago ovata) - 5 to 15 g.
fluid in the gast ointestinal
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the gastrointestinal tract.

the lumen of iii) Methyi cellulose- 1g. 1
to 4 times a day.
the interstitial sp ice into
intestine which induces peristaltic
ar
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This increases the bulk of the iv)Sodium carboxymethyl cellulose 1.5g 1
to 4 times a
the bowels.
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waves leading to evacuation of day.

commonly used are salts of magnesium,
ma
ma
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2. The saline purg:tives
sodium and pote ssium. Lubricant purgatives
ac
intestine. They
on both small and large
cy
cy
cy
3. These purgative:: act 3 to 6 hours.
LIQUID PARAFFIN: It is a mineral oi obtained from petroleim. It
effect within
produce a quick purgative
y
may be contains a mixture of hydrocarbons.

quantities of these purgatives
4. Sometimes snn:ll can occur. For exanmple, Mechanism of action: It has a mild action. It produces softening
absorbed and so systemic toxicity nervous system and lubricating effect on feces. It gets emulsified in the
of magnesium may produce central
absorption gastrointestinal tract and holds water. So the fecal matter is prevented
depressiOn. from becoming dry. This helps in easy evacuation.
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y
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Ph
Ph
Ph
h
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215
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Suppositories:
Adverse reactions: Suppositories are solid fornis of rectal medication intended
fat soluble vitamins like
ud
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1. Interference with the absorption of mainly for local effect. Drugs used in the form of suppcsitories are:
vitamin A, D and K.
spleen leading to chronic 1. Glycerin to initiate defecation relfex.
Occasional deposition in liver and
y
2.
inflammation. 2. Mecurials for diuretic effect.
Ph
Ph
Ph
8 to 30 ml. 3. Aminophylline for antispasmodic action.
ha
Dose:
DIOCTYL SODIUM
ULFOSUCCINATE:
ar
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4. Benzocaine to relieve pain and itching.
it is
In phammaceutical industry,
r
It is an anionic surfactant. feces due to

softening of
ma
ma
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ma
It produces
used as an emulsifying agent.
effect occurs in 24 to 48 hours. 67. ANTACIDS
lowering of surface tension. The
100 mg.
c
c
Dose 30 to Antacids are chemical substances which react with zastric acid
and lower the acidity gastric contents. These drugs relieve pain that
y
y
PREPARATIONS
66. ANO-RECTAL occurs in hyperchlorhydria and peptic ulcer.
administered of an ideal antacid:
and vomiting when Properties
Some drugs produce nausea adnministered by rectal route. This
can be
by oral route. These drugs administered 1. It should be an insoluble substance capable of neutralising acid.
is unconscious. Drugs
route is helpful when the patient thhe before entry into systemic 2 It should not liberate carbondioxide, since carbond oxide will
pass through liver
through rectum do not
enter nto circulation in an active produce a) pain due to stretching of the already inflammed
circulation. So ihesc drugs can
are the preparatios that can be
St
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St
suppositories gastric mucosa b) rebound acid secretion.
torm. Enemas and
administered through rectum. 3. It should not be absorbed
ud
ud
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rectunm
preparation introduced into the
ENEMA: Enema is a liquid 4. It should not produce either a laxative or constipati ng effect.
for local or systenmic action
y
y
Classification of antacids
Types of Enema
Ph
Ph
Ph
waslh may be
1. Evacuant enema: A
cathartic or cleaning bowel I. Classification based on absorption of antaciis
ha
matter, Also expulsion of

requircd to remove wornis, ucus or fecal
administered
Soap water or giyceriu Systemic antacids (produce Sodium bicarbonat
ar
ar
ar
gases may be required at times. purposes. This type of enema acts
Systenmic alkalosis)
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through rectum cain serve these producing irritation.

mechanically by distending the gut or by 2. Non-systemic antacids (do Magnesium oxide
ma
ma
ma
which can further be classified as: not produce systemic Calcium carbonate
2. Retention enema:
ac
administered to alkalosis) Bismuth salts

Opium with starch can be
a) Sedative enema:
cy
cy
cy
Bromethol or paraidehyde can also be Calcium phosphate
produce a sedative cifect.
y
Aluminium hydroxi ie gel

administered for basal anestliesia.
1arunic acid or meiallic
astringents can be Magnesium trisilica e
b) Astringent enema: Sodium carboxymethyl
administered for inizcvus coliiis.
saline glucõse can be cellulosC
enema: in dehydrated conditions,
.
c) Nutrient **
administered tirough rectum.
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St
ud
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u
y
y
Ph
Ph
Ph
h
y
y
216
St
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St
iv) ALUMINIUM HYDROXIDE GEL:
property:
II Classification based on adsorbent
ud
ud
ud
u
=
1. It is available in the formm of a viscous suspension or a dried
Adsorbent Aluminium hydroxide gel gel.
Magnesium trisilicate
y
antacids 2. It has adsorbent, astringent and demulcent properties.
(Adsorb HCI) Sodium carboxymethyl cellulose (SCMC)
- 3. It is a non-systemic antacid and it is not absorbed. It satisfies
Ph
Ph
Ph
Non-adsorbent Sodium bicarbonate almost all the properties of an ideal antacid. But it produces
ha
antacids (do not Sodium citrate slight constipation.
ar
ar
ar
adsorb HCI) Magnesium oxide 4. It prevents the absorption of phosphate in the intestine leading
r
Calcium carbonate to its deficiency. This can be prevented by administering

ma
ma
ma
ma
Bismuth carbonate aluminium phosphate gel instead of aluminium hydroxide gel.
Calcium phosphate 5. Dose: Aluminium hydroxide gel-4 to 8 ml. every 2 to 4 hours.
c
c
wlhich get absorbed and
Systemic antacids: They are antacids v) MAGNESIUM TRISILICATE: It reacts with hydrochloric acid
y
y
produce systemic alkalosis. and forms magnesiunm chloride and silicone dioxide. It becomes
antacid used. gelatinous in nature and forms a protective coating over the intestine.
SODIUM BICARBONATE: lt is the earliest
It has a slow but a prolonged action. Occasionally it may produce
are:
The disadvantages of sodium bicarbonate diarrhoea. Dose: 2 to 4g. every 4 hours.
1. It produces a quick but a short action. vi) SODIUM CARBOXYMETHYL CELLULOSE (sCMC): It is a
systemic alkalosis.
2. It gets absorbed and produces semisynthetic derivative of cellulose. It acts by absorbing
3. It releases carbondioxide which
produces a rebound secretion hydrochloric acid. It does not produce any adverse effect except a
St
St
St
St
of gastric acid. mild laxative effect.
ud
ud
ud
u
insoluble. They are
Non-systemic antacids: These antacids are
produce systemic alkalosis. 68. ANTIULCER DRUGS
not absorbed and they do not
y
y
oxide can
i)MAGNESIUM OXIDE: One gram of magnesium antacid. Antiulcer drugs: These drugs act by inhibiting gastric acid
It is a good
Ph
Ph
Ph
acid.
neutralise 500 ml. of 0.1 N hydrochloric when absorbed, the secretion or by promoting ulcer healing.
purgative effect. Also
ha
But it produces nmilc

depression of central nervous system.
magnesium 1ons may produce
ar
ar
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carbonate has similar properties except that it liberates Classification of antiulcer drugs:
Magnesium
.
rm
T
carbondioxide. Inhibitors of gastric acid
ma
ma
ma
granm of calcium carbonate can
ii) CALCIUM CARBONATE: One secretion
hydrochloric acid. It acts quickly. In the
ac
neutralise 210 nil. of ).1 N

acid and forms càlcium chloride. a)Anticholinergics Belladonna alkaloids
stomach, it reacts with hydrochloric
cy
cy
cy
with bicarbonates and formns Pirenzepine
In the intestine, calcium chioride reacts
y
This produces constipation. Also,

calcium carbonate gain. b) H2 receptor antagonists Cimetidine
may produce hypercalcemia.
prolonged use of calcium chloride Rantidine
produce constipation and also
ii) BISMUTH SALTS: Bismuth salts presently used are
Fomotidine
The preparations
stain the feces black in colour. c) Proton pump inhibitors Omeprazole
bis:muth carbonate and bismuth subnitrate.
St
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St
ud
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y
y
Ph
Ph
Ph
h
y
y
St
St
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Sucralfate a powerful inhibitor of gastric acid secretion which can totally abolish
2 Ulcer protectives HCI secretion.
ud
ud
ud
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Ulcer healing agents CarbenOxolone sodium
Adverse reactions: nausea, headache, GI disturbances and d zziness.
Inhibitors of gastric acid secretion
Ulcer protective and healing agents
y
alkaloids like
1. ANTICHOLINERGIC DRUGS: Belladonna
inhibiting gastric 1. SUCRALFATE: It is a complex of sulfated sucrose and
Ph
Ph
Ph
1) inhibiting gastric acid secretion 2)
atropine act by:
in the stomach. But they aluminium hydroxide. It acts by forming a gel which coats ukc er sites.
ha
motility wlhich increases the stay of antacid

The coating lasts for 6 hours and it is impenmeable to gastrie acid.
produce adverse effects like dryness of mouth.
ar
ar
ar
Also it is not disturbed by food. It is more effective in healing
anticholinergic action on
r
2. PIRENZEPINE: It has a selcctive duodenal ulcer. Dose: I g tablets before a meal and at bed time for
is 10 tinmes more potent than
ma
ma
ma
ma
muscarinic receptors in the stomach. It
4 to 8 weeks. An antacid should not be taken 30 minutes be:tore or
and blurred
cimetidine in ulcer healing. Adverse reactions: dry mouth after taking sucralfate.
c
c
vision.
2. CARBENOXOLONE SODIUM: ltis prepared from glycyrhetenic
It inhibits gastric acid
3. CIMETIDINE: It is a H2 receptor anagonist.
y
y
acid which is a liquorice glucoside. It promotes healing of gastric
secretion induced by histamine, insulin and
pentagastrin. It decreases
ulcer. it acts by stimulating mucus secretion which in turn jxotects
both volume and acid content of gastric juice without any effect on
ulcer site from gastric acid. It also has an anti-inflammator effect
It croses the placenta and is secreted in milk. It is
pepsin secretion. like corticosteroids. It is rapidly absorbed from stomach and is
used in the treatnent of 1) duodenal ucer 2) multiple peptic ulcers
excreted in bile.
3) stress induced ulcer.
Adverse reactions: water and sodium retention, potassiim devletion,
confusion.
Adverse reactions : gynecomastia, impotence and mental headache, heatburn and hypertension.
St
St
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St
in old patients. Dose: S0 to 100 mg. thrice daily after meals as tablets for 4 to 8
time.
Dose: 400 mg two times daily or 800 mg at bed weeks.
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times more potent
4. RANITIDINE: It is a H2 receptor antagonist 5
It selective and prolonged effect. A single dose
than cimetidiue. has a
y
y
It is a safer drug than cimetidine.
of 150 mg is effective for 12 hours.
Ph
Ph
Ph
tiredness and skin
Adverse reactions : nausea, vomiting, diarrhoea,
ha
produce gynecomastia or sexual impotence.

rashes. It does not
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compound. It is an effective H2
5. FOMOTIDINE: It is a thiazole
rm
than cimitedine and ranitidine

receptor antagonist. Ít is more potent
ma
ma
ma
acid secretion. it also produces healing of
in inhibiting gastric
of liver.
ac
metabolising enzymes
duodenal ulcer. It does not inhibit drug
cy
cy
cy
gastrointestinal symptoms.
Adverse effects: headache, dizziness and
y
6. OMEPRAZOLE: It is a substituted
benziidazole. It acts by
pump which is the final common step in gastric acid
inhibiting proton
suppression of gastric acid secretion.
secretion. It has a dose dependent
anticholincrgic or H2 receptor blocking action. It is
ft does not have
St
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St
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y
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Ph
Ph
Ph
h
y
y
221
220 Amno acid alkaloids Ergolamine
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1.
Ergosine
Ergotoxin (Ergotoxin is a
ud
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Section X
mixture of ergocornine,
ergocrystne and
y
ergocryptine)
Ph
Ph
Ph
2. Dihydrogenated amino Dihydroergotamine(DHE)
UTERUS
ha
DRUGS ACTING ON THE acid alkaloids (Hydergine)
ar
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3. Amine alkaloids Ergometrine
r
(Ergonovine)
ma
ma
ma
ma
Uterus: All the natural ergot alkaloids produce contraction of uterine
c
c
smooth muscle. But the effect depends on dose and stage of gestation.
y
y
a) Relationship to dose:
UTERINE RELAXANTS
69. OXYTOCICS AND 1. With small dose: force and fiequency of contraction is
increased with normmal relaxation.
2 With 1arge dose: contractions are forceful and prolonged.
Oxytocics (Ecbolics)
uterine contractions so as 3. With very high dose: sustained contracture.
Ecbolics are drugs which stimulate
its contents. The ecbolics
can be classified as: b) Relationship to degree of maturity and stage of gestation:
St
St
St
St
to help the expulsion
Uterus at any phase of estrous cycle or gestation and even an
Ergot alkaloids immature uterus is contracted. But uterus at full term or immediately
ud
ud
ud
u
1. Direct ecbolics
Posterior pituitary extract after delivery is highly sensitive. The ergot alkaloids are unsuitable
Drastic purgatives for labour because of
2. Indirect ecbolics
y
y
Local irritants like cantharidin 1. Frequent contraction of uterus without succeeding felaxation.
Ph
Ph
Ph
and they
are only of theoretical interest 2. Increase in tone of the cervix.
he indirect ecbo ics
ha
3. Dissociation of contraction of the fundus and the cervix.

are not discussed in this chapter.
ar
ar
ar
Vascular actions: All the ergot alkaloids have an adrenergic
rm
ERGOT: blocking and direct vasoconstrictor activity. With large doses, the
ma
ma
ma
is the compact mycelium ofa fungus vasoconstriction is accompanied by damage to capillary
Source and content:i: Ergot
ac
in the ovary of rye. Ergot

contains endothelium. Bui hydergin and ergometrine produce adrenergic
Claviceps purpurea which grows
cy
cy
cy
listamine, tyramine, acetylcholine, blockade but minimal vasoconstriction.
several substances like alkaloids,
y
steroids, acids etc.
Classification of Ergot alkaloids:

ofergot alkaloids are
Only the levorotatory fom
pharmacologically active. They are:
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
222 223
of 5-HT: The ergot alkaloids antagonise the actions transported to the posterior lobe of pituitary through the lypothalamo
Antagonism
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St
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St
Methysergide, a derivative of hypophyseal tract.
of 5- hydroxytryptamine.
used as a 5-HT antagonist.
crgometrine is routinely
ud
ud
ud
u
Absorption, fate and excretion: The absorption of amino acid 1. Uterus: Its effect depends on dose, species and stage f gestation.
y
on oral
alkaloids and their dihydrogenated derivatives is eratic In humans, a snmall dose increases the tone and anplitude of
administration. But the amine alkaloids are completely absorbed. contractions; bigger doses produce tonic contractions. Estrogen
Ph
Ph
Ph
metabolic increases the sensitivity of uterus to oxytocin. With advance of
The ergot alkaloids are metabolised in the liver. The
ha
pregnancy, the sensitivity is more.

