Professional Documents
Culture Documents
Chapters Pages
1. History of Pharmacy in India/Importance of Various Pharmacopeias ..... 1
2. Sources of Drugs ..... 16
3. Methods of Prepairing Herbal Remedies ..... 23
4. Prescription and Latin Words used in the Prescription ..... 32
5. Posology ..... 36
6. Communicable Diseases ..... 42
7. First Aid Treatment ..... 55
8. Classification of Microbes ..... 64
9. Contamination of Pharmaceuticals in Hospitals and
Environment by Microbes ..... 71
10. Sterilization ..... 83
11. Sterilization of Materials, Equipments and Utensils Used in Hospitals .... 92
12. Ophthalmic Preparations ..... 103
13. Blood Products and Plasma Substitutes ..... 112
14. Surgical Products ..... 119
15. Incompatability ..... 122
16. Cardiovascular System .... 127
17. Human Digestive System ..... 137
18. Brain and Spinal Cord .... 145
19. Drugs Acting on Cardiovascular System .... 151
20. Drugs Acting on Gastro-Intestinal Tract .... 162
21. Drugs Acting on Central Nervous System .... 169
22. Antigen, Antigen-antibody Reactions, Hypersensitivity,
Active and Passive Immunity and Types of Vaccines .... 193
23. History Development and Production of Antibiotics .... 207
24. Carbohydrate Metabolism .... 217
25. Chemotherapeutic Agents .... 224
26. Antiprotozal and Anthelmintic Drugs .... 252
27. Drugs and Cosmetic Acts, 1940 .... 261
28. Narcotic Drugs and Psychotropic Substances Act, 1985 .... 270
Aopendices (I to X) .... 277-336
Model Question Papers (1 to 5) .... 337-384
History of Pharmacy in India/ JL
Importance of various Pharmacopeias C h a pter
In ancient India, the sources of drugs were of vegetable, animal and mineral origin.
They were prepared empirically by few experienced persons. Knowledge of that medical
system was usually kept secret within a family. There were no scientific methods of
standardization of drugs.
Muslim Rule in India
The Indian system of medicine declined during the Muslim rule while the Arabic or
the Unani-Tibbi system flourished.
British Rule in India
The western or the so-called Allopathic system came into India with the British traders
who later become the rulers. Under British rule, this system got state patronage. At that
time, it was meant for the ruling race only. Later it descended to the people and become
popular by the close of 19th Century.
Before 1940
Initially, all the drugs were imported from Europe. Later some drugs of this system
began to be manufactured in this country.
1901: Establishment of the Bengal Chemical and Pharmaceutical Works, Calcutta by
Acharya Prafulla Chandra Ray.
1903 : A small factory at Parel (Bombay) by Prof. T.K. Gujjar.
1907 : Alembic Chemical Works at Baroda by Prof. T.K. Gujjar.
Drugs were mostly exported in crude form and imported in finished form. During
World War-I (1914 -1920), the imports of drugs were cut-off. Imports of drugs were resumed
after the War. There was complete absence of any restrictions on the quality of drugs
imported, so manufacturer abroad took advantage of the situation. The consequences
were as follows:
Foreign manufacturers dumped inferior quality medicines and adulterated drugs.
Markets were full of all sorts of useless and deleterious drugs were sold by unqualified
men.
Examples of maladie:
Poisoning due to quinine.
l
2 □ □ Drug Inspector Exam
Government of India controls the price of drugs in India by Drugs Price Order changed
from time to time.
PHARMACOPOEIA/FORMULARIES/COMPENDIA
The books containing the standards for drugs and other related substances are known
as pharmacopoeia and formularies - collectively these books are known as the drug
compendia.
The pharmacopoeias or formularies contain a list of drugs and other related substances
regarding their source, descriptions, standards, tests, formulae for preparing the same,
action and uses, doses, storage conditions etc.
These books are prepared under the authority of the Government of the respective
countries. The word "pharmacopoeia" is derived from the Greek words 'pharmacon'
meaning 'drug' and poieo' means 'make'. Literally it means that it is a list of medicinal
substances, crude drugs and formulae for making preparations from them.
These books are revised from time to time so as to introduce the latest information
available as early as possible after they become established. In order to keep the size of
book within reasonable limit it becomes necessary to omit certain less frequently used
drugs and pharmaceutical adjuvants from each new edition of the book. Therefore, in
each new edition of these books certain new monographs are added while the older ones
are deleted.
For the preparation of these books the expert opinion of medical practitioners, teachers
and pharmaceutical manufacturers are obtained.
CLASSIFICATION
The drug-compendia are classified as :
(i) Official compendia
(ii) Non-official compendia
A. Official Compendia
Official compendia are the compilations of drugs and other related substances which
are recognized as legal standards of purity, quality and strength by a Government agency
of respective countries of their origin. For example,
• British Pharmacopoeia (BP)
• British Pharmaceutical Codex (BPC)
• Indian Pharmacopoeia (IP)
• United States Pharmacopoeia (USP)
• National Formulary (NF)
• The State Pharmacopoeia of USSR and
• Pharmacopoeias of other countries
History o f Pharmacy in India/Importance o f various Pharmacopeias □ □ 5
B. Non-official Compendia
The book other than official drug compendia are used as secondary reference sources
for drugs and other related substances are known as non-official drug compendia. For
example, Merck Index
Extra Pharmacopoeia (Martindale), United States Dispensatory etc.
NATIONAL PHARMACOPOEIAS
Pharmacopoeias are generally prepared under the authority of the Government of the
respective countries - these pharmacopoeias are known as national pharmacopoeias.
Examples of some national pharmacopoeias are as follows :
Indian Pharmacopoeia, British Pharmacopoeia, United States Pharmacopoeia etc.
The drugs used may vary from nation to nation so, the respective pharmacopoeia
includes those drugs or dosage forms which are frequently used in that very country at
that time.
The National Pharmacopoeia is recognized as the reference book by the legislative
authority (by law) of the respective country, whenever a conflict arises regarding drugs,
these books will be referred.
INDIAN PHARMACOPOEIA
History
The historical developments of Pharmacopoeia in India traces back to 1563 and the
credit goes to Garcia da Orta a Portugese physician-cum-teacher. The idea of indigeneous
Indian Pharmacopoeia was conceived in 1837 which bore fruits in 1841 in the shape of
Bengal Pharmacopoeia and Conspectus of Drugs. The Bengali and Hindi version of London
Pharmacopoeia was made available in India from 1901 onwards.
The Indian Pharmacopoeial List, published in 1946 formed the seeding for the true
Official Indian Pharmacopoeia published in 1955. The first edition of Indian Pharmacopoeia
was published in 1955, but actually the process was started as early as 1944. In 1944,
Government of India asked the Drugs Technical Advisory Board to prepare the list of
drugs used, in India, having sufficient medicinal value to justify their inclusion in official
pharmacopoeia.
The Indian Pharmacopoeial List, 1946.
The list of drugs both included and not included in the British Pharmacopoeia along-
with standards to secure their usefulness, tests for identity and purity was prepared by
the committee and was published by the Government of India under the name 'The Indian
Pharmacopoeial List, 1946'.
The committee constituted under the chairmanship of Col. Sir R.N.Chopra along with
other nine members, prepared the list of drugs with the following details :
6 □ □ Drug Inspector Exam
Substances included in the British Pharmacopoeia for crude drugs, chemicals and their
preparations.
Substances not included in the British pharmacopoeia :
(a) Drugs of plant origin
(b) Drugs of animal origin
(c) Biological products
(d) Insecticides
(e) Colouring agents
(f) Synthetics
(g) Miscellaneous
(h) Drugs for veterinary use.
The Indian Pharmacopoeial List, 1946 was prepared by Department of Health.
Government of India in 1946.
The history of development of Indian Pharmacopoeia :
Years Events
1946 The Government of India published the Indian Pharmacopoeial List.
1948 The Government of India constituted a permanent Indian Pharmacopoeia
Committee. This committee was assigned the task of preparing Indian
Pharmacopoeia and to keep it up-to-date.
1955 The first edition of Indian Pharmacopoeia (IP) was published.
1960* Supplement of IP 1955 was published.
N.B. The work of revision of the Indian Pharmacopoeia as well as compilation
of new edition was taken up simultaneously under the chairmanship of Dr.
B.N.Ghosh, who died in 1958. After Dr. B.N.Ghosh, Dr. B. Mukherjee, the
Director of Central Drug Research Institute was appointed as the chairman
of Indian Pharmacopoeia committee.
1966* The second edition of IP was published.
1975 A supplement of IP 1966 was published.
1978 The Indian Pharmacopoeia Committee was reconstituted by the Government
of India, Ministry of Health and Family Welfare, under the chairmanship of
Dr. Nitya Nand, Director, Central Drug Research Institute, Lucknow.
1985 The third edition of IP was published in two volumes, Volume-I and Volume-
II by the Controller of Publications, on behalf of Government of India, Ministry
of Health and Family Welfare.
1989 Addendum (I) to IP 1985 was published.
1991 Addendum (II) to IP 1985 was published.
1996* The fourth edition of IP was published.
History o f Pharmacy in India/Importance o f various Pharmacopeias □ □ 7
VOLUME-I CONTAINS
Legal Notices, Preface, Acknowledgements, Introduction, General Notices, and
Monographs from A to O.
Volume-II Contains:
Monographs from P to Z, Appendices, Contents of Appendices and Index.
The Appendices includes the
(i Infra Red Spectra of drugs,
(ii Apparatus for tests and assays
(iii Biological tests and determinations,
(iv Chemical tests and assays,
(v Chromatography and electrophoresis
(vi Spectrophotometry
(vii Clarity and color of solutions
(viii Disintegration and dissolution tests
(ix Physical tests and determinations
(x Microbiological assays and tests,
(xi Limit tests of particulate matter
(xii Other tests and determinations
(xiii General information
(xiv Reagents and solutions
(xv Reference substances
(xvi Tables
Index
Under each monograph chemical structures, molecular weight, physical description,
solubility, identification tests, standards, assay method, storage etc., are given.
Published by: The Controller of Publications, Delhi, on behalf of Government of India,
Ministry of Health and Family Welfare. For the preparation of Pharmacopoeia of India,
the pharmacopoeias of other countries, like British, Europe, United States, USSR, Japan,
the National Formulary (USA) and Merck Index were consulted. The persons working in
pharmaceutical industry, drug control laboratories, research and teaching institutions also
actively participated. Under the Drugs and Cosmetics Act, 1940, the Indian Pharmacopoeia
is an official book that contains the standards for drugs and other related substances
included in the pharmacopoeia. The drugs and other related substances prepared by
pharmaceutical manufacturers must comply with these standards.
Example of a Monograph of an Official Drug
The w ord 'Monograph' m eans the written study of a subject. The pharm acopoeial
monographs (for example, in IP) give the following information about the drugs and
pharmaceutical aids :
8 □ □ Drug Inspector Exam
list which would avoid the confusion caused by different national standards, strengths
and names.
Published b y : World Health Organization
Prepared by : WHO Expert Advisory Panel on the International Pharmacopoeia and
Pharmaceutical Preparations.
1951: Volume-1 of First Edition of The International Pharmacopoeia was published.
1952: Volume-2 of First Edition of The International Pharmacopoeia was published
1959 : Supplement to First Edition was published
First Edition includes :
344 monographs on drug substances
183 monographs on dosage forms (capsules, injections, tablets and tinctures)
84 tests, methods and general requirements.
1967
Second Edition of The International Pharmacopoeia was published as Specification
for the Quality Control of Pharmaceutical Preparations.
Second Edition includes
New analytical techniques involving infrared spectroscopy, chromatography (column,
paper and thin-layer), non-aqueous titration, and radioactivity.
162 new pharmaceutical preparations were added.
114 monographs present in the first edition were deleted.
1975 Volume-1 of Third Edition of The International Pharmacopoeia was published.
1981 Volume-2 of Third Edition of The International Pharmacopoeia was published.
1982 Volume-3 of Third Edition of The International Pharmacopoeia was published.
1988 Volume-4 of Third Edition of The International Pharmacopoeia was published.
2003 Volume-5 of Third Edition of The International Pharmacopoeia was published.
Salient features of Third Edition
Emphasis on classical chemical techniques available in the developing world.
Drugs those are used all over the world by various WHO programs.
Drugs those degrade or are difficult to manufacture.
Drugs from WHO Model List of Essential Drugs, and their updates.
Volume-1: General methods of analysis
Volumes-2 and 3: Quality specifications of essential drug substances in the WHO
Model List of Essential Drugs.
Volume-4: Tests, methods, and general requirements. Quality specifications fori
pharmaceutical substances, excipients, and dosage forms.
10 □ □ Drug Inspector Exam
Volume-5: Contains tests and general requirements for dosage forms and quality
specifications for pharmaceutical substances and tablets, an a section on antimalarial drugs
and their most widely used dosage forms.
• Annual publication from 1998 onwards. In every year a new edition is published.
• Free access to Pharmacopoeia website
Meant for
The pharmaceutical and chemical industries, quality control personnel, analysts,
government regulators, academics and students of pharmacy. Published by The British
Pharmacopoeia Commission.
The British Pharmacopoeia (BP) 2012 is the leading collection of standards for UK
medicinal products and pharm aceutical substances. Produced by the British
Pharmacopoeia Commission Secretariat of the Medicines and Healthcare products
Regulatory Agency, the BP makes an important contribution to public health by setting
publicly available standards for the quality of medicines.
IMPORTANCE OF PHARMACOPOEIA
The Importance of Pharmacopoeia can be discussed from the following three angles :
(i) Drug industry
(ii) Administration
(iii) Academic
(i) From the point of view of drug industries. To market a new drug molecule
stupendous amount of money is required for the research and development. Very
few companies can bear this cost, especially the drug industries in developing
countries (like India) are unable to bear the expenditure. In that case the drugs of
products mentioned in the pharmacopoeias can be marketed without any further
research on it, because only the tested, safe and efficacious drugs and
pharmaceuticals are included in the pharmacopoeias.
Drugs and pharmaceuticals products are prepared from some raw materials, the
standards of which should rigorously be met with that of pharmacopoeia. Though
there are several other sources of information about the standard of drugs and
pharmaceuticals, the pharmacopoeia is the most reliable one. Assay methods and
identifications of drug of pharmaceuticals are given very clearly in the
pharmacQpoeias so it becomes easy for the drug industry to design the tests and
follow the methods confidently because the assay and identification methods are
tested and approved by the authority.
(ii) From the point of view of drug-administration. In every country there are drug
industries with varied intentions - among which the major one is 'to make profit'.
While making the profit some industries ignore the quality of the drugs and
pharmaceuticals. Since drugs are related to the health of human beings and animals,
this negligence is unpardonable. So every nation made his own Drugs and Acts
and Rules. Whenever a conflict surfaces between a drug industry and Government
History o f Pharmacy in India/Importance o f various Pharmacopeias □ □ 1j
the first reference book that is consulted, regarding the quality if the p oduct, is
the pharmacopoeia.
(iii) From the stand point of academic. The pharmacopoeias are mines of information
regarding drugs and pharmaceuticals. The researchers always consult it in first
hand for developing an assay method of certain drug, for testing the quality of a
dosage form. The microbiological and bioassays are given in details in the
appendices with statistical quality controls. The usage of the drug, the adverse
reaction, if any, and many more information are provided in the pharmacopoeias.
The reason for the popularity of pharmacopoeias among the students, researchers,
teachers is for the reliability of the information provided in it
24. Who has published National (d) Ministry of Health, Gove nment of
Formulary of India? India
(a) APTI 25. Where Indian Pharmacopoeial Lab is
(b) MCI situated?
(c) PCI (a) Kolkata (b) Mumbai
(c) Ghaziabad (d) Lucknow
ANSWERS
1. (a) 2. (a) 3. (a) 4. (b) 5. (a) 6. (b) 7. (c) 8. (e) 9. (a) 10. (a)
I I. (c) 12. (a) 13. (b) 14. (b) 15. (c) 16. (d) 17. (a) 18. (d) 19. (a) 20. (a)
21. (b) 22. (a) 23. (a) 24. (d) 25. (c)
□ □ □
Sources of Drugs C h a pter
RA. TNF is a cytokine associated with the pathology of autoimmune disease. Erbitux
(cetuximab) is an antibody that blocks the EGF receptor. A recently approved drug, Soliris
(eculizumab), has a very unique target: C5 of the complement cascade.
Advantages:
1. Huge amounts of drugs can be produced.
2. Drug can be obtained in pure form.
3. It is less antigenic.
Disadvantages:
1. Well equipped lab is required.
2. Highly trained staff is required.
3. It is a complex and complicated technique.
(c) Potassium citrate 14. Tick mark the anticancer drug of plant
(d) Bismuth subcarbonate origin.
8. Which is not unorganized drug? (a) Vincristine
(a) Gelatin (b) Cisplatin
(b) Opium (c) Methotrexate
(c) Musk (d) 5-Fluorouracil
(d) Aloes 15. Tick the anticancer drug belonging to
(e) None of these inorganic metal complexes:
(a) Dacarbazine
9. Which one of these drug is a entire
plant? (b) Cisplatin
(a) Lobelia (c) Methotrexate
(b) Senna (d) Vincristine
(c) Liquorice 16. Enzyme drug used for acute leukemia
(d) Belladonna treatment:
(a) Dihydrofolate reductase
10. What is Talc?
(b) Asparaginase
(a) Hydrated aluminium silicate
(c) Aromatase
(b) Hydrated magnesium silicate
(d) DNA gyrase
(c) Hydrated potassium silicate
(d) None of these 17. Which drug is recommended for the
treatment of sleeping disorder?
11. What is Light Kaolin?
(a) Rauwolfia serpentina
(a) Aluminium silicate having
(b) Valeriana officinalis
antidiarroeal action
(c) Centella asiatica
(b) Aluminium silicate having
antidiarroeal action (d) A1 of the above
(c) Aluminium magnesium silicate 18. Which drug is used for support of the
having antiseptic action excretory function of the kidney?
(d) Aluminium silicate having inert (a) Clove
nature (b) Melissa leaf
12. What is Bentonite? (c) Dandelion root
(a) Dry stigma of Crocus sativus (d) Hamamelis leaf
(b) Dry flower of Crocus sativus 19. What is source for green tea?
(c) Dry stigma of Citrullus sativus (a) Camellia sinensis
(d) Dry flower of Citrullus sativus (b) Centella asiatica
13. The Source for Saffron is— (c) Anthum
(a) Dry stigma of Crocus sativus (d) Sinensis
(b) Dry flower of Crocus sativus 20. What is goldenseal, yellow root?
(c) Dry stigma of Citrullus sativus (a) Root of Haemmalis
(d) Dry flower of Citrullus sativus (b) Root of Hydrastis canadensis
Sources o f Drugs □ □ 21
ANSWERS
! ■(c) 2. (b) 3. (b) 4. (b) 5. (a) 6. (d) 7. (b) 8. (e) 9. (a) 10. (b)
11. (a) 12. (a) 13. (d) 14. (a) 15. (b) 16. (b) 17. (b) 18. (c) 19. (a) 2 0 . (b)
21. (e) 22. (b) 23. (a) 24. (b) 25. (a) 26. (a) 27. (b) 28. (a) 29. (c) 3 0 . (d)
31. (c) 32. (c) 33. (a) 34. (c) 35. (c) 36. (d)
non
Methods o f Preparing Herbal 3
Remedies C h a p te r
In traditional herbal medicine systems, herbal remedies are prepared in several rather
standardized ways which usually vary based upon the plant utilized, and sometimes,
what condition is being treated. Some of these methods include: infusions (hot teas),
decoctions (boiled teas), tinctures (alcohol and water extracts), which are given here.
Infusions
Infusions are typically used for delicate herbs, leaves and fresh tender plants. Preparing
an infusion is much like making a cup of tea. Water is brought just to a boil and then
poured over an herb (or combination of herbs), it is covered and allowed to sit/steep for
10-15 minutes or so. It can be prepared in the drinking cup (by just pouring the heated
water over the herb in the cup) or by dropping the herb into the pot which the water was
heated in. Empty gauze tea-bags are even available at some herb stores which can be
filled with herbs and then sealed with a iron. If an infusion is prepared in the heating
pan/pot, it's best to use a ceramic pot with a lid (avoid metal pots). Stirring it a few times
while steeping (especially with cut herbs) is helpful. Keeping the infusion covered while
steeping is generally recommended as well (place a saucer on top of the cup, or a lid on
top of the pot). The ratio of herb to water can vary depending on the remedy, the plant,
and whether cut herb or powdered herb is used. Generally using 1 teaspoon of powdered
herb or 2 teaspoons of more bulky cut herb in a 6-8 ounce cup of water is sufficient. If
using a powdered herb; stir once halfway through the seeping time and let the powder
settle to the bottom of the cup, then drink the infusion off the top (leaving the sediment in
the bottom of the cup). If using a cut herb, strain the infusion with a tea-strainer after
seeping. Infusions are best prepared as needed and taken the same day it was prepared
and can be taken hot, warm, or cold.
Decoctions
Decoctions are usually the method of choice when herbal drug is tougher and more
fibrous plants, barks and roots (and which have water soluble chemicals). Instead of just
steeping it in hot water, the plant material is boiled for a longer period of time to soften
the harder woody material and release its active constituents. To prepare a decoction,
select a ceramic pot with a fitting lid. Measure the amount of herb needed (usually the
same ratio of 1 teaspoon powdered herb or 2 teaspoons of cut herb per 8 ounces of water)
into the pot and add the proper amount of cold water depending on how many cups of
23
24 □ □ Drug Inspector Exam
the decoction you wish to prepare. Turn on the heat to medium high and bring to a roiling
boil. Place the lid on the pot and reduce the heat to medium or medium-low so that the
mixture stays at a good simmer. If you can see steam escaping or smell the aroma of the
herb, your lid is not tight enough and valuable essential oils are escaping. After 20 minutes,
remove from heat and cool slightly. If using cut herbs, strain the mixture through a tea
strainer into a teacup. When straining, make sure to press on the cut herb pieces in the
strainer to get as much liquid/decoction out of the herb pieces as possible. If using
powdered herb, allow the powder to settle to the bottom of the pot and then pour off the
decoction from the top into a teacup (any sediment missed will settle to the bottom of the
teacup). Standard dosages for decoction are generally one-half to one cup, two or three
times daily. Again, the entire day’s dosage can be prepared in the morning (2-3 cups at
one time), and the remainder refrigerated until ready to use later in the day.
Tinctures
Tinctures are liquid preparations which are usually obtained using either 1 part of
herbal drug or animal matter and 10 parts of extraction solvent or 1 part of herbal drug or
animal matter and 5 parts of extraction solvent.
Tinctures are prepared by maceration or percolation (outline methodology is given
below) using only ethanol of a suitable concentration for extraction of the herbal drug or
animal matter, or by dissolving a soft or dry extract (which has been produced using the
same strength of extraction solvent as is used in preparing the tincture by direct extraction)
of the herbal drug or animal matter in ethanol of a suitable concentration. Selection of
process depends on nature of drug, cost of drug, and potency of drug. Tinctures are
usually clear. A slight sediment may form on standing which is acceptable as long as the
composition of the tincture is not changed significantly.
Production by maceration. Unless otherwise prescribed, reduce the herbal drug or
animal matter to be extracted to pieces of suitable size, mix thoroughly with the prescribed
extraction solvent and allow to stand in a closed container for an appropriate time. The
residue is separated from the extraction solvent and, if necessary, pressed out. In the latter
case, the 2 liquids obtained are combined.
Production by percolation. If necessary, reduce the herbal drug or animal matter to
be extracted to pieces of suitable size. Mix thoroughly with a portion of the prescribed
extraction solvent and allow to stand for an appropriate time. Transfer to a percolator and
allow the percolate to flow at room temperature slowly making sure that the herbal drug
or animal matter to be extracted is always covered with the remaining extraction solvent.
The residue may be pressed out and the expressed liquid combined with the percolate.
Percolation process is more efficient.
Methods o f Preparing Herbal Remedies □ □ 25
Liquid extracts
Liquid extracts are liquid preparations of which, in general, 1 part by mass or volume
is equivalent to 1 part by mass of the dried herbal drug or animal matter. These preparations
are adjusted, if necessary, so that they satisfy the requirements for content of solvent, and,
where applicable, for constituents.
Production. Liquid extracts are prepared by using ethanol of suitable concentration
or water to extract the herbal drug or animal matter, or by dissolving a soft or dry extract
(which has been produced using the same strength of extraction solvent as is used in
preparing the liquid extract by direct extraction) of the herbal drug or animal matter in
either ethanol of suitable concentration or water. Liquid extracts may be filtered, if
necessary.
Soft extracts
Soft extracts are semi-solid preparations obtained by evaporation or partial evaporation
of the solvent used for extraction.
Dry extracts
Dry extracts are solid preparations obtained by evaporation of the solvent used for
their production. Dry extracts usually have a loss on drying or a water content of not
greater than 5 percent.
Classification of Pharmaceutical dosage forms :
A. Gaseous dosage forms
B. Liquid dosage forms
C. Semisolid dosage forms
D. Solid dosage forms
A. Gaseous dosage form.
(i) Medicinal gases, inhalation/volatile anaesthetics (vaporised before administration
by inhalation)
(ii) Aerodispersions of solid particles (e.g., antiasthmatic inhalations) or liquid particles
(antiasthmatic inhalations or sprays)
B. Liquid dosage form
(i) Solutions - one homogenous phase, prepared by dissolving one or more solutes in
a solvent
(ii) Emulsions
• a dispersion system consisting of two immiscible liquids
• o/w or w/o
• cloudy appearance
26 □ □ Drug Inspector Exam
(iii) Suspensions
• A dispersion system where solid particles (dispersed phase) are dispersed in liquid
phase (dispersion medium)
• According to the size of dispersed particles (1 nm- 0,5 mm) a molecular, colloidal
and coarse dispersions can be distinguished
• May require shaking before administration
• Not intended for systemic administration of drugs with high potency
C. Semisolid dosage form
1. Unshaped (without specific physical shape)
(i) Ointments - Semisolid dosage forms with the oleaginous (hydrocarbon), water-
soluble or emulsifying base
- Oleaginous (hydrocabon) base: Petrolatum (Vaseline- white, yellow)
- Water-soluble base: Polyethylenglycol (PEG)- ointment - syn. macrogol
ointments
(ii) Pastes - semisolid dispersion system, where a solid particles (>25%, for example,
ZnO) are dispersed in ointments - mostly oleaginous (Petrolatum)
2. Shaped
(i) Suppositories (for rectal administration)
- Different shapes
- Melting/dissolving at body temperature
- Oleaginous (cocao butter) or aqueous (PEGs,glycerinated gelatine)
(ii) Pessaries (vaginal suppositories)
- Similar as above, PEGs or glycerinated gelatine are often used as base.
D. Solid dosage form
1. Unshaped (without specific shape)
- powders for external /internal use
2. Shaped
- Tablets
- Capsules
- Implants (Sterile disks inserted surgically into body tissues and designed to release
drug(s) over extended period of time)
- Transdermal patches
- Lozenges (consists of sugar and gum to medicate the mouth and throat)
Controlled-Release Dosage Forms
The release or liberation of the drug substance from the dosage form can be controlled
in certain types of dosage form. Release can be controlled in two ways, (1) the drug
Methods o f Preparing Herbal Remedies □ □ 27
substance is released at a specified rate or (2) the drug substance is released at a specified
location. These dosage forms are termed modified release dosage forms. Extended release
and delayed release are the most common type of modified release dosage forms. Extended
release dosage forms allow the rate of drug-substance release to be controlled in such a
manner as to allow a reduction in dosing frequency. The rate of drug-substance release is
controlled by the inclusion of excipients that retard drug substance release. Certain designs
of delayed release dosage forms contain functional excipients that release the drug
substance in response to a stimulus, such as the presence of a specific enzyme, biological
substrate or pH.
Novel Drug Delivery Systems
The method by which a drug is delivered can have a significant effect on its efficacy.
Some drugs have an optimum concentration range within which maximum benefit is
derived, and concentrations above or below this range can be toxic or produce no
therapeutic benefit at all. On the other hand, the very slow progress in the efficacy of the
treatment of severe diseases, has suggested a growing need for a multidisciplinary
approach to the delivery of therapeutics to targets in tissues.
Most of the pharmaceutical products are simple, fast-acting chemical compounds that
are dispensed orally (as solid pills and liquids) or as injectables. During the past three
decades, however, formulations that control the rate and period of drug delivery (i.e.,
time-release medications) and target specific areas of the body for treatment have become
increasingly common and complex.The goal of all sophisticated novel drug delivery
systems, therefore, is to deploy medications intact to specifically targeted parts of the
body through a medium that can control the therapy's administration by means of either
a physiological or chemical trigger. To achieve this goal, researchers are turning to advances
in the worlds of micro and nanotechnology. Some of the examples are given here.
(i) Micelles: These micelles are only tens of nanometers in diameter and are thus
ideally sized for enclosing individual drug molecules. Further, their hydrophilic
outer shells help protect the cores and their cpntents from chemical attack by the
aqueous medium in which they must travel. Finally, drug release is achieved via
common polymer degradation mechanisms, with the specificity of the delivery
(For example, cell-specific drug targeting) controlled by the synthetic design. For
example, micelles containing attached sugar-group ligands have been shown to
specifically target glyco-receptors in cellular plasma membranes.
(ii) Liposomes: Liposomes are a form of vesicles that consist either of many, a few or
just one phospholipid bilayer. The polar character of the liposomal core enables
polar drugrrtolecules to be encapsulated. Amphiphilic and lipophilic molecules
are solubilized within the phospholipid bilayer, according to their affinity towards
the phospholipids. Participation of nonionic surfactants instead of phospholipids
in the bilayer formation, results in niosomes. Channel proteins can be incorporated
28 □ □ Drug Inspector Exam
without loss of their activity within the hydrophobic domain of vesicle membranes,
acting as a size-selective filter, only allowing passive diffusion of small solutes
such as ions, nutrients and antibiotics. Thus, drugs that are encapsulated in a
nanocage-functionalized with channel proteins are effectively protected from
premature degradation by proteolytic enzymes. The drug molecule, however, is
able to diffuse through the channel, driven by the concentration difference between
the interior and the exterior of the nanocage.
(iii) Dendrimers and Fullerenes: Dendrimers also known as star polymers are
nanometer-sized, highly branched and monodisperse macromolecules with
symmetrical architecture. They consist of a central core, branching units and
terminal functional groups. The core together with the internal units, determine
the environment of the nanocavities and consequently their solubilizing properties,
whereas the external groups decides the solubility and chemical behaviour of these
polymers. Targeting effectiveness is affected by attaching targeting ligands at the
external surface of dendrimers, while their stability and protection from the
Mononuclear Phagocyte System (MPS) is being achieved by functionalization of
the dendrimers with Polyethylene Glycol Chains (PEG). To date, these delivery
systems remain largely unexplored, but researchers have demonstrated the
usefulness of attaching the anticancer agents 5-fluorouracil to polyaminoamine
dendrimers and methotrexate to hydrazide-terminated dendrimers formed from
poly (aryl ether).
( iv) Nanoparticles: Nanoparticles (nanospheres and nanocapsules of size 10-200 nm)
are in the solid state and are either amorphous or crystalline. They are able to
adsorb and/or encapsulate a drug, thus protecting it against chemical and
enzymatic degradation. Nanocapsules are vesicular systems in which the drug is
confined to a cavity surrounded by a unique polymer membrane, while
nanospheres are matrix systems in which the drug is physically and uniformly
dispersed. Nanoparticles as drug carriers can be formed from both biodegradable
polymers and non-biodegradable polymers. In recent years, biodegradable
polymeric nanoparticles have attracted considerable attention as potential drug
delivery devices in view of their applications in the controlled release of drugs, in
targeting particular organs / tissues, as carriers of DNA in gene therapy, and in
their ability to deliver proteins, peptides and genes through the oral route.
(v) Hydrogels: Hydrogels are three-dimensional, hydrophilic, polymeric networks
capable of imbibing large amounts of water or biological fluids. The networks are
composed of homopolymers or copolymers, and are insoluble due to the presence
of chemical crosslinks (tie-points, junctions), or physical crosslinks, such as
entanglements or crystallites. Hydrogels exhibit a thermodynamic compatibility
with water, which allows them to swell in aqueous media. They are used to regulate
Methods o f Preparing Herbal Remedies □ □ 29
ANSWERS
1. (a) 2. (b) 3. (b) 4. (a) 5. (a) 6. (a) 7. (a) 8. (a) 9. (a) 10. (d)
11. (b) 12. (b) 13. (c) 14. (d) 15. (c) 16. (c) 17. (a) 18. (d) 19. (c) 20. (b)
21. (a) 22. (b) 23. (a) 24. (d) 25. (b) 26. (a) 27. (d) 28. (a) 29. (e) 30. (d)
cm
Prescription and Latin Words used A
Date
Date must be written on the prescription by the prescriber at the same time when it is
written. The date on the prescription helps a pharmacist to find out the cases where
prescription is brought for dispensing long time after its issue. Prescriptions containing
narcotic or other habit-forming drugs must bear the date.
Name, Age, Sex and Address of the Patient
Name, age, sex and address of the patient must be written on the prescription. If it is
not written then, the pharmacist himself should ask the patient about these particulars
and put down at the top of the prescription. This avoids the possibility of giving the
finished product to a person other than the one it is meant for. Patient's full name must be
written instead of surname or the family name.
Age and sex of the patient especially in the case of children helps the pharmacist in
checking the medication and the dose. Therefore, there will be less danger of its being
administered to the wrong member of the family or the hospital ward having similar
names. The address of the patient is recorded to help for any reference at a later stage, to
contact the patient or to deliver the medication personally.
Superscription
The superscription is represented by a symbol, Rx, which is always written at the
beginning of the prescription. In the days of mythology and superstition the symbol was
considered as a prayer to Jupiter, the God of healing, for quick recovery of the patient but
now this symbol is understood as an abbreviation of the Latin word recipe, meaning "take
thou" or "you take”.
Inscription
This is the main part of the prescription. It contains the names and quantities of the
prescribed ingredients. The names of the ingredients are written each on a separate line,
followed by the quantity ordered and the last item written is generally the vehicle or
diluent.
*30
Prescription and Latin Words used in the Prescription □ □ 33
(c) Four times a day 12. The latin term ’More dicto' is
(d) Once time a day designated to
5. The latin term'Primonano'indicates (a) as directed
(b) frequently
(a) Early in the morning
(c) when required
(b) In the morning
(d) none of the above
(c) Every morning
(d) During the night 13. The latin term'semen in die' indicates
(a) once in a day
6. The latin term'Mitte' indicates
(b) three times a day
(a) Send (c) Twice a day
(b) Take (d) four times a day
(c) Send such
14. The term ’More dicto' indicates
(d) In the manner prescribed
(a) in the manner prescribed
7. The latin term collutorium'designated ~ (b) send such
to (c) to be added
(a) A mouth wash (d) as directed
(b) a eye wash
15. The latin term'tussi urgent' indicates
(c) poultice (a) when cough is troublesome
(d) none of the above (b) immediately
8. In a prescription, the term signature’ (c) when pain is severe
indicates (d) frequently
(a) direction to patient 16. Supercription indicates
(b) direction to doctor (a) direction to patient
(c) direction to pharmacist (b) direction to physician
(d) None of the above (c) symbol Rx
9. The latin word'Auristille' indicates (d) none of the above
(a) ear drop (b) capsule 17. Subcription is directed to
(c) a powder (d) a draught (a) patient
10. Cataplasma is related to (b) pharmacist
(a) powder (b) poultice (c) doctor
(c) cream '(d). ointment (d) all of the above
18. The latin term'nebula' indicates
11. Latin word'Siopus sit' indicates
(a) a spray solution
(a) when necessary
(b) nasal drop
(b) immediately
(c) a paste
(c) slowly
(d) none of the above
(d) as directed
Prescription and Latin Words used in the Prescription □ □ 35
ANSWERS
l.(a ) 2. (a) 3. (a) 4. ( a ) . 5. (a) 6. (a) 7. (a) 8. (a) 9. (a) 10. (b)
11. (a) 12. (a) 13. (a) 14. (a) 15. (a) 16. (c) 17. (b) 18. (a) 19. (a) 2 0 . (b)
21. (a) 2 2 . (a) 23. (a) 24. (a) 25. (b) 26. (a)
□ □ □
5
C h a pt er
1. Proportionate to age
(a) Young's Formulae
Age in yrs
Dose for the child x Adult dose
Age +12
(b) Dilling;s Formulae
Age in yrs
Dose for the child x Adult dose
20
(c) Fried's Formula
Age in yrs
Dose for the child x Adult dose
150
2. Proportionate to body weight
For example, adult dose of chloramphenicol is 25-50 mg/Kg
Suppose, the weight of Child is 30 Kg
Dose required is 30 mg/Kg body weight
Theefore, total dose = 30 x 30 = 900 me
Alcohol dilution
How would you prepare a 20ounce of 60% alcohol from 90% alcohol.
Solution. In this A1 and B2 are the strength of solution l(of 60% alcohol) and A2 and
B2 are the strength of concentrates(of 90% alcohol)
A1 = 60%,
and A2 = 90%,
B1 = 20 ounce
B2 = ?
60x20
B2 = ——— = 13.3 ounce
yu
36
Posology □ □ 37
Hence, 13.3 ounce of 90% alcohol must be diuted to 20 ounce with water to get 60%
alcohol.
Proof spirit
An alcohol-water mixture or a beverage containing a standard amount of alcohol, the
U.S. standard being 100 proof, or 50 percent, of ethyl alcohol by volume at 60°F
(approximately 15.6°(C). In India, 57.1 volumes of ethyl alcohol is considered to 100
volumes of Proof Spirit.
Examplel. Convert 90% v/v alcohol into proof spirit.
Solution.
57.1 volumes = 100 volumes
1 volume = 100/57.1 = 1.753
volumes of proof spirit 90 volumes of
alcohol volumes of proof spirit = 90 x 1.753 = 157.77
The proof strength of 90% alcohol = 157.77 - 100 = 57.770/P
Example 2. Convert 30% v/v alcohol into proof spirit.
Solution.
57.1 volumes = 100 volumes
1 volume = 100/57.1 = 1.753
volumes of proof spirit
30 volumes of alcohol = 30 x 1.753 = 52.59
volumes of proof spirit
The proof strength of 90% alcohol
= 52.59 - 100 = 47.41U/P
Isotonic solution
In the general sense, two solutions are isotonic when they contain the same amounts
of solutes, or dissolved substances, and therefore have the same osmotic pressure. As
commonly used in the medical field, though, isotonic solutions are solutions which have
the same concentration of solute as the cells in the human body. A cell placed in an isotonic
solution will neither gain nor lose water.
When two aqueous solutions of different concentrations or tonicities are separated by
a semi-permeable membrane such as a cell wall, water will migrate from the less
concentrated, or hypotonic, side to the more concentrated, or hypertonic, side in an attempt
to bring both sides into equilibrium. This process is known as osmosis. The greater the
difference in the two solutions' concentrations, the higher the osmotic pressure will be,
and the quicker the osmotic transfer will be.