products are excreted in urine.
ar
ar
ar
In contrast to ergot alkaloids, the sequence ot uterine
r
Adverse reactions: contractions induced by oxytocin is as follows: The bedy and the
ma
ma
ma
ma
1. Nausea, vomiting, miosis and postural hypotension. fundus contracts while the cervix dilates. This helps n the easy
2. Anginal pain due to coronary vasoconstriction. expulsion of the foetus. So it is suitable for labour.
c
c
to
3. Paraesthesiae, tingling, numbness and gangrene due 2. Mammary gland: Oxytocin stimulates the nodificd smooth
y
y
vasospasm. muscle (nmyoepithelium) and helps in the expulsion of miik.
4. Headache, drowsiness, depression and confusion.
Absorption, fate and excretion: Oxytocin is ineifective orally.
5. Rarely hemiplegia and cerebral haemorrhage.
Absorption is rapid on intramuscular injection. oxytocin 1se present
1.
1
Ergometrine tablet-0.5 to nmg.
2. Ergometrine injection-0.1 harmae
to 0.5 mg. intravenously.
in plasma, uterine tissue and placenta of pregnant women inactivates
oxytocin.
Adverse reactions:
St
St
St
St
3. Methylergometrine tablet-0.25 to 0.5 mg. 1. Water retention leading to water 1ntoxication on iitravenous
S.C., L.M. or L.V.
4. Methylergometrine injection-0.2 mg. by
ud
ud
ud
u
administration.
injection. 2. Premature birth and foetal death on injudicious use during
y
y
labour.
Therapeutic uses:
Prophylaxis and treatment of postpartum haemorrhage
Ph
Ph
Ph
1. Preparations and dose:
(ergometrine and methylergometrine are useful).
ha
(ergometrine is
1. Oxytocin injection-2 to 5 units by subcutaneous or
2. To hasten uterine involution after child birth
ar
ar
ar
intramuscular injection.
useful).
rm
dihydrogenated 2. Synthetic oxytocin injection (Syntocinon)-Dose as for oxytocin

3. In the treatment of hypertension (only
ma
ma
ma
injection.
derivatives are useful).
ac
DHE are useful). Therapeutic uses:

4. In tlie treatment of migraine (ergotamine and
cy
cy
cy
1. To induce labour at tem.
OXYTOCIN:
y
It iss a
2. To control postpartum hemorrhage.
Oxytocin is a polypcptide containing 9 amino acids.
pharmacologically active principle of posterior pituitary. Oxytocin is 3. To induce abortion during the 2nd or 3rd trimester.
with vasopressin in hypothalamic nuclei. It is 4. To promote ejection of milk (it is administered intra nasally).
synthesised along
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
225
Prostaglandins are C20 fatty acids ETHACRIDINE LACTATE It is an acridine conmpound. lt is
PROSTAGLANDINS:
St
St
St
St
one or more double administered extra-amniotically for second trimester abortion. lt
contain
containing cyclopentane ring. They symptoms like nausea and vomiting.
double bond is indicated by a suffix may produce gastrointestinal
ud
ud
ud
u
bonds. The number of the very rare.
is the richest source of But other toxic effects are
like PGF2. Humar seminal fluid
lungs, menstrural
prostaglandins. They are also present in iris,
Uterine relaxants (Tocolytics, Uterine sedatives)
y
kidneys. The prostaglandins are
fluid, brain, thymus, pancreas and Uterine relaxants have limited therapeutic value. They are
Ph
Ph
Ph
belonging to linolenic
synthesised from polyunsaturated fatty acids sometimes used to delay delivery in premature labour. Drugs with
ha
are synthesised at the site of action.

or alpha linolenic seri 2s. They potential uterine relaxant effect are orciprenaline, salbutamol,
ar
ar
ar
concentrations but they are destroyed Relaxin, a mixture of
They are active even in low isoxuprine, ether, halothane etc.
r
duration of action.
quickly. So they hare a short polypeptides is known to produce uterine relaxant effect. Relaxin
ma
ma
ma
ma
is found in the blood during pregnancy. It has also been detected
Pharmacological actions: found to be useful in premature
in human placenta. It has been
human myometrium.
c
c
1.Uterus: Most prc staglandins stimulate labour.
and amplitude of uterine
y
y
PGE and PGA stirulate the tone
contractions.
present in human
Gastrointestinal tract: Prostaglandins are
aebookSpdf
2.
PGA inhibit gastric acid secretion.
gastric mucosa. PGI: and
PGE2 and PGA2 produce
3. Cardiovascular system:
But PGF produces
vasodilatation and fall in blood pressure.
St
St
St
St
vasoconstriction.
ud
ud
ud
u
Prostaglandins produce luteolysis and
4. Reproductive system:
prevents the implantation
decrease in progestei one secretion. This
have been tried as
y
y
So prostaglandins
of fertilised ovum.
Ph
Ph
Ph
antifertility agents.
ha
therapeutic abortion.
Uses For induction »f labour and for
ar
ar
ar
effective method for
HYPERTONIC SALNE: There is no
rm
semester. Intra-amniotic
ma
ma
ma
teminating pregnarcy in the second effective in
is very much
injection of hypertonic saline (20%)
ac
250ml of amniotic fluid is

terminating pregnan:y. Usually, 100 to
cy
cy
cy
hypertonic saline is injected. It
withdrawn. An equal amount of
y
foetal death. Systemic

produces damage to placenta and
headache, thirst, hypertension
absorption of sodiu:n may produce
and congestive cardiac failure.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
Telegram - Study Pharmacy 226 Classification of antibiotics:
St
St
St
St
Section XIV |
1. Broad spectrum Tetracyclines
Chloramphenicol
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ud
ud
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antibiotics
Cycloserine
Narrow spectrunm antibiotics
y
2.
a)Effective against Penicillins
Ph
Ph
Ph
CHEMOTHERAPY Gram-positive bacteria Erythromycin
ha
Lincomycin
ar
ar
ar
Vancomycin
r
Novobiocin
ma
ma
ma
ma
b) Effective against Gram- Streptomycin
negative bacteria Kanamycin
c
c
Gentamicin
y
y
5. Antiprotozoal antibiotics
-
Clycloserine
Paraniomycin
Fumagillin
GENERAL cONSIDERATIONS
70. Antifungal antibiotics Nystatin
Chemotherapy: Chemotherapy is
specific infections with chemical
defined as the treatment of
agnets. In the broadest sense,
it OOkS Amphotericin
Griseofulvin
Hamycin
B
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St
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St
conditions where
antibiotics and also
includes therapy with Pimaricin
infection is not invoved e.g. nialgnancy.
ud
ud
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u
Antimalignant antibiotics Actinomycin D
5.
may be: Mechanism of action of antibiotics
A chemotherapeutic agent
y
y
Bacteriostatic if it inhibits the growth of bacteria. Antibiotics may act by any one of the following mechaniss:
1.
.
Ph
Ph
Ph
destroys and kills the bacteria. By inhibiting cell wall synthesis e.g. penicillins, cephe losporins,
2. Bactericidal if it
ha
substances e.g., cycloserine.

Chemotherapeutic agents include synthetic
ar
ar
ar
penicillin. 2. By inhibiting the function of cell nmembrane e.g. polymyxin,
sulfonamides and antibiotics e.g.
rm
novobiocin, nystatin.
synthesised by By inhibiting protein synthesis e.g. chloranphenicol,
ma
ma
ma
substances 3.
Antibiotics: Antibiotics are chemical tetracyclines, erythronmycin, lincomycin
produce suppression of
ac
and
various species of microganisms antibiotic is 4. By inhibiting nucleic acid synthesis e.g. actinoinycin D,
microroganisms. An
cy
cy
cy
growth and destruction of other effective against mitomycin.
spectrum of activity, if it is
y
said to have a narrow A broad

Gram-negative bacteria.
either Gram-positive or both Gram-positive and
spectrum antibiotic is effective against and chlamydia.
rickettsiae
Gram-negative bacteria and also against
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
228 229
So folic acid
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theory). They inhibit the enzyme folic acid synthetase.
NITROFURANS AND
71. SULFONAMIDES, (which is essential for bacterial growth) is not synthesised.
ud
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u
OTHER SYNTHETIC ANTIMICROBIAL AGENTS Absorption, fate and excretion:
1. Sulfonamides used for systemic infections are rapidly absorbed
y
for local
SULFONAMIDES from gastrointestinal tract. But sulfonamides used
effect on the intestine are poorly absorbed.
Ph
Ph
Ph
contain a
Sulfonamides are antimicrobial agents which
Sulfonamides are bound to plasma proteins to the Cxtent of
ha
derivatives of the parent 2.

sulfonamido (SO2 NH2) group. They are
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ar
ar
sulfonamide. S0%.
compound, para aminobenzene But in
They are distributed in all tissue fluids except CSF.
r
3.
is
Classification of sulfonamides: presence of meningeal inilammation, high concentration
ma
ma
ma
ma
present in CSF.
a) Sulfonamides for sy stemic intections 4. Sulfonamides are metabolised by acetylation.
.
c
c
Sulfadiazine in urine.
Short acting 5. Free and acetylated sulfonamides are excreted
y
Sulfadimidine
y
Sulfafurazole Adverse reactions:
Sulfamethizole Allergic reactions like fever, skin rashes, serum sickness and
I.
**
Sulfamethoxazole cutaneous photosensitisation.
Intermediate acting
Sultamoxole 2 Crystalluria due to precipitation of the acetylated fom of
Sulformethoxine sulfonanmide. This is an important toxicity.
3. Long acting toxicities like agranulocytosis and
Sulfadimethoxine 3. Haemopoietic
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St
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Sulfamethoxypyridazine thrombocytopenia.
4. Miscellaneous toxicities like psychotic episodes,
Sulfonamides 1or bowel Sulfasalazine
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b) hypothyroidism and goitre.
diseases
y
y
Antimicrobial activity: 1. Sulfadiazine tablets 3g. initially, followed by
I
to 1.5 g. every
Sulfonamides inhibit th: growth of:
Ph
Ph
Ph
4 to 6 hours.
Dose as for sulfadiazine.
ha
1. Gram-positive ard Gram-negative

bacteria. 2. Sulfadimidine tablets
Sulfanmethoxazole tablets - l to 2 g. initially. followed by 0.5.
ar
ar
ar
2. Actinomyces and Nocardia. 3.
to I g. every 12 hours.
rm
lymphogranuloma venerum and

3. Chlamydia organisms causing
Sulfadimethoxine tablets 3 to 6 g. every 6 hours.
ma
ma
ma
psittacosis. 4.
at very high
ac
Sulfonamides are mainly becteriostatic. But Therapeutic uses:

they nmay havve .
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cy
cy
urinary tract), Acute bacillary dysentry.
concentrations (especilly in the
y
bactericidal effect. 2 Ulcerative colitis (Sulfasalazine is used)

structural similarity Urinary tract infection and chancroid.
Mechanism of action: Sulfonamides have a Meningococcal nmeningitis.
(PABA). Because of this, sulfonamides 4.
to para amino benzoic acid (Woods-fields
incoporation into folic acid 5. Trachoma and inclusion conjuctivitis.
compete with PABA for
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St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
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2. Protozoa like Trichomonas vaginalis.
6. In the proplhylaxis of streptococcal tonsillitis.
3. Fungi like Candida albicans.
ud
ud
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u
TRIMETHOPRIM AND COTRIMOXAZOLE
Mechanism of action: By acting on DNA, nitrofurans produce
Trimethoprim is a pyrimidine derivative. It has antibacterial various changes in microoganisms.
y
and antimalarial properties. It is only bacteriostatic.
Adverse reactions:
Ph
Ph
Ph
effective against
Antimicrobial activity: Trimethoprim is
ha
Streptococci, Staplh. aureus, E. coli, Salmonella, Shigella, and Proteus. 1. Gastrointestinal disturbances like nausea and vomitin
ar
ar
ar
inhibits the enzyme 2. Skin rashes and polyneuritis.
Mechanism of action: Trimethoprim
r
dihydrofolate reductase. So the conversion of folic acid to 3. Megaloblastic anemia due to folic acid deficiency.
ma
ma
ma
ma
tetrahydrofolic acid is inhibited. 4. Hemolytic anemia in case of G-6-PD deficiency.
Sulfonamides Trimethoprim
Quinalones
c
c
y
y
NALIDIXIC ACID (GRAMONEG, NEG-GRAM): It Is a juinolone
PABA Folic acid Tetrahydrofolic acid
derivative. It is effective against Gram negative bacteria, cspecially
It is
E. coli. It is less effective against Aerobacter and Klebsie:la.
Sulfonamides act by inhibiting the conversion of PABA to folic ineffective against Gram positive bacteria.
act in the
acid. So a combination of sulfonamides and trimethoprim It is bac tericidal.
nucleotides. A Mechanism: It acts by inhibiting DNA replication.
same metabolic pathway, preventing the synthesis of
is called as
combination of trimethoprim and sulfamethoxazole
synergistic bactericidal Adverse reactions:
St
St
St
St
Cotrimoxazole. This combination has a
action.
1.Nausea, vomiting, diarrhoea
2. Allergic reactions like pruritus, urticaria and photoser.sitivity.
ud
ud
ud
u
Adverse reactions: Cotrimoxazole can produce:
. Nausea, vomiting and skin raslhes. 3. CNS effects like headache, malaise and drowsiness.
y
y
2. Anemia, leucopcnia and thrombocytopenia. Preparations and dose:
Ph
Ph
Ph
3. Stomatis, glossitis and crystalluria. in 4
Nalidixic acid tablets and syrup. For adults: 4 g. dily
ha
Therapeutic uses: Cotrimoxazole can be used for: divided doses. For children: 55 mg / kg body weight.
ar
ar
ar
1. Urinary infection due to E coli and Proteus.
.
In urinary tract infection and bacillary dysentry.

rm
Uses:
2. Respiratory infections, gonorrhea and typhoid fever.
ma
ma
ma
FLUOROQUINOLONES: They contain fluorine in their structure
NITROFURANS important drugs
and are chemically related to nalidixic acid. The
ac
Nitrofurans are synthetic antinmicrobial agents. They include Pefloxacin. Like

cy
cy
cy
are Ciprofloxacin, Norfloxacin, Ofloxacin and
nitrofurantoin, furazolidone, nitrofurazone and nifuroxime. the enzyne DNAA
y
nalidixic acid, they are bactericidal. They inhibit

in low
Antimicrobial activity: Nitrofurans are bacteriostatic gyrase. This prevents bacterial DNA replication.
They aie highly
high concentrations. They are and
concentrations and bactericidal in
effective against Enterobacteriaceae, H. influenzve
effective against: Pseudomonas aeruginosa.
. A variety of Gram-positive and Ciram-negative organisms.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
232
233
St
St
St
St
less. Nausea, vomiting and Mechanism of action: Penicillin is a bactericidal drug. It acts by
Adverse reactions: Relatively inhibiting the synthesis of bacterial cell wall. This action is produced
allergic reactions and
ud
ud
ud
u
diarrhoea are common. Rarely they produce by inhibiting the nthesis and cross linkage of peptidoglycans.
and convulsions.
CNS effects like confsion, nervousness
y
Therapeutic uses: 1. On oral administration, benzyl penicillin is inactivated by
Ph
Ph
Ph
1. Urinary tract intfect.ons gastric acid. Also food interferes with its absorption. Itis
ha
2. Severe G.I infections like gastroenteritis. rapidly absorbed after subcutaneous or intramuscular injection.
ar
ar
ar
3. Invasive external oitis die to Pseudomonas. 2. About 60 percent is bound to plasma proteins.
r
4. Chronic gram negative osteomyelitis. 3. It is distributed in kidneys, liver, plasma and intestine.
ma
ma
ma
ma
5. First choice in typlioid fever. 4. Normally it is not taken up by CSF. But high concentrations
are present in CSF during meningeal inflammation. It is
ANTIBIOTICS
c
c
eliminated through urine by tubular secretion.
72. PENICILLINS AND OTHER
y
y
POSITIVE
EFFECTIVE MAINLY AGAINST GRAM Preparations and dose:
ORGANISMS 1. Benzyl penicillin tablet-200,000 to 400,000 units every 4 hours.
2. Benzyl penicillin injection-200,000 to 600,000 units every 4
hours.
PENICILLINS
are obtained Repository preparations: Benzyl penicillin is rapidly eliminated
Penicillins, the most important of the antibiotics, through urine. So it has to be administered frequently at an interval
Penicillium chrysogenum.
from Penicillium notatun and
St
St
St
St
of 4 or 6 hours. This disadvantage is overcome by repository.
penicillins consists of preparations of penicillin. These preparations are relatively insoluble.
Chemistry: The basic structure of
ud
ud
ud
u
ring. These two rings So they act by slowly releasing penicillin and thus prolonging its
thiazolidine ring fused vith a beta lactum
(6-APA) nucleus. A side effect. The repository preparations of penicillin are:
constitute the 6-amino penicillanic acid
y
y
1. Procaine benzyl penicillin.
chain is attached to 6-APA nucleus.
Fortified benzyl penicillin. (a mixture of procaine benzyl
Ph
Ph
Ph
benzyl penicillin or 2.
The commonly used penicillin is penicillin and benzyl penicillin).
ha
penicillin G. 3. Benzathine penicillin (a dibenzylethylendiamine salt of benzyl

ar
ar
ar
spectrum antibiotic
Antimicrobial activity: Penicillin is a narrow penicillin).
rm
organisms. The sensitivity of

very effective against Gram- positive 4. Penicillin with probenecid (Probenecid competes with penicillin
ma
ma
ma
follows:
various organisms to penicillin is a for tubular. secretion. This decreases renal elimination of
ac
Highly sensitive Gonococci penicillin),.