Calculation for adjustment to Isotonicity
(a) Based on Freezing Point method
% w /v of adjusting substance required
0.52- a
38 □ □ Drug Inspector Exam
Where
a = Freezing point depression of unadjusted drug solution
b = Freezing point depression of 1% w /v adjusting substance
(b) Based on Molecular concentration
% w /v of adjusting substance required
0.03 x g molecular weight of the substance
No of ions into which the substance ionizes
Example 1 : Find out the proportion of dextrose needed to form a solution isotonic to blood
plasma.
Solution. The molecular weight of dextrose is 180 and it is non ionisable.
% w /v of adjusting substance required
0.03 x 180
= ----- ------ = 1.86%w/v
Example 2 : Find out a proportion of NaCl required to render a 1& solution o f cocaine HCl
isotonic to blood plasma.
Freezing point of 1% solution of Cocaine HCl = - 0.09°C
Freezing point of 1% solution of Cocaine HCl = - 0.576°C
This means that 4.7 g of zinc oxide would displace 1 g of theobroma oil
1 g of zinc oxide would displace 1 -f 4.7 g of theobroma oil
So, 4 g of zinc oxide will displace (4 x 1) -r 4.7 g of theobroma oil = 0.85 g
Therefore, the weight of base required to make medicated suppositories
= 20 - 0.85 g = 19.15 g
= 19.15 g Ans.
24. Total body surface area is more than 28. The dose of morphine sulphatw is
(a) 20,000m2 (a) 10-20 mg
(b) 20,000cm2 (b) 20-40 mg
(c) 2000m2 (c) 10-40 mg
(d) 20,00,000cm2 (d) 50 mg
25. The dose of old age patient is 29. The dose of adrenalinr is
(a) more than adult dose (a) 0.2-0.5 mg
(b) less than adult dose (b) 0.5 -1 mg
(c) equal to adult dose (c) 1.5 mg
(d) None of the above (d) 2 mg
26. The Young's formula for calculation 30. What will be dose for llyrs child id
of dose, deals with adult dose is 500mg as per Clark's
(a) surface area formula?
(b) age in month (a) 245 mg (b) 235 mg
(c) age in yrs (c) 265 mg (d) 225 mg
(d) All of the above 31. Calculate the quantities required to
27. Posology deals with make six glycerogelatin suppositories
(a) ingredients of formulation (4 g mould), each containing 100 mg
aminophylline (Displacement value =
(b) dose of drug
1.3)
(c) type of formulation
(a) 28.25 g (b) 28.65 g
(d) calculation of quantity of
(c) 28.35 g (d) 28.45 g
ingredients
ANSWERS
1. ((d) 2. (a) 3. (a) 4. (a) 5. (b) 6. ( 0 7. (b) (a) 9.
00
(b) 1 0 . (b)
11. (c)i 12. (a) 13. (a) 14. (b) 15. (b) 16. (b) 17. ((d) 18. (a) 19. 2 0 . (b)
21. (c) 22. (a) 23. (c) 24. (a) 25. (b) 26. (c) 27. (b) 28. (a) 29. 3 0 . (b)
31. (a)
□ □ □
Communicable Diseases
6
C h a pter
The diseases which spread from one person to another through contaminated food,
water or contact or through insecticides, animals etc., are called the communicable diseases.
These are caused by different causative agents (pathogens).
A. DISEASES C A USEB^\^VfRUSES
1. Chicken pox
Pathogen: Chicken pox virus (varicella)
Mode of transmission: By contact or through scabs
Incubation period: 12-20 days
Symptoms
(i) Fever, headache and loss of appetite
(ii) Dark red-coloured rash on the back and chest which spreads on the whole body.
Later, rashes change into vessicles.
(iii) After few days these vessicles start drying up and scabs (crusts) are formed.
(iv) These scabs start falling (infective stage)
Prevention and Cure
There is no vaccine against chicken pox as yet. But precautions must be taken as
follows:
(i) The patient should be kept in isolation.
(ii) Clothings, utencils, etc., used by the patient should be sterilised.
(iii) Fallen scabs should be collected and burnt.
One attack of chicken pox gives life long immunity to the person recovered from
this disease.
2. Measles
Pathogen: Virus (Rubeola)
Mode of transmission: By air
Incubation period: 3-5 days
Symptoms
(i) Common cold
(ii) Appearance of small white patches in mouth and throat.
(iii) Appearance of rashes on the body.
Communicable Diseases □ □ 43
Dengue fever is characterized by an onset of sudden high fever, severe he? iache,
pain behind the eyes and in the muscles and joints.
Dengue hemorrhagic fever is an acute infectious viral disease. It is an advanced stage
of dengue fever. It is characterized by fever during the initial phase and other symptoms
like headache, pain in the eye, joint pain and muscle pain, followed by signs of bleeding,
red tiny spots on the skin, and bleeding from nose and gums.
How does Dengue spread?
Dengue spreads through the bite of an infected Aedes aegypti mosquito. The
transmission of the disease occurs when a mosquito bites an infected person and
subsequently bites a healthy person. In doing so, it transmits blood containing the virus
to the healthy person and the person becomes infected with dengue. The first symptoms
of the disease occur about 5 to 7 days after the infected bite.
Aedes mosquito rests indoors, in closets and other dark places, and is active during
day time. Outside, it rests where it is cool and shaded. The female mosquito lays her eggs
in stagnant water containers such as coolers, tyres, empty buckets etc., in and around
homes, and other areas in towns or villages. These eggs become adults in about 10 days.
Incubation period
The time between the bite of a mosquito carrying dengue virus and the start of
symptoms averages 4 to 6 days, with a range of 3 to 14 days.
Diagnosis
Diagnosis is made through blood tests by scanning for antibodies against dengue
viruses. In addition the blood platelets counts also drastically reduce in the infected person.
Symptoms
Symptoms of Dengue fever
(i) Sudden onset of high fever, generally 104-105 °F (40 °(C), which may last 4-5 days.
(ii) Severe headache mostly in the forehead.
(iii) pain in the joints and muscles, body aches.
(iv) Pain behind the eyes which worsens with eye movement.
(v) Nausea or vomiting.
Symptoms of Dengue hemorrhagic fever
These include symptoms similar to dengue fever, plus other symptoms such as :
(i) Severe and continuous pain in the abdomen.
(ii) Rashes on the skin.
(iii) Bleeding from the nose, mouth, or in the internal organs.
(iv) Frequent vomiting with or without blood.
(v) Black stools due to internal bleeding.
(vi) Excessive thirst (dry mouth).
(vii) Pale, cold skin, weakness.
46 □ □ Drug Inspector Exam
Prevention
Following steps can be taken to prevent spread of dengue fever:
(i) Avoid water stagnation for more than 72 hours so that the mot quitoes do not breed
there.
(ii) Prevent mosquito breeding in stored water bodies, like ponds, wells etc.
(iii) Destroy discarded objects like old tyres, bottles, etc., as they collect and store rain
water.
(iv) Use mosquito repellents and wear long sleeved clothes to curtail exposure.
(v) Use mosquito nets, also during daytime.
(vi) Avoid outdoor activities during dawn or dusk when these mosquitoes are most
active.
(vii) Patients suffering from dengue fever must be isolated for at least 5 days.
(viii) Report to the nearest health centre for any suspected case of Dengue fever.
Treatment for dengue and dengue hemorrhagic fever
There is no specific treatment for dengue fever. Persons with dengue fever should rest
and drink plenty of fluids. Dengue hemorrhagic fever is treated by replacing lost fluids.
Some patients need blood transfusions to control bleeding.
1. Tuberculosis
Pathogen: A bacterium (Mycobacterium tuberculosis).
Mode of Transmission: Airbome-discharged through sputum, cough, sneeze, etc.
of the infected person.
Incubation period: 2-10 weeks during which the bacteria produce a toxin,
tuberculin.
Symptoms
(i) Persistent fever and coughing.
(ii) Chest pain and blood comes out with the sputum.
(iii) General weakness.
Prevention and Cure
(i) Isolation of patient to avoid spread of infection.
(ii) BCG vaccination is given to children as a preventive measure.
(iii) Living rooms should be airy, neat and with clean sorroundings.
(iv) Antibiotics be administered as treatment.
2. Typhoid
Pathogen: A Bacillus rod-shaped bacterium (Salmonella typhi)
Mode of transmission: Through contaminated food and water
Incubation period: About 1-3 weeks
Communicable Diseases □ □ 47
Symptoms
(i) Continuous fever, headache, slow pulse rate.
(ii) Reddish rashes appear on the belly.
(iii) In extreme cases, ulcers may rupture resulting in death of the patient.
Prevention and Cure
(i) Anti-typhoid inoculation should be given.
(ii) Avoid taking exposed food and drinks.
(iii) Proper sanitation and cleanliness should be maintained.
(iv) Proper disposal of excreta of the patient.
(v) Antibiotics should be administered.
3. Cholera
It often breaks out among crowded and areas with poor sanitary conditions.
Pathogen: Comma shaped bacterium (Vibrio cholerae)
Mode of transmission: Contaminated food and water. House - fly is the carrier.
Incubation period: 6 hours to 2-3 days.
Symptoms
(i) Acute diarrohoea, rice watery stool.
(ii) Muscular cramps.
(iii) Loss of minerals through urine.
(iv) Dehydration leads to death.
Prevention and Cure
(i) Cholera vaccination should be given.
(ii) Electrolytes (Na, K, sugar, etc.) dissolved in water should be given to the patient to
check dehydration (In market it is available as ORS-oral rehydration solution).
(iii) Proper washing and cooking of food.
(iv) Proper disposal of vomit and human excreta.
(v) Flies should not be allowed to sit on eatables and utensils.
4. Diphtheria
This disease generally occurs in children of 1-5 years of age.
Pathogen: Rod-shaped bacterium (Comybacterium diphtherea)
Mode of Transmission: Through air (droplet infection)
Incubation period: 2-4 days
Symptoms
(i) Slight fever, Sore throat and general indisposition.
(ii) Oozing semisolidmaterial in the throat which develops into a toughmembrane.
The membrane may cause clogging (blocking) of air passage, resulting into death.
48 □ □ Drug Inspector Exam
1. Malaria
Pathogen: Malarial parasite (different species of Plasmodium)
Mode of transmission: By bite of female Anopheles mosquitoes
Incubation period: Approximately 12 days
Symptoms
(i) Headache, nausea and muscular pain.
(ii) Feeling of chilliness and shivering followed by fever which becomes normal along
with sweating after some time.
(iii) The patient becomes weak and anaemic.
(iv) If not treated properly secondary complications may lead to death.
Prevention and Cure
(i) Fitting of double door and windows (with "Jali" i.e., wire mesh) in the house to
prevent entry of mosquitoes.
(ii) Use of mosquito net and mosquito repellents.
(iii) No water should be allowed to collect in ditches or other open spaces to prevent
mosquito breeding.
Communicable Diseases □ □ 49
(iv) Sprinkling of kerosene oil in ditches or other open spaces where water gets collected
(v) Antimalarial drugs to be taken.
2. Amoebiasis (Amoebic dysentery)
Pathogen: Entamoeba histolytica
Mode of transmission: Contaminated food and waterSymptoms
(i) Formation of ulcers in intestine.
(ii) Feeling of abdominal pain and nausea.
(iii) Acute diarrhoea and mucus in stool.
Prevention and cure
(i) Proper sanitation should be maintained.
(ii) Vegetables and fruits must be properly washed before eating.
(iii) Antibiotics may be given to the patients.
1. Filariasis
Pathogen: Filarial worm (Wuchereria bancrofti)
Mode of transmission: Bites of mosquitoes - Aedes and Culex.
Symptoms
(i) Fever
(ii) Collection of endothellial cells and metabolites in the wall of lymph vessels.
(iii) Swelling takes place in certain parts of the body like legs, breasts, scrotum, etc.
(iv) Swelling of legs which appear as legs of elephant, so this disease is also called
elephantiasis (Fig. 6.1)
Glycoprotein 120
Phospholipid membrane
Viraf capsid
Reverse transcriptise
■RNA
Protein 17
Transmembrane
Glycoprotein
Fig. 6.2.
Mode of transmission: AIDS maybe transmitted through any of the following means :
(i) Sexual contact with the affected person. In India, the most common route of HIV
transmission is through unprotected heterosexual sex.
(ii) Using the same syringe as that of affected person.
(iii) Blood transfusion which contains human immuno deficiency virus.
(iv) Organ transplantation of the affected person.
(v) Artificial insemination.
(vi) From mother to new born baby during the process of giving birth.
Incubation period: The average period is 28 months though it may range between 15
to 57 months
Symptoms : The sufferer may show one or more of the following symptoms :
Communicable Diseases □ □ 51
(a) Pain, swelling or redness of the 28. A defect in a vaccine product should
site be reported:
(b) Irritability (a) Using the Yellow Card Scheme
(c) Headache (b) Using the Black Triangle Scheme
(d) Cardiovascular collapse and other (c) To a report centre of the Medicines
anaphylactic reactions and Healthcare products
(e) Temperature above 37.5°C Regulatory Agency (MHRA)
26. If a vaccine carries the Black Triangle (d) Only to the vaccine manufacturer
symbol this indicates: (e) Only if it has caused an adverse
(a) It is a vaccine which must be reaction in a patient
adm inistered under hospital 29. The combined vaccine given at 2, 3
supervision and 4 months of age is:
(b) The vaccine is not yet licensed (a) DTaP/IPV/Hib
(c) All suspected reactions (serious (b) DTaP/IPV/PCV
and non-serious must be reported) (c) DTaP/IPV/MenC
(d) The vaccine can only be used on a (d) DTP/IPV/Hib
named-patient basis (e) DTaP/IPV/PPV
(e) Only reactions in children need to
30. By 14 months of age all children
be reported
should have received:
27. The Yellow Card Scheme: (a) Three doses of DTaP/IPV/Hib
(a) Reports submitted to the Yellow (b) Three doses of PCV
Card Scheme are entered on a (c) Two doses of MenC and one of
database operated by the riealth Hib/MenC
and Safety Executive (HSE)
(d) Two doses of MMR
(b) Is not applicable to vaccines given
(e) One dose of Td/IPV
Black Triangle status
(c) Allows patients to report 31. The number of doses of diphtheria/
suspected adverse reactions tetanus and polio vaccines required to
(d) Only serious adverse reactions ensure long-term protect throughout
should be reported for vaccines adulthood is:
that have been marketed for 6 (a) Three (b) Four
months or more (c) Five (d) Six
(e) Is a compulsory reporting system (e) None of the above
for suspected adverse reactions
ANSWERS
1. (b) 2. (a) 3. (d) 4. (b) 5. (b) 6. (c) 7. (b) 8. (c) 9. (a) 10. (d)
11. (b) 12. (c ) 13. (b) 14. (c ) 15. (c) 16. (a) 17. (c) 18. (b) 19. (a) 20. (a)
21. (e) 22. (a) 23. (d) 24. (a) 25. (a,b) 26. (c) 27. (c ) 28. (a) 29. (a) 30. (a)
31. (d)
□ □ □
First Aid Treatment
7
C h a pter
First Aid is the temporary help given to an injured or a sick person before professional
medical treatment can be provided. This timely assistance, comprising of simple medical
techniques, is most critical to the victims and is, often, life saving.
available at most government hospitals and public health centers. Some private
nursing homes have also started stocking it and treat snakebite cases.
Extent of Burns
The area of a burn gives an approximate indication of the degree of shock that will
develop and, in conjunction with depth, can be used as a guide to the required level of
treatment. The 'rules of nine' is a guide used to calculate the extent of a bum as a percentage
of the body’s total surface area, and to assess what level of medical attention is required.
In an otherwise healthy adult:
• Any partial-thickness burn of 1% or more (an area approximating to that of the
casualty's hand) must be seen by a medical practitioner.
• A partial-thickness bum of 9% or more will cause shock to develop, and the casualty
will require hospital treatment.
• A full-thickness burn of any size requires hospital treatment.
Severe Burns and Scalds
The priority is to cool the injury; the longer the burning goes unchecked, the more
severely the casualty will be injured. Resuscitate the casualty only when cooling is
underway. All severe bums carry the danger of shock.
Treatment of Severe Burns and Scalds
DO NOT overcool the casualty; this may dangerously lower the body temperature.
DO NOT remove anything sticking to the bum; this may cause further damage and
cause infection.
IX) NOT touch or interfere with the injured area. _________
DO NOT burst blisters.
DO NOT apply lotions, ointment, or fat to the injury.
• Lay the casualty down, protecting the burned area from contact with the ground,
if possible.
• Douse the burn with copious amounts of cold liquid. Thorough cooling may take
10 minutes or more, but this must not delay the casualty's transmission to hospital.
• While cooling the bums, check airway, breathing, and pulse, and be prepared to
resuscitate.
• Gently remove any rings, watches, belts, shoes, or smouldering clothing from the
injured area, before it starts to swell. Carefully remove burned clothing unless it is
sticking to the burn.
• Cover the injury with a sterile burns sheet or other suitable non-fluffy material, to
protect from infection. A clean plastic bag or kitchen film may be used. Bums to
the face should be cooled with water, not covered.
• Ensure that the emergency service is on its way. While waiting, treat the casualty
for shock. Monitor and record breathing and pulse, and resuscitate, if necessary
First Aid Treatment □ □ 59
Types
• Open fracture: Skin breaks causing open wound
• Closed fracture: Skin not broken
• Complicated fractures: Damage of adjacent organs
• Stress fracture: Hairline crack due to repeated stress
• Greenstick fracture: In children’s flexible bones
Symptoms
• Severe pain, Difficulty in movement, Swelling/ bruising / bleeding, Deformity /
abnormal twist of limb, Tenderness on applying pressure
First-aid
• Depends on type & location of fracture
For open fractures
• Control bleeding before treatment
• Rinse and dress the wound
For open/closed fractures
• Check the breathing
• Calm the person
• Examine for other injuries
• Immobilize the broken wound
• Apply ice to reduce pain / swelling
• Consult a doctor
DO NOT
Massage the affected area
• Straighten the broken bone
• Move without support to broken bone
• Move joints above / below the fracture
• Give oral liquids / food
1. When making a 911 call, what are the 2. What is first aid?
three W's? (a) Completing a primary survey
(a) Who, What, Where (b) The first help giverrto the victim
(b) Where, What and Why of an accident
(c) Why, When and Where (c) Assessing a victim's vital signs
(d) Who, What and When (d) Treating a victim for shock
First Aid Treatment □ □ 61
3. What treatment does a victim who's 9. A small animal that is almost tvisible,
life threatening condition is "not burrows into the skin an i causes
breathing" need? itching:
(a) The Heimlich Maneuver, two (a) Common wood tick
rescue breaths and CPR (b) Limon-Lyme tick
(b) Start CPR immediately (c) Rocky mountain spotted tick
(c) Twelve to fifteen rescue breaths (d) Chigger
per minute and correct CPR
The accepted treatment for a sprained
(d) You should follow the steps for ankle is:
rescue breathing
(a) Remove the shoe and check for
4. The best treatment for all heart attack swelling using the capillary reflex
victims is immediate CPR. method
True/False (b) Keep the shoe on, apply an ankle
5. Sharp, stabbing twinges of pain in the bandage for support, elevate and
chest is a sure sign of a heart attack. apply cold towels
True /False (c) Keep the shoe on, apply an ankle
splint and apply heat if possible
6. The accepted treatment for a femor or
(d) Have the victim walk or move as
thigh fracture is:
soon as possible to prevent
(a) Place a short padded splint on stiffness
each side of the leg
(b) This type of fracture is best 11. The accepted treatment for a nose
handled by a traction splint bleed is:
applied by those with special (a) Use direct pressure, elevation and
training pressure points to control the
(c) Move the victim before properly bleeding
applying a leg splint (b) Tilt the head back and tightly
(d) Bind both legs with two long squeeze the nostrils
splints using two cravats, one (c) Have the victim lean forward.
above and one below the break Apply gentle pressure on the
nostril. Apply cold towels.
7. The victim of a poisonous snake bite
(d) Lay the victim on his back and
is not at risk for getting rabies.
treat for shock. Apply heat if
True /False available
8. Some people are very allergic to insect. y2 What is the best definition of the
bites and stings. This condition is "Hurry Cases"?
called: '
(a) Breathing, bleeding and broken
(a) Septic shock v bones
(b) Cardiac arrest (b) Any condition that threatens a
(c) Toxic shock syndrome victim's life
(d) Anaphylactic shock
62 □ □ Drug Inspector Exam
(c) Any illness where the victim (d) Immediately scratch and rub the
vomits effected area to provide long-term
(d) Any accident requiring rescue relief from the itching
breathing 17. Which of the following techniques is
13. After you have surveyed an accident not suitable for moving an
scene and provided for your own unconscious victim?
safety you should: (a) Improvised stretcher
(a) Take charge, remain calm and act (b) Four-handed seat carry
with confidence to the level of your (c) Two person carry
training (d) Blanket drag
(b) Provide primary treatment for
18. Assuming you are properly trained,
shock
the best procedure to follow for a
(c) Call 911 or your local emergency water rescue is:
number
(a) Throw, row then go
(d) Provide immediate treatment for
(b) Try to reach from the shore, then
the "hurry cases"
#» throw a rope or rescue device, last
14. It is not necessary to determine if a go with support
person with an obstructed airway has (c) Swim with support, throw a rope
a pulse. or flotation device, reach with a
True/False pole from shore
15. To treat a first degree burn you should: (d) Reach, paddlef swim ________
(a) Apply a good quality bum cream 19. What is the appropriate treatment for
or ointment a suspected broken collarbone or
(b) Clean the area thoroughly with hot shoulder?
soapy water (a) Apply a simple sling. Bind the
(c) Apply a constricting band between sling to the chest with a cravat
the burn and the heart (b) Use the cross your heart padded
(d) Apply cool running water until chest support method
there is little or no remaining pain (c) Use the flail chest protection
16. A victim that has come in contact with system
poison ivy should: (d) Apply a m odified "Johnson
(a) Wait at least 20 minutes before Traction Splint"
washing the effected area with hot 20. Which statement about a simple sling
water and soap is true?
(b) Rinse the effected area (a) The part of the sling against the
immediately with soap and water chest goes over the shoulder on the
(c) Continue to wear clothes that have injured arm
come in contact with the plant (b) The "pigtail" protects the neck from
injury from the sling
First Aid Treatment □ □ 63
(c) The injured hand should be four (e) The part of the sling furthf t away
to six inches higher than the elbow from the chest passes over the
21. White or grayish-yellow patches on shoulder on the injured arm
someone's ears, noses or cheeks are 25. What is the best procedure for treating
signs of a known poisonous snake bite?
(a) Frostbite (a) Capture the snake. Place it in an
(b) Cold related stress disorder ice chest and take the snake and
(c) Anaphylactic shock victim to a hospital.
(d) Hypothermia (b) Place a constructing bandage 4
inches above the L ^ad of the snake
22. The primary symptom of the
to slow the spread of venom
advanced stages of hypothermia
(c) Keep the victim calm, keep the bite
requiring immediate medical attention
location lower than the heart, get
is violent shivering.
medical help immediately
True/False
(d) Treat the victim for shock and
23. The symptoms of Heat Stroke and continue the planned activity
Heat Exhaustion are very similar and
26. What is antidote in the poisoning of
are often confused.
heavy metals?
True/False
(a) Dimercaprol
24. Whitch of the following correctly (b) Calcium salt
describes the CPR technique for an (c) Normal saline
adult:
(d) Adrenaline
(a) Four cycles of 15 compressions
followed by 1 breath each minute 27. How the morphine poisoning is
(b) One cycle of one breath and 10 recognized?
compressions each 2 to 3 inches (a) Constipation
deep per minute (b) Redness on face
(c) Twelve cycles of one breath and 5 (c) cessation of breathing
compressions per minute (d) Pin point pupil
(d) Four cycles of two breaths and 15
compressions per minute
ANSWERS
1- (a) 2. (b) 3. (d) 4. (false) 5. (false)6. (b) 7. (true) 8. (d) 9. (d) 10. (b)
11. (c) 12. (b) 13. (a) 14. (true) 15. (d) 16. (b) 17. (b) 18. (b) 19. (a) 20. (c)
2 1 . (a) 22 . (false) 23. (false) 24. (d) 25. (c) 26. (a) 27. (d).
non
Classification of Microbes
8
Chapter
Microorganisms are unicellular, meaning they contain only a single cell. The cellular
organisms are broadly classified as prokaryotes and eukaryotes, aerobic and anaerobic,
and by type of metabolism.
Prokaryotes
These are microorganisms that are characterized by the absence of a distinct membrane-
bound nucleus and by DNA that are not organized into chromosomes. They can be sub
classified into archaebacteria and eubacteria with further sub-classification under those
types.
Archaebacteria
Methanogens- Anaerobic methane producing bacteria
Extreme halophiles- Bacteria that require high salt concentration to survive
Extreme thermophiles- Bacteria that require high temperatures and sulphur
Eubacteria
Gram-positive bacteria- Bacteria whose cell walls retain crystal violet dye during iodine
treatment, for example, lactic acid bacteria.
Gram-negative bacteria- Bacteria that vary in cell-wall structure and do not retain
crystal violet dye during iodine treatment.
Eukaryotes
These are organisms that have a membrane bound nucleus in the cell containing
chromosomes, and other membrane bound organelles, for example, fungi. These fungi
can be further classified into myxomycota and eumycota.
Myxomycota
These are fungi that do not contain a cell wall. They are also called slime-molds.
Eumycota
These are true fungi. They are the most important class of fungi and are exploited l^r
commercial purposes like fermentation. Examples are yeasts, mushrooms, sponge fungi,
rusts, and mildews.
Microorganisms can be classified according to their oxygen requirements, as aerobic
or anaerobic.
64
Classification o f Microbes □ □ 65
Aerobic
These are microorganisms that can grow and live in the presence of oxygen. In compost
heaps bacteria of this type generate heat when they convert carbon and nitrogen, reducing
the volume of waste. As they exhaust the oxygen in the compost pile they die leaving a
germ free product.
Anaerobic
These organisms are averse to air. They are useful in biodegradation, breaking down
organic chemicals into smaller compounds, producing methane and carbon dioxide. Some
anaerobic organisms can break down organic chemicals by fermentation. Such organisms
are useful at hazardous waste sites.
Types of Metabolism
Microorganisms can also be classified according to type of metabolism. Types include
autotrophs, heterotrophs, chemotrophs, chemoheterotrophs, and phototrophs.
Autotrophs {
These are microorganisms that use carbon dioxide as their carbon source.
Heterotrophs
These are microorganisms that use organic compounds as their carbon source.
Chemotrophs
These are microorganisms that use chemical bonds for production of adenosine tri
phosphate (ATP).
Chemoheterotrophs
These are microorganisms (such as fungi) that use organic compounds for a carbon
source and the energy of chemical bonds to produce ATP.
Phototrophs
/
These are microorganisms that use light for production of ATP.
Classification of Bacteria: Until recently classification has done on the basis of such
traits as:
_Shape
• b acilli: rod-shaped
• cocci: spherical
• spirilla : curved walls
• ability to form spores
• method of energy production (glycolysis for anaerobes, cellular respiration for
aerobes)
• nutritional requirements
• reaction to the Gram stain.
66 □ □ Drug Inspector Exam
The Gram stain is named after the 19th century Danish bacteriologist who developed
it.
• The bacterial cells are first stained with a purple dye called crystal violet.
• Then the preparation is treated with alcohol or acetone.
• This washes the stain out of Gram-negative cells.
• Bacteria that are not decolorized by the alcohol/acetone wash are Gram-positive.
• Gram-positive bacteria are encased in a plasma membrane covered with a thick
wall of peptidoglycan. Gram-negative bacteria are encased in a triple-layer. The
outermost layer contains lipopolysaccharide (LPS)
10. Acid fastness of mycobacterium (a) imparts colour to the to the dye.
tuberculosis is due to (b) imparts ionization properties to
(a) presence of mycoloic acid the dye
(b) presence of techoic acid (c) helps in the fixation of the material
(c) both of the above to the glass slide.
(d) none of the above (d) all of the above
11. Giemsa stain was developed for the 17. Negative staining is a techniq usefull
staining of in demonstrating
(a) mycobacteria (a) mychobacteria
(b) neisseria (b) spirochetes
(c) microfilariae (c) pasturella
(d) malarial parasite (d) clostridia.
12. Acid fast stain was first described by 18. In gram staining iodine is used as
(a) ziehl and neelsen (a) a stain for clouring the cell
(b) ehrlich (b) a decolourising agent
(c) Christian gram (c) a counter stain to colour the
(d) newman decolourised celld.
(d) mordant to fix the primary stain.
13. Which of the following is a basic dye
(a) methylene blue 19. In gram staining tech gram +ve cells
(b) Rose Bengal, appear
(c) acid fuchsin (a) Blue (b) Green.
(d) eosin (c) Red (d) Violet
14. Which of the following is an acidic 20. The colour of acid fast and non acid
dye? fast bacteria are respectively
(a) safranine (a) blue purple (b) purple blue
(b) Basic fuchsin, (c) red green (d) green red.
(c) crystal violet, 21. Three fundamental divisions of the
(d) rose Bengal bacterial cell occur in all species
(a) cell wall, cell or cytoplasmic
15. The process by which the internal and
membrane, and cytoplasm
external structures of cells and
microorganisms are preserved and (b) nucleus, cytoplasmic membrane,
fixed in position is called and cytoplasm
(a) staining (b) mounting (c) nucleus, cytoplasmic membrane,
chromatin
(c) fixation (d) decolourisation
(d) cell wall, nucleus and cytoplasmic
16. the auxochrome group presnt in a membrane
staining dye has which of the
following function
68 □ □ Drug Inspector Exam
34. /8.Which section shows a growth 39. Which of the following defines a
phase where the cells dividing at their Heterotroph?
maximum rate of division? (a) An organism that must obtain its
(a) A (b) B carbon in an organic form
(c) C (d) D (b) An organism that does not require
(e) A and C essential nutrients for growth
35. The term facultative anaerobe refers (c) An organism that produces all the
to an organism that trace elements it requires for
growth
(a) doesn't use oxygen but tolerates it
(d) An. organism that must obtain its
(b) is killed by oxygen.
carbon in an organic form
(c) uses oxygen when present or
grows w ithout oxygen when 40. Molecules that satisfy heterotophic
oxygen is absent nutritional requirements include all
(d) requires less oxygen than is but which of the following?
present in air (a) Water (b) Lipids
(e) prefers to grow without oxygen36. (c) Proteins (d) Water
The term obligate anaerobe refers 41. The primary sources of nitrogen for
to an organism thata) doesn't use heterotrophs include all except which
oxygen but tolerates itb) is killed of the following?
by oxygenc) uses oxygen when (a) Glucose
present or grows without oxygen (b) RN
when oxygen is absentd) requires
(c) Amino Acids
less oxygen than is present in
aire)prefers to grow without (d) Glucose
oxygen 42. Gram-negative bacteria: ^
37. A culture started with 4 cells and (a) bind crystal violet
ended with 128 cells. How many (b) are negatively charged
generations did the cells go through: (c) retain safranin
(a) 64 (b) 32 (d) bind Gram’s iodine
(c) 6 (d) 5 (e) all of the above
- ( e) 4 43. Gram-positive bacteria subjected to
38. Which of the foods listed would be lysozyme or penicillin may become
most likely to spoil as a result of (a) acid-fast
bacterial growth. (b) non-L forms
(a) a meat product with near neutral (c) mycoplasmas
PH (d) spheroplasts
(b) fruit in a high sugar syrup (e) Protoplasts
(c) a vegetable in a high salt, acid 44. What would be the term used to
brine (liquid) describe the shape of these
(d) all of the above e)there is no basis bacteria?
on wfych to make this judgment.
70 □ □ Drug Inspector Exam
ANSWERS
1. (b) 2. (d) 3. (d) 4. (c) 5. (a) 6. (a) 7. (b ) 8. (a) 9. (b) 10. (a)
11. (d) 12. (a) 13. (a) 14. (d) 15. (c) 16. (b) 17. (b) 18. (c) 19. (a) 2 0 . (b)
21. (a) 22. (c ) 23. (b ) 24. (d) 25. (a) 26. (b) 27. (c) 28. (a) 29. (c) 30. (a)
31. (e) 32. (c ) 33. (d) 34. (b) 35. (c ) 36. (b ) 37. (d) 38. (a) 39. (d) 4 0 . (d)
41. (d) 42. (e)- 43. (e) 44. (d) 45. (c ) 46. (c) 47. (c) 48. (a) 49. (c) 50. (d)
□ □ □
Contamination o f Pharmaceuticals in 3 7
A spoiled product may be described as one that has been rendered unfit for use. As
pharmaceutical and cosmetics are consumed by, or applied to, the user, manifestation of
spoilage are essentially subjective, spoiled products becoming objectionable perhaps even
therapeutically inactive. Microbial spoilage can be caused by bacteria, yeast or fungi which
are all extremely versatile their metabolic activities.This capacity for variation whether
due to mutation in genetic composition followed by selection or to change in behaviour
unaccompanied genetic change, allows adaptation to a very broad range of environmental
conditions.
Before spoilage can occur organisms whi&i are capable of altering the components of
a product insitu must first be introduced via raw materials, the processing plant, packaging ,
materials, operatives or elsewhere in the environment. Although spoilage does not
necessarily depend upon the growth of these contaminants it is generally facilitated if the
formulation and the ambient conditions of temperature and humidity encourage their
multiplication. When these criteria are satisfied changes in the product will occur and
may ultimately manifest themselves to the user in one or more of the following ways:
TOXIC EFFECTS
Microbial Toxins
Several species of microorganisms produce toxic molecules and may render a product
dangerous if they grow in it under conditions supporting toxin production. Endotoxins,
produced by Gram-negative bacteria such as Escherichia coli, are intimately bound to the
cell, lipopolysaccharidien nature and are not necessarily in activated by sterilization as
they are heat stable. Toxins of this type are poorly absorbed by the oral route but are very
important in connection with injectable products, particularly perfusion fluids. Exotoxins
are much more highly lethal and are bound less rigidly to the cell so that they are readily
liberated into the growth medium. The outstanding example, of course, is that produced
by Clostridium botulinum which is lethal to mice in doses of the order of 0.1 ng. Fortunately
conditions for growth and toxin production are quite strict; anaerobiosis, the presence of
suitable pH and nutrients and of few competing bacteria is required. Such conditions are
71
72 □ □ Drug Inspector Exam
not often attained in pharmaceuticals and cosmetics and we know of no case of botulism
arising from their use. Certain strains of Staphylococcus aureus produce a toxin,
characterized a specific polysaccharide but the organism must grow to a density of several
million cells per gram before its toxin become as problem. The evidence in connection
with other bacteria for example, Clostridiump erfringens, Bacilluscereus, Streptococcus
faecal, Proteus and Pseudomonas sp ecies less clear, but poisonous metabolites are certainly
produced by a variety of fungi. Over the last decade there has been much interest shown
in the aflatoxins produced by Aspergillus flayus. These heat-stable compounds exhibit
potent toxic and carcinogenic properties in animals A. flayus commonly infects peanuts,
cotton seed and grain which are all components of animal foods. Under poor storage
conditions mould growth occurs and toxic doses of aflatoxin accumulatein the food stuff.
While it is difficult to visualize his occurring with cosmetics or pharmaceuticals it is wise
to ensure that ingredients such as talc, kaolin or starch are not stored for long periods
under conditions supporting mould growth.
Metabolic Products
In addition to microbialt oxins, which are complex molecules and may be looked upon
as biosynthetic products, simpler catabolic products such as organic acids and amines,
whi<ph can be toxic to man, may be produced. Indeed, many microbial metabolites exhibit
pharmacological activity.
As these compounds are considerable toxic than are the classic bacterial toxins,
relatively high concentration have to be attained before spoiled product causes illness
and the senses often detect that something is wrong before food spoiled to this extent is
swallowed. This may not apply to medicine as they are expected to be unpleasant and,
indeed, frequently contain a flavouring agent in order to mask an unpleasant taste.
However, well-documented examples incriminating specific metabolic products in
pharmaceuticals are not easy to find.
Irritancy
Incidents of irritation following the application of cosmetics occasionally occur, and
the offending preparation may subsequent be shown to contain a high level of microbial
contamination. Direct evidence that irritation is caused by the presence of the micro
organism is lacking but it is reasonable suppose that, on some occasions the contaminant
provide a source of foreign protein evoking an allergic contact dermatitis reaction or that
high levels of a microbial metabolite will cause a primary irritant reaction. The eye, of
course, is particularly susceptible to infection from contaminated cosmetics and it is also
at risk from the direct effect of irritant metabolites left in a product even after the organisms
producing them have been eradicated.
Contamination o f Pharmaceuticals in Hospitals and Environment by Microbes □ □ 73
Change of Activity
An interesting aspect, but perhaps not one of great significance is the inactivation of
biologically active molecules by organisms contaminating a formulation. Several examples
have now been demonstrated in the laboratory and in some cases have been observed to
occur in practice A. classic example is the destruction of penicillins by penicillinases
enzymes produced by a broad range of microorganisms. Microbial enzymes which
inactivate chloramphenicol are also known and the destruction of preservatives and
disinfectants is established. Pharmacologically active substances can also be degraded.
For instance Kedzia, Lewon and Wisniewsk found t hat a loss of atropine of up to 20% in
eye drops could be caused by Corynebacterium and pseudomonas spp. Isolated from the
eye drops and atropine itself. Recently, Grant, de Szors and Wilson have shown that in the
laboratory, a strain of Acinetobacter lwoffi, obtained from distilled water, utilized aspirin
as a sole carbon source in a mineral salt solution. The same organism metabolized other
active esters; for instance it could degrade heroin to morphine. Another organism,
Corynebacterium hoffnaii, which was isolated from laboratory dust, metabolized the
analgesics aspirin, phenacetin and paracetamol. Loss of useful activity is not restricted to
pharmaceutical products. For instance emphasis on the need for detergents which are
biodegradable has had some repercussion and shampoos have been known to lose their
surface-active properties due to degradation of the surfactants by contaminating bacteria.
VISIBLE EFFECTS
Visible Growth
When microorganisms can actually be observed in or on a product then there is
obviously no doubt that microbial spoilage has occurred. I n fact, this is probably the most
common way in which it is manifest. In liquid formulations contaminants may be seen as
a sediment, turbidity or a pellicle while on more solid preparations colonies, often coloured,
of bacteria, yeasts or moulds may form.
Colour Changes
Sometimes visible spoilage is more striking, particularly if a colour change is involved.
Colour changes due to alterations in the components of a product may result from pH,
redox or other changes caused by the metabolic activities of an organism, or to pigment
production by the contaminants themselves.
Members of the Pseudomonas genusa reoften implicated in spoilage of this type. These
organisms metabolize a very broad range of compounds, and can also produce soluble
pigments ranging in colour from blue-green to brown. In addition, they can render conditions
suitable for less adaptable spoilage organisms for example, they can create conditions
favouring the growth of anaerobes. Similarly, in an acidic product, oxidative yeasts can
cause a rise in pH by utilizing organic acids and this will encourage bacterial growth.
74 □ □ Drug Inspector Exam
Gas Production
If microbial metabolism produces gas in a sufficient amount to exceed its solubility in
a product, visible bubbles frothing and other manifestations of an increase in pressure
occur. Products containing carbohydrate or other fermentable substrates are particularly
susceptible this type of spoilage. Of the latter, glycerol an essential ingredient in many
cosmetic preparations, is fermented particularly readily by some common water borne
organisms.
Other Changes
Microbial metabolism can result in the composition of a homogeneous product
becoming visibly heterogeneous Emulsions, for instance are notoriously susceptible
changes in physicochemical conditions; hydrolysis of the oil phase or changes in the pH
of the aqueous phase will upset the equilibrium and thus cause visible changes. In liquid
products changes of viscosity can be seen to occur when contaminants have broken down
large molecules, utilized sugars or caused the aggregation of particles in suspension.
Olfactory Effects
It has long been known that many microorganisms produce characteristic odours and
as early as 1923a variety of aroma-producing bacteria had been listed. These aromas include
the highly characteristic ones of sulphur-containing metabolites such as hydrogen sulphide,
the sickly smells of the fatty acids, the 'fishy' odours of the amines and the astringency of
ammonia. Often these are combined to produce the 'off odours of a spoiled product.
Changes in the aroma of a product due to contaminants vary from the production of a
nauseating smell to a slight change in the bouquet but all can be disastrous particularly to
cosmetic and toiletry preparations which depends so much upon their specific perfumes.
One of the most common olfactory warnings of spoilage is the typical smell of mould. The
responsible aromatic elements have not been clearly identified but some actinomycete
which taint water with undesirable earthy odours have recently been shown to produce
geosmina, strongly earth-smellingn, eutral oil . An alcoholic odour, producedf rom
fermentable substratesi, stypical of spoilage by yeasts.
Taste
Reports that products taste peculiar are often the first indications that they may be
spoiled. The sense of taste varies widely between individuals and these reports do not
invariably indicate microbial contamination. For this reason, and because of the hazards
involved, taste is not a practicable control procedure with which to detect spoilage at an
early stage. Nevertheless, the combined senses of smell and taste are highly perceptive to
changes in flavour, particularly in bland, unflavoured preparations where the presence of
microbial metabolites is not masked. Margalith and Schwartz have listed over 100 organic
compounds involved in the production of flavour by micro-organisms. These consist
mainly of alcohols, aldehydes, ketones, acetals, acids, amines, esters and phenols.
Contamination o f Pharmaceuticals in Hospitals and Environment by Microbes □ □ 75
Texture
The feel of topical preparations particularly cosmetic and toiletry ones, is vital to their
acceptability but texture may be marred by contaminants. For instance, creams can become
lumpy or ’gritty' and changes in viscosity of liquid preparations, which can be detected
when applied to the skin, may occur.
Audible Effects
Apart from immediate manifestations of toxicity, which happily appear to be rare,
audible manifestations of spoilage are the most dramatic. If visible effects of spoilage are
obscured by the pack, an explosion can be the first indication that a gas-producing micro
organism has successfully adapted itself to what may have been considered inimical
conditions.
LIQUIDS
Water
Water is a major constituent of living material and participates in many metabolic
reactions. Bacteria, in particular, require high concentrations of water in their immediate
environment and may be regarded as aquatic organisms. Hence, all products containing
large amounts of free water can be particularly susceptible to spoilage by bacteria. Without
effective treatment to minimize contamination, water can, within a few days, contain
large numbers of initially Gram-negative and Gram-positive bacteria, and subsequently a
wide variety of bacteria, moulds and yeasts. At this stage visible and olfactory spoilage
occurs and a foul taste may develop. Indeed contaminated deionized water has often
been incriminated as the original source of spoilage in a formulation. Often the responsible
organisms are pseudomonades which are not only highly resistant o preservative but are
also able to use the wide strange of organic compounds as substrate
Simple Aqueous Solutions
Some moulds will grow on such unlikely media as strong solutions of copper sulphate
or sulphuric acid and simple solutions of inorganic compounds support the growth of
76 □ □ Drug Inspector Exam
many sorts of microbe. The presence of organic material greatly increases the chance of
growth occurring as it not only provides a utilizable substrate but may serve to introduce
contaminants into the solutions. There may be deposition of turbidity due to algae, moulds,
bacteria or yeasts in a multiplicity of different solutions including ammonium carbonate,
neutral ammonium tartrate, calcium digluconate, potassium citrate and Amaranth Solution
B ., even when apparently preserved with chloroform. Many solutions are included in the
great diversity of mixtures in the B.P.C. and oiher formularies. These are often prepared
from aqueous concentrates which are themselves adequately preserved. However, the
preservative can be diluted out on mixing and the resulting preparation is then at risk. An
example of recent interest is peppermint water which has been implicated as a source of
contaminants in formulations containing this ingredient. In at least one case there is
evidence that potential pathogens have been transmitted to patients from i t .
Suspensions
Aqueous suspensions of inorganic material of or pharmaceutical subsequently support
microbial growth, particularly as added preservatives tend to be absorbed and inactivated
by the suspended matter. Unless growth is at the surface, as with mould contaminants, it
is not easily detected visually because of the opacity of these products. When the lid is
removed spoilage is sometimes manifested by an offensive odour or an unpleasant taste,
but otherwise large numbers of bacteria may unwittingly be taken with the preparation.
Thus, a medicament for the treatment of an intestinal disorder may exacerbate, rather
than alleviate, the condition.The oils often become blackened due to bacterial action, the
first organism lowering the redox potential and allowing the proliferation of anaerobic
sulphate-reducing bacteria, Desulphovibrio or Desulphotomaculum species, which oxidize
simple organic compounds and reduce sulphate so hydrogen sulphide. This then deposits
iron sulphide due to the abundance of iron present in the environment where the oil is
used.
Emulsions
O/w emulsions are particularly susceptible to spoilage as the water in the continuous
phase allows contaminant so spread throughout the product. Preservatives generally exert
their influence only within this phase, and at its boundaries but their concentration depends
on their relative solubilities in the particular oil and in water and on the oil water ratio in
the emulsion. In addition to partition effects the activity of preservatives may be further
diminished due to inactivation by compound such as the non-ionic emulgents. These
posses list bactericidal and may even be utilized by pseudomonad. In a comprehensive
view Wedderburn pointed out that many other material used in emulsions are susceptible
to microbial degradation.
Spoilage in emulsions can be manifest by change in rheological properties, including
separation or breaking down. Discolouration and decolonization, changes in odour and
taste and signs of visible growth also occur.
Contamination o f Pharmaceuticals in Hospitals and Environment by Microbes □ □ 77
SOLIDS
Raw Materials
Solid raw materials may serve as a source of contaminants which will later spoil a
formulated product. Natural earths such as kaolin, bentonite, Fuller'se arthor French chalk
contain anaerobics pore-bearing rods, moulds or Gram-negative bacteria which can render
a product objectionable or even dangerous. These materials are best sterilized by a gaseous
or heating process before formulation. Solids of biological origin, including egg and milk
products and dried animal and plant extracts, may also contain pathogens including
salmonellae E, coli and staphylo cocci. Spoilage of the solid raw material itself is largely
due to mould growth on the surface due to impropers to rage with inadequate coverings
in a damp environment or under conditions of fluctuating temperature.
Powders
Spoilage of products in powdered form due to visible mould growth also occurs under
damp conditions A. gain the possibility of illness due to microbial contamination is an
important consideration and it is particularly necessary to ensure that topical preparations
Contamination o f Pharmaceuticals in Hospitals and Environment by Microbes □ □ 79
do not contain Clostridia spores. There is no clear evidence of a relationship bt cween the
presence of contaminants and irritation due to cosmetic powders but more than a few
hundred organisms per gram is undesirable and powders for use on broken skin should
be prepared from sterilized raw materials. This precaution also applies to those powders
and other solid cosmetics which are intended to be applied in the region of the eyes.
Tablets, Pastilles and Lozenges
Visible spoilage of tablets, generally manifested as surfaced is colouration, may be
caused by the growth of moulds. Spores from the environment, container or tablet itself
may find sufficient moisture to initiate growth on the tablet surface ever under apparently
dry conditions. In experiments with Paracetamol Tablets, B.P. we have found that, while
spoilage could be prevented by attention to storage conditions and the value of
preservatives was limited, the incorporation of 0.1 % propyl p-hydroxybenzoate retarded
the onset and extent of mould growth, even under damp storage conditions in laboratory
and large-scale trials.
Interest has recently been shown in the carriage of contaminating pathogens by
products of this type. Synthetic drugs in tablet form usually carry less than 100 organisms
per tablet but those compounded with natural drugs may contain up to 105 organisms of
ten Gram-positive pore bearing bacteria, per tablet. Large numbers of enteric pathogens
such as salmonellae have also been found and tablets containing biological products have
been incriminated in out break so of salmonellosis. Pastilles and lozenges of the boiled
sweet type are not generally found to suffer from microbial spoilage as heating during
manufacture has a sterilizing action and often individual dry wrappings are used to prevent
surface contamination. However, when pastilles are dusted with starch powder, moulds
may be introduced and these can give rise to discolouration under poor storage conditions.
Solid Cosmetics
Lipsticks often contain preservatives but some are still subject to mould 'blooms'. Mould
grows on the lipstick while it is inside the lipstick case, often after the product has become
moistened by breath during use. Moisture, perhaps from saliva, may also initiate growth
in preparations of mascara which often contain many bacteria. There is also a danger of
contamination via the brush which can pick up organism from the skin during use and
similar dangers are present with solid cakes of make-up. Preservatives have limited use
in this situation, perhaps because they are adsorbed onto the solid material. In addition
their concentration must be limited for fear of irritation to the eyes.
Packaging Materials
Containers for pharmaceuticals and cosmetics are becoming increasingly elegant and
are now made from a large variety of materials, particularly plastics. This should result in
a reduction in microbial spoilage because plastics are not biodegradable like the cellulose
80 □ □ Drug Inspector Exam
materials, paper and card. In addition the latter, being absorbents, oak up liquids thus
providing a substrate for moulds. In any case, liners of paper and card and cork closures
often contain many micro-organisms and therefore frequently are a source of mould
contamination where as plastic closures are free from this defect. However, plastics suffer
from some disadvantage. They are porous to varying degrees and some allow the diffusion
of oxygen and carbon-dioxide and may thus facilitate microbial growth in the packed
product. They also encourage condensation of water and, if mould spores are present, can
facilitate spoilage by these organisms. Soap, for instance gives off moisture, and, if wrapped
with an impermeable plastic over paper or card, may become discoloured due to mould
growth on the damp paper. Sometimes paper wrappings can be protected from spoilage
by the incorporation of a preservative in to them, but this is not entirely without difficulties.
ANSWERS
1. (c) 2. (a) 3. (c ) 4. (d) 5. (a) 6. (c) 7. (d) 8. (a) 9. (d) 1 0 . (d)
11. (d) 12. (d) 13. (a) 14. (d) 15. (c) 16. (d) 17. (a) 1M b) 19. (d) 20. (a)
21. (a) 22. (a) 23. (c) 24. (a).
□□□
Sterilization
10
C h a pter
83
84 □ □ Drug Inspector Exam
Survivor curves
They are plots of the logarithm of the fraction of survivors (microorganisms which
retain viability following a sterilization process) against the exposure time or dose.
Expression of resistance
D-value
D-value is indicative of the resistance of any organism to a sterilizing agent. For
radiation and heat treatment, D-value is the time taken at a fixed temperature or the
radiation dose required to achieve a 90% reduction in viable count.
Z-value
Z-value represents the increase in temperature needed to reduce the D-value of an
organism by 90%.
Methods of Sterilization
The various methods of sterilization are given in Tablel along with their merits,
demerits and applications.
Procedure
The filter should be a membrane filter disc of cellulose esters or other suitable plastics,
having a nominal average pore diameter not exceeding 0.45 jam. The membrane should
be held firmly in a filtration unit which consists of a supporting base for the membrane, a
receptacle for the fluid to be tested, a collecting reservoir for the filtered fluid, and the
Sterilization □ □ 87
necessary tubes or connections. The apparatus is so designed that the solution to be filtered
can be introduced and filtered under aseptic conditions. It permits the aseptic removal of
the membrane for transfer to medium or it is suitable for carrying out the incubation after
adding the medium to the apparatus itself.
Cellulose nitrate filters are recommended for aqueous, oily and weakly alcoholic
solutions and cellulose acetate filters for strongly alcoholic solutions. The entire unit should
be sterilized by appropriate means with the membrane filter and sterile airways in place.
The method of sterilization should not be deleterious to the membrane, e.g., weaken it or
change the nominal average pore diameter. The sterile airways should provide free access
to the sterilizing agent. After sterilization, the apparatus should be free of leaks to the
atmosphere except through the sterile airways.
Procedures
Liquids and soluble or dispersible solids: Appropriate quantities of the preparation to
be examined are added directly into Medium 1 and Medium 2. Approximately equal
quantities of the preparation should be added to each vessel of medium. The test vessels
of Medium 1 is incubated at 30 - 35°C and the vessels of Medium 2 is incubated at 20-
25°C.
The volume of Medium 1 should be such that the air space above the medium in the
container is minimized. The volume of Medium 2 should be such that sufficient air space
is left above the medium to provide conditions that permit the growth of obligate aerobes.
Unless otherwise prescribed, in no case should the volume of material under test be greater
than 10% of the volume of the medium alone, i.e., 90% medium and 10% product. If a
large volume of product is to be tested it may be preferable to use concentrated media,
prepared so as to take the subsequent dilution into account. Where appropriate the
concentrated medium may be added directly to the product in its container. Wherever
possible solid articles such as devices should be tested by immersion in or filling with
culture media. Immerse all parts of each article in sufficient medium contained in one
vessel to completely cover all parts. The volume of Medium 1 should be such that the air
space above the medium in the container is minimized. The volume of Medium 2 should
be such that sufficient air space is left above the medium to provide conditions that permit
the growth of obligate aerobes. Place half the articles into Medium 1 and the remaining
half into Medium 2. Incubate the test vessels of Medium 1 at 30 - 35°C and the vessels of
Medium 2 at 20 - 25°C.
Ointments and oily preparations: Ointments and oily preparations may be tested by
the method of Direct Transfer if testing by the method of Membrane Filtration is not feasible,
i.e., when a suitable solvent is not available .
88 □ □ Drug Inspector Exam
Incubation and examination of sterility tests: All test vessels of Medium 1 are incubated
at 30 - 35°C. The vessels of Medium 2 are incubated at 20 - 25°C. All test and control
vessels, other than the subcultured vessels referred to below, must be incubated for at
least 14 days unless microbial contamination is detected at an earlier time.
If turbidity, precipitate, or other evidence of microbial growth during incubation is
seen: the suspected growth is examined microscopically by Gram stain; attempts are made
to grow single colonies using appropriate microbiological methods; colonies of each type
of micro-organism present are examined for colonial morphology and cellular morphology
by Gram stain; attempts are made to identify the isolates, as far as the genus, and preferably
species.
Interpretation of the test results: If microbial growth is not evident in any of the vessels
inoculated with the product, the sample tested complies with the test for sterility, if
microbial growth is evident the product does not comply with the test for sterility unless
it can be clearly demonstrated that the test was invalid for causes unrelated to the product
being examined. If the test is declared to be invalid it may be repeated with the same
number of units as in the original test. If there is no evidence of growth in any vessels
inoculated with the product during the repeat test the product passes the test for sterility.
This interpretation applies even if growth occurs in negative product control vessels. If
there is evidence of growth in the test vessels the product fails the test for sterility. Further
testing is not permitted under any circumstances.
19. For sterilization, the aqueous solution 25. The Q10 indicates
may be heated in presence of (a) thermal resistance of
bactericide microorganism
(a) 60°C for lhr (b) 80°C for lhr (b) viability of microorganism
(c) 98°C for 30 min (c) death time of microorganism
(d) 100°C for 15 min (d) either (a) or (c)
20. Which method is used for sterilization 26. Which is not true regarding
of silicones? advantafes of sterilization by ionizing
(a) autoclave radiation?
(b) heating with bactericide (a) short sterilisation time
(c) hot air oven (b) reliability of sterilisation
(d) tydallisation (c) negligible rise in temperature
(d) ability to sterilise equipment made
21. The kaolin is sterilized by of heat-sensitive materials, for
(a) autoclave example, polystyrene
(b) hot air oven
Sterilization □ □ 91
ANSWERS
l.(c) 2. (b) 3. (d) 4. (b) 5. (d) 6. (a) 7. (c) 8. (c) 9. (d) 10. (b)
11. (c) 12. (d) 13. (a) 14. (b) 15. (b) 16. (a) 1 7 .(b) 18. (d) 19. (b) 2 0 .(c)
21. (b) 22. (e) 23. (d) 24. (c) 25. (a) 26. (e) 27. (c).
□ □ □
Sterilization of Materials,
Equipments and Utensils Used in
Hospitals C h a pter
and coagulation of protein or the enzyme-protein system within the cells. These reactions
are catalyzed by the presence of water. Steam is water vapor; it is saturated when it contains
a maximum amount of water vapor.
No living thing can survive direct exposure to saturated steam at 250 F (120 (C) longer
than 15 minutes. As temperature is increased, time may be decreased. A minimum
temperature-time relationship must be maintained throughout all portions of load to
accomplish effective sterilization. Exposure time depends upon size and contents of load,
and temperature within the sterilizer. At the end of the cycle, re-evaporation of water
condensate must effectively dry contents of the load to maintain sterility.
Ethylene Oxide
Ethylene oxide is used to sterilize items that are heat or moisture sensitive. Ethylene
Oxide (EO) is a chemical agent that kills microorganisms, including spores, by interfering
with the normal metabolism of protein and reproductive, processes, (alkylation) resulting
in death of cells. Used in the gaseous state, EO gas must have direct contact with
microorganisms on or in items to be sterilized. Because EO is highly flammable and
explosive in air, it must be used in an explosion-proof sterilizing chamber inn a controlled
environment. When handled properly, EO is a reliable and safe agent for sterilization, but
toxic emissions and residues of EO present hazards to personnel and patients. Also, it
takes longer than steam sterilization, typically, 16-1C brs. for a complete cycle.
EO gas sterilization is dependent upon four parameters: EO gas concentration,
temperature, humidity, and exposure time. Each parameter may be varied. Consequently,
EO sterilization is a complex multi-parameter process. Each parameter affects the other
dependent parameters.
Others
Dry Heat
Dry heat in the form of hot air is used primarily to sterilize anhydrous oils, petroleum
products, and bulk powders that steam and ethylene oxide gas cannot penetrate. Death of
microbial life by dry heat is a physical oxidation or slow burning process of coagulating
the protein in cells. In the absence of moisture, higher temperatures are required than
when moisture is present because microorganisms are destroyed through a very slow
process of heat absorption by conduction.
Microwaves
The non-ionizing radiation of microwaves produces hyperthermic condition? that
disrupt life processes. This heating action affects water molecules and interferes with cell
membranes. Microwave sterilization uses low-pressure steam with the nonionizing
radiation to produce localized heat that kills microorganisms.
Formaldehyde Gas
Formaldehyde kills microorganisms by coagulation of protein in cells. Used as a
fumigant in gaseous form, formaldehyde sterilization is complex and less efficacious than
Sterilization o f Materials, Equipments and Utensils used in Hospitals □ □ 95
other methods of sterilization. It should only be used if steam under pressure wil’ damage
the item to be sterilized and ethylene oxide and glutaraldehyde are not available.
Hydrogen Peroxide Plasma
Hydrogen peroxide is activated to create a reactive plasma or vapor. Plasma is a state
of matter distinguishable from solid, liquid, or gas. It can be produced through the action
of either a strong electric or magnetic field, somewhat like a neon light. The cloud of
plasma created consists of ions, electrons, and neutral atomic particles that produce a
visible glow. Free radicals of the hydrogen peroxide in the cloud interact with the cell
membranes, enzymes, or nucleic acids to disrupt life functions of microorganisms
Ozone Gas
Ozone, a form of oxygen, sterilizes by oxidation, a process that destroys organic and
inorganic matter. It penetrates membrane of cells causing them to explode. Ozone is an
unstable gas, but can be easily generated from oxygen.
Chemical Solutions
Liquid chemical agents provide an alternative method for sterilizing heat sensitive
items if a gas or plasma sterilizer is not available, or the aeration period makes ethylene
oxide sterilization impractical. To sterilize items, they must be immersed in a solution for
the required time specified by the manufacturer to be sporicidal. All chemical solutions
have advantages and disadvantages; each sterilant has specific assets and limitations.
These chemicals are: peracetic acid, glutaraldehyde, and formaldehyde.
Ionizing Radiation
Some products commercially available are sterilized by irradiation. It is the most
effective sterilization method but is limited for commercial use only. Ionizing radiation
produces ions by knocking electrons out of atoms. These electrons are knocked out so
violently that they strike an adjacent atom and either attach themselves to it, or dislodge
an electron from the second atom. The ionic energy that results becomes converted to
thermal and chemical energy. This energy causes the death of microorganisms by disruption
of the DNA molecule, thus preventing cellular division and propagation of biologic life.
Their usefulness in sterilizing an object is limited by density and thickness of the
object and by the energy of the electrons. They produce their effect by ionizing the atoms
they hit, producing secondary electrons that, in turn, produce lethal effects on
microorganisms.
Cobalt 60 is a radioactive isotope capable of disintegrating to produce gamma rays.
Gamma rays are electromagnetic waves. They have the capability of penetrating to a much
greater distance than beta rays before losing their energy from collision. Cobalt 60 is the
most commonly used source for irradiation sterilization. The product is exposed to
radiation for 10 to 20 hours, depending on the strength of the source.
96 ZJD Drug Inspector Exam
Quality Assurance
To ensure that instruments and supplies are sterile when used, monitoring of the
sterilization process is essential.
Administrative Monitoring
Work practices must be supervised. Written policies and procedures must be strictly
followed by all personnel responsible and accountable for sterilizing and disinfecting
items, and for handling sterile supplies. If sterility cannot be achieved or maintained, the
system has failed. Policies and procedures pertain to;
1. Decontaminating, terminally sterilizing, and cleaning all reusable items; disposing
of disposable items.
2. Packaging and labeling of items.
3. Loading and unloading the sterilizer.
4. Operating the sterilizer.
5. Monitoring and maintaining records of each cycle.
6. Adhering to safety precautions and preventive maintenance protocol.
7. Storing of sterile items.
8. Handling sterile items ready for use.
9. Making sterile transfer to a sterile field.
Mechanical Indicators
Sterilizers have gauges, thermometers, timers, recorders, and/or other devices that
monitor their functions. Most sterilizers have automatic controls and locking devices.
Some have alarm systems that are activated if the sterilizer fails to operate correctly. Records
are maintained and review for each cycle. Test packs (Bowie-Dick test) are run at least
daily to monitor functions of each sterilizer, as appropriate. These can identify process
errors in packing or loading.
Chemical Indicators
A chemical indicator on a package verifies exposure to a sterilization process. An
indicator should be clearly visible on the outside of every on-site sterilized package. This
helps differentiate sterilized from unsterilized items. Several types of chemical indicators
are available :
1. Tape, labels, and paper strips printed with an ink that changes color when exposed
to one or more process parameters.
2. Glass tube with pellets that melts when a specific temperature is attained in
sterilizer.
3. Integrating or wicking paper with an ink or chemical tablet at one end that melts
and wicks along paper over time under desired process parameters. The color bar
reaches the "accept" area if parameters are met.
Sterilization o f Materials, Equipments and Utensils used in Hospitals □ □ 97
Biological Indicators
Positive assurance that sterilization conditions have been achieved can be obtained
only through a biologic control test. The biologic indicator detects nonsterilizing conditions
in the sterilizer. A biologic indicator is a preparation of living spores resistant to the
sterilizing agent. These may be supplied in a self-contained system, in dry spore strips or
discs in envelopes, or sealed vials or ampoules of spores to be sterilized and a control that
is not sterilized. Some incorporate a chemical indicator also. The sterilized units and the
control are incubated for 24 hours for Bacillus stearothermophilis at 131 to 141 F (55 to 66
(C) to test steam under pressure, for 48 hours for Bacillus Subtilis at 95 to 98.6 F (35 to 37
(C) to test ethylene oxide.
There are four systems in general use for dispensing drugs for inpatients.
floor stock. This combination system ie probably the most commonly used in hospitals
today and is modified to include the use of unit dose medications.
ANSWERS
l.(d ) 2. (a) 3. (d) 4. (c) 5. (d) 6. (d) 7. (d) 8. (a) 9. (d) 10. (a)
11. (c) 12. (c) 13. (d) 14. (d) 15. (d). 16. (d) 17. (d) 18. (d) 19. (d) 20.- (b)
21. (b) 22. (a) 23. (c ) 24. (d) 25. (c) 26. (c) 27. (b)
Ophthalmic Preparations
12
Chapter
The solutions, suspensions, and ointments are commonly used as ophthalmic products.
Most of the ophthalmic products are no longer prepared in the pharmacy.
Ophthalmic preparations are sterile products that are intended to be applied to the
eyelids or placed in the space between the eyelids and the eyeball.
Also make sure that there is not a suitable commercial product available that would
eliminate the need to extemporaneously prepare a product. The advent of new
formulations in the past few years has already drastically reduced the need for
many previously compounded items.
2 . Sterility of the final product is a must: strict adherence to aseptic technique as well
as any other preventative measures must be in place.
3. The pH of the final product must be within an acceptable range.
4. Anticipated stability of the final product must be known, as well as the
recommended storage requirements.
5. Adequate knowledge of potential diluents or vehicles is required in order to ensure
proper tonicity, viscosity, or dissolution of the final product.
6. Establishment of written procedures that fully document each step is an important
consideration in order to reduce the likelihood of errors. Whenever calculations
are required, there should be a secondary source available to verify the accuracy.
Also, if multiple dilutions are needed, it is recommended that a new syringe be
used for each step in order to minimize the impact of residual contents.
7. If the preparation of a product requires the breaking of an ampule or the
reconstitution of a powder (for example, cefazolin), it is recommended that the
final product be filtered prior to packaging in order to eliminate any particulate
matter.
8. The preparation of intra-ocular products requires the use of preservative-free
ingredients. Many preservatives have been found to be toxic to the inner ocular
tissues.
9. Finally, before dispensing the finished product, always indicate the storage
requirements, concentrations of ingredients, and the expected expiration date
The clarified solution is either filled directly into the final containers which are sealed
prior to heat sterilization or filled into a suitable container prior to filtration sterilization.
Clarified vehicle is used to prepare eye drop suspensions which are filled into final
containers and sealed prior to sterilization.
Sterilization
This can take the form of :
• Autodaving at 115°C for 30 minutes or 121°C for 15 minutes
• Heating at 98 - 100°C for 30 minutes together with either benzalkonium chloride
0.01 % w/v or chlorhexidine acetate 0.01 % w/v or phenylmercuric acetate or nitrate
0.002% w/v or thiomersal 0.01 % w/v.
• Filtration through a membrane filter having a 0.22% m pore size into sterile
containers using strict aseptic technique. Filling should take place under Grade A
laminar airflow conditions. A suitable filter holder for extemporaneous preparation
is needed. The filter assembly is sterilized by autoclaving before use.
• Dry heat sterilization at 160°C for 2 hours is employed for non-aqueous preparations
such as liquid paraffin eye drops. Silicone rubber teats must be used.
— Immediately following sterilization theeye drop containers must be converted with
readily breakable seal, such as a viskring, to distinguish between opened and unopened
containers.Labelling requirements are summarised in Tables 12.1 and 12.2.
Table 12.1. General Labelling requirements for eye drop containers Requirement
Include on label
Fully identify Title;either name and concentration of active ingredients or
the product reference to official monograph giving these details. If monograph
allows more than one concentration then state the one used
Specify storage "Store in a cool place" or "Protect from light"
conditions
State product Month and year of expiry
expiry date
Warning label "Not to be taken"
Specify volume e.g. 5mL
Ensure correct use e.g. "Shake the bottle" for a suspension
Hospital Wards Patient's name. The eye to be treated. Date of opening of bottle
Operating Theatres and/or date to discard Single dose for once-only use. Marked with
Clinics indication and concentration of active ingredient. No preservative.
Outer package fully labelled Single dose or multidose used once
only
Domiciliary "Avoid contamination of contents during use" Discard 4 weeks
after opening" Keep out of reach of children Plus instructions on
how to use
have the advantage over liquids of providing greater total drug bioavailability. However,
ointments take a longer time to reach peak absorption.
Eye ointments must be sterile and may contain suitable antimicrobial preservatives,
antioxidants and stabilizers. USP ophthalmic ointments packaged in multi-dose containers
are to contain an anti-microbial substance unless otherwise directed in the monograph or
if the formulation itself is bacteriostatic. The most commonly used agents include the two
mercurials, phenylmercuric nitrate and thiomersal, the parabens and chlorobutanol. It is
necessary also that such ointments are free from particulate matter that could be harmful
to the tissues of the eye. The EP and BP have limits for the particle size of incorporated
solids which will be met if all particles have been reduced to <25pm.
The basic components of an eye ointment are given below :
• Liquid paraffin 1 part
• Wool fat 1 part (to facilitate incorporation of water)
• Yellow soft paraffin 8 parts
• Hard paraffin as required to produce required consistency in hot climates
Preparation of Eye Ointments
Eye ointments are normally prepared using aseptic techniques to incorporate the finely
powdered active ingredient or a sterilized concentrated solution of the medicament into
the sterile eye ointment basis. Immediately after preparation the eye ointment is filled
into the sterile containers which are then sealed so as to exclude microorganisms. The
screw cap should be covered with a readily breakable seal.
All apparatus used in the preparation of eye ointments must be scrupulously clean
and sterile.
Certain commercial eye ointments may be sterilized in their final containers using
ionising radiation.
Preparation of Eye Ointment Basis
The paraffins and the wool fat are heated together and filtered, while molten, through
a coarse filter paper in a heated funnel into a container which can withstand dry heat
sterilization temperatures. The container is closed to exclude microorganisms and together
with contents is maintained at 160°C for 2 hours.
Containers for Eye Ointments
Eye ointments should be supplied in small sterilized collapsible tubes made of metal
or in a suitable plastic. The tube should not contain more than 5 g of preparation and must
be fitted or provided with a nozzle of a suitable shape to facilitate application to the eye
and surrounds without allowing contamination of the contents. The tubes must be suitably
sealed to prevent microbial contamination. Eye ointment may also be packed in suitably
designed single-dose containers.
108 □ □ Drug Inspector Exam
Labelling
This includes the following :
• The names and percentages of the active ingredients
• The date after which the eye ointment is not intended to be used
• The conditions under which the eye ointment should be stored - normally at a
temperature not exceeding 25°C
• The name and concentration of any antimicrobial preservative or other substance
added to the preparation
• A statement to the effect that the contents are sterile providing the container has
not been opened
1. Ophthalmic preparations come under (c) dilute with equal volume of sterile
which category? isotonic saline solution
(a) sterile (d) none of the above
(b) non-sterile 5 Common viscosity increasing agent in
(c) parenteral ophthalmics:
(d) none of the above (a) Polyvinyl alcohol
2. Which one of the following (b) Povidone
preservative should not be used in eye (c) Dextran
drops intended for prolonged use? (d) All of the above
(a) chlorhexidine acetate 0.01 % 6. pH of human tear is:
(b) phenylmercuric nitrate (a) 7.2 (b) 7.8
(c) benzalkonium chloride (c) 8 (d) 4.6
(d) methyl parabens
Ophthalmic solution is sterilized by:
3. Which of the following preservative (a) Autoclaving
is not suitable for eye drops containing
(b) Bacterial retentive filters
local anaesthetic?
(c) a and b above
(a) propyl parabens
(d) Hot air oven
(b) benzalkonium chloride
(c) phenyl ethyl alcohol ® Isotonicity value of ophthalmics:
(d) phenulmercuric acetate (a) 0.9% sodium chloride
(b) 2 .0% sodium chloride
4. The label for ophthalmic boric acid
should contain : (c) 0.6% sodium chloride
(a) dilute with equal volume of (d) None of the above
distilled water 9 The mean volume of tears in human
(b) dilute with equal volume of sterile eye under normal conditions is:
distilled water
Ophthalmic Preparations □ □ 109
ANSWERS
1. (a) 2. (b) 3. (b) 4. (c) 5. (d) 6. (a) 7. (c) 8. (a) 9. (b) 10 . (a)
11. (c) 12. (a) 13. (b) 14. (a) 15. (c) 16. (a) 17. (d) 18. (c) 19. (b) 20. (d)
21. (b) 22. (a) 23. (b) 24. (d) 25. (e) 26. (a) 27. (e) 28. (d) 29. (b) 30. (a)
nnn
Blood Products and 13
Plasma Substitutes C h a pter
BLOOD PRODUCTS
Whole blood. In most circumstances, blood component therapy has replaced the use
of whole blood. However, whole blood is still occasionally used for massive transfusion
in circumstances in which rapid correction of acidosis, hypothermia and coagulopathy is
required. This mainly occurs in military situations for trauma patients who require
resuscitation.
Red Blood Cells
RBCs are prepared from whole blood by removal of most of the plasma. They are
indicated in both acute haemorrhage and chronic anaemia. Red cell units have a
haematocrit of 70% (Citrate Phosphate Dextrose Adenine (CPDA-1) solution) or 55-60%
(Additive Solutions (AS)) with a shelf life of 35 days and 42 days respectively when
refrigerated at 1-6°C. A decision to give a transfusion should be reached both on the patient's
clinical situation and laboratory findings, not on Hb alone.3,4 Transfusion is often not
considered until Hb <7 g/dL but patients with unstable angina or acute Myocardial
Infarction (MI) may require transfusion at Hb <10 g/dL. A single unit of red blood will
typically increase Hb by lg/dL. Other RBC products include leukocyte-reduced
components, which can reduce febrile reactions and are an alternative to cytomegalovirus
(CMV)-seronegative components and prevent HLA alloimmunisation. Also, washed
components (RBC and platelets) remove harmful plasma antibodies.
Platelets
Each unit of platelets is prepared from a single whole blood collection by differential
centrifugation and contains at least 5.5 x 1010 platelets in 50 ml of plasma. They are stored
at 20-24°C in plastic containers under agitation and have a shelf life of 5 days. Each unit
can raise platelet count by 5-10 x 109/L. Alternatively, platelets are prepared by apheresis
(a process of filtration), contain >3 x 1011 platelets suspended in 200 ml plasma, and are
equivalent Lo 6 random donor platelet units. Platelets are not usualiycross matched will:
the recipient, but ABO type-specific platelets should be provided where possible as,
otherwise, the increment is 10-20% less in platelet count. Platelets are given to patients
with thrombocytopenia who are bleeding or those with severe thrombocytopenia as a
precaution. Patients rarely bleed spontaneously when platelet count is >20 x 109/L and
patients receiving chemotherapy can often tolerate counts of 5-10 x 109/L.
Blood Products and Plasma Substitutes □ □ 113
Granulocytes
These are mainly given to neutropenic cancer patients developing bacterial sepsis
unresponsive to conventional antibiotic therapy for at least 24-48 hours. Preparations
collected from normal donors by apheresis contain at least 1 x 1010 neutrophils/unit, but
the concentration can be increased by using donors stimulated by steroids and/or growth
factors. Granulocyte preparations can only be stored for 24 hours at 20-24°C. They need to
be crossmatched with the recipient's serum because of the large number of red cells they
contain and need to be irradiated because of the large number of lymphocytes present.
Granulocytes are only usually considered for patients with an absolute neutrophil
count <0.5 x 109/L and a good chance of marrow recovery. They usually need to be given
daily until patients can maintain an absolute neutrophil count >0.5 x 109/L without
transfusion or until the infection has resolved. Patients frequently have a febrile reaction
to granulocytes and these are more severe when amphotericin is infused at around the
time of the granulocyte infusion.
Fresh Frozen Plasma
Fresh Frozen Plasma (FFP) is produced by centrifugation of one donation of whole
blood, and collecting the supernatant liquid. The plasma is frozen within 8 hours of
collection in order to maintain the activity of factor V and factor VII. The main indication
for FFP is deficiency of multiple coagulation factors found in liver disease and Disseminated
Intravascular Coagulation (DIC). It is also often used for urgent reversal of warfarin
anticoagulation. Because of the large volume that would be required, FFP is not generally
used to replace individual clotting factors. In these situations specific factors are given
(see below under 'Factor' headings).
Cryoprecipitate is made by thawing FFP at 1-6°C and is generally used for patients
with von Willebrand's disease or severe hypofibrinaemia. A commercial preparation of
solvent /^detergent-treated frozen human plasma called Octaplas® is available but needs
ABO compatibility checks. Uniplas® is a human plasma product which has been shown
to be independent of ABO compatibility, but it is not yet widely used in the UK.
Plasma-transfused patients need to be observed for circulatory overload.6 The main
side-effects include fever, 7 chills, 7 bronchospasm,5 and adult respiratory distress
syndrome.
Albumin
This is available as 5% or 25% solution for the treatment of hypovolaemia and
hypoalbuminaemia. The cost-benefit of albumin in the treatment of hypovolaemia is
controversial, and it is largely being replaced by non-plasma colloidal solutions. It does,
however, still have a place in the management of liver disease and ascites. It is tested for
hepatitis C virus (HCV) RNA and virally inactivated, and not considered as a risk factor
for viral transmission. Its use has now largely been superseded by non-plasma colloidal
solutions.
114 □ □ Drug Inspector Exam
Immunoglobulin
Intravenous (IV) imm unoglobulin is used in the treatm ent of immuno-
thrombocytopenia, Guillain-Barre syndrome and autoimmune haemolytic anaemias. RhD
immunoglobulin is used to prevent exposure to D-positive red cells causing Rh sensitisation
in D-negative patients. This is usually given in pregnancy and immediately after birth to
prevent haemolytic disease of the newborn in future babies.
Antithrombin III Concentrate
This is prepared from human plasma and used to treat congenital deficiency of
antithrombin III. This condition presents as thromboembolic phenomena at an early age.
Side-effects of concentrate transfusion may include flushing, nausea, headache, and rarely
fever and allergic reactions. There may be a place for antithrombin III concentrate in the
management of acquired deficiency (for example, heparin resistance, cirrhosis with
coagulation disorders).
Drotrecogin Alfa (Activated)
This is recombinant activated protein C. In cases of severe sepsis, the protein C pathway
regulates thrombin production, preventing the formation of the microvascular thrombosis
which can lead to multiple organ failure. Caution needs to be used in patients with bleeding
diatheses, comorbidity leading to, or medication causing, increased bleeding tendency.