cy
cy
cy
Pneumococci
Adverse reactions:
y
Meningococci
Treponema pallidum The adverse reactions of penicillin are:
Moderately sensitive Bacillus anthracis 1. Intolerance which includes allergic and anaphylactic reactions.
Corynebacterium diphtheriae Allergy which is the major problem with penicillin may occur
Clostridum welchii in the form of skin rashes, renal disturbances and heniolytic
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
St
St
cardiovascular
anemia. The manifestations of anaphylaxis are Penicillinase resistant Methicillin
collpase, bronchospas and angioedema.
ud
ud
ud
u
penicillins Cloxacillin
2. Superinfection with Klebsiella,
Aerobacter and Candida. Dicloxacillin
3. Miscellaneous like nausea and
vomiting on oral administration Nafcillin
y
and sterile inflammatory reaction on intramuscular injection.
5. Broad spectrum Ampicillin
Ph
Ph
Ph
patients with syphilis.
4. Jarisch-Herxheimer reaction in penicillins Talampicillin
ha
Therapeutic uses: Amoxycillin.
ar
ar
ar
infections.
Streptococcal, pneumococcal and meningococcal 1. Acid resistant penicillins
r
1.
2. Veneral diseases like gonorrhea

and syphilis.
ma
ma
ma
ma
POTASSIUM PHENOXYMETHYL PENICILLIN (PENICILLIN V)
tetanus and gas gengrene.
3. Diphtheria, It has similar antibacterial spectrum as benzylpenicillin. It
4. Actinomycosis and anthrax.
c
c
5. In the prophylaxis of rheumatic
fever and streptococcal is not inactivated by gastric acid. Also, food does not interfere
y
y
nfections. with its absorption. Its concentration in piasma is higher than that
of benzylpenicillin. Dose: 250 to 500 mg. at 4 to
&
hourly
Semisynthetic Penicillins intervals. Potassium phenoxyethyl penicillin has similar
Disadvantage of benzyl penicillin:
antibacterial effect with no difference
1.
2.
Inactivation by gastric acid.
Inactivation by penicillinase (beta lactamase)
resistant organisms.
produced by 2. Penicillináse resistant penicillins
METHICILLIN: It is
df
effective against penicillinase producing
St
St
St
St
3. Narow spectrum of activity. Staphylococci. Dose: 1
g. every 4 to 6 hours by I.M or slow I.V
infusion.
4. Short duration of action.
ud
ud
ud
u
5. Probleim of anaphylaxis CLOXACILLIN: It is more potent than methicillin. Food iterferes
overcome these with its absorption. But it produces adequate serunm levels. it is free
Semisynthetic penicillins have been prepared to
y
y
disadvantages of benzyl penicillin. from toxicity except allergic reactions.
Ph
Ph
Ph
moulds of DICLOXACiLLIN: It is a derivative of cloxacillin. t is well
Preparation of semisynthetic penicillins: The
ha
nucleus. To this absorbed. So it gives a higher concentration in plasma. It is highly

P.chrysogenum, initially synthesise the 6-APA
ar
ar
ar
These natural side chains can be protein bound (95%) and does not cross placenta. Dose: 0.2: to I g
rm
various side chains are attached. orally.

radicals. Thus, a variety of
substituted with various organic
ma
ma
ma
can be synthesised. NAFCILLIN: It is less effective than benzylpenicillin. I is not
semisynthetic (newer penicillins)
ac
adequately absorbed on oral administration. So it is adminis: ered by

cy
cy
cy
Classification of semisynthetic penicillins: intramuscular injection.
y
1. Acid resistant Potassiunm phenoxymethyl Broad spectrum penicillins

penicillin
AMPICILLIN: It is an important penicillin effective against gram
Potassium phenoxyethyl positive bacteria like benzylpenicillin. But it is more effective against
penicillin
gram negative bacteria. lt is inactivated by penicillinase. it is acid
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
236
237
Mecillinam is administered parenterally. But its ester pivmecillinam
St
St
St
St
is effective on oral administration.
resistant and water soluble. It is absorbed orally.
intramuscular injection. It crosses
ud
ud
ud
u
Better blood levels are achieved on Penicillinase and Clavulanic Acid
to benzyl penicillin.
placental barrier. Adverse reactions are.similar
lesions, occur frequently. Penicillinase (betalactamase): It is an enzyme produced by
But skin rashes, especially maculopapular
y
penicillin resistant micro-organisms. This enzyme opens thhe
routes.
250 to 500 mg. 6 itourly by all inactivation.
Ph
Ph
Ph
Dose: betalactum ring of penicillins leading to their
ampicillin. It acts by
TALAMPICILLIN: it is a carboxylic ester of
ha
Streptomyces
wall. So by itself it has no Clavulanic acid: It is a compound produced by
releasing ampicillin in the intestinal
ar
ar
ar
the enzyme betalactamase. It
clavuligerus. It is a potent inhibitor of
antibacterial activity. It is effective orally.
r
But it protects penicillins from

has a weak antibacterial activity.
spectrum like
has a broader antibacterial inactivation by betalactamase and increases their effectiveness. Thus
ma
ma
ma
ma
AMOXYCILLIN: Ít
better blood levels. Also amoxycillin.
ampicillin. It is effective orally. It provides clavulanic acid increases the antibacterial spectrum of
it is highly protein bound.
Sulbactum is another betalactamase inhibitor like clavulanic
c
c
spectrun acid. It can be combined with ampicillin.
y
y
: Extended
Extended spectrum peicillins (ESP) amidino
penicillins and
penicillins (ESP) are carbo:xypenicillins, ureido Macrolide antibiotics
many gram- negative aerobes and
penicillins. They are effecti ve against their
effective against pseudomonas infections. Macrolide antibiotics contain a large lactone ring in
anaerobes. They are mosi group is Erythromycin.
with aminoglycoside antibiotics. structure. The important member of this
Also they are synergistic
Aminoglycosides are inact vated by ESP in vitro.
not be mixed together ir the same bottle. The
So these two should
following are the
ERYTHROMYCIN )OKS
St
St
St
St
important extended spectrum
penicillins. Source: It is obtained from a fungus, Streptomyces erythreus.
has a
CARBENICILLIN: It has similar spectrum as ampicillin but Antibacterial activity: Sensitive organisms are:
ud
ud
ud
u
!t is highly effective against Proteus
weaker antibacterial activ.ty: Gram-positive cocci including Streptococci, Staphylococci and
penicillinase. It is inactivated 1.
and Pseudomonas. It is inactivated by
y
y
by gastric acid. So it is
administered parenterally. Disadvantages: Pneumococci.
C. diphtheriae.
1) congestive heart failure due to sodium
content 2) bleeding due to Some strains of H. influenzae and
Ph
Ph
Ph
2.
bacteriostaic in low concentrations
ha
platelet aggregation. Mechanism of action: It is

carbenicillin. It is highly It acts by inhibiting protein
and bactericidal in high concentrations.
ar
ar
ar
TICARCILLIN: It is thie-iyl analogue of
a synergistic effect with synthesis by bacterial ribosomes.
rm
effective against Pseudo:nonas. It has

the serum concentration of
ma
ma
ma
aminoglycosides. Probenecid enhances
ac
ticarcillin. inactivated
1. Mainly absorbed from small intestine. It is partly
betalactamase. It is highly
cy
cy
cy
Al It is sensitive to juice.
It crosses by gastric
Pseudononas, Proteus and Klebsiella.
y
2. Readily diffuses into body fluids. Penetration

into CSF is poor.
So it is useful in neonatal meningitis. reached in presence of meningeal
on But high concentration is
It is an amidino penicillin. It has no action
- inflammation.
But is highly
and less ffective against Proteus. 3. Mostly eliminated in urine in a
metablised form.
It is bactericidal.
st E. coli, Salmonella and Shigella.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
239
Telegram - Study Pharmacy238 gram-negative bacteria. Also it has better tissue penetration. It is
St
St
St
St
Adverse reactions: effective against respiratory tract infections, cervicitis and urethritis.
on oral administration.
1. Nausea, vomiting and epigastric pain
Miscellaneous antibiotics
ud
ud
ud
u
fever, urticaria and dermatitis.
2. Allergic reactions like
cholestatic hepatitis and jaundice. LINCOMYCIN
3. Hepatic dysfunction like
y
Source: It is produced by Streptomyces lincolnesis.
Ph
Ph
Ph
divided doses. It is mainly bacteriostatic. It is effective
1. Erythromycin tablets-1 to 2 g. daily in Antibacterial activity:
ha
ethylsuccinate injection for intramuscular and against Gram- positive organisms like Streptococci, Staphylococci and
2. Erythromycin
ar
ar
ar
intravenous injection. Pneumococci.
r
3. Erythromycin glucoheptonate injection Mechanism of action: It acts by inhibiting protein sy nthesis by

ma
ma
ma
ma
4. Erythromycin lactobionate injection bacterial ribosomes.
Therapeutic uses: Absorption, fate and excretion : It orally effective.

is It is
c
c
distributed in liver, spleen, kidneys and lungs. It does rot bind to
In patients allergic to penicillin.
y
y
1.
organisms. CSF except in meningeal inflammation.
2. Infections caused by penicillin resistant
diphtheria. Adverse reactions:
3 In the treatment of
4. Prophylaxis against
rheumatic fever.". nausea, vomiting, diarrhoea and abdominal pain.
1. narrow
drawbacks of erythromycin are: 2. Dizziness, headache and bodyache.
Newer macrolides : The penetration 4. short half
3. poor tissue Jaundice, leucopenia and neutropenia.
spectrum 2. gastric irritation to overcome these
3.
synthesised in order
life. Newer macrolides were Pruritus, proctitis and vaginitis.
St
St
St
St
4.
Roxithromycin, Clarithromycin
problems. The ncwer macrolides are Preparation and dose: Lincomycin hydrochloride monohydrate
and Azithromycin.
ud
ud
ud
u
tablets-500 mg. 3 to 4 times daily.
It is long acting macrolide.
a semisynthetic
1. ROXITHROMYCIN:
erythromycin. It is more effective Therapeutic uses:
Antibacterial spectrum resembles
y
y
against Legionella but less
effective against B. Pertussis. It
is an
. Infections resistant to penicillin and erythromycin:
Ph
Ph
Ph
respiratory, genital tract and skin
in
altemate to erythromycin 2. Individuals, allergic to penicillin and erythromycin.
ha
infections. 3. Acute and chronic osteomyelitis.

ar
ar
ar
antimicrobial
It is a newer macrolide with
2. CLARITHROMYCIN: VANCOMYcIN: It is an antibiotic obtained fron the fungu5
rm
Also it is effective against

spectrum similar to erythromycin. Streptomyces orientalis. It is bactericidal and acts by inhibiting cell
ii) Other atypical
ma
ma
ma
conmplex (MAC) and
i) Mycobacterium avium wall synthesis. It is effective against Gram-positive organisms.
It is
tract infections, skin
is usefui in respiratory
ac
ineffective orally. Also it produces pain on intramuscular injection.

cy
cy
cy
s and otitis.
So it is administered by intravenous injection at a dose of g. daily.
2
group known as azalide
y
CIN: It belongs to a new FUCIDIN: The fungus Fusidium coccineum produces fucidic acid.
macrolides in that the lactone ring contains a
from has Fucidin is the sodium salt of fucidic acid. It has a steroidal structure.
, it is an azalide congener of erythromycin. It
it acts against certain But it does not have hormonal effects.
as erythromycin. But
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
241
240 Gram-negative organisms including E.coli., M. tuberculosis
organisms and
St
St
St
St
Fucidin effective against Gram-positive
is Salmonella and Shigella. It hasa bactericidal effect. Kanamycin is
erythromycin.
Neisseria. It acts synergist cally with
peniciliin and ineffective on oral administration. It is administered by intramuscular
injection. It is eliminated through kidneys by glomerular filtration.
ud
ud
ud
u
gastrointestinal disturbances
Adverse reactions o1 fucidin are
and local irritation on parenteral
administration. Adverse reactions: 8th nerve damage, renal damage and
y
a polypeptide antibiotic
obtained from Bacilhus curarimimetic action on skeletal muscles (like streptomycin)
BACITRACIN: Bacitracin i:.
antibacterial
thiazolidine ring. It has an Uses: Infection of urinary tract, respiratory tract and in tuberculosis.
Ph
Ph
Ph
suhtilis. Its structure contains a cell wall
inhibiting
ha
penicillin, it acts by
spectnum similar to penicillin. Like
not readily occur. GENTAMICIN: This aminoglycoside antibiotic is produced by
synthesis. Resistance tor baciracin does
ar
ar
ar
It is effective against E. coli,
it is Micromonospora purpura.
is ineffective orally. So
r
it
Being a polypepi ie, Pseudomonas, Proteus and Salmonella. It is bactericidal and it acts
ma
ma
ma
ma
administered by intramusciular injection. by inhibiting protein synthesis. Gentamicin is not significantly
nausea, albuminuria and nitrogen absorbed after oral administration. So it is given by intramuscular
Adverse reactions: Anorexia,
injection. It does not penetrate into CNS or CSF. It is eliminated
c
c
retention.
intestinal through urine by glomerular filtration.
y
y
dressing wounds and as an
Uses: Topical application for
antiseptic. Adverse reactions: Skin reactions and plhotosensitisation on topical
application, renal damage on parenteral administration.
AND OTHER ANTIBIOTICS Uses: As an intestinal antiseptic and for infected skin lesions.
73. AMINOGLYCOsIDES
MAINLY AGAINST GRAM
EFFECTIVE AMIKACIN: It is semisynthetic aminoglycoside. Its antibacterial
a
NEGATIVE ORGANISMS activity, adverse reactions and uses are similar to kananmycin.
St
St
St
St
Amikacin is highly effective against Pseudomonas.
Aminoglycoside antibiotics NEOMYCIN: It is an antibiotic obtained from Streptomyces fradiae.

ud
ud
ud
u
amino sugars It is effective mainly, against a variety of Gram-negative organisms.
Aminoglycosides are conpounds which contain
aminoglycoside antibiotics include It is bactericidal: Absorption of neomycin from gastrointestinal tract
in a glycosidic linkage.
The
y
y
amikacin, neomycin, is poor. So, it is used as an intestinal antiseptic.
streptomycin, kanamycin, gentamicin,
Ph
Ph
Ph
effective against
tramycetin, and paromom ycin. These anitbiotics are Adverse reactions: Oto-toxicity and nephrotoxicity.
ha
them have three common

Gram-negative bacteria. Also all of
Uses:
ar
ar
ar
toxicities viz.
rm
2) nephrotoxicity 1. For topical application on skin and eyes.