The preparation is contra-indicated in cases of internal bleeding, cerebral herniation,
intracranial neoplasm, chronic severe hepatic disease, and thrombocytopenia. There are
little safety data concerning pregnancy or breast-feeding, so the drug should only be given
if there is a definite indication. A study in 477 paediatric patients did not show any benefit,
although there are isolated reports that it promotes improvement in selected cases. Adverse
effects include headache, 5 bleeding, 16 pain, 5 and ecchymoses.14
Factor Vila (Recombinant)
This is used in patients with inhibitors to factors VIII and IX. It is indicated in patients
with haemophilia A and B, and in uncontrolled bleeding in a number of clinical situations.
Theoretical concerns about an increased risk of deep vein thrombosis and pulmonary
embolus have not been borne out in randomised trials.
Factor VIII Fraction, Dried
Also known as human antihaemophilic fraction, this is prepared from human plasma
by a suitable fractionation technique and indicated for the treatment and prophylaxis of
haemorrhage in haemophilia A. Large or frequently repeated doses in patients with blood
groups A, B or AB can lead to intravascular haemolysis. This is less likely to occur with
high-potency purified concentrates. Side-effects include allergic reactions, including chills
and fever.
Blood Products and Plasma Substitutes □ □ 115
Polygeline
Polygeline is a representative partially degraded gelatin. Various preparations can
serve as alternatives Infusion (Solution for infusion), polygeline 3.5% with electrolytes,
500-ml bottle
Uses: Correction of low blood volume
Contraindications: Severe congestive heart failure; renal failure
ANSWERS
1. (a) 2. (c) 3. (c) 4. (a) 5. (d) 6. (b) 7. (a) 8. (c) 9. (b) 10. (a)
11. (d) 12. (d) 13. (d) 14. (a) 15. (b) 16. (d) 17. (a) ‘ 18. (b) 19. (c) 20. (a)
21. (c) 22. (c) 23. (b) 24. (a) 25. (a) 26. (c) 27. (d) 28. (b) 29. (a) 30. (c)
31. (e)
□ □ □
Surgical Products
14
C h a pt er
range from 00 (very large, used to close the abdominal wall-about the size of large
fishing line) to 10-0 (very tiny, used for microvascular anastomosesas fine as a human
hair). Many different suture materials are available. The main classifications are
absorbable or nonabsorbable. A more subtle sub-classification is whether the suture
material is braided or non-braided. Non-absorbable sutures remain in place until they
are removed.
Because they are not dissolved by the body, they are less tissue-reactive and therefore
leave less scarring as long as they are removed in a timely fashion. They are best used
on the skin. Absorbable sutures are dissolved by the body's tissues. The great advantage
is that the sutures do not need to be removed. However, absorbable sutures tend to
leave a more pronounced scar when used as skin sutures. Absorbable sutures are
primarily used under the skin, where they are well hidden.
Braided sutures are made up of several thin strands of the suture material twisted
together. Braided sutures are easier to tie than non-braided sutures. However, braided
sutures have little interstices in the suture material, which can be a place for bacteria
to hide and grow, resulting in an increased risk of infection.
Non-braided sutures are simply a monofilament, a single strand. They are not made
up of the little subunits found in a braided suture. Nonbraided sutures are recommended
for most skin closures, especially wounds that may be at risk for infection.
Ligature
It is a cord, wire, or bandage used for tying or binding, used in surgery to close
vessels or tie off ducts.
Catgut
Catgut is the name applied to cord of great toughness and tenacity prepared from
the intestines of the sheep or goat, or occasionally from those of the hog, horse, mule,
pig, and donkey. To prepare it, the intestines are cleaned, freed from fat, and steeped
for some time in water, after which their external membrane is scraped off with a blunt
knife. They are then steeped for some time in an alkaline lye, smoothed and equalized
by drawing out, subjected to the antiseptic action of the fumes of burning sulphur, if
necessary dyed, sorted into sizes, and twisted together into cords of various numbers
of strands according to their uses.
ANSWERS
1 . (b) 2. (a) 3. (c) 4. (b) 5. (a) 6. (c) 7. (a) 8. (a) 9. (c) 10. (c)
1 1 . (a) 12. (a) 13. (d) 14. (a) 15. (c).
ana
Incompatibility
15
C h a pter
Many of the drugs and preparations are given only in combination. The selection
of drugs and preparations to be used in combination with each other requires a great
deal of care to avoid unwished for changes being brought about by their admixture.
Two drugs are said to be "incompatible," when on being brought into intimate contact
with each other unwished for changes either physical or chemical are brought about or
when their pharmacological actions would so interfere with each other as to be
detrimental. It is by no means an infrequent occurrence for a physician to prescribe
together two medicines which have almost opposite pharmacological actions but he
does so in such proportions that the action of the one serves but to correct some undesired
action of the other.
Incompatibility dependent upon the differing pharmacological actions of the drugs
administered together is known as Therapeutical or better Pharmacological
Incompatibility. An extreme example would be the administration of atropine and
pilocarpine together.
Incompatibility dependent upon chemical and physical changes can only occur when
the drugs are brought into intimate physical contact either by trituration in a mortar or
by solution. The incompatibility due to chemical changes occurring between preparations
dispensed together is known as Chemical Incompatibility. The changes may be of several
types and may be classified as follows: -
1. Resulting in chemical change without any visible change.
(a) The neutralization of acids by bases. *
(b) The breaking up of glycosides by acids (sugar is set free and the glycoside loses
in activity).
(c) The action of acids on the activity of pancreatic ferments and of alkali on gastric
ferments.
2. Resulting in precipitation of newly formed chemical substances due to the
interaction of two other chemical substances in solution.
* Important cases are printed in italics.
(a) Salts of the alkaline earths are precipitated by alkali hydroxides and carbonates,
phosphates, borates, oxalates (the corresponding insoluble salts of the alkaline
earths being formed). The free acids which would form corresponding salts are
also incompatible.
(b) Salts of the metals in solution are incompatible with hydrates, carbonates,
phosphates, oxalates and the corresponding acids; in many cases with proteins,
122
Incompatibility □ □ 123
tannins, acacia and often alkaloids and phenozone. Silver, mercurous, lead, and
bismuth salts also with bromides and iodides: the same metals and calcium,
barium and strontium, with sulphates and sulphuric acid.
(c) Hydrates or carbonates of the alkalies, sodium, potassium, and ammonia with
salts of metals and alkaline earths, and with alkaloids and some glucosides.
(d) Alkaloids form insoluble salts with other organic acids than acetic and citric; the
free alkaloid being very much less soluble than the salts is precipitated by alkali
hydrates and carbonates and by borax. Ammonium carbonate and the
bicarbonates do not so readily cause precipitation. Iodides, bromides, salicylates,
benzoates, usually cause a precipitate tannic acid, and iodine in a solution of
mercuric iodide; precipitation may be prevented in many of these cases by from
15-50% of alcohol. About 15% suffices to prevent that by bicarbonates and
carbonates. Alkaloides may give a precipitate with many metallic salts especially
those of mercury.
(e) Proteins are precipitated by alkaloids, many metal salts, tannin and alcohol.
3. Resulting in a change of color owing to the formation of some soluble but undesired
body owing to the interaction of two other substances in solution.
(a) Giving an objectional appearance tannic and gallic acids and iron preparations,
ammonia and carbolic acid; gallic acid and thymol. Ferric chloride with salicylates,
carbolic acid, creasote, guaiacol, salol, acetanilid, phenazone, phenacetin, oils of
wintergreen, cloves, pimenta, and thyme, podophyllin, aloin, gamboge, asafetida,
storax, myrrh, balsam of Peru, balsam of Tolu, morphine and apomorphine.
(b) The change in color is the indication of a chemical change objectionable from the
pharmacological side also. Salicylates, phenozone, acetanilid, with the free nitrous
acid in Spirits of Nitrous Ether (isonitroso-compounds are formed).
4. Resulting in the chemical splitting of one of the bodies and the formation of an
undesired body.
(a) Resulting in the freeing of a volatile body, which may in part or entirely,
dependent upon the amount formed, remain in solution. Hydrochloric acid with
nitric acid (nitrous oxides freed); strong acids with alcohol (ethers); acids and
carbonates; acids and sulphides; mineral acids with iodides, bromides, and
chlorates; ammonium salts and hydrates and carbonates of the alkalies.
(b) Resulting in the freeing of a liquid body, chloral and butylchloral with alkalies
(chloroform freed).
(c) Resulting in the freeing of dextrose or other sugar, glucosides with acids and
alkalies.
(d) Resulting in liberation of so much gas suddenly as to cause an explosion. Chromic
acid, concentrated nitric acid, nitrates, permanganates, chlorates, with such
substances as sulphur and sulphides, sulphites, iodides, phosphorus,
hypophosphites, reduced iron, and many organic bodies, sugar, tannin, etc. These
reactions only occur when the dry substances are triturated together or in some
cases when mixed in very concentrated solutions.
124 □ □ Drug Inspector Exam
5. In some cases when two solids are triturated together a soft sticky or a damp
mass, or a liquid is formed: the reaction is probably always to a certain extent chemical.
Such substances are camphor, carbolic acid, thymol, phenozone, phenacetin, chloral,
sodium phosphate, lead acetate.
12. Soluble inorganic salts react with 18. If sulphonamides are prescrib ,d with
hydroxides to yield: water what will happen
(a) Water soluble salts (a) Soluble free acids will be formed
(b) water-insoluble compound (b) insoluble free acids will be formed
'c) precipitate (c) insoluble base will be formed
(d) both (b) and (c) (d) soluble free base will be formed
13. In presence of strong base soluble salts 19. Identify the incompatibility, if the
of amine drugs liberate: sodium salicylate and Phenobarbital
(a) Free acids sodium is prescribed with Vit. B
(b) free base complex:
(c) both (a) and (b) (a) Hydrolysis
(d) none of the above (b) recemization
(c) oxidation
14. In a prescription cocain HC1, boric
acid, and sod. benzoate is prescribed (d) precipitation
with water, identify the correct 20. To overcome the above incompatibility
reaction: the salts should be dispensed:
(a) Sod. Borate will be precipitated (a) With acid
(b) cocaine will be precipitated (b) with base
(c) benzoic acid will precipitated (c) in form of solution
(d) none of the above (d) separately
15. Incompatibility of the above question 21. Identify the incom patibility in
will be eliminated by: following prescription:
(a) Boric acid Potassium chlorate - 0.6 gm
(b) sod. Benzoate Tannic acid Sucrose - 0.3 gm
(c) both (a) and (b) DTD ? 20
(d) none of the above (a) Recemization
16. Gentian violet in presence of acid (b) polymerization
compounds turns: (c) explosive combination
(a) Blue to green (d) none of the above
(b) green to yellow 22. Identify the incom patibility in
(c) purple to green following prescription:
(d) yellow to green Atropine sulphate - 0.006
17. To prevent change of color of dye in Phenobarbital 0.015
acid or base medium: Aspirin 0.300
(a) Another dye will be added (a) Therapeutic
(b) buffer will be added (b) chemical
(c) water will be added (c) physical
(d) none of the above (d) none of the above
126 □ □ Drug Inspector Exam
ANSWERS
I. (c) 2, (c) 3. (b) 4. (d) 5. (d) 6. (a) 7. (c) 8. (b) 9. (a) 10. (c)
11. (a) 12. (b) 13. (b) 14. (b) 15. (b). 16. (J) 17. (b) 18. (b) 19. (a) 20. (d)
21. (c) 22. (a) 23. (d) 24. (b) 25. (c) 26. (b) 27. (c)
□ □ □
Cardiovascular System
16
C h a pter
The heart is the pump responsible for maintaining adequate circulation of oxygenated
blood around the vascular network of the body. It is a four-chamber pump, with the
right side receiving deoxygenated blood from the body at low presare and pumping it
to the lungs (the pulmonary circulation) and the left side receiving oxygenated blood
from the lungs and pumping it at high pressure around the body (the systemic
circulation).
The myocardium (cardiac muscle) is a specialised form of muscle, consisting of
individual cells joined by electrical connections. The contraction of each cell is produced
by a rise in intracellular calcium concentration leading to spontaneous depolarisation,
and as each cell is electrically connected to its neighbour, contraction of one cell leads
to a wave of depolarisation and contraction across the myocardium.
This depolarisation and contraction of the heart is controlled by a specialised group
of cells localised in the sino-atrial node in the right atrium- the pacemaker cells.
1. These cells generate a rhythmical depolarisation,
which then spreads out over the atria to the atrio
ventricular node.
2. The atria then contract, pushing blood into the
ventricles.
3. The electrical conduction passes via the Atrio
ventricular node to the bundle of His, which divides
into right and left branches and then spreads out from
the base of the ventricles across the myocardium.
4. This leads to a 'bottom-up' contraction of the
ventricles, forcing blood up and out into the
pulmonary artery (right) and aorta (left).
5. The atria then re-fill as the myocardium relaxes.
The ’squeeze’ is called systole and normally lasts for about 250 ms. The relaxation
period, when the atria and ventricles re-fill, is called diastole; the time given for diastole
depends on the heart rate.
The ECG
The Electrocardiograph (ECG) is clinically very useful, as it shows the electrical
activity within the heart, simply by placing electrodes at various points on the body
surface. This enables clinicians to determine the state of the conducting system and of
127
128 □ □ Drug Inspector Exam
the myocardium itself, as damage to the myocardium alters the way the impulses travel
through it.
When looking at an ECG, it is often helpful to remember that an upward deflection
on the ECG represents depolarisation moving towards the viewing electrode, and a
downward deflection represents depolarisation moving away from the viewing electrode.
• The P wave represents atrial depolarisation- there is little muscle in the atrium
so the deflection is small.
• The Q wave represents depolarisation at the bundle of his; again, this is small
as there is little muscle there.
• The R wave represents the main spread of depolarisation, from the inside out,
through the base of the ventricles. This involves large ammounts of muscle so
the deflection is large.
• The S wave shows the subsequent depolarisation of the rest of the ventricles
upwards from the base of the ventricles.
• The T wave represents repolarisation of the myocardium after systole is complete.
This is a relatively slow process- hence the smooth curved deflection.
■Vrh of aorta
Pulmonary trunk
Circumflex branch
Right coronary atery Anterior interventricular
Left marginal
Antrioventricular nodal
Diagonal
Post, interventricular
Right marginal
Fig. 16.2.
CARDIOVASCULAR DISEASES
Types of cardiovascular disease includes angina, heart attack (myocardial infarction),
atherosclerosis, heart failure, cardiovascular disease, and cardiac arrhythmias (abnormal
heart rhythms). Other forms of cardiovascular disease include congenital heart defects,
cardiomyopathy, infections of the heart, coronary artery disease, heart valve disorders,
myocarditis, and pericarditis.
1. Heart Attack
Heart attack also called myocardial infarction, is a very serious condition in which
the heart is not receiving enough oxygen to function properly. Heart attack is a common
cause of death. The heart requires a steady supply of o*ygen in order to pump blood
effectively to all of the body. Oxygen is supplied to the heart in the blood that flows
through the coronary arteries. If a coronary artery becomes blocked, the portion of the
heart that gets its oxygen-rich blood from that specific artery becomes damaged. This
injury can become permanent within minutes and result in the death of the affected
heart tissue. Medically this is called myocardial necrosis or infarction.
Heart attacks often result from a build-up of plaque and inflammation in the arteries,
called atherosclerosis. This process narrows the coronary arteries and lowers the amount
of oxygen-rich blood that reaches the heart muscle. This is called angina. Arteries
narrowed by atherosclerosis are more likely to develop a blood clot that completely
blocks blood flow, resulting in a heart attack. Risk factors for atherosclerosis include
having high cholesterol.
2. Angina
Angina is a common type of chest pain that can occur when the heart muscle is not
receiving sufficient blood flow and oxygen. Angina is a symptom of some heart diseases,
especially atherosclerosis. Atherosclerosis is the build-up of plaque and inflammation
in the arteries of the body, including the arteries that supply blood to the heart muscle
(coronary arteries). Atherosclerosis narrows the coronary arteries and lowers the amount
of oxygen-rich blood that reaches the heart muscle. Arteries narrowed by atherosclerosis
are more likely to develop a blood clot that completely blocks blood flow, resulting in
a heart attack The chest pain of angina can be mild to severe.
The chest pain of angina is different from the chest pain of a heart attacK in that
angina generally occurs with activity or exertion and goes away with rest and/or
medication, such as nitroglycerin. In contrast, the chest pain of a heart attack does not
go away with rest or after taking nitroglycerin. To learn more about other important
symptoms and complications of angina, refer to symptoms of angina.
Angina can also be a symptom of other types of heart disease, such as aortic valve
disease, coronary artery spasm and cardiac arrhythmias, which can all reduce the amount
of blood and oxygen that reaches the heart muscle.
Angina can also be a symptom of anemia, in which a low number of red blood cells
in the blood reduces the amount of oxygen supplied to the heart muscle.
130 □ □ Drug Inspector Exam
Risk factors for developing angina are the same risk factors for developing heart
disease. These include having high cholesterol, hypertension, diabetes, high cholesterol
(hypercholesterolemia, hyperlipidemia), obesity, and a sedentary lifestyle.
3. Congestive Heart Failure
Congestive Heart Failure (CHF) is a condition in which the heart's function as a
pump is inadequate to deliver oxygen rich blood to the body. Congestive heart failure
can be caused by :
(a) diseases that weaken the heart muscle
(b) diseases that cause stiffening of the heart muscles, or
(c) diseases that increase oxygen demand by the body tissue beyond the capability
of the heart to deliver adequate oxygen-rich blood.
The heart has two atria (right atrium and left atrium) that make up the upper
chambers of the heart, and two ventricles (left ventricle and right ventricle) that make
up the lower chambers of the heart. The ventricles are muscular chambers that pump
blood when the muscles contract. The contraction of the ventricle muscles is called
systole.
Many diseases can impair the pumping action of the ventricles. For example, the
muscles of the ventricles can be weakened by heart attacks, infections (myocarditis) or
toxins (alcohol, some chemotherapy agents). The diminished pumping ability of the
ventricles due to muscle weakening is called systolic dysfunction. After each ventricular
contraction (systole) the ventricle muscles need to relax to allow blood from the atria
to fill the ventricles. This relaxation of the ventricles is called diastole.
Diseases such as hemochromatosis (iron overload) or amyloidosis can cause stiffening
of the heart muscle and impair the ventricles' capacity to relax and fill; this is referred
to as diastolic dysfunction. The most common cause of this is longstanding high blood
pressure resulting in a thickened (hypertrophied) heart. Additionally, in some patients,
although the pumping action and filling capacity of the heart may be normal, abnormally
high oxygen demand by the body's tissues (for example, with hyperthyroidism or anemia)
may make it difficult for the heart to supply an adequate blood flow (called high output
heart failure).
Congestive heart failure can affect many organs of the body. For example :
• The weakened heart muscles may not be able to supply enough blood to the
kidneys, which then begin to lose their normal ability to excrete salt (sodium)
and water. This diminished kidney function can cause the body to retain more
fluid.
• The lungs may become congested with fluid (pulmonary edema) and the person’s
ability to exercise is decreased.
• Fluid may likewise accumulate in the liver, thereby impairing its ability to rid
the body of toxins and produce essential proteins.
• The intestines may become less efficient in absorbing nutrients and medicines.
Cardiovascular System Anatomy and Physiology □ □ 131
1. ' Which is true regarding the (b) The cardiac action potential is
conduction system of the heart: conducted through the atria via
(a) Between action potentials, the cells Purkinje fibers.
of the sino-atrial node have a (c) The Purkinje fibers are specialized
steady resting potential. cardiac myocytes linked by gap
junctions.
132 □ □ Drug Inspector Exam
(d) The spread of cardiac excitation 5. Which is true for cardiac output:
speeds up at the atrio-ventricular (a) Is increased by aldosterone
node. released from the adrenal medulla.
2. Which is true regarding the ECG: (b) Is increased by stimulation of the
(a) The P wave of the ECG reflects vagus nerve.
atrial contraction. (c) Can be measured by dividing the
(b) The P-Q interval is normally about oxygen consumption by the
0.1s. difference in P 0 2 of the venous
(c) The QRS complex reflects the start and arterial blood.
of ventricular contraction. (d) Is largely determined by the end-
(d) The peak amplitude of the ECG diastolic volume.
recorded by the limb leads is about 6. The arterial blood pressure:
10 mV. (a) Is 120/80 mm Hg (16/10.6 kPa)
3. Which is true during the cardiac cycle (b) Depends solely on the cardiac
of a normal healthy young adult: output.
(a) During ventricular diastole the (c) Is the arithmetic average of the
pressure in the left ventricle is systolic and diastolic pressures.
close to 80 mm Hg (10.6 kPa). (d) Is due to the vascular resistance of
(b) During ventricular systole, the the capillaries.
pressure in the left ventricle 7. Concerning the control of the
reaches a maximum of about 25 vasculature:
mm Hg (3.3 kPa). (a) Autoregulation refers to the
(c) During the initial stage of nervous control of the blood
ventricular contraction the volume vessels.
of the ventricle does not change. (b) Reactive hyperemia is due to
(d) During ventricular systole, all the vasodilatation caused by
blood in the ventricles is ejected. accumulation of metabolites
4. Which is true concerning the normal during a period of exercise.
heart sounds: (c) Parasympathetic vasodilator fibers
(a) The first heart sound corresponds innervate the blood vessels of the
with the closure of the mitral and exocrine glands of the gastro
tricuspid valves. intestinal tract.
(b) The first heart sound occurs just (d) The diameter of the arterioles is
before the R wave of the ECG. entirely regulated by the
(c) The first heart sound is split into sympathetic nervous system.
two components during 8. Concerning the microcirculation:
inspiration. (a) The exchange of solutes between
(d) The second heart sound occurs the capillaries and tissues occurs
during the T-wave. mainly by bulk flow.
Cardiovascular System Anatomy and Physiology □ □ 133
{b) Radiates to the neck and Jiw but 38. Drug used in treating CHF: associated
not teeth. with a reversible thrombocytopenia:
(c) Rarely lasts longer than 10 seconds (a) dopamine (Intropin)
after resting. (b) hydralazine (Apresoline)
(d) Invariably worsens as exercise (c) methyldopa (Aldomet)
continues. (d) amrinone (Inocor)
(e) options (a) & (d) are true (e) digoxin (Lanoxin, Lanoxicaps
36. Diastolic pressure is related to 39. Precipitating causes of congestive
(a) resistance of the blood vessels to heart failure:
blood flow. (a) AV dissociation
(b) the amount of force developed (b) severe bradycardia
during contraction of the heart. (c) reduce synchrony of ventricular
(c) the volume of blood leaving the contraction
heart. (d) tachyarrhythmias
(d) the arteries' elasticity (e) All of the above
37. Males are at greater risk for 40. Mechanism by which vasodilators
hypertension improve myocardial performance in
(a) across the life span. CHF:
(b) before age 50. (a) increase heart rate
(c) after age 50. (b) promote diuresis
(d) none of the above (c) reduce afterload
(d) reduce pulmonary blood flow
ANSWERS
1. (c) 2. (b) 3- (c) 4. (a) 5- (d) 6. (a) 7. (a) 8. (d) 9. (b) 10.(d)
H. (d) 12. (a) 13. (a) 14. (c) 15. (e). 16. (a) 17. (b) 18. (d) 19. (c) 2 0 .<b)
21- (b) 22. (b) 23. (a) 24. (a) 25. (c) 26. (e) 27. (d) 28. (c) 29. (d) 3 0 .(c)
31. (a) 32. (e) 33. (a) 34. (e) 35. (e) 36. (a) 37. (b) 38. (d) 39. (e) 40. (c)
nnn
Human Digestive System
17
C h a pter
The human digestive system is a complex process that consists of breaking down
large organic masses into smaller particles that the body can use as fuel. The breakdown
of the nutrients requires the coordination of several enzymes secreted from specialized
cells within the mouth, stomach, intestines; and liver. The major organs or structures
that coordinate digestion within the human body include the mouth, esophagus, stomach,
small and large intestine, and liver.
Mouth
In the human body, the mouth (oral cavity) is a specialized organ for receiving food
and breaking up large organic masses. In the mouth, food is changed mechanically by
biting and chewing. Humans have four kinds of teeth: incisors are chisel-shaped teeth
in the front of the mouth for biting; canines are pointed teeth for tearing; and premolars
and molars are flattened, ridged teeth for grinding, pounding, and crushing food.
In the mouth, food is moistened by saliva, a sticky fluid that binds food particles
together into a soft mass. Three pairs of salivary glands—the parotid glands, the sub-
138 □ □ Drug Inspector Exam
maxillary glands, and the sublingual glands—secrete saliva into the mouth. The saliva
contains an enzyme called amylase, which digests starch molecules into smaller molecules
of the disaccharide maltose.
During chewing, the tongue moves food about and manipulates it into a mass
called a bolus. The bolus is pushed back into the pharynx (throat) and is forced through
the opening to the esophagus.
Esophagus
The esophagus is a thick-walled muscular tube located behind the windpipe that
extends through the neck and chest to the stomach. The bolus of food moves through
the esophagus by peristalsis: a rhythmic series of muscular contractions that propels
the bolus along. The contractions are assisted by the pull of gravity.
Stomach
The esophagus joins the stomach at a point just below the diaphragm. A valve like
ring of muscle called the cardiac sphincter surrounds the opening to the stomach. The
sphincter relaxes as the bolus passes through and then quickly closes.
The stomach is an expandable pouch located high in the abdominal cavity. Layers of
stomach muscle contract and chum the bolus of food with gastric juices to form a soupy
liquid called chyme.
The stomach stores food and prepares it for further digestion. In addition, the stomach
plays a role in protein digestion. Gastric glands called chief cells secrete pepsinogen.
Pepsinogen is converted to the enzyme pepsin in the presence of hydrochloric acid.
Hydrochloric acid is secreted by parietal cells in the stomach lining. The pepsin then
digests large proteins into smaller proteins called peptides. To protect the stomach
lining from the acid, a third type of cell secretes mucus that lines the stomach cavity.
An overabundance of acid due to mucus failure may lead to an ulcer.
Small Intestine
The soupy mixture called chyme spurts from the stomach through a sphincter into
the small intestine. An adult's small intestine is about 23 feet long and is divided into
three sections: the first 10 to 12 inches form the duodenum; the next 10 feet form the
jejunum; and the final 12 feet form the ileum. The inner surface of the small intestine
contains numerous fingerlike projections called villi. Each villus has projections of cells
called microvilli to increase the surface area.
Most chemical digestion takes place in the duodenum. In this region, enzymes
digest nutrients into simpler forms that can be absorbed. Intestinal enzymes are
supplemented by enzymes from the pancreas, a large, glandular organ lying near the
stomach. In addition, bile enters the small intestine from the gall bladder to assist in fat
digestion.
The enzymes functioning in carbohydrate digestion include amylase (for starch),
maltase (for maltose), sucrase (for sucrose) and lactase (for lactose). For fats, the principal
enzyme is lipase. Before this enzyme can act, the large globules of fat must be broken
Human Digestive System □ □ 139
into smaller droplets by bile. Bile is a mixture of salts, pigments, and cholesterol that is
produced by the liver and stored in the gall bladder, a saclike structure underneath the
liver.
Protein digestion is accomplished by several enzymes, including two pancreatic
enzymes: trypsin and chymotrypsin. Peptides are broken into smaller peptides, and
peptidases reduce the enzymes to amino acids. Nucleases digest nucleic acids into
nucleotides in the small intestine also.
Most absorption in the small intestine occurs in the jejunum. The products of
digestion enter cells of the villi, move across the cells, and enter blood vessels called
capillaries. Diffusion accounts for the movement of many nutrients, but active transport
is responsible for the movement of glucose and amino acids. The products of fat digestion
pass as small droplets of fat into lacteals, which are branches of the lymphatic system.
Absorption is completed in the final part of the small intestine, the ileum. Substances
that have not been digested or absorbed then pass into the large intestine.
Large intestine
The small intestine joins the large intestine in the lower right abdomen of the body.
The two organs meet at a blind sac called the cecum and a small fingerlike process
called the appendix. Evolutionary biologists believe the cecum and appendix are vestiges
of larger organs that may have been functional in human ancestors.
The large intestine is also known as the colon. It is divided into ascending, transverse,
and descending portions, each about one foot in length. The colon's chief functions are
to absorb water and to store, process, and eliminate the residue following digestion and
absorption. The intestinal matter remaining after water has been reclaimed is known as
feces. Feces consist of nondigested food (such as cellulose), billions of mostly harmless
bacteria, bile pigments, and other materials. The feces are stored in the rectum and
passed out through the anus to complete the digestion process.
Liver
The liver has an important function in processing the products of human digestion.
For example, cells of the liver remove excess glucose from the bloodstream and convert
the glucose to a polymer called glycogen for storage.
The liver also functions in amino acid metabolism. In a process called deamination,
it converts some amino acids to compounds that can be used in energy metabolism. In
doing so, the liver removes the amino groups from amino acids and uses the amino
groups to produce urea. Urea is removed from the body in the urine. Fats are processed
into two-carbon units that can enter the Krebs cycle for energy metabolism. The liver
also stores vitamins and minerals, forms many blood proteins, synthesizes cholesterol,
and produces bile for fat digestion.
Common Digestive System Disorders
There are five basic symptoms indicating a GIT problem. These symptoms are
generally associated with dietary problems or specific food allergies. It is critical that
140 □ □ Drug Inspector Exam
anyone suffering from serious GIT problems work closely with a physician to test for
the more developed and serious GIT diseases. The physician should also be experienced
in working with dietary factors and food allergies.
Nausea and Vomiting
Nausea and vomiting can vary from an unsettled feeling in the stomach to the
violent action of immediate vomiting. Patients with nausea and vomiting symptoms
should assume the ingestion of a reactive food i.e., food containing toxins) or poisoning
with a pathogen such as salmonella. Vomiting immediately after eating is usually
proceeded by excessive watery salivation. Some chronic low-intensity nausea can occur
for a protracted time due to sustained low-level food allergies or problems with food
combinations. Patients with low-level nausea usually have their symptoms disappear
with diet revision. Nausea and vomiting are also linked with migraines caused by food
allergies..
Bloating
Bloating can result from excessive gas in the digestive system, failure of the digestive
tract to sustain youthful peristaltic contractions, or a lack of sufficient quantities of
digestive enzymes and bile acids to rapidly break down food. Intestinal gas results from
food fermentation and from swallowing air while eating. The bloating from intestinal
gas is different from that which occurs in the colon.
Constipation
Constipation is the decreased frequency, or slowing, of peristalsis, resulting in harder
stools. When the GIT is slowed down, feces can accumulate in the colon with attending
pain and toxic reactions. A spastic colon results when the colon contracts out of rhythm
in painful spasms blocking movement of the stool. Some patients experience painful
days of constipation followed by forceful diarrhea and watery stool, often accompanied
with abdominal cramps.
Diarrhea
Diarrhea is the increased frequency of bowel movements that is also loose or watery.
If diarrhea increases, the possibility of celiac disease is considered. Celiac disease is a
seriou^ disease that allows certain macromolecules to pass through the intestinal wall.
If blood appears in the stool, ulcerative colitis is likely. Protracted bouts with diarrhea
can result in nutritional deficiencies due to the poor absorption of essential nutrients.
Abdominal Pain
Abdominal pain appears in different patterns and with varying intensities. Cramping
occurs because of muscle spasms in the abdominal organs. Severe cramping pain, often
called colic, usually occurs from problems with strong allergic response to food.
Abdominal cramping near the navel is typically from the small intestine, and near the
sides, top, and bottom of the lower abdomen, the pain is associated with the colon.
Human Digestive System □ □ 141
Diseases associated with central GIT disorders and diagnoses include aepression,
migraine, asthma, sinusitis, and fibromyalgia. These diseases have been identified with
specific patterns of food allergy response. All of these diseases also have links to Irritable
Bowel Syndrome. (IBS is more accurately referred to as RBS—Reactive Bowel Syndrome.)
Peptic Ulcer
A peptic ulcer is a hole in the gut lining of the stomach, duodenum, or esophagus.
A peptic ulcer of the stomach is called a gastric ulcer; of the duodenum, a duodenal
ulcer; and of the esophagus, an esophageal ulcer. An ulcer occurs when the lining of
these organs is corroded by the acidic digestive juices which are secreted by the stomach
cells.
For many years, excess acid was believed to be the major cause of ulcer disease.
Accordingly, treatment emphasis was on neutralizing and inhibiting the secretion of
stomach acid. While acid is still considered significant in ulcer formation, the leading
cause of ulcer disease is currently believed to be infection of the stomach by a bacteria
called "Helicobacter pyloricus" (H. pylori). Another major cause of ulcers is the chronic
us^ of anti-inflammatory medications, commonly referred to as NSAIDs (nonsteroidal
anti-inflammatory drugs), including aspirin. Cigarette smoking is also an important
cause of ulcer formation and ulcer treatment failure.
Jaundice
Jaundice is not a disease but rather a sign that can occur in many different diseases.
Jaundice is the yellowish staining of the skin and sclerae (the whites of the eyes) that
is caused by high levels in blood of the chemical bilirubin. The color of the skin and
sclerae vary depending on the level of bilirubin. When the bilirubin level is mildly
elevated, they are yellowish. When the bilirubin level is high, they tend to be brown.
Bilirubin comes from red blood cells. When red blood cells get old, they are destroyed.
Hemoglobin, the iron-containing chemical in red blood cells that carries oxygen, is
released from the destroyed red blood cells after the iron it contains is removed. The
chemical that remains in the blood after the iron is removed becomes bilirubin.
The liver has many functions. One of the liver's functions is to produce and secrete
bile into the intestines to help digest dietary fat. Another is to remove toxic chemicals
or waste products from the blood, and bilirubin is a waste product. The liver removes
bilirubin from the blood. After the bilirubin has entered the liver cells, the cells conjugate
(attaching other chemicals, primarily glucuronic acid) to the bilirubin, and then secrete
the bilirubin/glucuronic acid complex into bile. The complex that is secreted in bile is
called conjugated bilirubin. The conjugated bilirubin is eliminated in the feces. (Bilirubin
is what gives feces its brown color.) Conjugated bilirubin is distinguished from the
bilirubin that is released from the red blood cells and not yet removed from the blood
which is termed unconjugated bilirubin.
Jaundice occurs when there is (a) too much bilirubin being produced for the liver
to remove from the blood. (For example, patients with hemolytic anemia have an
abnormally rapid rate of destruction of their red blood cells that releases large amounts
142 □ □ Drug Inspector Exam
of bilirubin into the blood), (b) a defect in the liver that prevents bilirubin from being
removed from the blood, converted to bilirubin/glucuronic acid (conjugated) or secreted
in bile, or (c) blockage of the bile ducts that decreases the flow of bile and bilirubin from
the liver into the intestines. (For example, the bile ducts can be blocked by cancers,
gallstones, or inflammation of the bile ducts). The decreased conjugation, secretion, or
flow of bile that can result in jaundice is referred to as cholestasis: however, cholestasis
does not always result in jaundice.
(b) About half of the digested 10. The most common cause jf upper
carbohydrate is absorbed in the gastrointestinal hemorrhage
small intestine. (hematemesis or melena) is:
(c) Small peptides are absorbed in the (a) esophageal varices
small intestine. (b) gastric carcinoma
(d) The liver is the first organ to (c) peptic ulcer
receive the digestion products of (d) gastritis
dietary fats.
11. Hematochezia is found with:
7. Which is true regarding gastro (a) upper gastrointestinal bleeding
intestinal function?
(b) lower gastrointestinal bleeding
(a) The presence of large amounts of
(c) both
fat in the chyme will accelerate
(d) neither
gastric emptying.
(b) Distension of the ileum stimulates 12. Choose the best statement concerning
gastric motility. the pathogenesis of peptic ulcer.
(c) Total gastrectom y leads to (a) Acid must be increased.
malabsorption of vitamin B12. (b) Acid must be at least normal in
(d) Aldosterone inhibits the amount.
absorption of sodium and water (c) Acid must be present.
by the large intestine. (d) Acid need not be present.
8. Digestion begins in the mouth. Which 13. Which one of the following is a feature
of the follow ing statem ent is of the Zollinger-Ellison syndrome?
INCORRECT? (a) hypoglycemic attacks
(a)- The tongue aids in the digestion (b) obesity
of the food. (c) gastric hyperchlorhydria
(b) The saliva changes some of the (d) diabetes
starches in the food to sugar. (e) fainting spells
(c) The tongue keeps the food in place
in the mouthwhile the food is 14. The most common site of chronic
being chewed. gastric peptic ulcer is:
(d) The digestive juices can react more (a) lesser curvature at antral-body
easily with the food when chewed. junction
(b) anterior wall at duodenal verge
9. A two-week-old boy develops
(c) greater curvature in mid-antrum
persistent projectile vomiting. The
most likely diagnosis is: (d) esophago-gastric junction
(a) pyloric stenosis 15. The most frequent complication of
(b) esophageal atresia chronic duodenal ulcer is:
(c) annular pancreas (a) hemorrhage
(d) incomplete rotation of the gut (b) obstruction
(c) perforation
(d) malabsorption
144 □ □ Drug Inspector Exam
16. Chronic peptic ulcer of the stomach 20. Which cells produce pepsinogen?
occurs predominantly: (a) Zymogenic cells
(a) on the acid-secreting portion of the (b) Parietal cells
gastric mucosa (c) Mucous cells
(b) in an area of the stomach that has (d) Enteroendocrine cells
undergone squamous metaplasia
21. Crypts of Lieberkuhn is present in
(c) on areas of the gastric mucosa
adjacent to the acid secreting (a) oesophagus
mucosa (b) jejunum
(d) at the cardio-esophageal junction (c) large intestine
(e) adjacent to carcinoma (d) pharynx
17. Which is inconsistent with a diagnosis 22. Which is not true about Helicobacter
of benign gastric ulcer? pylori bacteria:
(a) absence of ulcer crater (a) Adhere to the gastric mucosa in
radiologically an alkaline layer "
(b) achlorhydria even after histamine (b) Are never seen in healthy people
challenge (c) Can be simply identified in the
(c) multiple defects seen endoscopy room by their urease
radiologically activity
(d) age less than 20 years (d) Are associated with peptic ulcer
relapse
18. Which of the follow ing is an
inflammatory bowel disease? 23. Effective ulcer treatment which works
(a) Crohn's disease without any action on gastric acid
secretion is:
(b) ulcerative colitis
(a) Lactulose
(c) both
(b) Aluminium hydroxide
(d) neither
(c) Sucralfate (d) Lactitol
19. What is Dysphagia? (e) Magnesium trisilicate
(a) inability to swallow or difficulty
in swallowing 24. Chagas’ disease may be suspected if a
patient has:
(b) lack of HC1 in stomach
(a) Constipation (b) Dysphagia
(c) decreased intestinal movement
(c) Heart failure (d) Jaundice
(d) all of the above
(e) option (a), (b) & (c)
ANSWERS
1. (b) 2. (a) 3. (a) 4. (d) 5. (c) 6. (c) 7. (c) 8. (a) 9. (a) 10. (c)
11. (b) 12. (c) 13. (c) 14. (a) 15. (a) 16. (c) 17. (b) 18. (c) 19. (a) 20. (a)
21. (b) 22. (b) 23. (c) 24. (e)
□ □ □
Brain and Spinal Cord
18
C h a pt er
The brain and spinal cord form the central nervous system. This complex system is
part of everything we do. It controls the things we choose to do -- like walk and talk
— and the things our body does automatically — like breathe and digest food. The
central nervous system is also involved with our senses — seeing, hearing, touching,
tasting, and smelling — as well as our emotions, thoughts, and memory.
145
146 □ □ Drug Inspector Exam
Fig. 18.2.
21. All the cranial nerves are related to 27. Increased vagal tone causes
parasympathetic nerves except (a) hypertension
(a) oculomotor (b) tachycardia
(b) facial (c) bradycardia
(c) accessory spinal (d) increase in cardiac output
(d) vagus 28. When a pheochromocytoma suddenly
22. Cholinergic fibre are present in:- discharges a large amount of
(a) Preganglionic Sympathetic nerve epinephrine into the circulation the
fibre patients heart rate would be expected
(b) Postganglionic Sympathetic nerve to
fibre (a) increase because epinephrine has
(c) Postganglionic parasympathetic a direct chronotropic effect on the
nerve fibre heart
(d) all of the above (b) increase because of increased
parasympathetic discharge to the
23. In parkinsons disease, the heart
concentration of which transmitter is
(c) decrease because the increase in
decreased?
blood pressure stimulates the
(a) adrenaline carotid and aortic baroreceptors
(b) nor adrenaline (d) decrease because of increased tonic
(c) dopamine parasympathetic discharge to heart
(d) acetylcholine
29. Which of the following conducting
24. Which of these vessels does not have systems has the slowest conducting
sympathetic control velocity
(a) cerebral (b) splanchnic (a) SAN
(c) cardiac (d) cutaneous (b) atrial muscle
25. Blood brain barrier is made up of (c) purkinje fibres
(a) astrocytes (d) AVN
(b) oligodendrocytes 30. Absolute refractory period in the heart
(c) oligodendroglia (a) corresponds to the duration of
(d) microglia relaxation
26. Positive bathmotropic effect on heart (b) lasts till half of cardiac contraction
is produced by (c) shorter than refractory period in
(a) stimulation of vagus nerve skeletal muscle
(b) stimulation of sympathetic nerves (d) lasts till cardiac contraction
(c) atropin 31. In contrast to the somatic nervous
(d) sectioning of vagus system, the autonomic nervous system
150 DO Drug Inspector Exam
ANSWERS
I. (a) 2. (d) 3. (c) 4. (d) 5. (d) 6. (b) 7. (a) 8. (b) 9. (b) 10. (a)
11. (a) 12. (c) 13. (a) 14. (b) 15. (b). 16. (b) 17. (a) 18. (b) 19. (d) 20. (c)
21. (c) 22. (d) 23. (c) 24. (a) 25. (a) 26. (b) 27. (c ) 28. (a) 29. (c) 30. (d)
31. (a) 32. (c) 33. (c) 34. (a)
ooo
Drugs Acting on
Cardiovascular System
19
C h a pter
1. CARDIAC GLYCOSIDE
These are important class of naturally occurring drugs whose actions include both
Cardiotonic and toxic effects. The desirable Cardiotonic has a great value in the treatment
of congestive heart failure and edema. The cardiac glycosides can be obtained both
from the plants (for example, Digitalis and Strophanthus) and certain animals, (for
example, poisonous toad).
Chemistry: Structurally, the cardiac glycosides are composed of sugar component
and steroid component.The steroid component is usually termedras genin or aglycone.
The aglycone component is responsible for pharmacological activity while sugar portion
is for its absorption. Some examples of cardiac glycosides and their sources are listed
in Table 19.1.
Aglycone. The steroid portion of the cardiac glycosides is characterized by its unusual
shape. The 'U-shape' is imparted by the A-B c is and C-D cis and B-C Trans ring. The
below given tructure shows the effect of unusual confirmation on the orientation of C-
18 and C-19 angular methyl groups relative to 14-OH and 5-H groups. Other important
steroidal substances can be distinguished fitom the cardiac glycoside by viewing the
'backbone' Skelton. For example, adrenocortical steroids typically possess A-B, B-C, C-
D all Trans configuration while the bile salts characterized by A-B cis and B-C, C-D
Trans orientation.
Table 19.1. List of naturally occurring glycosides along with their
composition and sources
151
152 □ □ Drug Inspector Exam
Digitoxigenin(Cardenolide), R , =
Bufatalin(Bufadenolide), R 1 = —
Digoxigenin, R=OH
The Cardenolides and Bufadenolides both contain 3-f3 and 14-P hydroxyls, the former
being the point of attachment for glycoside or sugar component. The Cardenolides may
contain additional hydroxyl group at C-12 or C-16 position, whose presence or absence,
differentiates the important genins, digitoxigenin, digoxigenin and gitoxigenin.
Drug Acting on Cardiovascular System □ □ 153
angiotensin II(is a potent vasoconstrictor. The angiotensin II is also further cleaved into
angiotensin III which is also a vasoconstrictor but less potent. The angiotensin III has
a significant role in controlling sodium excretion by renal tubules. The regulatory action
of renin - angiotensin system in controlling sodium and potassium balance and arterial
blood pressure is modified by vasodilators called 'kinin'.
The ACE is a zinc containing glycoprotein with a molecular weight of about 150,000.
ACE inhibitors prevent the conversion of angiotensin I into angiotensin II and thus act
as anti hypertensive drugs. These do not possess so many toxic effects as other
antihypertensive agents.
Captopril (Capoten). It was the first inhibitor introduced in clinical use.
Lisinopril (Zestil).It is a lysine derivative of enalaprilate, active metabolite of
enalapril. Like all ACE inhibitors, it is an active site directed inhibitor enzyme, using
the zinc ion in an effective binding interaction. It is similar to captopril and enalapril
in pharmacological action.
ACE inhibitors in prodrug form: Various ACE inhibitors are available as prodrug,
using captopril as prototype. On metabolic conversion, the active metabolite is generated.
The side effects associated with captopril like skin rashes, loss of sense of taste, etc., due
to presence of thio group in it which are not present in prodrugs. With the exception
of phosphorous containing fosinopril, these antihypertensive drugs have 2-(S)-
aminophenyl butyric ethyl ester moiety. These only differ in the substituents on the
amino group. These drugs are used in the treatment of mild to moderate hypertension
either alone or in combination with diuretics or calcium channel blockers.
Enalapril maleate (Vasotec). It is along acting ACE inhibitors. It, first metabolically
converted into diacid enalaprilate which is actual ACE inhibitor. Its half life is llhrs.
Benzapril hydrochloride (Lotensin). It is useful in the treatment of mild to moderate
hypertension in a dose of 10 mg/ day.
Quinapril hydrochloride (Acuretic). It is a tetrahydro isoquinoline analogue of
enalapril. It is first converted to active metabolite, quinaprilate to decrease the high
blood pressure.
Remipril (Altace). It unlike enalapril possesses high lipophilic properties which
facilitates its penetration in various tissues and consequently leading to high degree of
ACE inhibition.
Fosinopril sodium (Monorail). It is a phosphorous containing ACE inhibitor. It is
first converted into diacid, fossinoprillate by intestinal and liver enzyme to show anti
hypertensive action.
(h) Calcium channel blockers
These are vasodilators. The vasodilation action is due to uncoupling of the contractile
mechanism of vascular smooth muscle which requires calcium ions. CCBs can be divided
into three different drugs like phenyla lkylamines (verapamil); 1, 4 dihydropyridines
(nefidipine); and benzothiazepines (diltiazem). Table 19.2. Theseprototype compounds
sometimes are termed 'first generation' of calcium channel blockers as two of the groups
156 □ □ Drug Inspector Exam
drug classes have been expanded by the introduction of a 'second generation'of more
potent analogues.
Table 19.2. First and second generation CCBs
Chemical classification First generation Second generation
Phenylalkylamines Verapamil Bepridil, Anipamil
1, 4dihydropyridine Nifedipine Amlodipine, felodipine
Nicardipine, nimodipine
Benzothiazepine Diltiazem
It is used in the treatment of patient with variant angina. The side effects include
flush and headache. It has no effect on the heart rate.
ANSWERS
1 (b ) 2. (d) 3. (c) 4. (c) 5. (b) 6. (c) 7. (a) 8. (d) 9. (d) 10. (b)
11. (a) 12. (c) 13. (a) 14. (c) 15. (c). 16. (c) 17. (a) 18. (c ) 19. (d) 2 0 . (b)
21. (b) 22. (b) 23. (c) 24. (c ) 25. (c) 26. (b) 27. (d) 28. (b ) 2 9 . (b) 3 0 . (a)
31. (d) 32. (c) 33. (b) 34. (c) 35. (b) 36. (a) 37. (c ) 38. (c ) 39. (c) 40. (c)
41. (a) 42. (c) 43. (b) 44. (d) 45. (a) 46. (d)
□ □ □
Drugs Acting on
Gastro-Intestinal Tract
20
C h a pter
DIGESTANTS
These drugs are used to promote digestion of food as a replacement therapy in
condition of their deficiency specially in atrophic gastritis, gastric carcinoma, pernicious
anaemia or pancreatic insufficiency etc. Various proteolytic (pepsin, papain), lipolytic
(lipases) and amylolytic (diastase and takadiastase) enzymes are used in combination
as appetite stimulants and health tonics. Dilute hydrochloric acid (HC1) is advocated in
severe achlorhydria)
Emetics and Antiemetics Drugs
Vomiting or emesis is a protective mechanism which leads to expulsion of harmful
substances from the upper gastrointestinal tract (GIT). It involves the active participation
of Vomiting Centre (VC) present in the medulla oblongata either through direct afferent
input to it or via Chemoreceptor Trigger Zone (CTZ) and Nucleus Tractus Solitarius
(NTS) present in area postrema) Emetics may either act directly (apomorphine) or reflexly
on CTZ (Ipecacuanha). Apomorphine is a semisynthetic derivative acting as dopaminergic
agonist on CTZ. Apomorphine (6 mg) induces vomiting within 5-10 minutes when
injected intramuscularly or subcutaneously. Ipecacuanha containing emetine is used as
syrup (15-20 ml in adults). Copper sulphate, powdered mustard suspension or oil or
strong salt solution can also be used in emergency.
Antiemetics
These drugs are generally employed for the treatment of nausea or vomiting induced
by motion sickness, morning sickness, gastrointestinal disturbance, postoperative emesis,
cytotoxic drug or radiation-evoked emesis. Variety of drugs, having different chemical
and pharmacological profiles is useful antiemetic agents. They are classified as follows :
1. Antimuscarinic - Hyoscine, dicyclomine etc.
2. Hj-antihistaminics - Promethazine, Diphenhydramine dimenhydrinate,
cyclizine, Meclizine, Cinnarizine, etc.
3. Neuroleptics - Chlorpromazine, prochlorperazine, haloperidol, droperidol etc.
4. Prokinetics- They promote gastroduodenal peristalsis and speed gastric emptying
-Metoclopramide, domperidone, cisapride etc.
5. 5HT3 antagonist- Ondansetron, granisetron, bemesetron, renzapride, zacopride
etc.
6. Miscellaneous - Dexamethasone, benzodiazepine, Cannabinoids etc.
162
Drugs Acting on Gastro-Intestinal Tract □ □ 163
attention to certain psychosocial and emotional factors. If the above modifications are
insufficient then bulk forming agents should be the second line preferenca) Stimulants
should be used at last with least effective dose and for short period of tima)
Purgatives
Laxatives / aperients are agents having milder action and helps in elimination of
soft but formed stools. Purgatives / cathartics are agents having stronger action resulting
in more fluid evacuation.
Classification
I. Luminally active agents
(i) Bulk forming - Dietary fibre, psyllium, ispaghula, methyl cellulose
(ii) Stool softener - Dioctyl sodium sulphosuccinate (Docusates, Doss)
(iii) Lubricants - Liquid paraffin
(iv) Osmotic - Magnesium sulphate, magnesium hydroxide, sodium sulphate,
sodium potassium tartarate, lactulose, sorbitol, mannitol, polyethylene glycol
(PEG)
II. Stimulant (Contact) Purgatives
(i) Diphenylmethanes - Phenolphthalein, bisacodyl
(ii) Anthraquinones - Senna, cascara, rhubarb, aloes, danthron
(iii) Fixed oil - Castor oil
III. Prokinetic agents - 5 HT4 agonists, for example, Tegaserod
- Opioid receptor antagonists
Antidiarrheal Drug Therapy
Specific anti-microbials: Antimicrobials are useful in cases of severe infective diarrhea
produced by microorganisms like Shigella, Campylobacter, Salmonella, Y. enterocolitis etc
but very limited response is seen even in these cases. Rota virus diarrhea is generally
self-limiting and does not need any drug therapy. Antimicrobials should be regularly
used in cases of cholera (tetracyclines co-trimoxazole), Campylobacter (norfloxacin and
other fluroquinolones), Clostridium difficile (metronidazole, vancomycin), amoebiasis /
giardiasis (metronidazole).
Non-specific anti-diarrhoeal agents: Non-specific antidiarrhoeals constitutes mainly
absorbants, antisecretory and antimotility agents.
(a) Absorbants: Ispaghula, psyllium and methylcellulose are the most commonly
used absorbants. They absorb water and increase the stool bulk. They increase
stool viscosity and promote perception that there is decreased stool fluidity.
(b) Anti-Secretory agents- Sulfasalazine, mesalazine, olsalazine, balsalazine, bismuth
subsalicylate, atropine, octreotide etc.)
(c) Antimotily drugs: Codeine, dipheno.xylate, atropine, difenoxin, loperamide, a2
adrenergic agonist
Drugs Acting on Gastro-intestinal Tract □ □ 165
Opioids mainly act through 1 (motility) and a (secretory) receptors present in the
ENS, epithelial cells and muscles. Their function is to increase the tone of GIT.
Diphenoxylate, atropine, difenoxin are related to meperidina) Atropine is added to
decrease the abusive liability. Common side effects include CNS depression and
anticholinergic effects like dry mouth, flushing etc.)
Loperamide is an opioid analogue with a weak anticholinergic property. It is quickly
absorbed orally and is about 40 to 50 times more potent than morphine as an anti
motility agent. Available as capsule, solution and chewable forms, it has got poor CNS
penetration and no abuse liability with longer duration of action.
Cannabinoid receptor agonists decrease gut motility by decreasing Ach release from
enteric nerves. Certain calmodulin inhibitors which include chlorpromazine also have
antisecretory property. Zaldaride maleate is a novel drug effective against traveller's
diarrhea)
34. Two regions of cim etidine are 37. Which of the following antiemetics is
susceptible to metabolism. Which least likely to cause an oculogyric
regions? crisis?
A (a) trifluoperazine
(b) domperidone
H (c) metoclopramide
.N
YN
(d) prochlorperazine
38. What are the main neurotransmitters
*CN in the induction of vomiting from the
CTZ?
(a) C-4Me and methylene attached to
imidazole ring. (a) dopamine and histamine
(b) C-4Me and sulphur. (b) serotonin and histamine
(c) sulphur and NHMe (c) dopamine and serotonin
(d) C-4Me and NHMa) 39. The antimuscarinic drug atropine is
added to the antidiarrhoeal agent
35. Which is not true with regards to
diphenoxylate in order to:
Antiemetics?
(a) increase the absorption of
(a) include 5HT3 antagonists
diphenoxylate
(b) include Dopamine 2 agonists
(b) decrease the incidence of
(c) m etochlopram ide is anti-
respiratory depression
dopaminergic
encountered with diphenoxylate
(d) cyclizine causes drowsiness
(c) decrease the incidence of cough
(e) cyclizine is anticholinergic suppression encountered with
36. Which one of the following laxatives diphenoxylate
is a lubricant? (d) decrease the incidence of euphoria
(a) senna (b) docussate encountered with diphenoxylate
(c) castor oil (d) liquid paraffin
ANSWERS
1. (d) 2. (c) 3- (c) 4. (a) 5. (b) 6. (d) 7. (c) 8. (c) 9. (c) 10. (b)
11. (a) 12. (c) 13. (a) 14. (a) 15. (b) 16. (c) 17. (b) 18. (a) 19. (a) 20. (a)
21. (d) 22. (c) 23. (a) 24. (d) 25. (d) 26. (b) 27. (d) 28. (b) 29. (a) 30. (a)
31. (d) 32. (c) 33. (c) 34. (a) 35. (b) 36. (d) 37. (b) 38. (c) 39. (d)
mo
Drugs Acting on
Central Nervous System
21
C h a ptef
ANTOPSYCHOTIC DRUGS
The psychotic disorders are classified into three major groups :
(a) Anxiety disorders (phobia and sleeping disorders).
(b) Effective/mood disorders (depression)
(c) Personality disorders (Schizophreni(a)
A. Anxiolytic Drugs
• Benzodiazepines(BDZ). Diazepam, Lurazepam, Midazolam
Mode of action
Binding of GABA to its receptor trigger an opening of chloride conductance. The
influx of chloride ions causes hyperpolarization that moves the post synaptic potential
away from its firing threshold and thus inhibits the formation of action potential and
neural firing.
Actions
Reduction of anxiety (at low doses), Sedative and hypotonic actions (at higher doses),
Anticonvulsant, Muscle relaxant
• Barbiturate.
Mode of action
Interfere with sodium and potassium transport across cell membranes.
Actions
Depression of CNS (at low doses), Hypnosis and anesthesia (at high doses),
Respiratory depression, Enzyme induction (P-450 microsomal enzyme in liver
• Buspirone. Useful in the treatment of generalized anxiety disorders.
Action
The action is mediated by serotonin receptors.
B. Antidepressant Drugs
• Tricyclic/Plycyclic
Mode of action
• Inhibit the neuronal reuptake of norepinephrine and serotonin into presynaptic
nerve terminals which leads to increased concentration of monoamine in the
synaptic clef.
170 □ □ Drug Inspector Exam
AN TICON VULSA N T D RU G S
According to mechanisms of action, the classification of anticonvulsant drugs is as
follows :
1. Prolong inactivation of Na+ channels- reduces ability of neurons to fire at high
frequencies
• phenytoin
• carbamazepine
• valproic acid - may also enhance GABA activity
• lamotrigine
• topiramate - may also enhance GABA and decrease glutamatergic activity
2. Inhibit T-type Calcium channels
• ethosuximide
• valproic acid
3. Enhance GABA-ergic activity by increasing receptor response to neurotransmitter
• phenobarbital
• primidone
• diazepam
• clonazepam
4. Increase synaptic availability of GABA
• vigabatrin - inhibits gaba-transaminase, the enzyme that degrades GABA
• tiagabine - inhibits GABA uptake
5. Enhance depolarization-induced GABA release
• gabapentin
Structural features anti convulsant drugs. Most of the anticonvulsant drugs have
the common structure (shown below). For example, Hydantoins, succinnimides and
oxazolinodiones are isosterically related: NH(7+1 electrons), CH2(6+2 electrons) and
0(8electrons) all have 8 electrons.
172 □ □ Drug Inspector Exam
CLASSIFICATION OF OPIOIDS
Several classifications have been proposed (Table 21.1).
• Traditional: based upon analgesic potency
• Origin of drug: i.e., naturally occurring or manufactured
• Function: their action at the opioid receptor
In the traditional classification, the "strong" group includes drugs that are pure
agonists, whereas intermediate group includes partial agonists.
Table 21.1. Classification of opioids
Traditional O rigin Function
7. Mu (p) receptors are associated with: 12. Indicate the neurons, which are
(a) Analgesia, euphoria, respiratory located in the locus ceruleus or the
depression, physical dependence lateral tegmental area of the reticular
(b) Spinal analgesia, mydriasis, formation:
sedation, physical dependence (a) Dopaminergic
(c) Dysphoria, hallucinations, (b) Serotoninergic
respiratory and vasomotor (c) Nonadrenergic
stimulation (d) Gabaergic
(d) Analgesia, euphoria, respiratory
13. Which of the following analgesics is a
stimulation, physical dependence
phenanthrene derivative?
8. Which of the following opioid receptor (a) Fentanyl
types is responsible for euphoria and (b) Morphine
respiratory depression? (c) Methadone
(a) Kappa-receptors (d) Pentazocine
(b) Delta-receptors
14. Tick narcotic analgesic, which is a
(c) Mu-receptors
phenylpiperidine derivative:
(d) All of the above
(a) Codeine
9. Indicate the opioid receptor type, (b) D°7ocine
which is responsible for dysphoria and (c) Fentanyl ,
vasomotor stimulation:
. (d) Buprenorphine
(a) Kappa-receptors
(b) Delta-receptors 15. Which of the follow ing opioid
analgesics is a strong mu receptor
(c) Mu-receptors
agonist?
(d) All of the above
(a) Naloxone
10. Kappa and delta agonists: (b) Morphine
(a) Inhibit postsynaptic neurons by (c) Pentazocine
opening K+ channels (d) Buprenorphine
(b) Close a voltage-gated Ca2+
16. Indicate the narcotic analgesic, which
channels on presynaptic nerve
is a natural agonist:
terminals
(a) Meperidine
(c) Both (a) and (b)
(b) Fentanyl
(d) Inhibit of arachidonate
cyclooxygenase in CNS (c) Morphine
(d) Naloxone
11. Which of the following supraspinal
structures is im plicated in pain- 17. Select the narcotic analgesic, which is
modulating descending pathways? an antagonist or partial mu receptor
(a) The midbrain periaqueductal gray agonist:
(b) The hypothalamus (a) Fentanyl (b) Pentazocine
(c) The aria postrema (c) Codeine (d) Methadone
(d) The limbic cortex
Drug Acting on Central Nervous System □ □ 175
18. Which of the following agents is a full (a) Inhibiting brain stem respiratory
antagonist of opioid receptors? mechanisms
(a) Meperidine (b) Suppression of the cough reflex
(b) Buprenorphine leading to airway obstruction
(c) Naloxone (c) Development of truncal rigidity
(d) Butorphanol (d) Both (a) and (c)
19. The principal central nervous system 24, Most strong mu receptor agonists
effect of the opioid analgesics with cause:
affinity for a mu receptor is: (a) Hypertension
(a) Analgesia (b) Increasing the pulmonary arterial
(b) Respiratory depression pressure and myocardial work
(c) Euphoria (c) Cerebral vasodilatation, causing an
increase in intracranial pressure
(d) All of the above
(d) All of the above
20. Which of the follow ing opioid
analgesics can produce dysphoria, ^ W hich of the follow ing opioid
anxiety and hallucinations? analgesics can produce an increase in
the pulmonary arterial pressure and
(a) Morphine
myocardial work?
(b) Fentanyl
(a) Morphine
(c) Pentazocine
(b) Pentazocine
(d) Methadone
(c) Meperidine
21. Indicate the opioid analgesic, which (d) Methadone
has 80 times analgesic potency and ^
Morphine causes the following effects
respiratory depressant properties of
EXCEPT:
morphine, and is more effective than
morphine in maintaining (a) Constipation
hemodynamic stability? (b) Dilatation of the biliary duct
(a) Fentanyl (c) Urinary retention
(d) Bronchiolar constriction
(b) Pentazocine
(c) Meperidine 27. Therapeutic doses of the opioid
(d) Nalmefene analgesics:
(a) Decrease body temperature
22. Which of the follow ing opioid
(b) Increase body temperature
analgesics is used in combination with
droperidol in neuroleptanalgesia? (c) Decrease body heat loss
(d) Do not affect body temperature
(a) Morphine
(b) Buprenorphine 28. Which of the follow ing opioid
(c) Fentanyl analgesics is used in obstetric labor?
(d) Morphine (a) Fentanyl
(b) Pentazocine
23. Fentanyl can produce significant
(c) Meperidine
respiratory depression by:
(d) Buprenorphine
176 □ □ Drug Inspector Exam
29. Indicate the opioid analgesic, which (c) Mydriasis, chills and abdominal
is used for relieving the acute, severe cramps
pain of renal colic: (d) Miosis, tremor and vomiting
(a) Morphine 34. Which of the following opioid agents
(b) Naloxone is used in the treatment of acute opioid
(c) Methadone overdose?
(d) Meperidine (a) Pentazocine
30. Which of the follow ing opioid (b) Methadone
analgesics is used irt the treatment of (c) N aloxone
acute pulmonary edema? (d) Remifentanyl
(a) Morphine
35. Indicate the pure opioid antagonist,
(b) Codeine which has a half-life of 10 hours:
(c) Fentanyl (a) Naloxone
(d) Loperamide (b) Naltrexone
31. The relief produced by intravenous (c) Tramadol
morphine in dyspnea from pulmonary (d) Pentazocine
edema is associated with reduced:
36. In contrast to morphine, methadone:
(a) Perception of shortness of breath
(a) Causes tolerance and physical
(b) Patient anxiety
dependence more slowly
(c) Cardiac preload (reduced venous (b) Is more effective orally
tone) and afterload (decreased
(c) W ithdrawal is less severe,
peripheral resistance)
although more prolonged
(d) All of the above
(d) All of the above
32. Rhinorrhea, lacrim ation, chills,
37. Which of the follow ing opioid
gooseflesh, hyperventilation,
analgesics is a partial mu receptor
hyperthermia, mydriasis, muscular
agonist?
aches, vomiting, diarrhea, anxiety, and
hostility are effects of: (a) Morphine
(a) Tolerance (b) Methadone
(b) Opioid overdosage (c) Buprenorphine
(c) Drug interactions between opioid (d) Sufentanyl
analgesics and sedative-hypnotics 38. Indicate a partial mu receptor agonist,
(d) Abstinence syndrome which has 20-60 times analgesic
potency of morphine, and a longer
33. The diagnostic triad of opioid
duration of action:
overdosage is:
(a) Pentazocine
(a) M ydriasis, coma and
hyperventilation (b) Buprenorphine
(b) Coma, depressed respiration and (c) Nalbuphine
miosis (d) Naltrexone
Drug Acting on Central Nervous System □ □ 177
(a) Diamorphine
(b) Morphine
(c) Codeine
(d) Thebaine
44. Which of the following statements is
false regarding codeine?
(a) The structure is a weaker analgesic
than morphine.
(a) Diamorphine (b) Morphine (b) The structure acts as a prodrug.
(c) Codeine (d) Thebaine (c) The structure is converted to
morphine in the brain.
42. Morphine is an important analgesic.
(d) The coloured methyl group masks
What type of interactions are involved
an important binding group.
in binding the phenol group to the
target site? 45. Name the following structure. What
is this structure called?
Phenol
178 □ □ Drug Inspector Exam
(a) 6-acetylmorphine
(b) 3-acetylmorphine
(c) heterocodeine
(d) heteromorphine
46. Compare analgesic activity of 3-
acetylm orphine relative to
diamorphine and 6-acetylmorphine.
(a) 3-acetylmorphine should be more (a) There is an increase in activity.
active than 6-acetylmorphine and (b) There is a decrease in activity.
diamorphine.
(c) There is a loss of all activity.
(b) 3-acetylmorphine should be less
(d) The compound becomes an
active than 6-acetylmorphine and
antagonist.
diamorphine.
(c) 3-acetylmorphine should be more 49. The following molecule (etorphin(e)
active than 6-acetylmorphine and is used in veterinary medicine. What
less active than diamorphine. is it used for?
(d) 3-acetylmorphine should be less
active than 6-acetylmorphine and
more active than diamorphine.
17. Levorphanol is an analgesic which is
five times more active than morphine.
To which class of compounds does this
structure belong?
(a) Sedation
(b) Analgesia
(c) Treatment of diarrhoea
(d) Pupil constriction
50. Etorphine is used in veterinary
(a) Benzomorphans medicine. Name its antagonistic drug?
(b) 4-phenylpiperidines
(c) Morphinans
(d) Enkephalins
48. Levorphanol is an analgesic which is
five times more active than morphine.
What happens when the N-methyl
group is replaced with an N-allyl
group?
Drug Acting on Central Nervous System □ □ 179
88. Indicate the mechanism of hypnotic (b) A high risk of drug interactions
benzodiazepine action: based on liver enzyme induction
(a) Increasing the duration of the (c) Synergic CNS depression with
GABA-gated Cl- channel openings concomitant use of other drugs
(b) Directly activating the chloride (d) The form ation of active
channels metabolites
(c) Increasing the frequency of Cl- 94. Indicate the anxiolitic agent, which
channel opening events relieves anxiety without causing
(d) All of the above marked sedative effects:
89. Which of the following anxiolytics is (a) Diazepam
a partial agonist of brain 5-HT1A (b) Chlordiazepoxid
receptors? (c) Buspirone
(a) Buspirone (d) Clorazepate
(b) Alprazolam
95. Which of the following anxiolytics has
(c) Chlorazepat minimal abuse liability?
(d) Lorazepam (a) Oxazepam
90. Indicate the competitive antagonist of (b) Buspirone
BZ receptors: (c) Flumazenil
(a) Flumazeni’ (d) Alprazolam
(b) Buspirone 96. In contrast to benzodiazepines,
(c) Picrotoxin buspirone:
(d) Diazepam (a) Interact directly with gabaergic
91. Indicate the agent, which interferes system
with GABA binding: (b) Has more marked hypnotic,
(a) Chlordiazepoxide anticonvulsant, or muscle relaxant
(b) Bicuculline properties
(c) Thiopental (c) Causes less psychomotor
(d) Picrotoxin impairment and does not affect
driving skills
92. Antianxiety agents have:
(d) Has maximal abuse liability
(a) Sedative and hypnotic activity
(b) Muscle relaxing and anti 97. Which of the following sedative-
convulsant effects hypnotic drugs does not potentiate the
(c) Amnesic properties CNS depressant effects of
(d) All of the above ethanol,phenothiazines, or tricyclic
antidepressants?
93. Which of the following disadvantages (a) Buspirone
does not limit using benzodiazepines
(b) Phenobarbital
as antianxiety agents?
(c) Diazepam
(a) Tendency to develop psychologic
(d) Chloralhydrate
dependence
184 □ □ Drug Inspector Exam
108. Which of the following chemical 114. Indicate the barbituric acid derivative,
agents are used in the treatment of which has 4-5 days elimination half-
insomnia? life:
(a) Benzodiazepines (a) Secobarbital
(b) Imidazopyridines (b) Thiopental
(c) Barbiturates (c) Phenobarbital
(d) All of the above (d) Amobarbital
109. Select a hypnotic drug, which is a 115. Indicate the hypnotic benzodiazepine,
benzodiazepine derivative: which has the shortest elimination
(a) Zolpidem half-life:
(b) Flurazepam (a) Temazepam
(c) Secobarbital (b) Triazolam
(d) Phenobarbitone (c) Flurazepam
110. Tick a hypnotic agent - a barbituric (d) Diazepam
acid derivative: 116. Which of the following hypnotic drugs
(a) Flurazepam is more li’;ely to cause cumulative and
(b) Zaleplon residual effects?
(c) Thyopental (a) Zolpidem
(d) Triazolam (b) Temazepam
(c) Phenobarbital
111. Select a hypnotic drug, which is an
(d) Triazolam
imidazopyridine derivative:
(a) Pentobarbital 117. Which of the following hypnotic drugs
(b) Temazepam increases the activity of hepatic drug-
metabolizing enzyme systems?
(c) Zolpidem
(d) Chloral hydrate (a) Phenobarbital
(b) Zolpidem
112. Which of the following hypnotic
(c) Flurazepam
agents is absorbed slowly?
(d) Zaleplon
(a) Phenobarbital
(b) Flurazepam 118. Hepatic microsomal drug-
metabolizing enzyme induction leads
(c) Triazolam
to:
(d) Temazepam
(a) Barbiturate tolerance
113. Which of the following barbiturates (b) Cumulative effects
is an ultra-short-acting drug?
(c) Development of physical
(a) Secobarbital dependence
(b) Amobarbital (d) "hangover" effects
(c) Thiopental
119. Hypnotic benzodiazepines are more
(d) Phenobarbital
powerful enzyme inducers than
barbiturates.
186 □ □ Drug Inspector Exam
(d) Increase the duration of slow wave drowsiness, dysphoria, and mental or
sleep motor depression the following day?
142. Which of the following hypnotic drugs (a) Temazepam
causes least suppression of REM (b) Triazolam
sleep? (c) Flurazepam
(a) Flumazenil (d) None of the above
(b) Phenobarbital 147. Indicate the hypnotic drug, which
(c) Flurazepam binds selectively to the BZ1 receptor
(d) Secobarbital subtype, facilitating GABAergic
143. Although the benzodiazepines inhibition:
continue to be the agents of choice for (a) Thiopental
insomnia, they have: (b) Zolpidem
(a) The possibility of psychological (c) Flurazepam
and physiological dependence (d) Phenobarbital
(b) Synergistic depression of CNS 148. Which of the following statements is
with other drugs (especially correct for zolpidem?
alcohol) (a) Causes minor effects on sleep
(c) Residual drowsiness and daytime patterns
sedation (b) The risk of development of
(d) All of the above tolerance and dependence is less
144. Hypnotic benzodiazepines can cause: than with, the use of hypnotic
(a) A dose-dependent increase in both benzodiazepines
REM and slow wave sleep (c) Has minimal muscle relaxing and
(b) Do not change sleep patterns anticonvulsant effects
(c) A dose-dependent decrease in both (d) All of the above
REM and slow wave sleep 149. Which agent exerts hypnotic activity
(d) A dose-dependent increase in REM with minimal muscle relaxing and
sleep and decrease in slow wave anticonvulsant effects?
sleep (a) Flurazepam
145. Which one of the following hypnotic (b) Triazolam
benzodiazepines is more likely to (c) Zaleplon
cause rebound insomnia? (d) None of the above
(a) Triazolam 150. Zolpidem and zaleplon have
(b) Flurazepam effectiveness sim ilar to that of
(c) Temazepam hypnotic benzodiazepines in the
(d) All of the above — management of sleep Disorders
146. Which of the following hypnotic (a) True
benzodiazepines is more likely to (b) False
cause "hangover” effects such as
Drug Acting on Central Nervous System □ □ 189
ANSWERS
1. (a) 2. (b) 3. (a) 4. (d) ' 5. (c) 6. (d) 7. (a) 8. (c) 9. (a) 10. (b)
11. (a) 12. (c) 13. (b) 14. (c) 15. (b) 16. (c) 17. (b) 18. (c) 19. (d) 20. (c)
21. (a) 22. (c) 23. (d) 24. (c) 25. (b) 26. (b) 27. (a) 28. (c) 29. (d) 30. (a)
31. (d) 32. (d) 33. (b) 34. (c) 35. (b) 36. (d) 37. (c) 38. (b) 39. (c) 4 0 .(b)
41. (b) 42. (b) 43. (c) 44. (c) 45. (a) 46. (b) 47. (c) 48. (d) 49. (a) 50. (c)
51. (c) 52. (b) 53. (a) 54. (c) 55. (b) 56. (a) 57. (b) 58. (c) 59. (d) 60. (c)
61. (b) 62. (a) 63. (d) 64. (b) 65. (b) 66. (c) 67. (b) 68. (d) 69. (a) 70. (b)
71. (c) 72. (c) 73. (a) 74. (d) 75. (b) 76. (a) 77. (b) 78. (d) 79. (b) 80. (d)
81. (b) 82. (b) 83. (a) 84. (c) 85. (d) 86. (c) 87. (a) 88. (c) 89. (a> 90. (a)
91. (b) 92. (d) 93. (b) 94. (c) 95. (b) 96. (c) 97. (a) 98. (b) 99. (d) 100. (c)
101. id) 102. (a) 103. (b) 104. (d) 105. (b) 106. (b) 107. (c) 108. (d) 109. (b) 110. (c)
111. (c) 112. (d) 113. (c) 114. (c) 115. (b) 116. (c) 117. (a) 118. (a) 119. (b) 120.(d)
121. (d) 122. (b) 123. (d) 124. (c) 125. (a) 126. (a) 127. (b) 128. (d) 129. (b) 130. (c)
131. (a) 132. (c) 133. (b) 134. (d) 135. (b) 136. (d) 137. (c) 138. (d) 139. (a) 140. (c)
141. (b) 142. (c) 143. (d) 144. (c) 145. (a) 146. (c) 147. (b) 148. (d) 149. (c) 150. (a)
151. (a) 152. (a) 153. (c) 154. (b) 155. (d) 156. (b) 157. (c) 158. (d) 159. (d) 1 60.(d)
161. (d) 162. (a) 163. (a) 164. (a) 165. (a) 166. (a) i67. (c) 168. (a) 169. (c) 170. (d)
171. (e) 172. (b) 173. (e) 174. (a) 175. (b) 176. (b) 177. (b) 178. (b) 179. (d) 180. (a)
181. (b)
□no
Antigen, Antigen-antibofly Reactions, ^
ANTIGEN
Antigens are foreign substances that when introduced into a body, can induce an
immune response. The antigens in vaccines can be killed or modified-live viral or
bacterial strains. The sole purpose of antigens in vaccines is to stimulate the body's
immune system with an harmless version of the agent in order to protect against more
virulent strains later.
ANTIGEN-ANTIBODY REACTIONS
The antigens and the antibodies combine specifically with each other. This interaction
between them is called Antigen-Antibody reaction. It may be abbreviated as Ag-Ab
reaction. These form the basis for humoral immunity or antibody mediated immunity.
These reactions form the basis for detection of infectious disease causing agents and
also some non-specific Ag's like enzymes. When Ag-Ab reactions occur invitro, they are
known as serological reactions. The reactions between Ag and Ab occur in three stages.
1. Primary stage: This reaction involves formation of Ag-Ab complex. The reaction
is rapid and it obeys the general laws of physical chemistry and thermodynamics.
The two molecules are held together by non-covalent forces, hydrogen bonding,
ionic bonding and sometimes hydrophobic bonding.
2. The second stage leads to visible events like precipitation, agglutination, lysis of
cells, killing of Ag, neutralization of toxins, fixation of complement and
enhancement of phagocytosis.
3. The third stage includes destruction of Ag or its neutralization.
Salient features of Ag-Ab reactions
1. Immune complex: Since the reaction is specific, an Ag combines only with its
homologous Ab and vice versa.
2. Specificity of Ag-Ab reaction: An Ab will combine only with that Ag which
causes its production. The specificity may be compared to a Lock and Key system.
3. Binding sites of Ag and Ab: The entire of the Ag participates in the reaction.
But the part of the Ag that combines wi h the Ab is called epitope or antigenic
determinant. An Ag may have 10, 50 or upto 100 antigenic determinants. The
part of the Ab that combines with Ag is called paratope or antigen binding site.
Most Ab's are bivalent, whereas IgM has 5 to 10 paratopes.
193
194 □ □ Drug Inspector Exam
HYPERSENSITIVITY
It refers to undesirable (damaging, discomfort producing and sometimes fatal)
reactions produced by the normal immune system. Hypersensitivity reactions require
a pre-sensitized (immune) state of the host. Hypersensitivity reactions can be divided
into four types: type I, type II, type III and type IV, based on the mechanisms involved
and time taken for the reaction. Frequently, a particular clinical condition (disease) may
involve more than one type of reaction.