1)ototoxicity
ma
ma
ma
2. As an intestinal antiseptic.
3) neuromuscular blockade
firom Streptomyces 3. In gastroenteritis due to pathogenic E.coli.
ac
STREPTOMYCIN: It is an antibiotic obtained So

for the treatment of tuberculosis.
cy
cy
cy
FRAMYCETIN: It is produced by Streptomyces decaris. Its
giriseus. It is the drug of choice chapter on
y
discussed in detail in the antibacterial activity and toxicity are similar to neomycin. It is not
this antibiotic has been
"Chemotherapy of Tuberculosis" (Chapter 76) absorbed from gastrointestinal tract.
antibiotic obtained from Uses: For local effect on skin and gastrointestinal tract.
KANAMYCIN: It is ar aminoglycoside
It is effective against several
Streptomyces kanamyceticus.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
242
PAROMOMYCIN: antibiotic obtained
It is an from Streptomyces 2 nd generation Cefoxitin, Cefuroxime. Cefaclor.
It is also
St
St
St
St
antibacterial activity is similar to neomycin. 3 rd generation Cefotoxime, Ceftazidime, Ceftizoxime.
rimosus. Its
from gastrointestinal
effective against E. histolytica. lts absorption 4 th generationCefepime, Cefpirome
ud
ud
ud
u
tract is poor.
sterilisation of the bowel. Antibacterial activity: Cephalosporins are effective agai:1st both
Uses: Chronic amoebic dysentry and
y
Gram-positive and Gram-negative bacteria.
Miscellaneous antibiotics
Ph
Ph
Ph
1. The sensitive Gram-positive organisms are Staphylococci,
polypeptide antibiotic obtained from Aerobacillus
ha
COLISTIN: It is a Pneumococci and C.diphtheriae.

It is effective against
Gram-1negative organisms like
ar
ar
ar
colistinus. 2. The sensitive Gram-negative organisins are E. coli
Pseudomonas, E.coli and Shigella. It has a bactericidal effect. It is
r
gastrointestinal tract. So it 1s K.pneumoniae, P. mirabilis and N. gonorrhoea.

not significantly absorbed form
ma
ma
ma
ma
into CSF is poor even
adinistered by intramuscular injection. Entry 3. Insensitive organisms are P. aeruginosa and Bacierioaes.
in presence of meningeal
inflammation.
c
c
injection, skin rashes and Mechanism of action; The cephalosporins are bactericida. They
Adverse reactions: Pain at the site of
y
y
act by the same mechanism as penicillin by inhibiting c:ll wall
renal damage. synthesis of bacteria. But they bind to a different protein of the cell
antibiotics
POLYMYXIN B: Polymyxins are a group of related wall.
Bacillus polymyxa. Polymyxins are
obtained from various starins of
used polymyxin. The
polypeptides. Polymxin B is the commonly Absorption, fate and excretion: Cephalosporins are administered
polymyxins are
antibacterial activity, absorption, toxicities and uses of orally or intravenously. Intramuscular injection is painful. They bind
similar to colistin. to plasma proteins. The extent of protein binding varis with
St
St
St
St
from Streptomyces individual cephalosporins. Penetration into CSF is poor. Most of
CYCLOSERINE: It is an antibiotic obtained
is effective in the treatment of tuberculosis. them areeliminated by tubular secretion. Their elimina tion is
orchidaceous. It
ud
ud
ud
u
decreased by probenecid.
TETRACYCLINES
74. CEPHALOSPORINS, Adverse reactions: The cephalosporins produce:
y
y
EFFECTIVE
AND OTHER ANTIBIOTICS Skin rashes, fever and serum sickness.
Ph
Ph
Ph
1.
AND GRAM
AGAINST BOTH GRAM POSITIVE
ha
2. Eosinophilia, neutropenia and splenomegaly.

NEGATIVE ORGANISMS
ar
ar
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3. Azotemia and anaphylactoid reaction.
rm
4. Renal damage
ma
ma
ma
CEPHALOSPORINS
acremonium.
ac
Cephalosporins are derived from Cephalosporium Therapeutic uses:

nucleus of penicillins.
cy
cy
cy
They have a structural resemblance to 6-APA
1. Infections resistant to penicillin.
y
Classification: 2. Patients allergic to penicillin.
Cephalexin, Cephalothin, Cefazolin. 3. Urinary tract infections produced by E. Coli and Aerobucter.
st generation
a
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
244 245
St
St
St
St
TETRACYCLINES 4. They are excreted mainly in urine by glomerular filtration.
antibiotics. They are
Tetracyclines are broad spectrum
ud
ud
ud
u
Granm-negatve organisms, Adverse reactions:
effective against Gram-positive organisims, 1. Intolerance like skin rashes and photosensitivity.
organisms.
actinomyces, rickettsiae and chlanydia
y
Streptomyces 2. Gastrointestinal disturbances like nausea, vomiting, diarthoea.
Chlortetracyline 1S obtained from
Source:
Ph
Ph
Ph
3. Liver damage like jaundice and fatty changes.
aureofacieus.
ha
tronm Streptomyces rimosus. 4. Renal disturbances like proteinuria, aminoaciduria and

Oxytetracycline is obtuned
ar
ar
ar
catalytic hydrogenation of glycosuria. (Fanconi-like syndrome).
Tetracycline is obtained from
r
5. Dental effects like yellow staining of teeth.

chlortetracycline.
ma
ma
ma
ma
naphthacene derivatives. They 6. Bone changes like decrease in linear growth.
Chemistry: Tetracyclines are radicals.
unsatu:ated cyclohexane 7. Superinfection and deficiency of vitamin K due to inhibition
c
c
contain four partialy
of intestinal microflora.
y
y
Antimicrobial activity:
Pneunmococci, Gonococci, Preparations and dose:
1. Highly sensitive organisms: .
H. ducreyi, Brucella etc. Capsules of tetracycline, chlortetracycline and oxytetracycline
H. influenza, H. pertu.ssis,
E. coli, Aerobacter. -1 to 2 g. per day in 3 or 4 divided doses.
2. Moderately sensitive organisms:
Salmonella, Shigella tc. Injections of oxytetracycline-100 mg. every 6 or 8 hours by
3. Sensitive chlamydia
organisms: Those causing psittacosis, intramuscular injection.
and lynnphogranuloma
trachoma, inclusion conjunctivitis Ophthalmic ointments and eye drops containing tetracyclines.
St
St
St
St
venerui. Therapeutic uses:
Sensitive protozoa: E. istolytica.
ud
ud
ud
u
4. 1. Ricketsial infections like murine, epidemic and scrub typhus.
are bacteriostatic. They act
Mechanism of action: Tetracyclines 2. Chlamydia infections like rachoma and inclusion
ns:
by the following mechanis
y
y
conjunctivitis.
1. Inhibition of enzye
systerms and protein synthesis. Bacillary and amoebic dysentry.
Ph
Ph
Ph
3.
2. Chelation of cations
like calcium and magnesium.
ha
4. Veneral diseases like gonorthoea and syphilis.

glucose.
Interference with phosphorylation of
ar
ar
ar
3.
Semisynthetic Tetracyclines: The senisynthetic tetracyclines are
rm
Absorption, fate and excretion: demethylchlortetracyline, methacycline, lymecycline and

from gastrointestinal
ma
ma
ma
1. Tetracyclines are adequately absorbed doxycycline. The antibacterial spectrum of these tetracyclines does
not differ from natural tetracyclines. But these compounds offer the
ac
tract.
aluminium.
like calcium, magnesium and following advantages:
cy
cy
cy
2. They chelate cations
Milk and antacids c:ntain
these cations and hence they prevent
.
y
tetracyclines should not be Better absorption from gastrointestinal tract.

So
the absorption of teracyclines. 2. Higher and sustained blood levels.
administered with nmilk and antacids.
fluids
distributed in body tissues and 3. Longer duration of action.
3. Tetracyclines are widely
including CSF. 4. Greater facility of parenteral administration.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
St
St
4. Chloramphenicol sodium succinate for parenteral ise. Dose:
CHLORAMPHENICOL Same as oral dose.
ud
ud
ud
u
5. Chloramphenicol ophthalmic ointment.
is a broad spectrum
Source and clhemistry: Chloramphenicol It is now
antibiotic. It is elaborated by Streptomyces venizulae. Therapeutic uses:
y
is nitrobenzene derivative.
prepared synthetically. Chloranmphenicol a 1. Typhoid fever
Ph
Ph
Ph
Antibacterial activity: Antibacterial spectrum closely resembles 2. Influenzal meningitis.
ha
Plague (for which a large dose is required).

that of tetracyclines. It is effective against
3.
ar
ar
ar
organisms. 4. Trachoma, whooping cough and urinary tract infection.
1. A variety of Gram-positive and Gram-negative
r
(more susceptible).
ma
ma
ma
ma
H. pertussis
2. Salm. typhi, H. influenzae and
|75. ANTIFUNGAL ANTIBIOTICS
3. Rickettsiae and chlamidiae.
c
c
is bacteriostatic. It acts
Mechanism of action: Chloramphenicol Fungal infections can occur on the skin, mucous imembranes,
y
y
by inhibiting bacterial protein synthesis. subcutaneous tissues or deep seated organs. These infections can
is completely occur as primary disease or secondary to treatment with antibiotics.
Absorption, fate and excretion: Chloramphenicol distributed
absorbed from gastrointestinal tract. it is uniformly Classification of antifungal antibiotics:
is very high. It
throughout the body fluids. Penetration of CSF . Nystatin
secreted in milk. It is metabolised Topical antifungal
crosses placental bamier and is also antibiotics Pimaricin
in liver by conjugation with glucuronic
acid. The glucuronide formed
Hamycin
St
St
St
St
is rapidly excreled in urine. Trichomycin
Candicidin
Adverse reactions:
ud
ud
ud
u
and
1. Intolerance in the form of skin rashes, drug fever 2. Systemic antifungal Griseofulvin
angioneurotic edema. antibioticss Amphotericin B
y
y
2. Bone marrow depression is very
a important toxicity. It is due
Topical antifungal antibiotics
Ph
Ph
Ph
to nitrobenzene radical. The manifestations are
NYSTATIN: It is a polyene antibiotic obtained from Str-ptomyyces
ha
agranulocytosis, thrombocytopenia and aplastic aneniia.

infants. This occurs due noursei.
ar
ar
ar
3. Gray baby syndrome in neonates and
The intial symptoms are
to lack of glucuronyl transferase.
rm
Antifungal activity:
irregular respiration. They gradually
ma
ma
ma
vomiting, lethargy and 1. Nystatin has no effect on bacteria or protozoa.
and death.
lead to gray cyanosis, shock
It is not absorbed from gut, skin or mucous membranes. lt is
ac
2.
4. Miscellaneous effects ike
headache, depression, menta! to
toxic on parenteral administration. So its use is restricted
cy
cy
cy
confusion and peripheral neuritis. local Candida infections.
y
Preparations and dose Mechanism of action:

1. Chloramphenico capsules -l to 3 g. daily in divided doses. It binds with cell membrane producing changes in pemeability
2. Chloramphenicol palmitate oral
suspension for paediatric use.
and loss of cation.
3. Chioramphenicol
monostcaroylglycolate as a dry syrup.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
248
St
St
St
St
AMPHOTERICIN B: It is a polyene antitungal antibiotic obtained
vaginal tablets or
Preparations: Nystatin tablets. suspension, from Streptomyces nodosus. Depending on the concentration,
it
ud
ud
ud
u
Ointment. acts as a fungistatic or fungicide. It is effective against a variety
Therapeutic úses: of deep seated mycotic infections like Blastomycosis,
y
1. Local Candida inf«ctions of mouth, skin and
vagina. Histoplasmosis and Cryptococcosis. Its absorption from gut is poor.
Ph
Ph
Ph
Also it produces pain on intramuscular injection. So it is
2. Monilial infection of vagina.
ha
antibiotic obtained administered intravenously. It is available as Amphotericin B

PIMARICIN: It is anotlier polyene antifungal
ar
ar
ar
Streptomyces notalensis. It is not absorbed orally. Also
it lotion and Amphotericin B injection.
from
r
is toxic for parenteral use.

ma
ma
ma
ma
Synthetic antifungal agents: In addition to antifungal
and cephalosporium.
Uses: Keratitis due to species of fusarium antibiotics, a variety of synthetic antifungal agents arc available.
It is used as an ointmeiit.
c
c
They are the following
obtained from
y
y
HAMYCIN: It is ano ther polyene antibiotic
well absorbed after oral FLUCYTosINE: It is an oral antifungal agent effective against
Streptomyces pimprina. It is fairly systemic infections. It is widely distributed in tissues including
ingestion. CSF. It is relatively non-toxic for mammalian cells.
It is most
Uses: Vaginal candidia sis and thrush. effective in infections due to yeast and fungi. A few adverse
TRICHOMYCIN and CANDICIDIN: These are polyene
antibiotics. effects are alopecia, bone marrow depression and abnormal liver
Trichomonas and Candida. function.
They are used for treating vaginitis due
St
St
St
St
Systemic antifungal antibiotics CLOTRIMAZOLE: It is used exclusively as a topical agent. It is
toxic on parenteral administration. So it is not useful for systemic
ud
ud
ud
u
griseofiuhvum.
GRISEOFULVIN: It is isolated from Penicillium
fungal infections. Rarely it may produce ,local erythema and
Epidermophyton,
Antifungal activity: It inhibits the growth of blistering.
y
y
It is mainly fungistatic. It acts
Microsporum and Trichophyton.
MICONAZOLE: It is an imidazole derivative with a broad spectrum
Ph
Ph
Ph
by:
of antifungal activity. It also has antibacterial activity. It is useful
ha
1) interfering wita mitosis. in systemic infections of Candida and Aspergillus. It is administered

ar
ar
ar
2) producing abnormal metaphase
configuration. intravenously.
rm
3) disorienting microtubules. KETOCONAZOLE: It is an imidazole derivative with a spectrum

ma
ma
ma
griseofulvin similar to miconazole. But it: can be administered orally. It is more
Absorption, fate and excretion: Small particles of
ac
are absorbed well from the gut. It is

bound to keratin of the skin. effective against Coccidioides.
cy
cy
cy
Excretion is mostly through feces.
y
76. CHEMOTHERAPY OF TUBERCULOSIS

Uses
and body.
1. Ring wom infections of scalp. groin, feet, hands
Tuberculosis is an infectious disease caused by the
2. Fungal infection of the nails. mycobacteria, M. tuberculosis and M. bovis. It was once considered
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
St
St
to be an incurable disease. But now, effective chemotherapeutic
Adverse reactions:
agents are available for its treatment.
ud
ud
ud
u
1.Intolerance like fever, malaise or jaundice.
2. Peripheral neuritis due to pyridoxine deficiency is ai important
y
toxicity.
1. Primary or standard drugs 3. CNS effects like convulsions and psychosis.
Ph
Ph
Ph
Bactericidal Isonicotinic acid
a) 4. Epigastric distress, dyness of mouth and urinary retntion.
ha
hydrazide
Isoniazid tablet, syrup or injection 3 to
ar
ar
ar
Rifampicin Preparations and dose :
mg- per kg. by oral or parenteral route.
r
Streptomycin 5
ma
ma
ma
ma
Pyrazinamide
-
RIFAMPICIN: It is a semisynthetic derivative of rifamycin B
Bacteriostatic Ethambutol (isolated from Streptomyces mediteranei). It is bactericidal and it acts
b)
Para aminosalicylic acid by inhibiting DNA dependent RNA polymerase. It is well absorbed
c
c
on' oral adnministration. It is widely distributed in tissues.
t is
y
y
Thiacetazone
imetabolised to desacetyl rifampicin. This metabolite is equally
2. Secondary or reserve drugs tuberculocidal and undergoes enterohepatic circulation. Adverse
a) Bactericidal Capreomycin reactions : Hepatitis is the major adverse effect. Also it produces skin
Kanamycin rashes, eosinophilia and leucopenia. Rifampicin imparts an orange red
) Bacteriostatic Ethionamide colour to urine, sweat, tear and other secretions.
Cycloserine Dose: 10 mg. per kg. daily by mouth.
St
St
St
St
e=aurdera
Primary or Standard drugs STREPTOMYCIN: It is an aminoglycoside antibiotic. It is obtained
ISONICOTINIC ACID HYDRAZIDE (INH): It is the most effective from Streptomyces griseus,
ud
ud
ud
u
drug.
drug used in the treatment of tuberculosis. It is a tuberculocidal Antibacterial activity: Streptomycin is mainly effectire against
Gram-negative organisms. It is bacteriostatic in low concentrations
y
y
Mechanism of acion: Suggested mechanisms are:
and bactericidal in lhigh concentrations. The sensitive orgaisms are:
Ph
Ph
Ph
1. Inhibition of phospholipid synthesis and damage to cell M. tuberculosis, E. coli and P. aeruginosa (highly sensitive), Strep.
ha
membrane. pyogens, Strep. faecalis, Strep. viridans (moderately sensitive).

Chelation of intracellular and extracellular divalent cations.
ar
ar
ar
2.
Inhibition of the synthesis of RNA and DNA.. Mechanism of action:
rm
3.
Streptomycin combines with bacterial ribosome:i. This
ma
ma
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1.
Inhibition of various oxidative enzymes.
.
4.
prevents RNA-ribosome conmbination.
ac
Absorption, fate and excretion: 2. Streptonmycin induces bacterial ribosomes to synthes se wrong
cy
cy
cy
1. INH is well absorbed on both oral and parentera amino acids and proteins (which are fatal to bacteria).
y
administration. 3. Inhibition of enzymes like xanthine oxidase.
It is distributed in all body tissues and fluids including

CSF.
2. Absorption, fate and excretion:
3. It is mainly metabolised in the liver by acetylation. 1. Streptomycin is poorly absorbed from the gut. So it can be
4. It is almost conpletely exoreted in urine within 24. hours. used as an intestinal antiseptic.
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y
y
Ph
Ph
Ph
h
y
y
252
253
THIACETAZONE: It is a thiosmicarbazone derivative. It is used
St
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It crosses
injection. with INH or as a substitute for PAS. It is absorbed orally.
2. It iswell absorbed on intramuscular
But high placenta and also it is secreted in milk.
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fluids except CSF.
3. It diffuses into ail body
presence of meniigeal
concentration in CSF is achieved in Adverse reactions: Drug fever, skin rashes, anemia, liver and kidney
y
intlammation. damage.
Elimination is through
It ispartly metabo ised in the lever.
Ph
Ph
Ph
4.
kidney by glomeruiar filtration. Secondary or Reserve Drugs
ha
CAPREOMYCIN: It is a polypeptide antibiotic obtained from
ar
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ar
Adverse reactions: Streptomyces capreolus. It is inactivated in the gastrointestinal tract.
streptomycin; abcess and fever
r
1. Nausea and vomiting witlh oral So it is administered by parenteral route. It is effective against
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on intramuscular irjection. mycobacteria resistant to drugs of first choice. Adverse effects are
dyscrasias.
2. Intolerance in the
sormm
of skin rashes and blood allergy, renal disturbances and 8th nerve danmage.
toxicity. It leads to loss of
c
c
3. 8th nerve damage s an important
KANAMYCIN: It is an aminoglycoside antibiotic obtained from
equilibrium and de afiness.
y
y
cylindruria. Streptomyces kanamyceticus. It is effective against mycobacteria
Renal effets like a buminuria and
4. resistant to drugs of first choice. It is completely absorbed from gut.
skeletal muscles.
5. Curarimimetic effect on Adverse effects are nephrotoxicity and 8th nerve damage.
endocarditis.
Superinfection with Candida, leading to
6. ETHIONAMIDE: It is chemically related to INH It is effective
Preparations and dose: against tubercle bacilli resistant to other drugs. It acts by inhibiting
1.Streptomycin sulpnate tablet and syrup 0.5 to
: 2 g. daily in protein synthesis. It is rapidly absorbed from gastrointestinal tract.
effects are
A significant concentration is present in CSF. Adverse
St
St
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St
divided doses.
allergic reactions, gastrointestinal symptoms and neurological
g. daily.
1
2. Streptomycin injec tion: 0.5 to

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nicotinamide. The disturbances.
PYRAZINAMIDE: It is chemically related to
efficacy of pyrazinamide is increased when combined with INH CYCLOSERINE: It is an antibiotic having tuberculostatic effect. It
y
y
in
Pyrazinamide is well abs»rbed from the gut and it is widely distributed is well absorbed from the gut. Significant concentration is present
effect. Dose: 20 to effects are neurological and psychic effects.,
Ph
Ph
Ph
in tissues. Toxic hepatitis is a serious adverse CSF. The serious adverse
ha
35 mg./kg. (maximum 2 5G). Short term regimen for tuberculosis: Tlis common regimen
It is used with other
ar
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ETHAMBUTOL: It is a bacteriostatie drug. used in tuberculosis consists of:
It is effective against
rm
bactericidal drugs as a substitute for PAS.

streptomycin. It is absorbed 1
NH 300 mg
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mycobacteria resistant to INH, PAS and 450 mg
Rifampicin for 2 months
after oral administration
ac
Ethambutol 800 mg
peripheral neuritis.
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Adverse reactions: Op:ic neuritis and Pyrazinamide 1.58
y
followed by:
Dose: 15 mg/kg per day.
1 NH 300 mg
It is a.synthetic compound for 4 months
PARA AMINOSALICY:.IC ACID (PAS): Rifampicin 450 mg
streptomycin or NH. Also the dose is high
which is less potent than
now.
(10 to 15g daily). So, it is rarely used
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y
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Ph
Ph
Ph
h
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254
CHEMOTHERAPY OF LEPROSY
Dose: 600 mg. for two consecutive days in a monti.
77.
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ETHIONAMIDE: It is a fast acting drug than dapsone. But it is more
Leprosy is a disease caused by Mycobacterium leprae. Lesions expensive and more toxic. It is orally effective and is administered daily.
ud
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characteristic features of this
of the skin and peripheral nerves are CLOFAZIMINE: It is a phenazine dye with an anti-inflammatory
tihe treatment leprosy.
disease. The following are the drugs used for
y
effect. It has a weak bactericidal action. It can be used in 1) capsone
Classification of drugs resistant leprosy 2) tuberculoid leprosy 3) for relieving pain of lepra
Ph
Ph
Ph
reactions. It produces a reddish black colour on the skin.
ha
Sulfones Dapsone
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Rifampicin ANTIBIOTICS: Antibiotics such as Ofloxacin, Minocycline and
2. Antitubercular drugs
r
Ethionamide Clarithromycin are tried in the treatment of leprosy. They are 1ried in
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monotheray or in multidrug therapy. They can be used in cases either
Phenazines Clofazimine
allergic or resistant to dapsone.
Antibiotics Ofloxacin
c
c
Minocycline Lepra reaction: The acute exacerbation which occurs during the
y
y
Clarithremycin. course of leprosy is calied as lepra reaction. It occurs due to various
factors like infections, malaria or treatment with sulfones. Lepra
reactions are treated with clofazimine or chloroquine. Dapsone is not
Dapsone is
DIAMINO DIPHENYL SULFONE (DDS, Dapsone):
ae
withdrawn but continued in full doses throughout lepra reactions.
is bacteriostatic. It acts by the
chemically related to sulfonamides. It
same mechanism as sulfonamides.

78. CHEMOTHERAPY OF
completely
Absorption, fate and excretion: Daspone S
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It widely distributed in body URINARY TRACT INFECTIONS
absorbed from gastrointestinal tract. is
high concentration is present in skin, especially
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tissues and fluids. A
eliminated Urinary tract înfection (UTI) occurs in both sexes (cominonly
leprosy affected skin. It is metabolised as glucuronide and
in females). These infections may be acute or chronic. Most f the
in urine.
y
y
urinary tract infections occur due to Gram-negative bacilli. The
Adverse reactions: causative organisms are:
Ph
Ph
Ph
Sensitisation of skin leading to exfoliative dermatitis.
ha
1. Very common E. coli

Hemolysis in patient with G-6-PD deficiency.
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2. Less common Aerobacter
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3. Blood dyscrasias like agranulocytosis. Pseudomonas aeruginosa

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4. Hypothyroidism and goitre. Proteus mirabilis
Klebsiella
ac
at a
Preparations and dose: Tablets of dapsone administered
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dose of 100 mg. daily. Occasional Steptococci and Staphylococci
y
is effective orally.
RIFAMPICIN: It is a bactericidal antibiotic wlhich Classification of drugs:
effects. But it imparts an orange red colour
It no serious adverse
has
to urine, saliva and other secretions. Drugs effective in urinary tract infections can be classifieci as:
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y
y
Ph
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Ph
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y
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257
256
Antibiotics
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Sulfonanides
Syntletic drugs AMPICILLIN: It is a semisynthetic penicillin effective against Gram-
Nitrofurantoin
positive and Gram-negative bacteria. Il is effective oraly and
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Cotrimoxazole
parenterally. It is bactericidal to Proteus, Aerobacter and E. coli.
Methenamine mandalate
CEPHALOTHIN: It is a cephalosporin with an antibacterial activity
y
Nalidixic acid
similar to ampicillin. It is highly effective against Klebsiella
Ph
Ph
Ph
Ampicillin
Antibiotics infections. High cost is a disadvantage.
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Cephalothin
Streptomycin STREPTOMYCIN, KANAMYCIN and GENTAMICIN: These are
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Kanamycin aminoglycoside antibiotics. They are effective against E.coli and
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Gentamicin Proteus. They are effective parenterally. Ototoxicity and

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Fluoroquinalones nephrotoxicity are their disadvantages.
Cycloserine FLUOROQUINALONESs Fluoroquinolones, especially norfloxacin
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Polymyxin B and ciprofloxacin are highly effective. They are now routinely used
y
y
in urinary tract infection. They are useful even if renal function is
Synthetic Drugs and other subnormal. They are ideal agents for nosocomial pyelonephritis and
effective against E.coli
SULFONAMIDES: They are Short acting
sulfonamides complicated cases of urinary tract infections.
iract infection.
organisms causing urinary Long acting sulfonamides are useful CYCLOSERINE: It is a bactericidal agent effective against E. coli
useful.
like sulpladimidine is infections. Its effect is independent of urinary pH.
therapy.
for prolonged bacteriostatic effect against
urinary
POLYMYXIN B: It is a bactericidal drug effective against
NITROFURANTOIN: It kas a activity. t is effective
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reduces its antibacterial Pseudomonas. It is toxic for routine use.
pathogens. Alkalinity
resistant to other drugs.
against infections sulfamethoxazele and
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COTRIMOXAZOLE: It is a
combination of
effect.
79. CHEMOTHERAPY OF SEXUALLY
has a bactericidal
trimethoprim. This combination not be used in TRANSMITTED DISEASES
effect. So it should
y
y
Trimethoprim has a teratcgenic
Ph
Ph
Ph
pregnancy. Sexually transmitted diseases (veneral diseases) are those which
(MANDELAMINE): It is a salt of
ha
METHENAMINE MANDALATE are urinary are transmitted by sexual contact. These diseases nclude syphilis,
mehenamine (both of which bactericidal gonorrhea, non-gonococcal urethritis, chancroid, lymphograuloma
ar
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mendelic acid and acid have
methenamine and mandelic venerum and granuloma ignuinale.
rm
antiseptics). Both agent (e.g. ascorbic acid) may

acidifying
effect at acid pH. So ar
ma
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orally. It
irugs. Methenamine is effective Syphilis
with these
be combined gastric discomfort.
ac
any toxic effect except Syphilis is an infectious disease caused by the spirochete
does not produce It can be
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advantages over other drugs. Treponema pallidum.
NALIDIXIC ACID: It has no
y
resistant to other drugs. Early syphilis: It extends for a period of 4 years since its
used against organisms acquisition. Treatment is as follows.
1. Procaine penicillin - 6 lakh units daily for 10 days.
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y
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Ph
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258 259
Telegram - Study
PAM
Pharmacy
2. units, once two days for
-6 lakh in days. 12
Lymphogranuloma Venerum
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3. Benzathine penicillin 24 nmega units as a single dose.
It is caused by a chlamydia. Tretament is:
Late syphilis: It extends beyond 4 years after its acquisition. It can
ud
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be treated with penicillin at the same dose as in early syphilis. But Tetracycline-0.5 g. 4 times a day for 2 to 3 weeks.
the duration of treatment is 20 days. Granuloma Inguinale
y
Other drugs: Tetracyclines and erythromycin can be used. But It is caused by Donovania granulomatis. Treatment is:
they are less effective than penicillin. These drugs can be used only .
Ph
Ph
Ph
Tetracycline-0.5 g. 4 times a day for 2 weeks.
when the patient is hypersensitive to penicillin.
ha
2. Ampicillin-250 mg. 4 times a day for 3 to 11 weeks
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Gonorrhea ADS
r
Gonorrhea is caused by Goncoocci.