Type I Hypersensitivity. It is also known as immediate or anaphylactic
hypersensitivity. The reaction may involve skin (urticaria and eczema), eyes
(conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma)
and gastrointestinal tract (gastroenteritis). The reaction may cause from minor
inconvenience to death. The reaction takes 15-30 minutes from the time of exposure to
the antigen. Sometimes the reaction may have a delayed onset (10-12 hours). Immediate
hypersensitivity is mediated by IgE. The primary cellular component in this
hypersensitivity is mast cell or basophil. The reaction is amplified and/or modified by
platelets, neutrophils and eosinophils. A biopsy of the reaction site demonstrates mainly
mast cells and eosinophils. The mechanism of reaction involves preferential production
of IgE, in response to certain antigens, allergens.
Type II Hypersensitivity: It is also known as cytotoxic hypersensitivity and may
affect a variety of organs and tissues. The antigens are normally endogenous, although
exogenous chemicals (haptens) which can attach to cell membranes can also lead to
type II hypersensitivity. Drug-induced hemolytic anemia, granulocytopenia and
thrombocytopenia are such examples. The reaction time is minutes to hours. It is primarily
mediated by antibodies of IgM or IgG class and complement. Phagocytes and K cells
may also play a role.
Type III Hypersensitivity: It is also known as immune complex hypersensitivity.
The reaction may be general (for example, serum sickness) or may involve individual
organs including skin (for example, systemic lupus erythematosus, Arthus reaction),
kidneys (for example, lupus nephritis), lungs (for example, aspergillosis), blood vessels
(for example, polyarteritis), joints (for example, rheumatoid arthritis) or other organs.
This reaction may be the pathogenic mechanism of diseases caused by many
microorganisms. The reaction may take 3-10 hours after exposure to the antigen (as in
Arthus reaction). It is mediated by soluble immune complexes. They are mostly of IgG
class, although IgM may also be involved. The antigen may be exogenous (chronic
bacterial, viral or parasitic infections), or endogenous (non-organ specific autoimmunity:
e.g.systemic lupus eythematosus, SLE). The antigen is soluble and not attached to the
organ involved. Primary components are soluble immune complexes and complement
(C3a, 4a and 5a). The damage is caused by platelets and neutrophils.
Antigen, Antigen-antibody Reactions, Hypersensitivity, Active and Passive Immunity □ □ 195
donors, selected from the USA. One millilitre contains not <150 IU of rabies antibody.
It is given as part of post-exposure prophylaxis to non-immune individuals with a
rabies prone exposure.
Human Tetanus Immunoglobulin. Human tetanus immunoglobulin is presented as
a vial size of 250 IU. Each millilitre contains 40-180 mg/ml human protein of which at
least 95% are gammaglobulins (IgG). This product is prepared from plasma from screened
donors, selected from the USA. One millilitre contains not <100 IU of tetanus antibody.
It is unlikely that this preparation would be used for health care workers; it is given
both as part of the management of tetanus prone wounds where there is heavy soil/
manure contamination and as part of the management of all wounds if the individual
is thought to be non-immune.
Human Varicella-Zoster Immunoglobulin. Each vial contains 250 mg protein (40-180
mg/ml) of which at least 95% are gammaglobulins (IgG). This product is prepared from
plasma from screened donors, selected from the USA. One millilitre contains not <100
IU of Varicella-Zoster antibody. It is given as part of post-exposure prophylaxis to
specified non-immune individuals exposed to chickenpox.
TYPES OF VACCINES
There are many approaches to design vaccines against a microbe. These choices are
typically based on fundamental information about the microbe, such as how it infects
cells and how the immune system responds to it, as well as practical considerations,
such as regions of the world where the vaccine would be used. The following are some
of the options that researchers might pursue:
• Live, attenuated vaccines
• Inactivated vaccines
• Subunit vaccines
• Toxoid vaccines
• Conjugate vaccines
• DNA vaccines
• Recombinant vector vaccines
Live, Attenuated Vaccines
Live, attenuated vaccines contain a version of the living microbe that has been
weakened in the lab so it can't cause disease. Because a live, attenuated vaccine is the
closest thing to a natural infection, these vaccines are good "teachers'1 of the immune
system: They elicit strong cellular and antibody responses and often confer lifelong
immunity with only one or two doses.
Inactivated Vaccines
Scientists produce inactivated vaccines by killing the disease-causing microbe with
chemicals, heat, or radiation. Such vaccines are more stable and safer than live vaccines:
Antigen, Antigen-antibody Reactions, Hypersensitivity, Active and Passive Immunity □ □ 197
The dead microbes can’t mutate back to their disease-causing state. Inactivated vaccines
usually dttn't require refrigeration, and they can be easily stored and transported in a
freeze-dried form, which makes them accessible to people in developing countries.
Most inactivated vaccines, however, stimulate a weaker immune system response than
do live vaccines. So it would likely take several additional doses, or booster shots, to
maintain a person's immunity. This could be a drawback in areas where people don’t
have regular access to health care and can't get booster shots on time.
Subunit Vaccines
Instead of the entire microbe, subunit vaccines include only the antigens that best
stimulate the immune system. In some cases, these vaccines use epitopes the very
specific parts of the antigen that antibodies or T cells recognize and bind to. Because
subupjt vaccines contain only the essential antigens and not all the other molecules that
make up the microbe, the chances of adverse reactions to the vaccine are lower. Subunit
vaccines can contain anywhere from 1 to 20 or more antigens. Of course, identifying
which antigens best stimulate the immune system is a tricky, time-consuming process.
Toxoid Vaccines
For bacteria that secrete toxins,‘or harmful chemicals, a toxoid vaccine might be the
answer. These vaccines are used when a bacterial toxin is the main cause of illness.
Scientists have found that they can inactivate toxins by treating them with formalin,, a
solution of formaldehyde and sterilized water. Such "detoxified" toxins, called toxoids,
are safe for use in vaccines. Vaccines against diphtheria and tetanus are examples of
toxoid vaccines. ;
Conjugate Vaccines
If a bacterium possesses an outer coating of sugar molecules called polysaccharides,
as many harmful bacteria do, researchers may try making a conjugate vaccine for it
Polysaccharide coatings disguise a bacterium’s antigens so that the immature immune
systems of infants and younger children can't recognize or respond to them. Conjugate
vaccines, a special type of subunit vaccine, get, around this problem. The vaccine that
protects against Haemophilus influenzae type B (Hib) is a conjugate vaccine.
DNA Vaccines
Once the genes from a microbe have been analyzed, scientists could attempt to
create a DNA vaccine against it. Still in the experimental stages, these vaccines show
great promise, and several types are being tested in humans. DNA vaccines take
immunization to a new technological level. These vaccines dispense with both the
whole organism and its parts and get right down to the essentials: the microbe's genetic
il. In particular, DNA vaccines use the genes that code for those all-important
198 □ □ Drug Inspector Exam
11. The most suitable site(s) for (b) A 25 mm needle length is suitable
intram uscular and subcutaneous for all age groups
vaccination is/are: (c) A 16 mm needle length is only
(a) Anterolateral aspect of the thigh recommended for pre-term or very
(b) Deltoid area of the upper arm small infants
(c) Fatty area of buttock (d) The deltoid area of the upper arm
(d) Anywhere in buttock is generally preferred for infants
(e) All of the above under 1 year old
{e\ The anterolateral region of the
12. Which of the following is/are true ^ thigh is generally preferred for
when giving a vaccine:
older children and adults
(a) If the skin is clean no further
cleaning is necessary 15. If given in the same limb as another
. (b) The skin should be disinfected ! vaccine, the second vaccine should be
| separated by at least:
prior to administering any vaccine
(a) 0.5 cm
(c) Only visibly dirty skin needs to
be washed with soap and water (b) 1.5 cm
(d) The needle should be sufficiently (c) 2.5 cm
long (25 mm) for all ages except (d) 3.5 cm
for pre-term and very small (e) None of the above
children 16. Which of the following is/are true
(e) Skin should be stretched, not about anthrax:
bunched (a) It is spread by spores of the
13. After giving a vaccine you should anaerobic bacillus Bacillus
always: anthracis
(a) Observe the recipient for (b) H al an incubation period of 2-7
immediate adverse reactions days
(ADRs) (c) Can cause cutaneous, inhalational
(b) Keep the recipient under longer and gastrointestinal infections
observation in the surgery (d) The treatm ent of choice is
(c) Dispose of equipment used for erythromycin
vaccination in a 'sharps' box (e) Human cases require isolation to
(d) Keep accurate and accessible control spread
records of both the recipient and 17. W hich of the follow ing may be
the vaccine given considered for anthrax vaccine:
(e) All of the above (a) Textile workers working with goat
L4. Which of the following is/are true hair
about vaccine administration: (b) Veterinary surgeons
(a) It is better to inject vaccine into (c) Household contacts of a human
fat than muscle case of anthrax
(d) Bonemeal workers
Antigen, Antigen-antibody Reactions, Hypersensitivity, Active and Passive Immunity □ □ 201
(e) Health Care staff working on an (b) Can be used for post exposure
Infectious Diseases Unit prophylaxis
18. Which of the following is/are true (c) Should be protected from light in
about anthrax vaccine: storage
(a) It is a live attenuated vaccine (d) Can be used safely after freezing
(b) The vaccine course consists of (e) Can be stored at room temperature
three doses given at 3 week 22. Which of the following is/are true
intervals about oral cholera vaccine:
(c) It can be given to pregnant women (a) The vaccine is recommended for
(d) It is administered by intramuscular use in children under the age of 2
injection years
(e) A reinforcing dose should be given (b) There is data suggesting a excellent
every 3 years to those at continued protective efficacy profile after
risk booster doses
19. Anthrax: (c) The vaccine when constituted
(a) Is a notifiable disease should be a blue liquid
(b) Prim arily affects carnivorous (d) The vaccine is not recommended
for prevention of travellers
animals
diarrhoea
(c) Is a common animal disease in
(e) Immunisation does not protect
Western Europe
against V Cholerae serogroup 0139
(d) Is fatal in around 20% of cases
(e) Is almost an entirely occupational 23. Cholera vaccine should not be given
disease in the UK to the following:
(a) Severely immunocompromised
20. Adverse reactions to anthrax vaccine
individuals
can include:
(b) Anyone who is acutely unwell
(a) Swelling at the injection site
(c) Pregnant and breast-feeding
(b) Urticaria
women
(c) Regional lymphadenopathy
(d) Anyone who is HIV positive
(d) Generally a higher risk of a
(e) Those with pre-existing gastro
reaction after subsequent doses if
intestinal disorders
there was a reaction to the first
dose 24. Which of the following is/are true
(e) Cutaneous anthrax at the injection about Diphtheria:
site in a very small number of (a) Corynebacterium diphtheriae is
cases the only bacterium causing
diphtheria
21. Cholera vaccines:
(b) Those carrying C diphtheriae are
(a) Should be stored in their original
always ill
packaging
(c) Diphtheria toxin affects the heart,
nerves and adrenal tissues
202 □ □ Drug Inspector Exam
(d) Infected people may be infectious (b) Has been conjugated with either
for up to four weeks if untreated non-toxic variant of diphtheria
(e) Corynebacterium diphtheriae may vaccine or tetanus toxoid
cause skin infections (c) Is available as DTaP/IPV/Hib or
25. Which of the following is/are true Hib/PC V
about Diphtheria vaccines: (d) Is thiomersal-free
(a) They are live attenuated vaccines (e) Contains live organisms
(b) They are produced in two 28. Which of the following is/are true
strengths about Hepatitis A vacdne:
(c) They contain an adjuvant to (-a) The vaccine may cause mild
improve immunogenicity jaundice 2-6 weeks after
__ (d) Higher dose diphtheria vaccines administration_______________
should be used for primary (b) It can be given to pregnant women
immunisation in the UK schedule when clinically indicated
in those under 10 years (c) Hepatitis A antibody levels should
(e) Diphtheria vaccine is thiomersal be tested to check for a response
free (d) Is only effective if given to
26. Which of the following is/are true unvaccina tec&cpntacts f>f Hepatitis
about Diphtheria vaccine: A within 72 hours of the onset of
(a) It is only available in combination jaundice in the index case
with other vaccines (e) Should not be given to someone
(b) When given as a primary who may already be incubating
immunisation course 2 weeks Hepatitis A infection
should be allow ed between 29. Which of the following Hepatitis A
vaccinations vaccine products is/are available:
(c) The first booster dose of diphtheria (a) Combined H epatitis A and B
vaccine should be given at least vaccine
12 months after the last in the (b) Combined H epatitis A and C
primary course vaccine
(d) There should be 3 years between (c) Monovalent Hepatitis A Vaccine
the first and second booster doses (d) Combined H epatitis A and
(e) If it has been given as part of a typhoid vaccine
vaccination following a tetanus (e) Combined Hepatitis A and cholera
prone wound the routine booster vaccine
is always necessary
30. Which of the following is/are true:
27. Which of the following statements is/ (a) Influenza is caused by type A, B
are true about Hib vaccine: or C viruses
(a) Made from capsular (b) In flu e n z a A is th e u su a l ca u se o f
polysaccharide that has been epidemics
extracted from cultures of Hib
bacteria
Antigen, Antigen-antibody Reactions, Hypersensitivity, Active and Passive Immunity □ □ 203
42. Small pox vaccine contains (b) tkey occur on the surface of
(a) living virus vaccine lwnphocytes
(b) living culture of B.C.G (c) thjey predominate in the primary
(c) attenuated staphylococcus response to antigen
(d) dead virus vaccine (d) they are glycoproteins
(e) they mediate allergic reaction
43. Gamma globulin is separated from
serum by 48. 5-T-cell antigen receptors are
(a) agglutination distinguished from antibodies by
(b) dialysis which of the following
(c) centrifugation —— (a) T-Cell receptors are glycosylated
(d) salting out <b) T-cell receptors must interact with
/• antigen uniquely presented by
44. Chemically, Interferon's are other cells but nof~witi»__ijee
(a) carbohydrate antigen
(b) protein (c) T-Cell receptors bind various
(c) lipid cytokines
(d) phospholipid (d) T-Cell receptors bind complement
45. The adult dose of tuberculin in to lyse cells
Montoux test is (e) T-cell receptors are mediators of
(a) 0.1 ml allergic reactions
(b) 1 ml 49. All of the following are true of antigen
(c) 0.001 ml EXCEPT which one of the following?
(d) 0.01 ml I (a) They contain epitopes .
(b) They will react with antibodies .
46. Which is true for Rubella infection?
(c) They contain antigenic
(a) Can be asymptomatic
determinants .
(b) May be indistinguishable from
(d) They can elicit an immune
parvovirus B19
response .
(c) Is usually preventable by
(e) They contain paratopes
vaccination
(d) May be acquired by having close 50. Which of the following
contact with an infant with immunoglobulins is present normally
congenital rubella syndrome in plasma at the highest
(e) Can have serious side effects when concentration?
occurring in a woman in the third (a) IgG (b) IgM
trimester of pregnancy (c) IgA - (d) IgD
(e) IgE
47. All of the following are true with
respect to IgM antibodies EXCEPT 51. All of the following are true about
which one antibodies, EXCEPT which one ?
(a) they fix complement (a) They fix complement .
Antigen, Antigen-antibody Reactions, Hypersensitivity, Active and Passive Immunity □ □ 205
ANSWERS
1. (c) 2. (c) 3. (a) 4. (d) 5. (c) 6. (e) 7. (e) 8. (c) 9. (d) 10 . (a)
11. (b) 12 . (d) 13. (a) 14. (c) 15. (c) 16. (b) 17. (a) 18. (c) 19. ,(a) 20. (b)
2 1. (a) 22. (d) 23. (a) 24. (c) 25. (b) 26. (a) 27. (a,b) 28. (b) 29. (c) 30. (a)
31. (d) 32. (b) 33. (c) 34. (d) 35. (c) 36. (b) 37. (b) 38. (d) 39. (c) 40. (a)
41. (a) 42. (a) 43. (b) 44. (b) 45. (a) 46. (a) 47. (e) 48. (b) 49. (e) 50. (a)
51. (e) 52. (d) 53. (d) 54. (d) 55. (b) 56. (d) 57. (d) 58. (b) 59. (c) 60. (b)
61. (a) 62. (c) 63. (d) 64. (a) 65. (b) 66. (b) 67. (c)
mn
History Development and
Production of Antibiotics
23
C h a pter
The great modern advances in chemotherapy have come from the chance discovery
that many microorganisms synthesize and excrete compounds that are selectively toxic
to other microorganisms. These compounds are called an tibiotics and have
revolutionized medicine. The period since World War II has seen the establishment and
extremely rapid growth of a major industry, using microorganisms for the synthesis of,
amongst other compounds, chemotherapeutic agents. The development of this industry
has had a dramatic and far-reaching impact. Nearly all bacterial infectious diseases that
were, prior to the antibiotic era, major causes of human death have been brought under
control by the use of chemotherapeutic drugs, including antibiotics.
The first chemotherapeutically effective antibiotic was discovered in 1929 by
Alexander Fleming (1881-1955), a British bacteriologist,\who had long been interested
in the treatment of wound infections. On returning from a vacation in the countryside,
he noticed among a pile of petri dishes on his bench one that had been streaked with
a culture of Saphyloccocus aureus which was also contaminated by a single colony of
mold. As Fleming observed the plate, he noted that the colonies immediately surrounding
the mold were transparent and appeared to by undergoing lysis. He reasoned that the
mould was excreting into the medium a chemical that caused the surrounding colonies
to lyse. Sensing the possible chemotherapeutic significance of his observation, Fleming
isolated the mold, which proved to be a species of Penicillium, and established that
culture filtrates contained an antibacterial substance, which he called penicillin.
Ten years later a group of British scientists headed by H. W. Florey (1898-1968) and
E. Chain (1906-1979) resumed the study of penicillin. Clinical trials with partly purified
material were dramatically successful. By this time, however, Britain was at war; and
the industrial development of penicillin was undertaken in the United States, where an
intensive program of research and development was begun in many laboratories. Within
three years, penicillin was being produced on an industrial scale. Today it remains one
of the most effective chemotherapeutic agents for the treatment of many bacterial
infections.
Rather than being a single substance, penicillin turned out to be a class of compounds.
The various penicillins vary with respect to the chemical composition of their side
chain. The penicillin that was first isolated in Peoria, Illinois, designated penicillin G,
carried a benzyl side chain. The penicillin isolated soon after in England, designated
penicillin F, carried an isopentanyl side chain. By varying the composition of the fungal
growth media, a variety of penicillins collectively termed biosynthetic penicillins, have
207
208 □ □ Drug Inspector Exam
been synthesized. Penicillin G proved the most successful and later it became possible
to remove the side chain and replace it by a variety of chemical substituents, thereby
producing semisynthetic penicillins. For example, penicillin V is resistant to acid and
therefore can be administered orally because it is not inactivated in the stomach;
ampicillin is also acid resistant and also effective against enteric bacteria; oxacillin is
resistant to the action of -lactamase, the enzyme produced by certain "penicillin-resistant"
strains of bacteria.
The remarkable chemotherapeutic efficacy of penicillin for certain bacterial infections,
primarily those caused by Gram-positive bacteria, prompted intensive research into
new antibiotics. In the 1940s, a second clinically important antibiotic, streptomycin,
effective against both Gram-negative bacteria and Mycobacterium tuberculosis, was
discovered by A. Schatz and S. Waksman. This was the first example of a broad-
spectrum antibiotic. Other antibiotics with even broader spectra of activity, such as the
tetracyclines, were subsequently discovered. The search for new antibiotics remains an
empirical enterprise. So far, they have proved very effective as antibacterial agents,
although some bacteria do acquire resistance to antibiotics^ so there is a continuous
search for new and effective antibacterial agents. Antibiotics have proved less effective
in the treatment of fungal infections. Antifungal antibiotics, such as nystatin and
amphoterecin B are considerably less successful therapeutically than their bacterial
counterparts, at least in part because their toxicu_y is far less selective. There are no
known antiviral antibiotics.
Since 1945, thousands of different antibiotics produced by fungi, actinomycetes or
unicellular bacteria have been isolated and characterized. A small fraction of these are
of therapeutic value. Their nomenclature is complicated as one antibiotic may be sold
under several different names. For example, in the United States the compound, which
in Europe has the generic name rifampicin, is called rifampin.
FERMENTATION PROCESS
Though there are different perceptions of the nature of the process, fermentation can
be defined as the breakdown or catabolism of organic compounds by microorganisms
under both aerobic and anaerobic conditions. This breakdown yields end products.
End-products Obtained by Fermentation
Types of end products of fermentation include:
• Microbial cells (for example, bacteria, yeast, fungal spores)
• Microbial enzymes (for example, milk clotting enzymes or rennets, recombinant
fungal and bacterial rennets for cheese manufacture)
• Microbial metabolites (for example, alcohols- ethanol, butanol, 2, 3-butanediol,
isopropanol; chemicals- lactate, propionate, proteins, vitamins, antibiotics; and
fuels- methane)
• Recombinant products (for example, hormones)
History Development and Production o f Antibiotics □ □ 209
Alcohol Fermentation
Various bacteria and yeasts metabolize sugars into ethanol through different pathways
using different enzyme systems. Alcohol fermentation is used for the industrial
production of alcohols and alcoholic beverages. In the preparation of alcoholic beverages
several factors have to be considered, such as flavor, taste, appearance, and safety.
These require special procedures and standards. The commercial producers of alcoholic
beverages each have their own protocols which give their product a distinct taste and
flavor, and these are often kept confidential. The process is as follows:
Sugar (Carbohydrate)---------2Ethanol + 2Carbon Dioxide
There are four different phases in bacterial growth during fermentation. A good
understanding of these phases is very important for effective management of the whole
fermentation process.
Lag Phase
At the start of the process microorganisms are added to the nutrient medium and
allowed to grow. The number of microorganisms will not increase because they try to
adapt to the environment.
Log Phase
The microorganisms are adjusted to the new environment and they multiply at a
4very rapid pace thus increasing the cell number exponentially.
Stationary Phase
As the microorganisms grow they produce metabolites which are toxic to microbial
growth. Also, the nutrient medium is used up, slowing down or stopping cell growth.
Death Phase
Microorganisms produce toxic metabolites to the extent that they cause the death of
the microorganisms
Factors That Influence Microbial Growth
Temperature, water, pH, and nutrients can influence microbial growth.
Temperature
Most microorganisms that are mesophiles require temperatures of 25-40 C for optimum
growth. As temperatures increase or decrease the growth rate is adversely affected.
Thermophiles require high temperatures over 50 C; they cannot survive at low
temperatures. Psychrophiles require very low temperatures -15 to 20 C for survival and
growth.
Water
Microorganisms require optimum amounts of water to maintain their metabolism
and produce required products.
PH
Optimum pH for bacteria is 6.5-7.5, yeasts 4-5, molds 4-7. The pH of the medium
should be maintained at optimum level for the microorganism being employed to ensure
better product yield. Nutrients
210 □ □ Drug Inspector Exam
V
Dessiccation
This involves removal of water from the culture. Dessiccation is used to preserve
actinomycetes (a form of fungi-like bacteria) for very long period of time. The
microorganisms can be preserved by desiccating on sand, silica gel, or paper strips.
Agar Slopes
Microorganisms are grown on agar slopes in test tubes and stored at 5 to -20 C for
six months. If the surface area for growth is covered with mineral oil the microorganisms
can be stored for one year.
Liquid Nitrogen
This is the most commonly used technique to store microorganisms for a long
period. Storage takes place at temperatures of less than -196° C and even less in vapor
phase. Microorganisms are made stationary and suspended in a cryo-protective agent
before storing in liquid nitrogen. ■
Drying
This method is especially used for sporulating microorganisms (organisms that
produce spores). They are sterilized, inoculated, and incubated to. allow microbial growth,
then dried at room temperature. The resultant dry soil is stored at 4° to 5° C.
Lyophilization
This process is also known as freeze-drying. The microbial culture is first dried
under vacuum, filled in ampoules (glass vessels) then frozen. This is a most convenient
technique, since it is'cheap to store and easy to ship. The disadvantage is that it is
difficult to open the freeze dried ampoules; also, several subcultures have to be done
to restore the original characteristics of the microorganisms.
Strain Improvement v
The yield of products will be much less when naturally available microorganisms
are used for fermentation in optimum growth medium. Providing optimum growth
conditions increases the yield only marginally. To increase the productivity of the
microorganisms it is necessary to modify their genetic structure since it is genomes that
determine the productivity of organisms. The culture medium and nutritional
requirements also change slightly when the genetic structure’ of the microorganism is
changed and hence they are also modified according to the new requirements'to ensure
maximum product yield. Genetic change of the microorganism can be done by inducing
mutations in the microorganisms, recombinant technology, end selecting natural variants.
Preparation of the Inoculum
Microbial inoculum has to be prepared from the preservation culture so that it can
be used for the fermentation process. The aim of inoculum preparation is to select
microorganisms with high productivity and to minimize low productive, mutant strains.
The process involves several steps.
First generation culture is prepared from the preservation culture on agar slants
which is then sub-cultured to prepare "working culture". At this stage the microorganisms
212 □ □ Drug Inspector Exam
start growing. In small scale fermentation processes working culture is used as inoculum,
but for large scale fermentation inoculum preparation involves additional steps.
Second, sterile saline water or liquid nutrient medium containing glass beads is
added to the agar slants and shaken so that microbial suspension is prepared. This
suspension is transferred to a flat bed bottle which contains sterile agar medium. The
microorganisms are allowed to grow by incubating the bottle.
Third, the microbial cells from the flat bed bottles are transferred to a shaker flask
containing sterile liquid nutrient medium and is placed on a rotary shaker bed in an
incubator. Microorganisms grow at a rapid rate due to aeration.
Fourth, microbial cells from the shaker flask can be used as seed culture which are
then added to a small fermenter and allowed to grow for 1-2 days. This simulates
conditions that exist in the larger fermenter to be used for production of metabolites.
Finally, the microorganisms are transferred to the main fermentation vessel containing
essential media and nutrients.
Culture Medium
Media requirements depend on the type of microorganism being used in the
fermentation process, but the basic requirements remain the same—source of energy,
water, carbon source, nitrogen source, vitamins, and minerals. Designing the media for
small scale laboratory purpose is relatively easy, but media for industrial purpose are
difficult to prepare.
The culture medium should: allow high yield of the desired product and at fast rate,
allow low yield of undesired products, be sterilized easily, yield consistent products
i.e., minimum batch variation, be cheap and readily available, be compatible with-the
fermentation process, and not pose environmental problems before, during, or after the
fermentation process.
The culture medium will affect the design of the fermenter. For example,
hydrocarbons in the media require high oxygen content so an air-lift fermenter should
be used. Natural media ingredients are cheap but they have high batch variation. On
the other hand pure ingredients (also called defined media or formulated media) have
very little batch variation but are expensive. The media should support the metabolic
process of the microorganisms and allow bio-synthesis of the desired products.
Carbon & Energy source + Nitrogen source + Nutrients
Product(s) + Carbon Dioxide + Water + Heat + Biomass
Media are designed based on the above equation using minimum components
required to produce maximum product yield.
Important components of the medium are carbon sources, nitrogen sources, minerals,
growth factors, chelating agents, buffers, antifoaming agents, air, steam, and
fermentations vessels.
Carbon Sources
Product formation is directly dependent on the rate at which the carbon source is
metabolized; also the main product of fermentation determines the type of carbon
source to be used. Carbon sources include carbohydrates, oils and fats, and hydrocarbons.
History Development and Production o f Antibiotics □ □ 213
Carbohydrates
These are the most commonly used carbon sources in the fermentation process.
Starch is easily available carbohydrate obtained from maize, cereals, and potatoes. It is
widely used in alcohol fermentation. Grains like maize are used directly in the form of
ground powder as carbohydrate. Malt and beer made from barley grains contain high
concentrations of different carbohydrates like starch, sucrose, cellulose and other sugars.
Sucrose is obtained from sugar cane and molasses. Molasses is one of the cheapest
sources of carbohydrate. It contains high sugar concentration and other components
like nitrogenous substances and vitamins and is used in alcohol, SCP (Single-cell Protein),
amino acid, and organic acid fermentations.
Oils and Fats
Vegetable oils are used as a carbon source. Oils provide more energy per weight
compared to sugars. They also have anti-foaming properties but are generally used as
additives rather than as the sole carbon source. Examples are olive oil, cotton seed oil,
soya bean oil, linseed oil, and lard (animal fat).
Hydrocarbons
C12-C18 alkanes can be used as carbon sources. They are cheap, and have more
carbon and energy content per weight than sugars. They can be used in organic acids,
amino acids, antibiotics, enzymes, and proteins fermentation.
Nitrogen Sources
Ammonia, ammonium salts, and urea are the most commonly used nitrogen sources
in the fermentation process. Ammonia also serves the purpose of pH control. Other
substances used as nitrogen sources are corn-steep liquor, soya meal, peanut meal,
cotton seed meal, amino acids, and proteins.
Minerals
Calcium, chlorine, magnesium, phosphorous, potassium and sulfur are the essential
minerals for all media. Other minerals like copper, cobalt, iron, manganese, molybdenum,
and zinc are needed in trace amounts and are generally present as impurities in other
components. Ihe specific concentration on these elements depends on the microorganism
being used.
Growth Factors
Vitamins, amino acids, and fatty acids are used as growth factors in the fermentation
process to complement the cell components of the microorganisms.
Chelating Agents
Chelating agents prevent formation of insoluble metal precipitates. They form
complexes with the metal ions present in the medium and can be utilized by the
microorganisms. Chelating agents are not required in large scale fermentation processes
since some of the other ingredients like yeast extract will perform the function of
forming complexes with the metal ions.
214 □ □ Drug Inspector Exam
of the fermentation broth, and then the antibiotic is removed from the broth by filtration,
precipitation, and other separation methods.
The penicillin was first made at the end of the second world war using the fungus
Penicilium notatum, the process made 1 mg dm"3. Today, using a different species (P.
chrysogenum) and a better extraction procedures the yield is 50 g dm"3.
The production of tetracycline by fermentation was disclosed by Minieri et. al. in
1953. The composition of the medium and the strain of streptomycete are both important
factors, since Streptomyces aureofaciens is capable of producing at least two antibiotic
substances as pointed out by Backus et. al. in 1954.
ANSWERS
1. (b) 2. (a) 3. (c) 4. (a) 5. (b) 6. (a) 7. (b) 8. (a) 9. (d) 10. (c)
11. (d) 12. (c) 13. (c) 14. (c) 15. (d) 16. (d)
□□ □
Carbohydrate Metabolism
24
C h a pter
(b) Three molecules of NADH and (d) The FO subunit of the ATP
one molecule of FADH 2 are synthase contains the catalytic
produced in one turn of the citric centre that synthesizes ATP.
acid cycle. g The reaction w hich irreversibly
(c) Oxygen is not used in the citric commits sugar to the glycolytic
acid cycle, so the cycle can occur pathway is catalyzed by:
in anaerobic conditions. (a) hexokinase or glucokinase.
(d) The citric arid cycle produces the (b) phosphofructokinase.
water that is formed during the
(c) phosphoglucomutase.
complete oxidation of glucose.
(d) glucose phosphate isomerase.
4. Which of the following statements (e) aldolase.
about the electron transport chain is
correct? ^• NAD+ contains which of the
following?
(a) The electron transport chain is
made up of a chain of electron (a) thiamine
carriers with decreasing electron (b) lipoic acid
affinity. (c) niacin
(b) The electron transport chain is (d) riboflavin
made up of a chain of electron (e) CoA
carriers with increasing redox g Phosphoglycerate kinase functions in
potential. carbohydrate metabolistn to produce
(c) The electron transport chain is ATP via:
made up of a chain of electron (a) oxidative phosphorylation.
carriers with decreasing oxidising
(b) substrate level phosphorylation.
power.
(c) oxidative decarboxylation.
(d) The electrons transferred from
carrier to carrier in the electron (d) phosphorolysis.
transport chain gain energy. 9. Glucose-l-phosphate is produced from
5. Which of the following statements glycogen via:
about the generation of ATP in the (a) oxidative phosphorylation.
electron transport chains is correct? (b) substrate phosphorylation.
(a) The FI subunit of the ATP (c) glycogen kinase activity.
synthase contains the motor which (d) phosphorolysis.
is driven to rotate by the proton jq
Which of the following is important
flow. in transferring energy frorri the
(b) The FI subunit of the ATP glycolytic pathway to the TCA cycle?
synthase contains the catalytic (a) NADH + H+
centre that synthesizes ATP.
(b) FADH2
(c) The FO subunit of the ATP
(c) citrate
synthase binds ADP and Pi tightly
(d) acetyl CoA
before ATP synthesis occurs.
(e) GTP
220 □ □ Drug Inspector Exam
20. In the citric acid cycle, a flavin (c) Oxaloacetate is used as e ubstrate
coenzyme is required for: but is not consumed in the cycle.
(a) condensation of acetyl-CoA and (d) Succinate dehydrogenase channels
oxaloacetate electrons directly into the electron
(b) oxidation of fumarate transfer chain.
(c) oxidation of isocitrate (e) The condensing enzyme is subject
(d) oxidation of malate to allosteric regulation by ATP and
(e) oxidation of succinate NADH
ANSWERS
1. (b) 2 . (d) 3. (b) 4. (b) 5. (b) 6. (a) 7- (c) 8. (a) 9. (b) 10 . (a)
11. (b) 12 . (a) 13. (a) 14. (a) 15. (c) 16. (e) 17. (e) 18. (d) 19. (c) 20. (e)
2 1. (d) 22 . (e) 23. (a) 24. (b) 25. (d) 26. (a) 27. (b) 28. (a) 29. (c) 30. (a)
31. (e) 32. (a) 33. (a) 34. (d) 35. (d) 36. (a) 37. (b)
□ □ □
Chemotherapeutic Agents
/
25
C h a pter
Chemotherapeutic agents are chemicals that have selective action either on Parasites
or microorganisms. They are used for the treatment or control of diseases caused by
pathogenic invading organisms or cells. Depending on parasites on which they act,
they are classified as Anthelmintic, antiprotozoal, antifungal, antibacterial, antiviral,
and antimalarial, etc.
The term 'Sulphonamides' is a generic name for the derivatives of p-amino benzene
sulphonamide (sulphanilam ide).The Sulphonamides was the first effective
chemotherapeutic drug, used for the treatment of bacterial infections in man. Once,
Domagh in 1932 discovered the antibacterial effect of azodye, Prontosil, it was concluded
that its metabolic product, sulphanilamide is responsible for antibacterial activity.
Although, these remain effective antibacterial agents but their uses are decreased in the
present era due to availability of better antibiotics. However, still combination of
sulphamethoxazole and trimethoprim is commonly used to treat microbial infection
These are classified as follows :
1. Sulphonamides employed for treatment of systemic infection. Depending upon
duration, they can be further subdivided into:
(z) Short to intermediate acting Sulphonamides, for example, Sulphadiazine,
sulphafurazole, Sulphamethoxazole, sulphaphenazole. These are absorbed rapidly,
with plasma half life up to 5-11 hrs.
(ii) Long acting Sulphonam ides for example, Sulpham ethoxypyridazine,
sulphadimethoxine. These are rapidly absorbed but excreted slowly. These have
long duration of action.
2. Poorly absorbed Sulphonamides, employed for the treatment of local
gastrointestinal infection for example, sulphaguanidine, succinyl sulphathiazole,
phthalyl sulphathiazole.
3. Topically used Sulphonamides for example, silver sulphadiazine, mefenide,
suphacetamide. These are meant for ophthalmic use and for wound & bum
infection.
Antibiotics are specific substances derived from or produced by living organise.
These substances in small concentration are capable of inhibiting the life processes of
other organisms.
Classification of antibiotics
Among the several criteria used to classify antibiotics, the main ones are (i)
biosynthesis; (ii) spectrum of activity; (iii) chemical structure.
224
Chemotherapeutic Agents □ □ 225
A. Biosynthesis
According to biosynthesis, antibiotics can be divided into following classes :
1. Antibiotics derived from amino acids: Cycloserine, Chloramphenicol, penicillin's,
cephalosporins, gramicidin, polymixin, viomycin, and capreomycin.
2. Antibiotics derived from carbohydrates: Streptomycin, kanamycin, neomycin,
gentamicin, lincomycin, and spectinomycin.
3. Antibiotics derived from acetate and propionate: Fusidic acid, griesofulvin,
macrolide antibiotics, polyene antibiotics, tetracyclines.
4. Miscellaneous antibiotics: Novobiocin, puromycin, rifamycin, vancomycin
(B) Spectrum of activity
1. Broad spectrum antibiotics: Some penicillin's (e.(g) ampicillin, carbenicillin), some
cephalosporin's (cephaloridine), Chloramphenicol, macrolides, rifamycins,
tetracycline's, sparsomycins, some aminoglycosides (neomycin, kanamycin,
gentamicin, paromomycin).
2. Antibiotics active predominantly against Gram positive bacteria: Bacitracin, most
penicillin's (e.(g) benzylpenicillin, cloxacillin, dicloxacillin, oxacillin), fusidic acid,
erythromycin, lincomycin.
3. Antibiotics active against Gram negative bacteria: Polymixin B, Sulphomyxin.
4. Antifungal Antibiotics: Amphotericin B, candicidin, fumagillin, haymycin,
nystatin.
5. Anti amoebic antibiotics: Paromomycin, puromycin.
6. Anti neoplastic antibiotics: Adriamycin, bleomycin, daunorubicin, methramycin,
mitomycin C, actinomycins.
(C) Chemical structure
Here, antibiotics are classified based on chemical structure. None of classification is
satisfactory. However, in the present chapter, this classification is followed to classify
the antibiotics into penicillin's, cephalosporin's, Chloramphenicol and derivatives,
tetracycline's? polyene antibiotics, macrolide antibiotics, aminoglycoside antibiotics,
antracyclines;’lincomycin group, nucleoside antibiotics.
Table 25.1. Classes of antibiotics and their properties
Chem ical Exam ples B iological Spectrum M ode of
Class sources (effective action
against)
Neisseria,
Legoinella,
M ycocplasm a
Polypeptides Polymyxin Bacillus gram-negative Damages
polymyxa bacteria cytoplasmic
membranes
Bacitracin Bacillus Gram- Inhibits steps in
subtilis positive murein
bacteria (peptidoglycan)
biosynthesis
and assembly
Polyenes Am photericin Streptomyces Fungi Inactivate
modosus membranes
containing
sterois
N ystatin Streptomyces Fungi Inactivate
noursei (Candida) membranes
containing
sterois
Rifamycins Rifampicin Streptomyces Gram-positive Inhibits
mediterranei and Gram- transcription
negaive (eubacerial
bacteria, RNA
M ycobac polymerase)
terium
tuberculosis
Tetracyclines Tetracycline Streptomyces Gram -positive Inhibit
species an Gram- translation
negative (protein
bacteria synthesis)
Rickettsias'
Semisynthetic Doxycycine Gram -positive Inhibit
tetracycline and gram- translation
negative (protein
bacteria synthesis)
Rickettsias
Ehrlichia,
Borrelia
Chloramphenicol Chloram p Streptomyces Gram-positive Inhibits
henicol venezuelae and Gram- translation
negative (protein
bacteria synthesis)
228 □ □ Drug Inspector Exam
glucosamine. Streptomycin acts as a triacidic base due to presence of two strong basic
guanidine and weakly basic methyl amino group.