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AIDS (acquired immuno deficiency syndrome) is caused hy a
Treatnment of acute uncomplicated cases of gonorrhea:
1. Penicillin G 4.8 mega units with g. of probenecid.
1
retrovinus called Human immunodeficiency virus (HIV).
transmitted by sexual intercourse, contaminated needles and syriuges
I
is
c
c
2. Ampicillin -3.5 g. with
1
g. of probenecid. and by blood transfusion. It is also transmitted from the mothe to
y
y
3. Amoxycillin -3.5g with
1
g. of probernecid. the foetus. This virus infects lymphocytes, brain cells and other cells.
mega unit of
1
It affects the immune system leading to infections and cancer. Drath
4. Procaine penicillin 1.2 mega units with
crystalline penicillin. This is followed by two such injections is certain and there is no cure for AIDS.
at an- interval of 24 hours. In patients hypersensitive to AZIDOTHYMIDINE: It is a synthetic analogue of thymidine. It icts
penicillin, other drugs like tetracycline,kanamycin, by inhibiting viral transcriptase. It crosses placenta. Also, it is secre ted
cephaloridine or cotrimoxazole can be given.
Treatment of complicated cases of gonorrhea:
di in milk: It can be given orally and intravenously. It decrea ses
mortality. Dose: 200 to 250 mg. orally every 4 to 8 hours.
St
St
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1. Procaine penicillin-2 mega units daily for 8 to 10 days.
DIDANOSINE: It is a nucleoside analogue of deoxyacdenosine. It acts
2. Tetracycline-0.5 g. four times daily för 7 to 10 days.
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by 1. getting incorporated into viral chains 2. by inhibiting revese
Non-gonococcal urethritis transcriptase. It is used in patients with advanced HIV infections.
y
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This may be due to Chlamydia rachomatis infection of urinary EFAVIRENZ: It is a non-nucleoside. It inhibits reverse transcriptase.
tract. The treatment is: Unlike other drugs, it crosses blood brain barrier. t is administered
Ph
Ph
Ph
Tetracycline-500 mg. 4 times a day for 2 weeks. once a day. Development of resistance is slow for efavirenz.
ha
1.
2. Doxycycline-200 mg. initially followed by 100 mg. every 24 SAQUINAVIR: It is a peptide derivative. It acts by inhibiting HV
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hours for 2 weeks. .protease enzyme. It is now used along with azidothymidine.
rm
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Chancroid
It is caused by Ducrey's bacillus: This organism is insensitive
80. CHEMOTHERAPY OF VIRAL INFECTIONS
ac
to penicillin. Treatment is
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:
A virus consists of nucleic acid enclosed in a shell of protein.

500 :mg oral 4 times a day for 7 to 10 days.
y
1. Erythromycin
it does not have a cell wall or enzymes as present in bacteria. Viruses
2. Azithromycin 1g. oral daily are of two types:
3. Ciprofloxacin 500 mg twice a day for 3 days. 1. DNA containing viruses.
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y
y
Ph
Ph
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h
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y
260
261
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2. RNA containing vi:uses.
parasitic to the host cell. So an gonadotoxic and embryotoxic in animals. So it is contraindicated
The viruses are in imately also. during pregnancy. It is well tolerated as an aerosole.
toxic effect on the host cell
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antiviral drug is likely to produce
Natural substances
Classification of antiviral agents:
y
INTERFERONS: Interferons are produced by body cells in response
lodoxuridine to viral infections. The interferons protect the cell from subsequent
Ph
Ph
Ph
1. Synthetic antivira
Thiosemicarbazones viral infections. They do not produce toxicity to the host. Interferons
ha
agents
Amantadine are proteins with a molecular weight of about 63,000. The are
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Ribavirine effective against both DNA and RNA viruses. Interferons are species
r
Interferons specific. For example, interferons from chicks produce antiviral

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Natural substances
Gamma globulin effects only in chicks but not in mice or humans.
Mechanism: The interferons do not prevent the penetration of virus
c
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Synthetic antiviral afents into cells. Also they do not inactivate the virus. They inhibit the
thymidine. It acts by
y
y
IODOXURIDINE: It is chemically related to replication of a virus.
synthesis of DNA. So the utilisation
competing with thynmidin: in the GAMMA GLOBULIN: Albumin, alpha, beta and gamma globulins
It interferes with DNA synthesis of host
of thymidine is preventel. are the plasma proteins. Gamma globulin carries antibodies.
Ganmma
use.
also. So it is too toxic for systemic globulin is synthesised by cells of lymphoid system.
comea and herpes encephalitis.
Use: Herpetic ulcreatiois of Gamma globulins against a particular infection can be obtained.
THIOSEMICARBAZONES: Methisazone is the antiviral from: 1. Patients recovering from the disease. 2. Patients immunised
against that disease. Gamma globulin thus obtained is called human
St
St
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ffective against vaccinia and small pox virus.
thiosemicarbazone. It is e
It is given at a dose of 5 g. daily,
for one specific gamma globulin. Gamma globulins can be used for
It is effective by mouth.
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diarrhoea, blood dyscrasias therapeutic and prophylactic effects.
week. Adverse effects: 11ausea, vomiting.
and liver damage.
81. DISINFECTANTS AND ANTISEPTICS
y
y
is effective against
AMANTADINE (1-Adamantanamine): It
rubella). It acts by
Ph
Ph
Ph
influenza, munmps and
myxoviruses (which cause A disinfeclant or germicide is a substance which kills
into host cell. So it is useful
as
ha
preventing the penetration of virus effects are micro-organism in the inanimate environment.
establised infections. Adverse
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a prophylactic than agaiist
disturbances. An antiseptic is a chemical disinfectant that can be safely
rm
psychic and neurologica:

applied to skin or mucous membranes
synthesis. It has a
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ACYCLOVIR: It acts by inhibiting viral DNA
affecting the host. It is highly Classification of antiseptics and disinfectants:
ac
selective effect on the virus without

id Salicylic acid and Boric acid
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effective against herpes viruses. Acids Benzoic acid,
Sodium and potassium hydroxide
y
analogue. It has a broad Alkalies

RIBAVIRINE : It is a purine nucleoside is Formaldehyde and Gluteraldelhyde
against DNA and RNA viruses. It 3. Aldehydes
spectrum of antiviral activity effective against Alcohols Ethyl alcohol
the drug of choice
tor Lhasa fever. It is also 4.
syncytial. virus. it is teratogenic, 5. Sufactants Soaps and Benzalkonium
intluenza virus and respiratory
Chlorine and lodine
6. Halogens
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y
y
Ph
Ph
Ph
h
y
y
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7. Plhenols Phenol and Cresol Phenols: Phenol and cresol have bactericidal and fungicidal
ud
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8. Oxidising Hydrogen peroxide and Potassium effects. Both have corrosive effect on gastrointestinal tract.
agents permanganate
Crystal violet and Acriflavine Oxidising Agents : Hydrogen peroxide produces antiseptic effect
9. Dyes
y
10. Heavyy Silver, Zinc and Mercurial compounds. due to release of nascent oxygen. It is used for cleaning wounds and
abscess. Potassium permanganate has oxidising and ast ingent
Ph
Ph
Ph
metals,
properties. It is used as a gargle and mouth wash.
ha
Acids
ar
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Dyes: Crystal violet is a potent antiseptic. It is applied topically
1. Benzoic Acid: It is used as a preservative and for treating fungal
r
for the treatment of bums, boils, impetigo and mycotic infections of

infections.
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the skin. Acriflavine, an acridine dye is an antiseptic. It is used for
2. Salicylic Acid: It has bacteriostatic, fungicidal and keratolytic the treatment of infected burns and wounds.
properties. Whitefield's ointment contains salicylic acid and benzoic
c
c
Heavy Metals
acid. It is widely used in fungal infections.
y
y
1. Siver nitrate has antiseptic and astringent properties. It is used
3. Boric acid It is a bacteriostatic and fungistatic agent. It is used as eye drops in conjunctivitis.
as an aqueous solution, drops or lotion. 2. Zinc sulphate is used as an astringent lotion. It is used for
indolent ulcers and to assist granulation.
Alkalies: Alkalies like sodium and potassium hydroxides are Mercury compounds act by inhibiting SH enzymes of bacteria.
highly iritant. So they are used only for disinfecting excreta. Mercuric oxide is used as an ointment in the treatment of
conjuctivitis.
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Aldehydes: Formaldehyde is highly imitant. It is used for
disinfecting surgical gloves, instruments and excreta. Gluteraldehyde
82. CHEMOTHERAPY OF MALARIA
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is less irritant. It is used for sterilising rubber, plastic and metal
appliances. Malaria is caused by a parasitic protozoa which belongs o the
y
y
genus Plasmodium. The symptoms of malaria are fever, rigor and
Alcohols: 70 percent solution of ethyl alcohol is used as antiseptic. splenomegaly.
Ph
Ph
Ph
Itis also used for sterilisation of surgical instruments.
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Life cycle of Malarial Parasite:

Surfactants Surfactants. are chemical compounds which lower the
ar
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The life cycle of malarial parasite can be classified into:
surface tension of solutions. They are also called as detergents. Soap
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is an anionic surfactant. It is effective against Gram-positive and 1. An asexual cycle which occurs in the infected host
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ma
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acid-fast organisms. Benzalkonium is a cationic surfactant. It is 2. A sexual cycle which occurs in the mosquito.
ac
useful for cleaning and disinfecting bums, wounds, surgical Asexual cycle
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nstruments etc.
The stages are as follows
y
Halogens: Chlorine is used for purification of water. Chloramine 1. When a female anopheles mosquito bites a normal individual,
acts by releasing chlorine. it is used for disinfection. lodine has a it introduces sporozoites into circulatior
bactericidal, fungicidal, amoebicidal and sporicida! effects. lodine is 2. The sporozoites ar immediately carird to the liver. They
used for the treatnient of wounds and abrasions. grow and sponilate in the liver.
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Ph
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Telegram - Studymerozoites
Pharmacy
3. Later,
264
are released
265
from the liver. These merozoites
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enter the red blood cells and multiply there. The rupture of
b) Therapeutic classification
red blood cells releases more merozoites. These merozoites 1. True causal prophylactics:
These drugs destory the sporozoites
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attack fresh red blocd cells and nultiply there. Fever and chill before they enter the liver. No drug of this type is available.
of malaria coincides with the rupture of red blood cells.
2. Causal prophylactics: They are primaquine, proguanil and
y
4. Some of the merozo:tes go to the liver and multiply there. This pyrimethamine. These drugs prevent the maturation of sporozoites
in
Ph
Ph
Ph
is called exoerythroc ric cycle. Merozoites now released from the liver. So the liberation of merozoites from the liver is
prevented.
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the liver produce relapse of fever.

3. Suppressives: They are quinine, chloroquine,
mepacrine,
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5. Some of the merozoites differentiate into male proguanil and pyrimethanmine. These drugs prevent the
rupture of
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(microgametocytes) and female (macrogametocytes) sexual

erythrocytes. The liberation of merozoites is prevented.
forms. This
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prevents fever and chill.
Sexual cycle: When a niosquito bites an infected individual, these
gametocytes are sucked along with blood. In the gut wall of 4. Radical curatives: They are panmaquine, primaquine and
c
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mosquito. the male and fenale gametocytes unite to forni a zygote. pentaquine. These drugs eradicate exoerythrocytic phase. So relapse
y
y
This later develops ir to ookinate and oocyst. From the oocyst, of fever is prevented.
sporozoites are released. The sporozoites are introduced when the 5. Gametocides: Most of the antimalarial drugs have
ganmetocidal
mosquito bites another indi vidual. The asexual cycle now continues effect. Destruction of gametocytes prevents a fresh individual
from
in the host. getting malarial infection.
Classification of Antimalarial drugs
a) Chemical classification oharn QUININE: Quinine is an alkaloid obtained from cinchona bark. It
is the oldest antimalarial drug.
cerebral malaria.
It is still used in the treatment of
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1. Cinchona alkaloids Quinine Pharmacological actions
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2. 4-aminoquinolines Chloroquine a) Antimalarial action: Quinine is a suppressive agent. So it
Hydroxychloroquine prevents fever and chill of malaria.
y
y
Amodiaquine
b) Other actions Quinine has:
.
Ph
Ph
Ph
3. 8-aminoquinolines Pamaquine
local anaesthetic effect.
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Primaquine
Pentaquine 2. quinidine-like effect on the myocardium.
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3. hypotensive effect.
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Acridines Mepacrine
4. gastrointestinal-irritant effect.
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5. Biguanides Progunail
5. analgesic and antipyretic effect.
Chlorproguanil
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Cycloguanil 6. oxytocic effect.

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7. curarimimeic effect.
y
6. Diamidopyrimidines Pyrimethamine
7. Miscellancous Mefloquine
Absorption, fate and excretion : Quinine is well absorbed
from gastrointestinal tract. About 7% is. bound to plasma proteins.
Halofantrine
It does not enter into CSF, but erosses placental barier. Quinine is
Qinghaosu
metabolised in the liver and excreted in urine.
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ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
266
St
St
St
St
3. Miscellaneous like psychotic episodes, seizures and ototoxiCity.
Adverse reactionss uses: Chloroquine can be used in malaria,
ud
ud
ud
u
agranulocytosis, Therapeutic
1. Intolerence the form of skin rashes,
in amoebiasis, giardiasis, taeniasis, and arthritis.
HYDROXYCHLOROQUINE and AMODIAQUINE: Thesce two
y
lheadaclhe, ringing in ears
2. Cinchonism characterised by nausea, dugs have similar actions and uses as chloroquine.
vision, colour vision and
Ph
Ph
Ph
(tinnitus), deafness, blurred 8-amino
PRIMAQUINE: Primaquine belongs to the group of
ha
photophobia. gametocytes.
hemoglobinuria and quinolines. It acts on the exoerythrocytic cycle and on
occurring as hemolysis,
3. Black water fever
ar
ar
ar
infection. mature
fever. This occurs in chronic
Plasmodium falciparum Some of the gametocytes are destroyed. The remaining cannot
r
and ventricular
effects like renal damage in the mosquito.
4. Miscellaneous
ma
ma
ma
ma
absorbed on
arrhythmia. Absorption, fate and excretion: Primaquine is well
in liver, lungs. brain and heart.
oral administration. It is concentrated
c
c
It is rapidly metabolised and eliminated in urine.
y
y
Quinine bisulphate
as tablets - 300 to 600 mg
Quinine hydrochloride Adverse reactions:
Quinine ethylcarbonate
injection-300 to 600 mg. by 1. Nausea, vomiting and epigastric distress.
Quinine dihydrochloride
2. Leukopenia, agranulocytosis and methemoglobinemia
intramuscular or intravenous injection.
3. Hemolysis in G-6-PD deficiency.
antimalarial, analgesic and antipyretic.
Therapeutic uses: As an PAMAQUINE and PENTAQUINE: Blood dyscrasiatic effects are
derivative. It has
CHLOROQUINE: It is a4 aminoquinoline more with these drugs. So they are not used at present.
St
St
St
St
acts by inhibiting the incorporation
suppressive effect like quinine. It The other actions PROGUANIL: Proguanil is a biguanide. It has
suppres sive and
and DNA of plasmodia.
of phosplhate into RNA gameto« ytes by
ud
ud
ud
u
causal prophylactic effect. Also it affects
of chloroquine are extraintestinal preventing their maturation in the mosquito. Proguanil is slowly
1. Effectiveness against
giardiasis, taeniasis and tract. It is 2ound to
but adequately absorbed from gastrointestinal
y
y
amoebiasis. It is excretec through
plasma proteins to the extent of 10 percent.
Ph
Ph
Ph
and antihistaminic effect.
2. Anti-inflammatory urine. It is free from significant toxic effects except
gastro ntestinal
ha
activity.
3. Local anaesthetic
and anticholinesterase
disturbances. Rarely it produces hematuria and decrease
in
ar
ar
ar
myocardium.
4. Depressant effect on leucocyte count. The suppressive dose is 309 to 600 mg. by
rm
: Chloroquine is well
absorbed
Absorption, fate and excretion initially. This is followed by 300 mg. daily for 5 days.
mouth
ma
ma
ma
in liver, spleen, kidney
It is distributed
from gastrointestinal tract. eliminated in urine. Chlorproguanil and cycloguanil have similar but prolonged
ac
in the liver and

and lungs. It is metabolised
cy
cy
cy
antimalarial action.
Adverse reactions:
y
scalp PYRIMETHAMINE It belongs to the gro p of

rashes, bleaching of the
1. Intolerance in the form of skin causal prophylactic
diamidopyrimidines. It is a suppressive and
hair, cye lashes and eyebrows.
like loss of accomnmodation,
blured vision, agent. Also like proguanil, It prevents the maturation of
2. Visual disturbances. and lenticulai opacitics
eyes
diplopia, difficulty in. focussing retinopathy). gametocytes in the mosquito.
(collectively called chloroquine
***
*
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St
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St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
Classification of drugs
St
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Pyrimethamine is incompletely absorbed :
from small
intestine. It is slowly eliminated in urine. A. Tissue amoebicides
Rarely it produces
ud
ud
ud
u
For both intestinal and Metronidazole
MEFLOQUINE: It is a quinoline methanol extraintestinal amoebiasis Tinidazole
y
compound. It is
administered as a single dose (i.5 g.). It is Secnidazole
highly effective against
Ph
Ph
Ph
P. falciparum resistant to Emetine
chloroquine. lt acts against erythrocytic
ha
stage. Dehydroemetine
.
ar
ar
ar
For extraintestinal Chloroquine
HALOFANTRINE It is a
phenanthrene methane compound. It
r
amoebiasis only
is as atfective as ch oroquine.
ma
ma
ma
ma
Also it is effective against B. Luminal amoebicides
chloroquine resistant strains of malarial parasite. Diloxanide furoate
It is palatable Halogenated hydroxy
unlike other antimalarial drugs.
c
c
quinolines
y
y
Adverse effects : rise n liver enzymes, cough, Tetracycline.
G.I. disturbances,
prurtus and rashes.
QINGHAOSU It is olbtained from the chinese
:
IMIDAZOLE DERIVATTVES
plant Artemisia
annua Lin. It is available as artemisine, artemeter
and artesunate. METRONIDAZOLE: It is an imidazole
Tablets and intravenous formulations should derivative effective against
be dissolved in 5% amoeba, giardia and a variety of anaerobic bacteria.
NaHCO3 immediately b:fore use. This It is effective in
drugs is well tolerated. both ntestinal and extraintestinal amoebiasis.
It is almost completely
St
St
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St
absorbed from intestine. It achievs a significant
concentration in
vaginal secretion, semen, saliva and CSF. It is
metabolised in the liver
ud
ud
ud
u
by oxidation and glucuronide conjugation. It is
83. CHEMOTHERAPY OF AMOEBIASIS excreted in urine.
Adverse reactions: anorexia, nausea and a signficant metallic
y
y
in the mouth.
taste
Ameobiasis is a protozoal disease
caused by Entamceba
Ph
Ph
Ph
histolytica. Amoebiasis cin be classified as:
Uses: amoebiasis, giardiasis and anaerobic
infections.
ha
1. Intestinal ameobiasi
i with syniptoms of dysentry, amoeboma
ar
ar
ar
etc. Dose: 600 to 800 nmg. orally, three times
a day for 5 to 10 days.
rm
Extraintestinal amoebiasis which may affect TINIDAZOLE: It is in imidazole derivative.

liver, lungs or
ma
ma
ma
brain. It is chemically related
to metronidazole. It is effective in anioebiasis
and giardiasis. Dose:
ac
Life cycle of E. histolyti:a: E. histolytica exists in two forms: 600 to 800 mg. 3 times daily for 5 days.
cy
cy
cy
I. The cyst which is an inactive form. SECNIDAZOLE: It is a newer nitroimidazole
y
2. The trophozoite which is compound. Tt has a

an active form. longer half life. It is an effetive antiamoebic drug.
Dose: 500 mg as
Cysts enter the intest ine as contamination a single dose.
of water and food.
In the intestine, trophozoices
are released from the cyst. The
trophozoites may remain in t'ie colon or invade
other organs like liver.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
274
St
St
St
St
Preparations and dose: Metronidazole tablet-200 mg. thrice for
1. a
SURAMIN SODIUM: Iu is complex organic urea compound.
days. It is also available as gel.
ud
ud
ud
u
10 a
It is not absorbed from gastrointestinal tract. Intramuscular
injection
necrosis. So it is administered by intravenous trichomoniasis, giardiasis and amoeb asis.
produces pain and loca!
So the effect
Therapeutic uses: In
y
injection. lt is intensively bound to plasma proteins.
of a single dose lasts for 3 months. Giardiasis
Ph
Ph
Ph
:
ha
substitute It
can be. used as Giardiasis is caused by a protozoa, Giardia lamb. ia.
It a
2. PENTAMIDINE ISETHIONATE
nausea, vomiting.
produces cholera-like symptoms such as anorexia,
ar
ar
ar
for suramin.
is ti:e drug
diarrhoea, abdominal pain and loss of weight. Mepacrine
r
Tryparsamide, Mel B, (Melarsoprol)

3.ORGANIC ARSENICALS of choice for giardiasis. Drugs like metronidazole, 4-aminoquinolines.
ma
ma
ma
ma
and Mel W (trimelarson) are effective in African
trypanosomiasis.
tinidazole and furoxone can also be used.
But they are more toxic.
c
c
South American trypanosomiasis No
: effective drug iS
85 ANTHELMINTIC DRUGS
y
y
available at present for the treatnment of this disease.
Trichomoniasis Anthelmintics are drugs used in the treatment of worni

gastrointestinal tract
This disease is caused by protoza, Trichomonas
a vaginalis. Itis infestations. Wom infestation may occur in the
tissues (e.g. filar.a). An
(e.g.) round wom, tape worm, hook wom
and purulent vaginal or in
characterised by profuse, frothy, malodorous
di:.charge. For local treatment, drugs like halogenated hydroxyquinolines
organic arsenicals, furazolidone etc. can be
used. But metronidazole is
anthelmintic may act as:
JCLL
Vermifuge which expels the worms by paralysing them
1
St
St
St
St
cecive, even when given oraily.
2. Vermicide which kills the woms.
It is
METRONIDAZOLE: It is a nitroir:idazole compound.
ud
ud
ud
u
lamblia.
effective against Trichomonas, E. histolytica and Giardia Classification of drugs:
absorbed
Absorption, fate and excretion: Metronidazole is well Mebendazole
y
y
Round womm
is eliminated in urine, partly in a free Albendazole
from gastrointestina! tract. it
Ph
Ph
Ph
form. Its metabolites may stain urine Pyrantel
form and partly in a metabolised
ha
Minor quantity is eliminated in saliva and

reddish brown in colour. Mebandazole
Hook worm
ar
ar
ar
milk. Albendazole
rm
Pyrantel
Adverse reactions:
ma
ma
ma
Thread wori
Mebendazole
A metallic and unpleasant taste. 3.
ac
1.
Albendazole
Anorexia, nausea and epigastric distress.
cy
cy
cy
2. Pyrantel
y
Dizziness, vertigo, ataxia and incoordination.

***
3 Albendazole
1ape wom
4. No blood dyscrasias except occasionai ncutropenia. Praziquantel
5. Urticaria, flushing and pruritus. Niclosamide
**
6. Dryness of mouth, vulva or vagina. Hydatid disease Albendazole
7. Disultiram-like effect with alcohol.
5.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
Headache, drowsiness and abdominal cramps.
St
St
St
St
276 2.
3. Rarely hypotension and bradycardia.
ud
ud
ud
u
Broad spectrum anthelmintics Visual disturbances, leukopenia and hematuria.
4.
MEBENDAZOLE: t is a benzimidazole derivative. It is a broad to its toxicity and
The use of thiabendazole is now limited due
y
spectrum anthelmintic. It is effective against round worm, hook work side effects.
and thread worm. Alsc, it is effective in mixed worm infestations and
Ph
Ph
Ph
hydatid desease. Drugs used in Round Worm infestation
ha
in the small
Mechanism of action Round wom (Ascaris lumbricoides) usually lives
ar
ar
ar
gastrointestinal tract. The
intestine. But it wanders all over the
r
1. Inhibition of cytoplasmic microtubule synthesis used against round worm infestation.

following are the drugs
ma
ma
ma
ma
2. Inhibition of glucose uptake
1. PIPERAZINE: Piperazine acts by paralysing the muscles of
succinate production.
3. Secretion of anticholinesterase. round wom. This occurs due to inhibition of
c
c
elinminated by peristaltic movements of the
Adverse reactions: The paralysed worms are
y
y
1.Mild nausea, vomting and diarrhoea gut.
2. Mild abdominal pain Preparations and dose: Peperazine is available ds citrate, adipate
mouth.
3. Reversible neutropenia and agranulocytosis and hydrate salts. Dose: 5 g. as single dose by
derivative. It acts by
4. Hypospernia in higher dose. 2. THIABENDAZOLE: It is a benzimidazole
parasite. Dose:
ALBENDAZOLE: It is also a benzimidazole. Aiso itis a broad interfering with essenial metabolic pathways of the
It is repeated for 3 successive
spectrum anthelmintic. It is effective against round wom, hook worm, 25 mg. per kg. after evening meal.
St
St
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St
thread worm, and tape wom infestations. Also it is effective in days after breakfast.
derivative. It has a broad
hydatid disease. 3. MEBENDAZOLE: It is a benzimidazole
ud
ud
ud
u
spectrum of anthelmintic activity. Dose: 100 mg. twice daily for 3
Mechanism of action: It blocks glucose uptake in the larval and
adult stage of the parasite. This depletes glycogen stores and decreases days.
y
y
producing depolarizing
the formation of ATP.This eads to imunobilization and death of the 4. PYRANTEL PALMOATE: It acts by
worm. This leads to paralysis of the
Ph
Ph
Ph
worm. neuromuscular blockade of the
as a single dose.
ha
Adverse reactions: No side etfect for one to three day course. Rare wom. Dose: 10 mg. per kg.
toxicities are It acts by producing contracture of the muscles
ar
ar
ar
5. TETRAMISOLE:
the worm. Also it inhibits
1. Epigastric distress, nau sea and diarrhoca. of the worm. This leads to paralysis of
rm
Dose: 2.5 to 5 mg. per kg. as a single

ma
ma
ma
2. Headache and dizzines: the production of succinate.
3. Hepatotoxicity, bone marrow depression and alopecia on long dose.
ac
term use (e.g hydatid disease). anthelmintic drug. It is

7. ALBENDAZOLE: It is a broad spectrum
cy
cy
cy
THIABENDAZOLE: It is the. first benzimidazole anthelmintic used at a single dose of 400 mg.
y
introduced for treatment. It :s practically useful in all types of

intestinal worms, Mechanis.i »f action is same as mebendazole. It Drugs used in Tape Worm infestation
beef tape
also has analgesic, antipyretic and antiinflammatory actions. The type of tape worms which commonly occur are
tape worm. The head (scolex) of these worms is
Adverse reactions. wom and pork
*
.Nausea, vomiting and dizziness

St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
St
St
St
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1. Bone mairow depression leading to leucopenia, ane mia and
c)Pyrimidine antagonists Fluoro-uracil
ud
ud
ud
u
thrombocytopenia.
Fluorodeoxyuridine
Damage of intestinal mucosa leading to ulceration, perforation
Cytosine arabinoside
and hemorhage.
y
3. Radioactive isotopes Radio iodine Damage of hair follicels causing alopecia.
Ph
Ph
Ph
Radio phosphorus
4. Damage of gonads causing inhibition of spematogunesis in
ha
Radio gold males and amenorrhoea in females.
ar
ar
ar
4. Miscellaneous ii) Emetic effect The alkylating agents produce nausea and vomiting
r
a) Vinca alkaloids Vincristine i) Immunosuppressant effect: The alkylating agents suppress

ma
ma
ma
ma
Vinblastine immune response by blocking antibody production.
b) Antibiotics Actinomycin-D
iv) Radiomimetic effect: Similar to radioactive isotoes, the
c
c
Mitomycin-C alkylating agents produce the following effects
y
y
Rubidomycin . Intestinal ulceration and bone marrow depression.
c) Others -Asparaginase
2. Foetal abnornnalities and genetic changes.
Procarbazine
Inhibition of antibody production.
nag
3.
Cis-platin
So, the alkylating agents are also called as radiomimetic agents'.
d) Hormones
(O Androgens
Estrogens Absorption, fate and excretion: Except mechlorethamine, all the
St
St
St
St
produces
Progestins other alkylating agents are effective orally. Mechlorethamine
Corticosteroids severe iritation. So it is administered intravenously. These irugs are
ud
ud
ud
u
quickly distributed in the body. They are hydrolysed in tissues.
Alkylating agents
Therapeutic uses : The alkylating agents can be used in
y
y
Initially sulfur mustard was used in World War I. Later nitrogen the treatment of: 1) Hodgkin's disease 2) Chronic leukemia
mustards were developed and used in World War II. But their
Ph
Ph
Ph
3) Bronchogenic and ovarian carcinoma.
ha
cytotoxic properties were discovered only after World War

Antimetabolites
ar
ar
ar
Mechanism of action
rm
in
1. The alkylating agents ionise to fonm ethyieninmonium cations. A metabolite is a chemical substance which takes part
ma
ma
ma
These cations transfer the alkyl group to cell constituents such cellular metabolic reactions. An antimetabolite blocks a metabolic
ac
as amino, carboxyl, sulfhydryl or phosphate groups. reaction, due to its structural similarity to the metabolite.
cy
cy
cy
2. The alkylating ágents are strongly nucleophilic. So they react
Folic acid antagonists
y
with nucleic acid bases and inhibit the synthesis of DNA. This
interferes with cell divisions and growth. METHOTREXATE : It is an analogue of folic .acid. So it acts as a
folic acid antagonist.
Mechanism of action: In a cell, folic acid is converted to
i) Cytotoxic etfect: These drugs affect rapidly growing cells and
tetrahydrofolic acid (THF) by the enzyme folate rductase.
produce the following effects:
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
284
285
6-Mercaptopurine is rapidly
St
St
St
St
Methotrexate competes witi folic acid for the enzyme, folate Absorption, fate and excretion: It is metabolised by xanthine
absorbed from gastrointestinal tract.
ud
ud
ud
u
reductase. xanthine oxidse. So the action of
oxidase. Allopurinol inhibits
when it is used with allopurinol.
Folic acid Tetrahydrofolic acid 6-Mercaptopurine is prolonged
reduciase
y
So folic acid is not converted to THF. In the absence of
THF, Adverse reactions:
Ph
Ph
Ph
growth is to leukopenia and
synthesis of DNA does not occur. So cell division and Bone marrow depression leading
ha
1.
inhibited. thrombocytopenia.
ar
ar
ar
like ulceration, perforation and
Gastrointestinal effects
r
hemorrhage.
Bone marrow depr:ssion leading to granulocytopenia,
ma
ma
ma
ma
1.
chronic
reticulocytopenia and iymphopenia. Therapeutic uses: Acute leukemia, choriocarcinoma and
2. Ulceration and hemorrhage of gastrointestinal tract. myeloid leukemia.
c
c
3. Foetal abnormalities since it crosses placental barier.
y
y
4. Immunosuppressant effect. Pyrimidine antagonists
It binds to
Methotrexate is well absorbed
FLUORO-URACIL: It is fluorinated pyrimidine.
Absorption, fate and excretion :
thymidilate synthetase. This prevents the synthesis of thymine, an
orally. It is eliminated in ur ne, mostly in a free fom. methotrexate, fluoro- uracil is
essential component of DNA. Like
Tm
gastrointestinal tract.
Adverse reactions: toxic to bone marrow and
5
Leukopenia, thromboc:topenia and megaloblastic anemia. daily by intravenous infusion for
1.
Dose: 15mg/kg. body weight
alternate days.
St
St
St
St
2. Diarhoea and intestinl ulceration. days followed by 7.5 mg/kg. on
3. Alopecia due to damaye of hair follicles. ovaries.
Use:Carcinoma of stomach, colon, rectum and
ud
ud
ud
u
The toxicities of methotrexate cannot be reversed by folic acid.
The reason is, the enzymic inechanism leading to its conversion as Radioactive Isotopes
THF is blocked. Since THF is unsuitable for therapeutic use, a related
y
y
It has a half life
RADIO IODINE 1311 is the isotope that is used.
compound folinic acid (N°-fomyl THF, citrovorum factor)
is used.
Na*°"I, dose of 100 to 200
Ph
Ph
Ph
at a
of 8 days. It is administered
as
carcinoma of the thyroid.
Preparation and dose : Methotrexate tablets-2.5 to 10 mg. for
ha
millicuries. It is effective in follicular

mg. for children. isotope that is used. It has a
ar
ar
ar
adults and 2.5 to 5
RADIO PHOSPHORUS : P is the
distributed in tissues where the tunover
rm
Therapeutic uses :
Acute ymphatic leukemia, acute myeloid half life of 14.3 days. It is
marrow and spleen. Because of wide
ma
ma
ma
leukemia, choriocarcinoma aid breast cancer. of phosphorus is high e.g. bone
generalised irradiation including lungs
distribution, it may produce
ac
Purine antagonists bone marrow may produce leukopenia,

and gonads. Iradiation of
cy
cy
cy
6-MERCAPTOPURINE: It is an analogue of purine. thrombocytopenia and aplastic anemia.
y
phosphate °"P either orally or