It is bactericidal drug, often used in combination with other drugs such as
ethambutol and Isoniazid, to treat pulmonary infection in patients with resistant tubercle
bacilli.
Ethionamide(TrectorSC): Its mechanism of action is supposed to be similar to
Isoniazid. Gastrointestinal intolerance is its common side effects.
p-Amino salicylic acid(PAS): It is a bacteriostatic and highly specific for M
tuberculosis. At one time, PAS was considered a first line drug alongwith Isoniazid and
streptomycin. However, due to introduction of more effective and better tolerated drugs
like rifampinand ethambutol, it has an alternative status. Cycloserine (Seromycin). It is
an antibiotic, isolated from three different Streptomyces species, S. orchidaceous,
garyphalus and S. lavenulus. It shows its antibacterial action by inhibiting the step of
cross linking of peptides in the formation of bacterial cell wall.
Capreomycin sulphate(Capsalate sulphate): It is a polypeptide complex, isolated
from Streptomyces capreolus. It consists of four components like la, IB, IIA and IIB.
Damage to the 8th cranial nerve(hearing loss) and renal damage are its serious toxic
effects. Hence, it is only given in place of streptomycin in the treatment of tuberculosis
when organism is resistant.
Thalidomide
It is the drug of choice for the treatment of Erythema nodosum leprosum but
contraindicated in pregnancy or child bearing age due to its teratogenic nature.
Anti HIV drugs
Several distinct classes of drugs are now used to treat HIV infection like:
1. Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTI): These drugs
contain faulty version of the building blocks (nucleotide) used by reverse transcriptase
to convert RNA to DNA. When reverse transcriptase uses these faulty building blocks,
the new DNA can’t be built correctly. In turn, HIV's genetic material of the cell and
prevents the cell from producing new virus (they are chain-terminating drugs). Hence,
they act by incorporating themselves into DNA of the virus to stop the building process.
Zidovudine (AZT = ZDV, Retrovir),Didanosine (ddl, Videx), Zalcitabine (ddC, Hivid),
Stavudine (d4T, Zerit), Lamivudine (3TC, Epivir) are the examples.
2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): In contrast to NRTIs,
NNRTIs are not incorporated into viral DNA; they inhibit HIV replication directly by
binding non-competitively to reverse transcriptase at its catalytic site. These drugs,
unlike the nucleoside analogues, don't require phosphorylation to become active. These
are highly selective against HIV-1 and very potent in vitro.Nevirapine (Viramune) and
Delavirdine (Rescriptor) are the examples.
3. Protease Inhibitors: These drugs are specific for the HIV-1 protease and
competitively inhibit the enzyme, preventing the maturation of virions, capable of
infecting other cells. Saquinavir (Invirase), Ritonavir (Norvir), Indinavir (Crixivan),
Nelfinavir (Viracept) are the examples.
4. Fusion inhibitors(FI's): HIV enters cells in a series of steps: (i) HIV attaches to
the cell (ii) HIV binds to the cell, and (iii) HIV fuses to the host cell. These act by
blocking HIV from fusing to the cell, preventing the virus from entry into a healthy cell.
Enfuvirtide is the example of this class.
ANTIFUNGAL DRUGS
Drugs for the treatment of Systemic mycotic infections
The drugs used in the treatment of subcutaneous and systemic mycoses are
amphotericin B, flucytosine, and the new group of azoles, ketoconazole, fluconazole
and itraconazole.
A. Amphotericin B (Fungizone)
It is a naturally occurring polyene macrolide antibiotic, produced by Streptomyces
nodosus. In spite of its toxic potential, amphotericin B is the drug of choice used in the
treatment of systemic mycoses. It is sometimes used in combination with flucytosine so
that lower(less toxic) levels of amphotericin are possible.
(B) Flucytosine (Ancobon)
It is a synthetic pyrimidine anti metabolite, used only in combination with
amphotericin for the treatment of systemic mycoses and meningitis caused by
Cryptococcus neoformans and Candida species.
Chemotherapeutic Agents □ □ 231
A. Griseofulvin (Fulvicin)
It is naturally occurring spirane> isolated from Penicillium griseofulvum. The drug
is principally fungistatic, effective against the dermatophytes-Trichophyon, Microsporum
and Epidermophyton. It interacts with microtubules within the fungus to disrupt the
mitotic spindle and inhibits mitosis. It also accumulates in infected, newly synthesized
keratin containing tissues, making them unsuitable for the growth of fungi.
(B) Polyene antibiotic
(*') Nystatin(Mycostatin): It is effective against Candida albicans infection of the
skin, G I tract and vagina. It is isolated from Streptomyces noursei. Its structure, chemistry,
mode of action and resistance resemble those of amphotericin (B) The aglycone portion
of nystatin is called nystatinolide. It consists of lactone ring containing single tetraene
and diene moieties separated by two methylene group.
(ii) Natamycin(Pimaricin): It is polyene antibiotic, obtained from cultures of S.
natalensis. It consists of 26 member lactone ring containing tetraene chromophore, an
?,?-unsaturated lactone carbonyl group, three hydroxyl groups, a carbonyl group, a
trans epoxide and a glycosidically joined mycosamine.
It causes both potassium leakage and cell lyses at the same concentration. This is
unlike to amphoteracin B which shows potassium loss at fungistatic concentration and
cell lyses at fungicidal concentration. The drug is supplied as a 5% ophthalmic suspension
intended for the treatment of fungal conjunctivitis, blepharitis and keratitis.
(C) Imidazoles
(i) Miconazole nitrate(Monistat-Derm).It is a broad spectrum, effective against
dermatophytes, C an d id a species and vaginal infections caused by Trichophyton
232 □ □ Drug Inspector Exam
glabrata. Its mechanism of action, anti fungal spectrum and metabolism are same
as ketoconazole.
(ii) Econazole nitrate(Spectrazole). It is the deschloro derivative of miconazole. Its
actions are like miconazole.
(iii) Clotrimazole(Lotrimin).It is used primarily as topical agent, effective against
dermatophytic infections, cutaneous candidiasis, vulvovaginal candidiasis.
(iv) Other imidazoles
Sulconazole nitrate (Exelderm), Oxiconazole (oxistat), Tioconazole, etc are other
imidazbles, used for the treatment of superficial infection
(D) Triazoles
Terconazole (Terazol). It is a ketal triazole with mechanism of action similar to
imidazoles. It is used for vaginal candidiasis.
(E) Tolnaftate (Tinactin)
It is a thioester of ?-naphthol and fungicidal against dermatophytes, Microsporum
and Epidermophytes species that is responsible for tinea infections.
(F) Phenols and their derivatives
Clioquinol and haloprogin are phenolic derivatives, still used as antifungal drugs
for superficial mycoses. Ciclopirox olamine is not a phenol but has properties like those
of phenols is a good antifungal drug. All of these agents appear to interfere with cell
membrane integrity.
Haloprogin (Halotrex).It is used as a 1% cream for the treatment of superficial tinea
infections.
Clioquinol (Vioform). It is light sensitive yellowish white powder that is insoluble
in water. It has been used as a powder for many skin conditions, such as atopic dermatitis,
eczema, psoriasis and impetigo. A 3% ointment or cream has been used for trichomonas
vaginalis vaginatis.
Ciclopirox olamine (leprox). It is a broad spectrum anti fungal drug, for topical use.
It is a drug of choice in the cutaneous candidiasis, tinea corporis, tinea pedis, etc.
(G) Acids and their derivatives
Benzoic acid, salicylic acid, propionic acid, zinc propionate, sodium caprylate,
undecylenic acid, triacetin are either acids or their derivatives which show anti fungal
activity. These are useful for the treatment of superficial mycoses.
ANTINEOPLASTIC AGENTS
Antineoplastics drugs are the drugs that prevent or inhibit the maturation and
proliferation of neoplasms. Antineoplastic agents travel the body and destroy cancer
cells. Man}> of the side effects associated with antineoplastic agents occur because
treatment destroys the body's normal cells in addition to cancerous cells.
General Toxicities of Antineoplastic / Anticancer Drugs are:
(/) Bone marrow depression
Chemotherapeutic Agents □ □ 233
(ii) Lymphocytopenia
(iii) GIT Stomatitis
(iv) Diarrhoea
(i>) Nausea and Vomiting
(xfi) Alopecia
(vii) Hyperuricaemia
(viii) Hair loss.
Classification of Antineoplastic Agents / Anticancer Drugs
1. Alkylating Agents
• Nitrogen mustards: Melphalan, Cyclophosphamide, Ifosfamide
• Nitrosoureas
• Alkylsulfonates
• Ethyleneimines
• Triazene
• Methyl Hydrazines
• Platinum Coordination complexes: Cisplatin, Carboplatin, Oxaliplatin
2. Antimetabolites
• Folate Antagonists: Methotrexate
• Purine antagonists :6-mercaptopurine
• Pyrimidine antagonists: 5-Fluorouracil, Cytarabine
3. Natural Products
(a) Plant Products
• Vinca Alkaloids: Vincristine, Vinblastine
• Taxanes: Paclitaxel, Docetaxel
• Epipodophyllotoxins: Etoposide
• Camptothecins: Irinotecan
(b) Microorganism Products
• Antibiotics: Doxorubicin, Bleomycin
• Enzymes: L-Asparaginase
Miscellaneous
• Hydroxyurea, Imatinib Mesylate, Rituximab, Epirubicin, Bortezomib, Geftinib,
Leucovorin, Pamidronate, Gemcitabine
1. All of the following antiviral drugs are 6. Tick the drug, inhibiting viral reverse
the analogs of nucleosides, EXCEPT: transcriptase:
(a) Acyclovir (a) Zidovudine
(b) Zidovudine (b) Vidarabine
(c) Saquinavir (c) Rimantadine
(d) Didanozine (d) Gancyclovir
2. Tick the drug, a derivative of 7. Tick the drug, inhibiting viral
adamantane: proteases:
(a) Didanozine (a) Rimantadine
(b) Rimantadine (b) Acyclovir
(c) Gancyclovir (c) Saquinavir
(d) Foscamet (d) Zalcitabine
3. Tick the drug, a derivative of 8. Tick the drug of choice for herpes and
pyrophosphate: cytomegalovirus infection treatment:
(a) Foscamet (a) Saquinavir
(b) Zidovudine (b) Interferon alfa
(c) Vidarabine (c) Didanozine
(d) Acyclovir (d) Acyclovir
4. Tick the drug, inhibiting viral DNA 9. Tick the drug which belongs to
synthesis: nonnucleoside reverse transcriptase
(a) Interferon inhibitors:
(b) Saquinavir (a) Zidovudine
(c) Amantadine (b) Vidarabine
(d) Acyclovir (c) Nevirapine
5. Tick the drug, inhibiting uncoating of (d) Gancyclovir
the viral RNA: 10. All of the following antiviral drugs
(a) Vidarabine are antiretroviral agents, EXCEPT:
(b) Rimantadine (a) Acyclovir
-(c) Acyclovir (b) Zidovudine
(d) Didanozine (c) Zalcitabine
(d) Didanozine
Chemotherapeutic Agents □ □ 235
45. Tick the drug belonging to 49. Which of the following statements is
gonadotropin-releasing hormone true regarding the properties of
agonists: benzylpenicillin?
(a) Leuprolide (a) It is a bacteriostatic agent.
(b) Tamoxifen (b) It is active over a wide range of
(c) Flutamide bacterial species.
(d) Anastrozole (c) It is resistant to 6-lactamases.
46. Which of the following statements is (d) Certain individuals may have an
false? allergic response to it.
(a) A bacterial cell is prokaryotic 50. What essential feature of a penicillin
whereas an animal cell is is involved in its mechanism of action?
eukaryotic. (a) Carboxylic acid
(b) A bacterial cell has a cell wall (b) p-lactam ring
whereas an animal cell does not. (c) Acyl side chain
(c) Bacterial and animal cells both (d) Thiazolidine ring
have a well defined nucleus.
51. What type of reaction is catalysed by
(d) Bacteria may contain enzymes that a 13-lactamase enzyme?
are not present in animal cells.
(?) The final cross-linking reaction to
47. Which of the following is the general form the bacterial cell wall.
mechanism of action for (b) The hydrolysis of the acyl side
erythromycin? chain from penicillin structures.
(a) Inhibition of a metabolic enzyme. (c) The hydrolysis of the four-
(b) Inhibition of cell wall synthesis. membered ring present in
(c) Disruption of protein synthesis. penicillins.
(d) Inhibition of nucleic acid (d) The biosynthesis of the penicillin
transcription and replication. structure from the amino acids
48. Below given is the general structure valine and cysteine.
is representative of sulfonamides. 52. The following structure (methicillin)
was an important penicillin that was
introduced in the 1960s to counter the
R !HN---- ^ V - S=G threat of penicillin-resistant strains of
^ —& H ER 2 S. aureus.
Which of the following statements is
true for active sulfonamides?
(a) R1 can be H or an alkyl group
(b) R2 must be hydrogen
(c) The aromatic ring is essential
(d) The sulfonamide functional group
can be replaced with an ester
Chemotherapeutic Agents □ □ 239
59. Which of the following antibiotics is 63. Which of the following statements is
responsible for Gray Baby Syndrome? true regarding the following structure
(a) Chloramphenicol (nevirapine)?
(b) Doxycycline
(c) Erythromycin
(d) Streptomycin
60. The following structure is a synthetic
antibacterial agent.
O
Quinoline rii
Decahydroisoquinoline ring
Quinoline i
Decahydroisoquinoline ring
Into which binding subsite of the protease enzyme's active site does the quinoline
ring system fit?
(a) SI (b)S2
(c) S3 (d)S4
70. The following structure (ritonavir) is a protease inhibitor.
thiazoly! ring thiazolyl ring
Ph
What feature of the protease enzyme was the inspiration for the design of this
particular structure?
(a) The presence of a flap region over the active site.
(b) The presence of isoleucine residues in the flap region.
(c) The presence of aspartyl groups in the active site.
(d) The symmetrical nature of the active site.
71. Which of the following protease inhibitors was developed by a hybridisation
strategy?
(a) Ritonavir (b) Indinavir
(c) Saquinavir (d) Amprenavir
72. The following protease inhibitor (palinavir) illustrates an extension strategy
involving the group shown in blue.
Chemotherapeutic Agents □ □ 243
f OH
VA
CQ f OH
HO glycoprotein (lipid) HO
O AcHN
•T'O “'OH
+ Glycoprotein or
glycoplipid
AcHN
HO HO
Sialic acid
tricyclic system
Tetracyclic system
OH
OAc
Pyrimidine ring
Me
The piperazine ring has an important interaction with an amino acid in the binding
site. Which amino acid is involved?
(a) Aspartic acid (b) Glutamic acid
(c) Methionine (d) Leucine
248 □ □ Drug Inspector Ejxam
Hydroxamic acid
Hydroxymetl"
What is the name of the structure? to an enzyme, such that the enzyme
(a) Thalidomide activates a prodrug?
(b) Fumagillin (a) ADAPT (b) GDAPT
(c) Depsipeptide (c) ADEPT (d) GDEP
(d) Aclarubicin 91. A patient has been taking anti-
90. What sort of therapy involves tuberculous therapy for MDR-TB. His
administration of an antibody linked drugs regimen contains 6 drugs. The
Chemotherapeutic Agents □ □ 249
ANSWERS
1. (c) 2. (b) .3- (a) 4. (d) 5. (b) 6. (a) 7. (c) 8. (d) 9. (c) 10. (a)
11. (b) 12. (b) 13. (c) 14. (a) 15. (a) 16. (b) 17. (a) 18. (b) 19. (d) 20. (b)
21. (d) 22. (c) 23. (a) 24. (c) 25. (b) 26. (b) 27. .(d) 28. (b) 29. (b) 30. (a)
31. (b) 32. (b) 33. (b) 34. (c) 35. (d) 36. (a) 37. (b) 38. (b) 39. (a) 40. (b)
41. (d) 42. (b) 43. (a) 44. (b) 45. (a) 46. (c) 47. (c) 48. (c) 49. (d) 50. (b)
51. (c) 52. (a) 53. (c) 54. (c) 55. (c) 56. (a) 57. (b) 58. (b) 59. (a) 60. (c)
61. (a) 62. (b) 63. (b) 64. (b) 65. (b) 66. (b) 67. (b) 68. (a) 69. (c) 70. (d)
71. (b) 72. (b) 73. (d) 74. (d) 75. (d) 76. (c) 77. (a) 78. (c) 79. (b) 80. (d)
81. (b) 82. (b) 83. (c) 84. (a) 85. (a) 86. (c) 87. (b) 88. (b) 89. (cj 90. (c)
91. (d) 92. (b) 93. (e) 94. (a) 95. (c) 96. (d) 97. (c) 98. (a) 99. (d) 100. (a)
101. (d) 102. (c) 103. (c) 104. (b) 105. (d) 106. (a) 107. (c) 108. (d) 109. (a) 110.(d)
111. (d) 112. (b) 113. (c) 114. (d) 115. (a)
cm
Antiprotozal and Anthelmintic Drugs
26
C h a p te r
This group of antiprotozoal drugs includes the drugs effective against plasmodia,
entameoba, giradia, trichomonas and leishmania species etc. These can be classified as:
antimalarial drugs, antiamoebics, drugs for trichomoniasis, giardiasis, leishmaniasis,
antimonials, etc.
ANTIMALARIAL DRUGS
Anti-malarial drugs can be classified according to anti malarial activity and structure.
1. According to antimalarial activity:
(a) Tissue schizonticides for causal prophylaxis: These drugs act on the primary
tissue forms of the plasmodia which after growth within the liver, initiate the
erythrocytic stage. By blocking this stage, further development of the infection
can be theoretically prevented. Pyrimethamine and Primaquine have this activity.
(b) Tissue schizonticides for preventing relapse: These drugs act on the hypnozoites
of P. vivax and P. ovale in the liver that cause relapse of symptoms on reactivation.
Primaquine is the prototype drug; pyrimethamine also has such activity.
(c) Blood schizonticides: These drugs act on the erythrocytic forms of the parasite
and thereby terminate clinical attacks of malaria. The most important drugs in
anti malarial chemotherapy include chloroquine, quinine, mefloquine,
halofantrine, pyrimethamine, sulfadoxine, sulfones, tetracyclines etc.
(d) Gametocytocides: These drugs destroy the sexual forms of the parasite in the
blood and thereby prevent transmission of the infection to the mosquito.
Chloroquine and quinine have gametocytocidal activity against P. vivax and P.
malariae, but not against P. falciparum. Primaquine has gametocytocidal activity
against all plasmodia, including P. falciparum.
(e) Sporontocides: These drugs prevent the development of oocysts in the mosquito
and thus ablate the transmission. Primaquine and chloroguanide have this action.
2. According to the Structure:
(a) Aryl amino alcohols: Quinine, quinidine (cinchona alkaloids), mefloquine,
halofantrine.
(b) 4-aminoquinolines: Chloroquine, amodiaquine.
(c) Folate synthesis inhibitors: Type 1 - competitive inhibitors of dihydropteroate
synthase - sulphones, sulphonamides Type 2 - inhibit dihydrofolate reductase -
Antiprotozal and Anthelmintic Drugs CIO 253
Classification
(a) Antimonials
(a) Sodium stibogluconate
(b) Meglumine antimonate
(b) Diamidine
(a) Pentamidine
(c) Miscellaneous
(a) Amphotericin B
(b) Ketoconazole
(c) Miltefosine
(d) Paromomycin sulfate
(e) Allopurinol
Antimonials: Sodium stibogluconate and meglumine antimonate are the pentavalent
antimonial compounds containing l/3rd antimony by weight.
Pentamidine: It is an aromatic diamidine derivative effective against Leishmania,
Pneumocystis and Trypanosoma. It is only available as parenteral preparation.
Others
Paromomycin sulfate: It is an aminoglycoside antibiotic, now the drug of choice for
Kala-Azar. It is not significantly absorbed from the GI tract. The amount absorbed is
excreted by glomerular Alteration.
Miltefosine: It is an alkylphosphocholine analog that has been approved by the
FDA for the treatment of Leishmaniasis. It is given in a dose of 2.5 mg/kg for 28 days
orally and has produced excellent results. Vomiting, diarrhea, elevation of liver enzymes
is the main side effects. The drug is teratogenic and should be cautiously used during
pregnancy
Antiprotozal and Anthelmintic Drugs □ □ 257
1. Tick the drug used for malaria 7. Tick the antimalarial drug belonging
chemoprophylaxis and treatment: to 8-aminoquinoline derivatives:
(a) Chloroquine (a) Doxycycline
(b) Quinidine (b) Quinidine
(c) Quinine (c) Primaquine
(d) Sulfonamides (d) Chloroquine
2. Tick the drug used for amoebiasis 8. All of the following antimalarial drugs
treatment: are 4-quinoline derivatives, EXCEPT:
(a) Nitrofurantoin (a) Chloroquine
(b) Iodoquinol (b) Mefloquine
(c) Pyrazinamide (c) Primaquine
(d) Mefloquine (d) Amodiaquine
3. Tick the drug used for trichomoniasis 9. Tick the antimalarial drug belonging
treatment: to pyrimidine derivatives:
(a) Metronidazole (a) Mefloquine
(b) Suramin (b) Pyrimethamine
(c) Pyrimethamine (c) Quinidine
(d) Tetracycline (d) Chloroquine
4. Tick the drug used for toxoplasmosis 10. Tick the drug used for trypanosomosis
treatment: treatment:
(a) Chloroquine (a) Melarsoprol
(b) Tetracyclin (b) Metronidazole
(c) Suramin (c) Tetracycline
(d) Pyrimethamine (d) Quinidine
5. Tick the drug used for balantidiasis 11. Tick the antimalarial drug having a
treatment:: gametocidal effect:
(a) Azitromycin (a) Mefloquine
(b) Tetracycline (b) Primaquine
(c) Quinine (c) Doxycycline
(d) Trimethoprim (d) Sulfonamides
6. Tick the drug used for leishmaniasis 12. All of the following antimalarial drugs
treat .lent: influence blood schizonts, EXCEPT:
(a) Pyrimethamine (a) Mefloquine
(b) Albendazole (b) Chloroquine
(c) Sodium stibogluconate (c) Primaquine
(d) Tinidazole (d) Quinidine
258 □ □ Drug Inspector Exam
ANSWERS
1. (a) 2. (b) 3. (a) 4. (d) 5. (b) 6. (c) 7. (c) 8. (c) 9. (b) 10. (a)
11. (b) 12. (c) 13. (d) 14. (b) 15. (b) 16. (a) 17. (c) 18. (d) 19. (b) 20. (c)
21. (d) 22. (c) 23. (b) 24. (d) 25. (c) 26. (a) 27. (a) 28. (d) 29. (b) 3 0 .(a)
31. (b) 32. (c) 33. (b) 34. (d) 35. (b) 36. (a)
non
Drugs and Cosmetic Act; 1940
27
C h a pter
The object of the Act is to regulate the import, manufacture, distribution and sale
of drugs. Under the provisions of this Act, the Central Government appoints the Drugs
Technical Advisory Board to advise the Central Government and the State Governments
on technical matters arising out of the administration of this Act. The board can constitute
subcommittees for the consideration of a particular matter.
Drug
The definition of 'drugs' is an inclusive one. It includes all medicines for external
or internal use of human beings or animals or any substances itended to be used for or
in the diagnosis, treatment, mitigation or prevention of diseases in human beings or
animals.
The Drugs Technical Advisory Board.
The Central Government shall, as soon as may be, constitute a Board (to be called
the Drugs Technical Advisory Board) to advise the Central Government and the State
Governments on technical matters arising out of the administration of this Act and to
carry out the other functions assigned to it by this Act. The Board shall consist of the
following members, namely,
(i) The Director General of Health Services, ex officio, who shall be Chairman;
(ii) The Drugs Controller, India ex officio;
(iii) The Director of the Central Drugs Laboratory, Calcutta, ex-officio-,
(iv) The Director of the Central Research Institute, Kasauli, ex-officio;
(v) The Director of the Indian Veterinary Research Institute, Izatnagar, ex-officio;
(vi) The President of the Medical Council of India, ex-officio;
(vii) The President of the Pharmacy Council of India, ex-officio;
(viii) The Director of the Central Drug Research Institute, Lucknow, ex-officio;
(ix) Two persons to be nominated by the Central Government from among persons
who are in charge of drugs control in the States ;
(x) One person, to be elected by the Executive Committee of the Pharmacy Council
of India, from among teachers in pharmacy or pharmaceutical chemistry or
pharmacognosy on the staff of an Indian university or a college affiliated thereto;
(xi) One person, to be elected by the Executive Committee of the Medical' Council
of India, from among teachers in medicine or therapeutics on the staff of an
Indian university or a college affiliated thereto ;
262 □ □ Drug Inspector Exam
(xii) One person to be nominated by the Central Government from the pharmaceutical
industry
(xiii) One pharrmacologist to be elected by the Governing Body of the Indian Council
of Medical Research ;
(xiv) One person to be elected by the Central Council of the Indian Medical Association;
(xv) One person to be elected by the Council of the Indian Pharmaceutical Association;
(xvi) Two persons holding the appointment of Government Analyst under this Act,
to be nominated by the Central Government.
The nominated and elected members of the Board shall hold office for three years,
but shall be eligible for re-nomination and re-election
The Drugs Consultative Committee
(1) The Central Government may constitute an advisory committee to be called
"the Drugs Consultative Committee" to advise the Central Government, the
State Governments and the Drugs Technical Advisory Board on any matter
tending to secure uniformity throughout [(Note: Ins. by Act 3 of 1951, sec.3 and
Sch., for "the States") India] in the administration of this Act.
(2) The Drugs Consultative Committee shall consist of two representatives of the
Central Government to be nominated by that Government and one representative
of each State
(3) The Drugs Consultative Committee shall meet when required to do so by the
Central Government and shall have power to regulate its own procedure.
Sections 5 and 7 not to apply to Ayurvedic, Siddha or Unani drugs
Nothing contained in sections 5 and 7 shall apply to [(Note: Subs, by Act 68 of 1982,
sec.2, for certain words (w.e.f. 1-2-1983)). Ayurvedic, Siddha or Unani] drugs.
Standards of quality
[(l)(Note: Subs. Act 21 of 1962, sec. 2, for sub-section (1) (w.e.f. 27-7-1964)) For the
purposes of this Chapter, the expression "standard quality" means -
(a) In relation to a drug, that the drug complies with the standard set out in [(Note:
Subs, by Act 13 of 1964, sec.7, for "the Schedule" (w.e.f. 15-9-1964)) the Second
Schedule], and
((b) In relation to a cosmetic, that the cosmetic complies with such standard as may
be prescribed.]
(2) The Central Government, after consultation with the Board and after giving by
notification in the Official Gazette not less than three months' notice of its intention so
to do, may be a like notification add to or otherwise amend [(Note: Subs, by Act 13 of
1964, sec.7, for "the Schedule" (w.e.f. 15-9-1964)) the Second Schedule], for the purposes
of this Chapter, and thereupon [ (Note: Subs, by Act 13 of 1964, sec.7, for "the Schedule"
(w.e.f. 15-9-1964))the Second Schedule] shall be deemed to be amended accordingly/
Drugs and Cosmetics Act, 1940 □ □ 263
Misbranded Drugs
For the purposes of this Chapter, a drug shall be deemed to be misbranded, -
(a) If it is so coloured, coated, powdered or polished that damage is concealed or
if it is made to appear of better or greater therapeutic value than it really is ; or
(b) If it is not labeled in the prescribed manner ; or
(c) If its label or contained or anything accompanying the drug bears any statement,
design or device which is false or misleading in any particular.]
Adulterated Drugs
For the purposes of this Chapter, a drug shall be deemed to be adulterated, -
(a) If it consists, in whole or in part, of any filthy, putrid or decomposed substance
; or
(b) If it has been prepared, packed or stored under insanitary conditions whereby
it may have been contaminated with filth or whereby it may have been rendered
injurious to health ; or
(c) If its contained is composed in whole or in part, of any poisonous or deleterious
substance which may render the contents injurious to health; or
(d) If it bears or contains, for purposes of colouring only, a colour other than one
which is prescribed ; or
(e) If it contains any harmful or toxic substance which may render it injurious to
health; or
(f) If any substance has been mixed therewith so as to reduce its quality or strength.
Spurious Drugs
For the purposes of this Chapter, a drug shall be deemed to be spurious, -
(a) If it is imported under a name which belongs to another drug ; or
(b) If it is an imitation of, or is a substitute for, another drug or resembles another
drug in a manner likely to deceive or bears upon it or upon its label or contained
the name of another drug unless it is plainly and conspicuously marked so as
to reveal its true character and its lack of identity with such other drug ; or
(c) If the label or container bears the name of an individual or company purporting
to be the manufacturer of the drug, which individual or company is fictitious or
does not exist ; or
(d) If it has been substituted wholly or in part by another drug or substance ; or
(e) If it purports to be the product of a manufacturer of whom it is only truly a
product.
Misbranded Cosmetics
For the purposes of this Chapter, a cosmetic shall be deemed to be misbranded -
(a) If it contains a colour which is not prescribed ; or
(b) If it is not labeled in the prescribed manner ; or
264 □ □ Drug Inspector Exam
((c) If the label or container or anything accompanying the cosmetic bears any
statement, which is false or misleading in any particular.
Spurious Cosmetics
For the purposes of this Chapter, a cosmetic shall be deemed to be spurious,-
(a) If it is imported under a name which belongs to another cosmetic ; or
(b) If it is an imitation of, or is a substitute for, another cosmetic or resembles
another cosmetic in a manner likely to deceive or bears upon it or upon its label
or container the name of another cosmetic, unless it is plainly and conspicuously
marked so as to reveal its true character and its lack of identity with such other
cosmetic ; or
(c) If the label or container bears the name of an individual or a company purporting
to be the manufacturer of the cosmetic which individual or company is fictitious
or does not exist ; or
(d) If it purports to be the product of a manufacturer of whom it is.
Inspectors
(1) The Central Government or a State Government may, by notification in the
Official Gazette, appoint such persons as it thinks fit, having the prescribed
qualifications, to be Inspectors for such areas as may be assigned to them by the
Central Government or the State Government, as the case may be.
(2) The powers which may be exercised by an Inspector and the duties which may
be performed by him, the drugs or [(Note: Subs, by Act 21 of 1962, sec.17 for
"class of drugs" (w.e.f. 27-7-1964)) classes of drugs or cosmetics or classes of
cosmetics] in relation to which and the conditions, limitations or restrictions
subject to which, such powers and duties may be exercised or performed shall
be such as may be prescribed.
(3) No person who has any financial interest [(Note: Subs, by Act 21 of 1962, sec.17,
for "in the manufacture, import or sale of drugs" (w.e.f. 27-7-1964)) in the import,
manufacture or sale of drugs or cosmetics] shall be appointed to be an Inspector
under this section.
(4) Every Inspector shall be deemed to be a public servant within the meaning of
21 of the Indian Penal Code, and shall be officially subordinate to such authority.
[(Note: Ins. by Act 68 of 1982, sec.18 (w.e.f. 1-2-1983)), having the prescribed
qualifications,] as the Government appointing him may specify in this behalf.]
Qualification for Drug Inspector. Qualifications for drug inspector are:
(z) Degree in Pharmacy
(ii) Degree in medicine with one year post graduate training under a Government
analyst or a chemical examiner.
Drugs and Cosmetics Act, 1940 □ □ 265
Powers of Inspectors
(1) Subject to the provisions of sec 23 and of any rules made by the Central
Government in this behalf, an Inspector may, within the local limits of the area for
which he is appointed, -
(a) [(Note: Subs, by Act 68 of 1982, sec.19, for clauses (a), ((b) and ((c) (w.e.f. 1-2-
1983)). inspect, —
(/) Any premises wherein any drug or cosmetic is being manufactured and the
means employed for stand arising and testing the drug or cosmetic ;
(ii) Any premises wherein any drug or cosmetic is being sold, or stocked or exhibited
or offered for sale, or distributed ;
(b) Take samples of any drug or cosmetic, -
(z) Which is being manufactured or being sold or is stocked or exhibited or offered
for sale, or is being distributed ;
(ii) From any person who is in the course of conveying, delivering or preparing to
deliver such drug or cosmetic to a purchaser or a consignee ;
(c) At all reasonable times, with such assistance, if any, as he considers necessary,
(0 Search any person, who, he has reason to believe, has secreted about his person,
any drug or cosmetic in respect of which an offence under this Chapter has
been, or is being, committed ; or
(ii) Enter and search any place in which he has reason to believe that an offence
under this Chapter has been, or is being, committed ; or
(iii) Stop and search any vehicle, vessel or other conveyance which, he has reason
to believe, is being used for carrying any drug or cosmetic in respect of which
an offence under this Chapter has been, or is being, committed, and order in
writing the person in possession of the drug or cosmetic in respect of which the
offence has been, or is being, committed, not to dispose of any stock of such
drug or cosmetic for a specified period not exceeding twenty days, or, unless the
alleged offence is such that the defect may be removed by the possessor of the
drug or cosmetic, seize the stock of such drug or cosmetic and any substance or
article by means of which the offence has been, or is being committed or which
may be employed for the commission of such offence ;
[(cc) (Note: Ins. by Act 35 of 1960, sec.5 (w.e.f. 16-3-1961)) examine any record,
register, document or any other material object found [(Note: Subs, by Act 68 of 1982,
sec.19, for certain words (w.e.f. 1-2-1983)) with any person, or in any place, vehicle,
vessel or other conveyance referred to in clause ((c)], and seize the same if he has reason
to believe that it may furnish evidence of the commission of an offence punishable
under this Act or the rules made thereunder ;]
[(cca) (Note: Ins. by Act 68 of 1982, sec.19 (w.e.f. 1-2-1983)) Require any person to
produce any record, register, or other document relating to the manufacture for sale or
for distribution, stocking, exhibition for sale, offer for sale or distribution of any drug
266 □ □ Drug Inspector Exam
or cosmetic in respect of which he has reason to believe that an offence under this
Chapter has been, or is being, or is being, committed ;]
(d) Exercise such other powers as may be necessary for carrying out the purposes
of this Chapter or any rules made there under.
(2) The provisions of [(Note: Subs, by Act 68 of 1982, sec.19, for "the Code of
Criminal Procedure, 1898" (w.e.f. 1-2-1983)) the Code of Criminal Procedure, 1973] shall,
so far as may be, apply to any search or seizure under this Chapter as they apply to any
search or seizure made under the authority of a warrant issued under [(Note: Subs, by
Act 68 of 1982, sec.19, for "section 98" (w.e.f. 1-2-1983)) section 94] of the said Code.
[(2A) (Note: Ins. by Act 68 of 1982, sec.19 (w.e.f. 1-2-1983)) Every record, register or
other document seized under clause (cc) or produced under clause (cca) shall be returned
to the person, from whom they were seized or who produce the same, within a period
of twenty days of the date of such seizure or production, as the case may be, after copies
thereof or extracts therefrom certified by that person, in such manner as may be
prescribed, have been taken.]
(3) If any person willfully obstructs an Inspector in the exercise of the powers
conferred upon him by or under this Chapter [(Note: Ins. by Act 68 of 1982, sec.19
(w.e.f. 1-2-1983) or refuses to produce any record, register or other document when so
required under clause (cca) of sub-section (1),] he shall be punishable with imprisonment
which may extend to three years, or with fine, or with both.]
Persons bound to disclose place where drugs or cosmetics are manufactured or
kept. - Every person for the time being in charge of any premises whereon any drug
[(Note: Ins. by Act 21 of 1962, sec. 15 (w.e.f. 27-7-1964)) or cosmetic] is being manufactured
or is kept for sale or distribution shall, on being required by any Inspector so to do, be
legally bound to disclose to the Inspector the place where the drug [(Note: Ins. by Act
21 of 1962, sec. 15 (w.e.f. 27-7-1964)) or cosmetic] is being manufactured or is kept, as the
case may be.
Reports of Government Analysts
(1) The Government Analyst to whom a sample of any drug [(Note: Ins. by Act 21
of 1962, sec. 15 (w.e.f. 27-7-1964)) or cosmetic] has been submitted for test or analysis
under sub-section (4) of section 23, shall deliver to the Inspector submitting it is signed
report in triplicate in the prescribed form.
(2) The Inspector on receipt thereof shall deliver one copy of the report to the person
from whom the sample was taken [(Note: Subs, by Act 13 of 1964, sec. 17, for certain
words (w.e.f. 15-9-1964)) and another copy to the person, if any, whose name, address
and other particulars have been disclosed under section 18A], and shall retain the third
copy for use in any prosecution in respect of the sample.
(3) Any document purporting to be a report signed by a Government Analyst under
this Chapter shall be evidence of the facts stated therein, and such evidence shall be
conclusive unless the person from whom the sample was taken [(Note: Subs, by Act 13
of 1964, sec.17, for "or the said warrantor" (w.e.f. 15-9-1964)) or the person whose name,
Drugs and Cosmetics Act, 1940 □ □ 267
address and other particulars have been disclosed under section 18A] has, within twenty-
eight days of the receipt of a copy of the report, notified in writing the Inspector or the
Court before which any proceedings in respect of the sample are pending that he
intends to adduce evidence in contravention of the report.
(4) Unless the sample has already been tested or analysed in the Central Drugs
Laboratory, where a person has under sub-section (3) notified his intention of
adducing evidence in contravention of a Government Analyst's report, the Court
may, of its own motion or in its discretion at the request either of the complainant
or the accused cause the sample of the drug [(Note: Ins. by Act 21 of 1962, sec.15
(w.e.f. 27-7-1964)) or cosmetic] produced before the Magistrate under sub-section (4)
of Section 23 to be sent for test or analysis to the said Laboratory, which shall make
the test or analysis and report in writing signed by, or under the authority of, the
Director of the Central Drugs Laboratory the result thereof, and such report shall be
conclusive evidence of the facts stated therein.
(5) The cost of a test or analysis made by the Central Drugs Laboratory under
sub-section (4) shall be paid by the complainant or accused as the Court shall direct.