Mechanism of action: It acts by inhibiting the synthesis and
its
Dose: 5 to 6 millicuries as sodium
interconversion purines. 6Mercaptopurine gets converted to intravenously.
ribonucleotide. This inhib:ts the synthesis of purine which is
Uses: Polycythemia vera.
necessary for DNA synthesis
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
286 287
St
St
St
St
It has been
RADIO GOLD: Au is the isotope that is used. It has a half lie Asparaginase thus has a selective effect on cancer cells.
reticulum cell sarcoma.
used in lymphoblastic leukemia and
ud
ud
ud
u
of 2.69 days. It emits both beta and ganma radiations. The beta
rays produce localised destruction of tissues. It is used as colloidal PROCARBAZINE: It is an orally active drug effective against
gold solution. This colloidal solution does not enter into blood. So Hodgkin's disease. Its adverse reactions are bone marrow
y
it produces selective tissue destruction. Phagocytes carrying gold depression, restlessness and disorientation.
Ph
Ph
Ph
particles reach the lymph nodes. This helps in irradiation of regional CIS-PLATIN: It is useful in cancer of testis and ovary.
It attacks
ha
lymph nodes. nephrotoxic. It is administered

DNA. It is a strong emetic and also
ar
ar
ar
Miscellaneous agents intravenously.
r
They are vineristine and vinblastine. They Carboplastinis the second generation drug. It is less toxic.
VINCA ALKALOIDS
ma
ma
ma
ma
are obtained from the periwinkle plant, Vinca rosea. Also nousea and vomiting is mild.
Mechanism of action: Inhibition of mitotic spindles. HORMONES: Some the cancers are lhonmone dependait. For
of
c
c
may support cencer of
example androgen, the male sex hormone,
y
y
Cytotoxic elfects: They manifest on bone marrow, hair follicles and prostate and testis. Estrogen, the female sex hormone nmay support
gastrointestinal tract. The mani festations are similar to those produced cancer of breast and ovary. In these conditions,
the opposite sex
by alkylating agents. are used in cancer nmanly for
hormones are used. Corticosteroids
well heing of
rm
immunosuppressant effect and also for improving the
Adverse reactions
1.Neurological symptoms like peripheral neuropathy. the patient T
non-steroidal compound with an antiestrogenic
2. Mental depression and psychotropic effects.
TAMOXIFEN: It is a
effect. It binds to estrogen receptors in tissues and blocks the action
St
St
St
St
3. Bone arrow depression. treatment of advanced breas! cancer.
of estrogen. It is effective in the
Uses: Hodgkin's disease and acute lymphatic leukemia.
ud
ud
ud
u
ACTINOMYCIN-D: It is an antibiotic obtained from species of
streptomyces. It acts by inhibiting DNA dependent RNA synthesis.
y
y
It is very toxic and hence its use is limited. Mostly it is used as an
Ph
Ph
Ph
experimental tool in biological research.
ha
Dose 15 micrograms per kg. daily by intravenous route for 5 days.

ar
ar
ar
MITOMYCIN-C: It is an antibiotic obtained from Streptomyces
rm
caespitosus. Its cytoxtoic properties are similar to alkylating agents.

ma
ma
ma
It is effective in myeloid leukemia and Hodgkin's disease.
ac
RUBIDOMYCIN It is an antibiotie obtained from Streptomycs

cy
cy
cy
coeruleorubidus. It acts by inhibiting DNA dependent RNA
y
synthesis. It is effective in acute leukemia in children.

1-ASPARAGINASE: Asparagine is a non-essential amino acid for
normal colls. But it is essential for eancer ceils. Asparaginase, an
enzyme prepared from E. coli, converts asparagine to aspartic acid
So asparagine is not available for the growth of cancer cells.
St
St
St
St
ud
ud
ud
u
y
y
Ph
Ph
Ph
h
y
y
238
289
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St
Adverse reactions
Section XV 1. Nausea, vomiting and headache.
ud
ud
ud
u
2. Burning sensation in the eyes and lacrimation.
3. Anginal pain, tachycardia and hypertension.
y
MISCELLANEOUS 4. Muscle pain and muscle spasm.
Ph
Ph
Ph
Preparations and dose : Dimercaprol injection-2.5 mg. per kg.
ha
every 4 hours for the first 2 days and then every 12 hours for the
ar
ar
ar
next 10 days.
r
Therapeutic uses: In the treatment of acute poisoning caused by

ma
ma
ma
ma
arsenic, mercury, gold, antimony, bismuth and thallium.
87. HEAVY METAL ANTAGONISTS d-PENICILLAMINE : It is a monothiol compound containing one SH
c
c
(Chelating agents) group. It is obtained by alkaline hydrolysis of benzyl penicillin. It
y
y
chelates nmetals like copper, lead and mercury and forms water soluble
antimony, silver, gold, complexes. Unlike BAL, it is well absorbed from gastrointestinal
Heavy metals like arsenic, ead, bismuth,
variety of poisonous effects. Some tract.
produce a
f
cadmium and thallium
to inhibition of sulfhydryl
beavy metals produce their toxicity due Adverse reactions
may occur due to the formation of
group of enzymes. Also, toxicity groups. 1. Gastrointestinal imtation and alteration in taste.
phosphat:, imidazole and carboxyl
complexes with amino,
2. Optic neuritis and nephrotic syndrome..
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conmpounds have a high affinity
Chelating agents: Some organic 3. Allergic reactions leading to fever, skin rashes, and leukopenia.
combine with metallic ions and
for metallic ions. These compounds
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form non - toxic, water- soluble complexes which are eliminated by Preparations and dose:
agents.
the kidneys. Such compoundis are called as chelating d-Penicillamine capsules-250 mg. 4 times a day.
combine with
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compounds which
Chelating agents are dëfined as
non-ioniscd ring complexes. These agents are Therapeutic uses
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metals to form stable,
caused by heavy metals. The 1. In poisoning due to copper, lead and mercury.
Ised in the treatment of poisoning
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therapeutic application. In the treatment of hepatolenticular degeneration (Wilson's

following are the chelating agents which have 2.
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Dimercaprol is a disease) where there is accumulation of copper in tissues.
DIMERCAPROL (BRITISH ANTIL EWISITE, BAL)
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3. In rheumatoid arthritis.
groups). The SH groups of dimercaprol
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dithiol (containing two SH mercury poisoning
like mercury and cadmium. ACETYL d-PENICILLAMINE: It is effective in
bind with arsenic and other heavy metals
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from inactivation. Also it It is less potent and less toxic tuhan d-penicillamine. Dose: g. daily
1
So it protects the SH group enzymes

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in 3 divided doses for 10 days.
reactivates the inhibited enzyme s.
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CALCIUM DISODIUM EDETATE: Ethylene diamine tetra-acetic

Dimercaprol is absorbed after
Absorption, fate and excreion: reached in 2 hours. acid (EDTA) is capable of chelating calcium. Salts of EDTA when
is
intramuscular injection. Maximum blood level used as drugs are called as edetates. Disodium edetate binds to
within 8, to 24 hours. it is excreted in
it is completely metabolised calcium. But calcium disodium edetate can exchange calcium for lead
urine as a glucuronide.
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Telegram - and
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other heavyPharmacy
metais. ineffective orally.
It is It is given parenterally Classification of drugs:
with dimercaprol, to treat lead poisoning.
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1. Drugs effective in acute Colchicine
Adverse reactions stage Phenylbutazone
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1.Thrombophlebitis. Indomethacin
2.Gastrointestinal disturbances like nausea and diarthoea. Corticosteroids
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3. Oliguria and renal, failure. 2. Drugs effective in chronic
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4. A febrile flu like state. stage
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a) Uricosuric agents Probeneciid

DITHIOCARB: It is a chelating agent.useful in:
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Sulphinpyrazone
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i) Nickel carbonyl poisoning Azapropazone

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ii) Acute thallium poisoning b) Inhibitors of uric acid Allopurinol
ii) Wilson's disease synthesis
Dose: 300 mg. by intravenous route initially, followed by 2 g. daily
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Drugs effective in acute stage
for 7 days by oral route.
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1. COLCHICINE It is an alkaloid isolated from tie meadow
DESEFERIOXAMINE: It is a specific iron chelator. It inhibjts iron saffron, Colchicum autumnale.
absorption in the gastrointestinal tract. It is useful in
hemochromotosis and transfusion hemosiderosis. Mechanism of action: Colchicine inhibits phagocytos is of urate
DIETHYLENE TRIAMINE PENTA ACETIC ACiD (DTPA): The
calcium salt of D.T.P.A. is effective in acute iron poisoning. It is
also effective in the treatment of hemorchromotosis. It can be
ae cystals by leukocytes. This produces a decrease in infammatory
reaction.
Dose 1
mg. followed by 3.5 mg. every 3 hours by oral route until
pain is relived or till side effects appear.
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administered by oral and parenteral route.
Adverse reactions : Diarrhoea, anemia and leucopenia. Heamaturia
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THE TREATMENT OF and oliguria may also occur.
88. DRUGS USED IN
GOUT 2. PHENYLBUTAZONE: It has an anti-inflammatory and

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uricosuric effect. At a dose of 600 mg. daily, it produc es relief of
both pain and immobility of joints.
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Gout occurs due to abnomality of purine matabolism which
3. INDOMETHACIN: It is effective in acute attacks of gout. It is
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leads to over production of uric acid. Increased uric acid production

leads to deposition of sodium urate microcrystals at the joints and in administered at a dose of 25 to 50 mg. every 4 to 8 hours. It relieves
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kidney. The symptoms of gout are acute attacks of pain and swelling pain even within 2 hours after the first dose.
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of joints. 4. CORTIcOSTEROIDS :
Prednisone or ACTH is effective in acute
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.
attacks of gout. The effect is due to suppression of in. lanmatory
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reaction. Relapse may occur when these drugs are withd awn.
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292
Drugs effective in chronic stage
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It can be used asa
PROBENECID: It is an uricosuric agent.
gout. It acts by
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prophylactic. It isuseless in acute attacks of
inhibiting the tubular reabsorption of uric acid.
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Dose: 0.5 g. three times daily by oral route.
Occasionally nausea,
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Adverse reactions : Relatively non-toxic.
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vomiting and skin rashes may be produced.

SULPHINPYRAZONE: It is also an uricosuric agent like
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The.
probenecid. But it is six times more potent than probenecid.
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has a slight
mechahism of action is similar to probenecid. Alsa, it
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anti- inflammatory effect.
Dese: 100 to 200 mg. thr>e times daily.
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y
Adverse reactions: Anorexia, nausea, aggravation of peptic
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ulcer
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and bone marrow depression.
AZAPROPAZONE: t is also an uricosuri1c agent like
It is
sulphinpyrazon. But it is useful in the treatment of acute stage.
also used for the treatmen of rheumatoid arthritis
It has anti-inflammatory, analgesic and antipyretic
reactions: GI effects and headache.
and
effects. Adverse
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osteoarthritis.
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ALLOPURINOL It is an inhibitor of uric acid synthesis. It acts by
inhibiting the enzyme xanthine oxidase. So the oxidation of purine
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bases to uric acid is inhibited.
increased
Dose: 50 mg. per day by oral route initially and gradually
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maximum of 300 to 600 mg. per day.
(in 2 to 3 weeks) to a
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leucopenia and
Adverse reactions : Nausea, vomiting, diarrhoea,
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liver damage.
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y

@phar Madurai Medical College,

No.1, SOwBAGYA NAGAR 3rd STRE

MADURAl 625 006

Sixth Edition 2004 in their

@pharmae as simplicity of language, neatness of presentation

to gain your appreciation and encouragement

4 31. Sympathetic blocking drugs

58 42. Antihypertensive agents 133

23. Centrally acting muscle relaxants 62

effective against both gram positive and gram

53. Anterior pituitary hormones 170

67. Antacids 215

Section XII : Drugs acting on the uterus

69. Oxytocics and uterine relaxants 220

70. General considerations 226

Note on dosage and other informations

publication of this work. 5. Clinical Pharmacology

6. Chemotherapy which deals with the effects of drugs

also includes the treatment of cancer.

drug is slowly absorbed

size is large, the

membrane. circulation afte non-vascular

is released slowly for

(enteral) route are termed as

1. Absorption is rapid and quick.

3. Intramnuscular: The drug

The drg may be inactivated by gastric

2. systemic circilation without

membrane of nose. e.g. posterior

e.g. aminophylline for

metabolised into an active drug. For exanmple, l-dopa is an inactive

Females have less ability to nmetabolise diugs.

hydrolysed by 'cholinestierase' and converted into eholine and acetic

b. Synthetic reactions: Synthetic reactions also called s

duration of action. through skin.

small intestine through bile.

ii. intracellularly -e.g. anticancer drugs. action.

a. Action through physical properties variation in drug effects.

Tolerance can be classified into:

administration of a drug. When it occurs by nature,

is a dummy i. Additive effect: Here, the total

for this purpose. e.g. the effects of ephedrine and

pathologica conditions e.g. hyperthyroid individuals require large

ii. Antagonism: Two drugs act on

applied locally can

which produces the

11. Carcinogenesis No drug:

digitalis is low. experimental animals.

i. an overpowering desire to take the drug.

iii. development of psychic and physical dependence.

the concentration of the active principle. Techniques like colorimetry.

standard. In bioassay, the concentration of test sample is estimated

7. lmplantation of drug pellets e.g. desoxycorticosterone acetate

Inactivation of drugs by microsomal 1. Matching

Alcohols are hydrocarbons. They may contain one or more

@pharmae Ethyl alcohol is the nmain constituent of al kinds of alcoholic

v. antiseptic since it destroys micro-organisns.

and also produçes a carinative effect.

higher inhibitory centres. This is followed by progressive dépression,

once daily for

heavy, colourless liquid with a characteristic sweet,

with a pun gent odour. It is highly inflammable and explosive.