ANSWERS
1. (a) 2. (c) 3. (b) 4. (b) 5. (b) 6. (b) 7. (c) 8. (a) 9. (c) 10. (c)
11. (e) 12. (c) 13. (a) 14. (b) 15. (b) 16. (d) 17. (b) 18. (d) 19. (d) 20. (d)
21. (c) 22. (a) 23. (c) 24. (a) 25. (a) 26. (a) 27. (a) 28. (c) 29. (a) 30. (d)
31. (a)
COT
Narcotic Drugs and Psychotropic
Substances Act, 1985
28
C h a pter
DefiniL~-;s
(i) "addict" means a person addicted to any narcotic drug or psychotropic substance;
(ii) "Board" means the Central Board of Excise and Customs constituted under the
Central Boards of Revenue Act, 1963 (54 of 1963),
(iii) "cannabis (hemp)" means -
(a) charas, that is, the separated resin, in whatever form, whether crude or
purified, obtained from the cannabis plant and also includes concentrated
preparation and resin known as hashish oil or liquid hashish;
(b) ganja, that is, the flowering or fruiting tops of the cannabis plant (excluding
the seeds and leaves when not accompanied by the tops), by whatever name
they may be known or designated; and
1. Ins. by Act 2 of 1989, s. 2 (w.e.f. 29.5.1989).
2. This Act came in to force in the whole of India on 14-11-1985: Vide
Notification No. S.O. 821 (E) dated, 14-11-1985, Gazette of India,
Extraordinary, 1985, Part II, sec-3 (ii).
(c) any mixture, with or without any neutral material, of any of the above forms
of cannabis or any drink prepared there from;
iv) "cannabis plant" means any plant of the genus cannabis;
(v) "coca derivative" means -
(a) crude cocaine, that is, any extract of coca leaf which can be used, directly or
indirectly, for the manufacture of cocaine;
(b) ecgonine and all the derivatives of ecgonine from which it can be recovered;
(c) cocaine, that is, methyl ester of benzoyl-ecgonine and its salts; and
(d) all preparations containing more than 0.1 percent, of cocaine;
(vi) "coca leaf" means -
(a) the leaf of the coca plant except a leaf from which all ecgonine, cocaine and
any other ecgonine alkaloids have been removed;
(b) any mixture thereof with or without any neutral material, out does not
include any preparation containing not more than 0.1 per cent, of cocaine;
(vii) "coca plant" means the plant of any species of the genus Frythroxylon;
1* (i)"controlled substance" means any substance which the Central
Government may, having regard to the available information as to its possible
use in the production or manufacture of narcotic drugs or psychotropic substances
270
Narcotic Drugs and Psychotropic Substances Act, 1985 □ □ 271
(xix) "poppy straw concentrate" means the material arising when poppy straw has
entered into a process for the concentration of its alkaloids
(xx) "preparation", in relation to a narcotic drug or psychotropic substance, means
any one or more such drugs or substances in dosage form or any solution or
mixture, in whatever physical state, containing one or more such drugs or
substances;
(xxi) "Prescribed" means prescribed by rules made under this Act;
(xxii) "production" means separation of opium, poppy straw, coca leaves or cannabis
from the plants from which they are obtained;
(xxiii) "Psychotropic substance" means any substance, natural or synthetic, or any
natural material or any salt or preparation of such substance or material included
in the list of psychotropic substances specified in the Schedule;
(xxiv) "to import inter-State" means to bring into a State or Union territory in India
from another State or Union Territory in India;
(xxv) "to import into India", with its grammatical variations and cognate expressions,
means to bring into India from a place outside India and includes the bringing
into any port or airport or place in India of a narcotic drug or a psychotropic
substance intended to be taken out of India without being removed from the
vessel, aircraft, vehicle or any other conveyance in which it is being carried.
Explanation.—For the purposes of this clause and clause (xxvi), "India" includes
the territorial waters of India;
(xxvi) "to export from India", with its grammatical variations and cognate expressions,
means to take out of India to a place outside India;
(xxvii) "to export inter-State" means to take out of a State or Union territory in India
to another State or Union territory in India;
(xxviii) "to transport" means to take from one place to another within the same State
or Union Territory;
(xxviia)"use" in relation to narcotic drugs and psychotropic substances, means any kind
of use except personal consumption;
(xxix) Words and expressions used herein and not defined but defined in the Code of
Criminal Procedure, 1973 (2 of 1973) have the meanings respectively assigned to
them in that Code.
ANSWERS
1. (d) 2. (a) 3. (a) 4. (b) 5. (c ) 6. (b) 7. (c ) 8. (d) 9. (a) 10. (a)
11. (b) 12. (c ) 13. (c) 14. (a) 15. (d). 16. (d) 17. (a) 18. (c ) 19. (a) 2 0 . (b)
21. (b) 22 . (d) 23. (b) 24. (a).
□ □ □
Appendix-/ □ □ 211
719
280 □ □ Drug Inspector Exam
78. Cbtton (Cotton wool. G o ssy p iu m her- 90% o f cellouse Filtering medium,
Purified cotton) baceum , Gossypium surgical dresings
barbadense
(Malvaceae)
79. Silk Bombyx mori Protein (fibroin) Sutures, seives and
(Bombycidae)<> ligatures
Glucose
l^-ATP
Hcxoktnase r
| v~—♦ ADP
Glucose 6-PtwsphMt
Ptiosphoglucose
KonwraM
1
Fructose A-phosphale
Phosphofnicto- l ^ AV>
Unn* f^~*.ADP
FractoM 1. S-tfsphosphato
am oum
!
Trios* phosphate
EnoUse
Phosphomol pyruvate
P^. tr -" *
«"•“ Jp—^ATP
Pyruvate
Flow chart o f Glycolytic pathway.
288 □ □ Drug Inspector Exam
Acetyl CoA
O
ch3 ■ SCoA CoA — SH
Condensation
CH2— COO'
COO
I I
HO — CH C — COO'
| II
C H, CH — COO '
Cis Aconitate
Succinate a-Ketoglutrate
thiokinase dehydrgenase
complex
CH2 — COO
CoASH GTP
(ATP) GDP
(ADP) I W2
Substrate liver + p;
C — SCoA o = C — COO
phosphorylation
Succinyl CoA a-Ketoglutarate
Oxidative
decarboxylation
^Citric Acid Cycle.
Appendix-Ill □ □ 289
Glucose-6-phosphate
Glucose - NADP
2* 2*
6-phosphate Mg or Ca
dehydrogenase
• S * NADPH+H*
6-Phosphogluconoladone
I h 2o
Hydrolase 2+ 2♦ „ 2*
1 Mg , Mn or Ca
6-Phosphogluconate
^ — NADP
6-Phosphogluconate 2+ 2+ _ 2+
dehydrogenase Mg , Mn or Ca
S * NADPH+H*
Ribose-5-phosphate
Enediol S-Keto-6-Phosphogluconate
form Ketoisomerase
P -C O ;
Ribulose 5-phosphate
5-p
I Epimerase
Xylulose 5-phosphate
Transketolase
Ribose-5-phosphate Sedoheotulose-7-phosphate
TPP, Mg
GtycerakJehyde
3-phosphate
Transaldolase
Erythrose Fructose
-4-phosphate -6-phosphate
Transketolase
Xylulose 5-phosphate -► Fructose-6-phosphate
TPP, Mg ^
Glyceraldehyde 3-phosphate
lIb: ‘HjO
2-Phyosphogtycerate Glycerol
Fructose e-phosphate
!
Glucose 6 -phosphate
H,0 - J
Glucose 3-phosphafase
Glucose
ducom ogtnsis.
Appendix-fV D O 291
Appendix
NATIONAL IMMUNISATION SCHEDULE
Beneficiaries Age Vaccine No. o f doses Route o f administration
Infants 6 weeks to 9 months DPT 3 Intramuscular
OPV 3 Orftl
BCG 1 Intradermal
Children 9 -12 months Measles 1 S.C.
16-24 months DPT 1 I.M.
OPV 1 Oral
5-6 years DPT I.M.
Typhoid S.C.
10 years Tetanus toxoid I.M.
Typhoid 1 S.C.
16 years Tetanus toxoid l.M. ;
Typhoid 1 S.C. 1
Pregnant women 16-36 weakes Tetanus toxoid 2 l.M. j
Appendix
FORMULAE USED IN POSOLOGICAL CALCULATION
Young’s Rule. (Age below 12 years) Child’s dose = — ^- ar- _ x Adult dose
, ' Age in years + 12
Dilling’s Rule (Age between 12-20 years) Child’s dose = x Adult dose
Fried’s formula (for infants under 1 year) Child’s dose = x Adult dose
Avoirdupois System
According to this system, the standard unit for weighing is pound and all other measures
of mass are derived from pound, it is represented by lb.
1 lb = 16 oz (Avoir)
1 lb = 7000 grains
1 oz = 7000/16 = 437.5 grains
Apothecaries System
It is known as troy system. The standard weight in this system is grain.
20 grain = 1 scruple
60 grain = 1 drachm
480 grain =1 ounce (Apothe)
8 drachm = 1 ounce (Apothe)
12 ounce (Apothe) = 1 pound (Apothe)
5760 grain = 1 pound (Apothe)
Appendix-VI! □ □ 297
POSOLOGICAL TABLE
CHEMICAL STRUCTURES
(Categorywise)
1. General Anaesthetics
Ultrashort acting barbiturates
CH3
H
OxXN'spP
V Nv SNa
C A -1 N CH2 - CH - CH2 ^ ____NH
CH3 — CH2 — CH2CH n CH3CH2 — C *C - ” C H ||
I 0 I 0
Ctt3 ch 3
Thiopentone sodium Methohexitone
5-Ethyi 5-(1-methylbutyl) 5-AflyH -methyl-5-(1 -methylpent-2-ynyl)
-2 -thiopentone sodium 1 barbituric acid
2. Local Anesthetics
(/') Ester Type (ii) Amide Type
H2N- f V COOC2H5
, ch3
Benzocaine
(Ethyl p-aminobenzoate)
CjHs (• 7 — NH CO CH,N y ° 2Hs
\=/ ^ C j Hj
NH COOCH2CH2N \ c h
2n 5
Lignocaine
Procaine
(2 -Oiethylamino-2 ‘, 6 ’-acetoxylide)
2-(Diethylamino ethyl p-aminobenzoate)
Appendix-VIll □ □ 317
3. Adrenergic Drugs
(/) Catecholamines
HO
H Q - f o - OH — CH2 — NHCH3 0 5
H ,-^ > - CH — C H j — NH,
OH OH
Adrenaline Nor-adrenaline
(1-{3’, 4'-Dihydroxyphenyl (1 -(3',4'-Dihydroxyphenyl)
2-methylamino ethanol) 2-amino ethanol
H O.
H0 O CH C H 2N H C H (C H 3>2
OH
■5oprenalin§
(1 -(3',4'-Dihydroxyphenyt) 2-is6propyiammo eiha«ol)
(/'/') Non Catecholamines
HOCH-j
OH OH CH3
Salbutamol Ephedrine
1-(4'-hydroxy, 3'-hydroxymethy!) (2-methytamino 1-phenyl propan-1-ol)
2-tert butyl amino ethanol
HO HOy _
CH — CH2NHCCH3 CHiNHCiCHJz
OH HO OH
Phenylephrine Terbutaline
(1 -(3’-Dihydroxyphenyl) (2-(Tert butylamino)
2-methyiamino ethanol) 1'(3',5'-dihydroxyphenyl ethanol))
4. Cholinergic Drugs
(/') Ester of Choline
O O
II
(CH3)3 n — c h 2 c h 2 — O — C — CH3 (CH3)3 N — CH2 CH — O — c — CH3
I
Acetylcholine CH 3
Methacholine
((J-Methyl acetylcholine)
(ii) Cholinomimetic alkaloids
c 2h 5
Pilocarpine
(3-Ethyldihydro-4 (1 -methyl-1 H-imidazol-
5yl-methyl)-2(3H)-furanone)
3 18 □ □ Drug Inspector Exam
O n 'O
TolazoKne
(2-Benzyl 2-imidazoline)
(ii) P-blockers
OH
OH
w ^ H s S mino1
6. Anticholinergic Drug
( 0 Solanaccous alkaloids
CHj — CH — CH2 CH2OH C H j— CH — CH2 CH;
/ I I
N — CH3 CH — O — COCH N — CH3 CH — O — CO — CH
I i \==/ \
C H j— CH — CH2 CH2 — CH — CH2
Atropine Hyoscine
CH2 — CH — CH2
Propantheline bromide
■
ce,
c2h5 C -N
II H H
0
Phenobarbitone * Barbiton*
(5-Ethyl-5-phenyl (5,5-Diethyl barbituric add)
barbituric add)
(ii) Non Barbiturates
CH3
0 CH3 — CH CH — CH3
II
0 , 0 . C H ,0 - - P — ONa
° 'C H '°
1 I
OH ch3
Tridofos sodium
Paraldehyde
(2.2,2-Trichloro ethanol dihydrogen
( 2 , 4 , 6-Trimethyl S-Moxane)
phosphate monosodium salt)
8. Anticonvulsant Drugs
(i) Hydantoins (ii) Oxazolidinediones
ch 3,
C ®H s
cshsY
NV,
T r ONe
4 ——N
nw
ch 3-x°y°
y " " N — CHj
^ V O ^ O
ch3-4 r
O? ..... —CHj
Phenytoinsodium Troxidone Paramethadione
(5 ,5-Diphenyl hydantoin) (2,4,4-Trimethyl oxazol (5-Ethyl 3,5-dimethyl
2 , 4-dione) oxazoHcNne 2,4-tSone)
(iii) Succinimides (iv) Miscellaneous
n
II I
*------(-CH3 <W
CjHg CzHg I
CONH2
Ethosuxirrvde Primidone Carbamazepine
(3-Ethyl 3-methyl (5H-Dibenz[b, qazepine
2,5-pyrolidine dione) -5-carboxamide)
320 □ □ Drug Inspector Exam
9. Psychoactive Drugs
(/) Phenothiazine derivatives
/— \
(C H 2)3 - N n -c h 3
I N— '
SN
Cl a
I I
(C H 2)3 - N ( C H 3)2
Chlorpromazine Prochlorperazine
2-chloro1Q[3-dimethylamino) 2-Chloro-10-[3-(4-methyl-1 -
propyl] phenolthiazine piperazinyl) propyl] phenothiazine
(ii) Butyrophenones
OH
COCH2 ch 2 CH2 ■
■ - 0 - ■ o o -
Haloperidol
(4-[4-(p-chlorophenyl)-4-hydroxypiperidino]
-4-fluorobutyro phepone)
(iii) Tricyclic Antidepressants
N
CH2 CH2 CH 2N (CH3)2 CH CH 2 C H 2N (CH3)2
Imipramine Amitriptyline
10,11-Dihydro M,N-dimethyl 3 -{ 1 0 ,11-Dihydro 5H dibenz
-5H-dibenz [b, f] azepine -5-propanolamine [a, d] cycloheptene-5-ylidene)
N'.N-dimethyl propylamine HCI.
(*v) MAO inhibitors
NH,
a ch 2 c h 2n h nh 2 H2 S0 4
Phenelzine
(P-Phenethylhydrazine) Tranylcypromine
(Trans-2-Phenylcyclopropanamine)
(v) Antianxiety Drugs
NHCH,
-> 0
Chlordiazepoxide
(7-Chloro-2-(methylamino)-5-phenyl-
3H-1, 4-benzodiazepine-4-oxide)
Appendix-VIII □ □ 321
o K
CH3
K J Cr N
Nikethamide
CHa
Amphetamine
(N,N-Diethylnicotinamide) (1-Methyl phenylethyl amine)
Caffeine
( 1 , 3,7-Trimethylxanthine)
11. Opoid Analgesics
( 0 Naturally occurring opoid analgesics
Morphine
(ii) Synthetic opoid analgesics
C8h 5 c o o c 2h 5 Cr6n
H5 N(CH3)2
N
CH3CH2CO — C — CH2 _ CH — CH3
I
CH3
C6H5
Pethidine
(Ethyl 1-methyl 4-phenyl Methadone
piperidine 4-carboxylate)
(6-Dimethylamino-4, 4-diphenyl 3-heptanone)
(CH2)2 - C 6H5
C gH s^ — O — CH2CH3
C- . HCl
CbH5CH2/ ^ CH — CH3
I
CH2
I
NfCH^
Dextroproxyphene hydrochloride
(4-Dimethylamino-1, 2-diphenyl 3-methyl
2-butanol propionate)
(iii) Narcotic antagonist
Nalorphine
322 DO Drug Inspector Exam
COOH COOH
ococh3 o -co
Mefenamic acid
2-(2,3-dimethyl phenyl amino) benzoic acid
(iii) Indole acetic acid
c h 2c o o h
■ " O p : ch3
CO
Cl
Indonriethacin
(1 -p-chtorobenzoyO-5-methoxy
2-mefhyl indole-3-aceiic acid)
(iv) Arylpropionic acid derivatives
CH 3 ch ,
ch .
I
^ ch- ch. Y V CHCOOH CHCOOH
ch3/ \=/ CH3 ° - 4 ^ A ^ J
Ibu profen
(2(p-lsobulylphenyl) propionic acid) Naproxen
(li-(6-m ethoxy napthyl)-2-propionic acid)
(v) PyrazoJe derivatives
OH
c6hs
O. ,L
"n — <6h 5
- c
J ___ J = o X - i o 0""5
CH3 — CH j — CH2 — CH j ch3— ch2— ch2— ch2
Phenylbutazone Oxyphenbutazone
(1,2-OiphenyMn-butyl>3,S-pyrazoiidine dione) (1 p-HydroxyphenyK-phenyMi1
bu!yl*3.5-pyrazo!kiine t ! ;
Appendix-VIH OO 323
13. Antihistamines
(/') Aminoalkylethers (ii) Ethylenediamines
ch 3
■CH,
Mepyramine malsate
(2'-[(2-Dimethylaminoethyl)(p-niethoxy benzyl)
amono] pyridine)
(iii) Alkylamincs (iv) Phenothiazines
CHa
ci I •
O x ,CH— C H j c h 2 n ;
CH,
- O s c h — CH 2'CH 2 n;
.CH, CH* CH — N(CH3)2
'C H , 'C H ,
(v) Miscellaneous
ch 3
Cyprophetadine
(1-m ethyl-4-(5H-dibenz (a.d) cycio-heptenylidine) piperidine)
14. Cardiovascular Drugs
(/) Cardiac tonics
o
324 □ □ Drug Inspector Exam
/ -----v . c 2 h5 (ch 3 ) 2 c h x
W, * o
N H 2 —\ O V " CONH CH, CH2< .NCH2 CH2 — C — C — NH2
W c 2 hs (CH3 )2 C H / I h3 po4
Procainamide
(4-Amino N-[2 -(diethylamino) ethyl] I I I
benzamide)
Disopyramide Phosphate
g (4-(di-isopropyiamino)-2-phenyl
* ^ 2 -(2 '-pyridyl) carbamate phosphate)
N N
II |^
1
OH
°H ( CH
c h 33
O
CHCOOH
o c h 2 — C — CH2N CH— CH3 II
CH.COOH
ch3
Timolol maleate
(/ JT \
CH,________ CH(CH3 ) 2
CH3Q - V V\\- CH
CH-XHoN —
CH2N — fCH-X
2 (CH — —C—V 2 ) 3 y -O C H 3
CH3 O - S = Z / I \ = Z _ OCH, . HCl
3 ■ CN 3
Verapamil hydrochloride
(5-[N-(3',4'-Dimethoxyphenethyl) N-methylamine]
2-(3",4"-<fimethoxyphenyl)-2-isopropyl valeronitrile)
(Hi) Antihypertensivc agent
NH2
HO \ O V - CH2 — C — COOH
HO - * |
CH3
Methyldopa
(3-Hydroxy-«-methyl-2-tyrosine) [2-(2,6-dichloro anilino-2-imidazoline]
CH,
« , j O q O
h I I
OCHo
OCH3
X OCH3
Appendix-VM □ □ 325
CH20 N 0 2
I
chono2
I
c h 2o n o ?
Nifedipine
Glyceryl trinitrate (1 ,4-Dihydro-2,6-dimethyM-(2-nitro phenyl)
(v) Lipid lowering agents -3,5-py-ridine acid dimethylester)
CH,
ch 2c h 3
CH,
Clofibrate
(2-(4-Chlorophenoxy)-2-methyl propionate)
15. Steroidal Drugs
(i) Androgens
OH OH
Testosterone
(17-p-hydroxy androst-4-ene-3-one) (17-p-hydroxy estr-4-ene-3-one)
OH 1
(ii) Oestrogens
OH
Oestradiol Stiibosterol
(1,3,5-Estratriene 3,17-ft diol) (3,4-bis (p-hydroxy phenyl) hex 3,4-ene)
326 □ □ Drug Inspector Exam
(iii) Progestogens
CH,
(Preg-4-ene-3,20-dione)
(tv) Adrenocortical hormones
c h 2o h c h 2o h c h 2o h
N --------N
Acetazolamide
(2-(Acetylamino) 5-sulfonamido 1, 3 ,4-thiadiazole)
(ii) Thiazides
O,
h 2no 2s-
C l'
H
Chlorthiazide Hydrochlorthiazide
(6-chlo ro -2H -1,2, 4-benzothiadiazine (6-chloro-2H-1. 2 , 4-benzothiadiazine
-7-sulphonam ide-1,1-dioxide) 7-sulphomide-1, 1-dioxide)
(iii) High ceiling diuretics
CO O H
NH — CH.
H2N02S :1 _ 1
C*CH2
Frusemide l
(4-chioro-N-(urfuryU5-sulphamoyl <^5
anth ranic acid) Ethacrynic acid
(2,3-Dichloro-4-(2-methylene butyryl)
phenoxy acetic acid)
Appendix-VIIl □ □ 327
Spironol^ctpne
17. Antimalarials
(/) Naturally occurring alkaloid
Quinine
(//') 4-Ammoquinolines
Cl
Primaquine
(8-(4-Amino-1-methyfbutylamino)
6 -methoxy quinoline)
(v) Diaminopyrinidines
Pyrimethamine
(2,4-Diamino-5-p-chlorophenyl-6-ethyl pyrimidine)
328 □ □ Drug Inspector Exam
18. Sulphonamides
COOH
Sulphacetamide
(p-Amino benzene sulphacetamide)
19. Antibiotics
CHOH — CH — CH2OH
NHCO CHCI2
Chloramphenicol
(2,2-Dichloro-N[a-hydroxy methyl] p-hydroxy-p-nitro phenyl] acetamide)
C6 H5 CH2C — NH
COOH
CH3 OH n (CH3)2
Appendix-VIII □ □ 329
^>nN - conh2
N
CONHNH, .
1 Pynanamide
Aminosalicylic acid Isoniazid (Pyrazine-2-carboxamide)
(4-pyridine carboxyKc
acid hydrazide) CH
+ + I
c h 3c h 2 — ch — nh 2 ch 2 c h 2 nh 2 — c h — ch 2 ch 3 . 2 Cl"
I
CH2OH
Ethambutol hydrochloride
(2 , 2 ‘-(ethylenediamine) di-1 -butanol)
Dapsone
(4', 4'-Diaminodiphenyl sulphone)
21. Antineoplastic agents
(/') Alkylating agent
.^Cpr"' ,1>
ch 3— n
I
l2_L^ !L
nh 2
Jn^O
II
o
Fluorouracil
(2 ,4-Dioxo 5-fluoro pyrimidine)
SH H
I
CONHCH — CH2 CH2 COOH
Methotrexate
N-[4-[(2, 4-diamino-6-pteridinyl methyl]
methylamino]benzoyl] glutamic acid
60 ^N '
6 -Mercaptopurine
330 □ □ Drug Inspector Exam
COONa
CH.
If I II
I I O
topanoic acid Sodium diatrizoate
3-Amino a-ethyl 2, 4, 6-tri
iodohydrocinnamic acid CH2 cooch 2 ch 2 CH3
S 03Na NaO .
S 03Na
Br O
Sodium Sulphobromophthalein Fluorescein sodium
23. Vitamins
-CH ,
Vitamin K (Phytomenadione)
Appendix-VIlI □ □ 331
HO“ f ^ i r CH2OH
CH.
Cl
CH, "■per Cl Cl
Cl
CH,
Cl
CH,
NHj
N'
Proflavine
(3, 6-Diaminoacridine)
(iii) Surfactant
CH,
/n\ ©i e
(/ \V - C H 2— N — RC I
R * C8H 17 to C 18H3y
CH 3
Benzalkonium Chloride
(iv) Nitrofuran derivative
o
ll
,N - / ° V CH * N — N ' ^ N H
1 ll I____Uo
Nitrofurantoin
(1-([(5-Nitro-2-furanyl) methylene] amino]-2,4-imidazolkline dione)
332 □ □ Drug Inspector Exam
Chlorpropamide
( b) Biguanides
NH NH
II II
a CH2 CHzNH C — NH — C — NHz
Phenformin
□ □
Appendix-lX □□ 333
Appendix
SCHEDULES
□ □
Model Paper-1
62. Which one of the following one is true department follow ing onset of
regarding Ectopic pregnancy? symptoms of myocardial infarction.
(a) Occurs in about 10%' of Which of the follow ing is a
pregnancies ' • contraindication for treatment with t-
(b) The risk is increased in those with PA?
a history or pelvic inflammatory (a) Worsening chest pain that began
disease earlier in the evening.
(c) Usually presents between 2 and 4 (b) History of cerebral hemorrhage.
months of gestation (c) History of prior myocardial
(d) Patients usually have a negative infarction.
pregnancy test (d) Hypertension.
63. All are related with Pelvic 67. A patient is undergoing the induction
inflammatory disease except. stage of treatment for leukemi(a) The
(a) Usually arises from nurse teaches family members about
haem atogenous spread from infectious precautions. Which of the
another site following statem ents by family
(b) Is most commonly a chlamydial members indicates that the family
infection needs more education?
(c) Untreated can progress to a (a) We will bring in books and
pyosalpinx magazines for entertainment.
(d) 20% of patients develop chronic (b) We will bring in personal care
pain items for comfort.
(c) We will bring in fresh flowers to
64. A nurse is adm inistering IV
brighten the room.
furosemide to a patient admitted with
congestive heart failure. After the (d) We will bring in family pictures
infusion, which of the following and get well cards.
symptoms is NOT expected? 68. A nurse is caring for a patient with
(a) Increased urinary output. acute lymphoblastic leukemia (ALL).
(b) Decreased edem(a) Which of the fo llo w in g is the most
(c) Decreased pain. likely age range of the patient?
(d) Decreased blood pressure. (a) 3-10 years, (b) 25-35 years.
(c) 45-55 years, (d) over 60 years.
65. There are a number of risk factors
associated with coronary artery 69. A patient is admitted to the oncology
disease. Which of the following is a unit for diagnosis of suspected
modifiable risk factor? Hodgkin's disease. Which of the
(a) Obesity (b) Heredity. following symptoms is typical of
Hodgkin’s disease?
(c) Gender (d) Age
(a) Painful cervical lymph nodes.
66. Tissue plasminogen activator (t-PA) is (b) Night sweats and fatigue.
considered for treatment of a patient
(c) Nausea and vomiting.
who arrives in the emergency
(d) Weight gain.
Model Paper-] □ □ 343
70. The Hodgkin's disease patient 75. For laboratory scale batch fermentor,
undergoes a lymph node biopsy for sizes ranges from
definitive diagnosis. If the diagnosis (a) 2-5L (b) 5 - 10L
of Hodgkin's disease were correct, (c) 1-2L (d) >10L
which of the following cells would the
Precursor used in penicillin
pathologist expect to find?
production is
(a) Reed-Stemberg cells.
(a) phenylacetic acid
(b) Lymphoblastic cells.
(b) phenoxyacetic acid
(c) Gaucher's cells.
(c) phenylacetamide
(d) Rieder's cells
(d) all of the above
71. A patient is about to undergo bone
marrow aspiration and biopsy and Rideal-walker test is used for
expresses fear and anxiety about the (a) streptococci
procedure. Which of the following is (b) staphylococci
the most effective nursing response? (c) phenol (c) pseudomonas
(a) Warn the patient to stay very still 73 Antisera are sterilized by
because the smallest movement (a) autoclaving
will increase her pain. (b) steam under low pressure
(b) Encourage the family to stay in the (c) hot air areas
room for the procedure.
(d) Alteration
(c) Stay with the patient and focus on
slow, deep breathing for 79. Presence of particulate matter in
relaxation. parenterals could lead to
(d) Delay the procedure to allow the (a) physical occlusion
patient to deal with her feelings. (b) inflammatory reaction
72. Penicillin is ---------------------metabolite (c) antigenic responses
(a) Primary (b) Secondary (d) all of the above
(c) Both (d) None of these 80. Which salt is used to treat mania and
depression?
73. Amount of inocculum to be added in
the production of tetracycline is (a) Calcium folinate
(a) 2-10% (b) 5-15% (b) Lithium citrate
(c) 20-255 ; (d) <5% (c) Potassium citrate
(d) Bismuth subcarbonate
74. Which microbial strain produces
tetracycline even in the presence of Which one of these drug is a entire
Cl- ions? plant?
(a) S viriditaciens (a) Lobelia (b) Senna
(b) S. rimosus (c) Liquorice (d) Belladonna
(c) S.aureofacien 82. What is Light Kaolin?
(d) S mediolanum (a) Aluminium silicate having
antidiarroeal action
344 □ □ Drug Inspector Exam
ANSW ERS
1. (d) 2. (b) 3. (c) 4. (c) 5. (c) 6. (d) 7. (d) 8. (a) 9. {a) 10. (b)
11. (a) 12. (b) 13. (b) 14. (c) 15. (c) 16. (a) 17. (c) 18. (a) 19. (c) 20. (b)
21. (c) 22. (a) 23. (d) 24. (d) 25. (a) 26. (a) 27. (a) 28. (b) 29. (c) 30. (b)
31. (b) 32. (b) 33. (b) 34. (b) 35. (d) 36. (d) 37. (c) 38. (b) 39. (b) 40. (a)
41. (b) 42. (?) 43. (b) 44. (b) 45. (d) 46. (d) 47. (c) 48. (a) 49. (?) 50. (?)
51. (?) 52. (a) 53. (a) 54. (a) 55. (c) 56. (a) 57. (c) 58. (d) 59. (a) 60. (b)
61. (a) 62. (b) 63. (a) 64. (c) 65. (a) 66. (b) 67. (c) 68. (a) 69. (b) 70. (a)
71. (c) 72. (b) 73. (a) 74. (d) 75. (c) 76. (d) 77. (c) 78. (d) 79. (d) 80. (b)
81. (a) 82. (a) 83. (a) 84. (c) 85. (c) 86. (a) 87. (C) 88. (c) 89. (b) 90. (a)
91. (d) 92. (a) 93. (d) 94. (b) 95. (d) 96. (b) 97. (d) 98. (a) 99. (a) 100. (a)
101. (a) 102. (a) 103. (d) 104. (b) 105. (d)
□ □ □
Model Paper-2
(d) High degree of accuracy implies (c) H2-blockers will heal 85-95% of
high degree of precesion also duodenal ulcers in 8 weeks
54. Streptomycin can NOT be given orally (d) Triple therapy can eradicate H.
for treatment of tuberculosis because. pylori in 80% of patients in one
week
(a) It gets degraded in the GIT
(b) It causes severe diarrhoea 60. Regarding Heparin all statement true
(c) It causes metallic taste in the except.
mouth (a) Is a heterogeneous mixture of
(d) It is not absorbed from the GIT sulphated polypeptides
(b) Potentiates the actions of
55. Cyclophosphamide as anticancer
antithrombin III
agent acts as.
(c) Can be reversed by protamine
(a) Alkylating agent before
sulphate
metabolism
(d) Can induce an idiosyncratic
(b) Alkylating agent after metabolism
thrombocytopenia
(c) Phosphorylating agent after
metabolism 61. Regarding Cushing's syndrome all
(d) DNA intercalating agent statement are wrong except.
(a) 80% of cases are due to pituitary
56. The Volume of distribution of a drug adenomas
administered at a dose of 300 mg and
(b) Most ACTH secreting pituitary
exhibiting 30 microgram/mL
adenomas are more than 2 cm in
instantaneous concentration in plasma
diameter
shall be.
(c) Cortisol production is suppressed
(a) 10 L (b) 100 L
by low-dose dexamethasone
(c) 1.0 L (d) 0.10 L
(d) Adrenal carcinomas are more
57. Barbiturates with substitution at the common than adrenal adenomas
following position possess acceptable
62. Following myocardial infarction, a
hypnotic activity :
hospitalized patient is encouraged to
(a) 1,3-Disubstitution practice frequent leg exercises and
(b) 5,5-Disubstitution ambulate in the hallway as directed
(c) 1,5-Disubstitution by his physician. Which of the
(d) 3,3-Disubstitution following choices reflects the purpose
58. Regarding peptic ulceration all of exercise for this patient?
statement true except. (a) Increases fitness and prevents
(a) Duodenal is more common than future heart attacks.
gastric ulceration (b) Prevents bedsores.
(b) Zollinger-Ellison syndrome is (c) Prevents DVT (deep vein
associated with gastrin thrombosis).
hyposecretion (d) Prevent constipations.
Model Paper-2 □ □ 351
63. A patient arrives in the emergency 66. A patient received surge y and
department w ith symptoms of chem otherapy for colon cancer,
myocardial infarction, progressing to com pleting therapy 3 months
cardiogenic shock. Which of the previously, and she is now in
following symptoms should the nurse rem ission. At a follow-up
expect the patient to exhibit with appointment, she complains of fatigue
cardiogenic shock? following activity and difficulty with
(a) Hypertension concentration at her weekly bridge
(b) Bradycardia games. W hich of the following
(c) Bounding pulse explanations could account for her
(d) Confusion symptoms?
(a) The symptoms may be the result
64. A patient with a history of congestive of anemia caused by
heart failure arrives at the clinic chemotherapy.
complaining of dyspnea. Which of the
(b) The patient may be
following actions is the first the nurse
immunosuppressed.
should perform?
(c) The patient may be depressed.
(a) Ask the patient to lie down on the
(d) The patient may be dehydrated.
exam table.
(b) Draw blood for chemistry panel 67. A 34 year old female has recently been
and arterial blood gas (ABG). diagnosed with an autoimmune
(c) Send the patient for a chest x-ray. disease. She has also recently
(d) Check blood pressure. . discovered that she is pregnant. Which
of the follow ing is the only
65. A clinic patient has recently been immunoglobulin that will provide
prescribed nitroglycerin for treatment protection to the fetus in the womb?
of angina. He calls the nurse (a) IgA (b) IgD
complaining of frequent headaches. (c) IgE (d) IgG
Which of the following responses to
the patient is correct? 68. A second year nursing student has just
(a) "Stop taking the nitroglycerin and suffered a needlestick while working
see if the headaches improve." with a patient that is ositive for AIDS.
(b) "Go to the emergency department Which of the following is the most
important action that nursing student
to be checked because
nitroglycerin can cause bleeding in should take?
the brain." (a) Immediately see a social worker
(c) "Headaches are a frequent side (b) Start prophylactic AZT treatment
effect of nitroglycerine because it (c) Start prophylactic Pentamide
causes vasodilation." treatment
(d) "The headaches are unlikely to be (d) Seek counseling
related to the nitroglycerin, so you 69. Grade -II disinfectants have minimum
should see your doctor for further RW coefficient is
investigation."
352 □ □ Drug Inspector Exam
ANSW ERS
1. (c) 2- (b) 3- (d) 4- (c) 5. (c) 6. (c) 7. (d) 8- (c) 9- (b) 10. (c)
11. (?) 12. (b) 13. (d) 14. (c) 15. (d) 16. (b) 17. (c) 18. (b) 19. (c) 20. (c)
21. (c) 22. (a) ■23. (a) 24. (d) 25. (d) 26. (b) 27. (d) 28. (d) 29. (d) 30. (d)
31. (c) 32. (a) 33. (b) 34. (b) 35. (c) 36. (b) 37. (a) 38. (d) 39. (d) 40. (a)
41. (b) 42. (b) 43. (b) 44. (b) 45. (a) 46. (d) 47. (d) 48. (a) 49. (b) 50. (b)
51. (b) 52. (a) 53. (c) 54. (d) 55. (b) 56. (a) 57. (b) 58. (b) 59. (?) 60. (a)
61. (a) 62. (c) 63. (d) 64. (d) 65. (c) 66. (c) 67. (d) 68. (b) 69. (b) 70. (b)
71. (a) 72. (d) 73. (a) 74. (a) 75. (d) 76. (d) 77. (c) 78. (b) 79. (a) 80. (b)
81. :.b) 82. (?) 83. (a) 84. (c) 85. (d) 86. (d) 87. (a) 88. (b) 89. (d) 90. (b)
91. (a) 92. (c) 93. (a) 94, (d) 95. (c) 96. (a) 97. (d) 98. (a) 99. (d) 100. (a)
101. (d) 102. (d) 103. (c) 104. (b) 105. (a) 106. (b)
□ □ □
Model Paper-3
{a) Patient controlled analgesia (PCA) the following is the most accurate
is more effective than intermittent statement?
parenteral dosing (a) Transfusion reaction is most likely
(b) The total opiate dose is usually immediately after the infusion is
reduced with a PCA completed.
(c) Fentanyl is more water soluble (b) PRBCs are best infused slowly
than morphine through a 20g. IV catheter.
(d) Epidural morphine can result in (c) PRBCs should be flushed with a
late respiratory depression 5% dextrose solution.
58. Regarding cardiovascular disease in (d) A nurse should remain in the room
the surgical patient all are true except. during the first 15 minutes of
(a) Following a myocardial infarct infusion.
elective surgery should be deferred 61. A patient who has received
for over 6 months chemotherapy for cancer treatment is
(b) 60% of post-operative re given an injection of Epoetin. Which
infarctions are clinically silent of the following should reflect the
(c) The mortality of a post-operative findings in a complete blood count
myocardial infarct is about 40% (CBC) drawn several days later?
(d) The risk of a post-operative infarct (a) An increase in neutrophil count.
is reduced in hypertensive patients (b) An increase in hematocrit.
59. A clinic patient has a hemoglobin (c) An increase in platelet count.
concentration of 10.8 g/dL and reports (d) An increase in serum iron.
sticking to a strict vegetarian diet. 62. A nurse is caring for a patient with a
Which of the follow nutritional advice platelet count of 20,000/microlrter.
is appropriate? Which of the following is an important
(a) The diet is providing adequate intervention?
sources of iron and requires no (a) Observe for evidence of
changes. spontaneous bleeding.
(b) The patient should add meat to her (b) Limit visitors to family only.
diet; a vegetarian diet is not (c) Give aspirin in case of headaches.
advised. (d) Impose immune precautions.
(c) The patient should use iron
63. A nurse is caring for patients in the
cookware to prepare foods, such
as dark green, leafy vegetables and oncology unit. Which of the following
is the most important nursing action
legumes, which are high in iron.
when caring for a neutropenic patient?
(d) A cup of coffee or tea should be
added to every meal. (a) Change the disposable mask
immediately after use.
60. A hospitalized patient is receiving (b) Change gloves immediately after
packed red blood cells (PRBCs) for use.
treatment of severe anemia. Which of (c) Minimize patient contact.
Model Paper-3 □ □ 361
AN SW ERS
1. (c) 2. (b) 3. (d) 4. (c) 5. (c) 6. (c) 7. (d) 8. (c) 9. (b) 10. (c)
11. (?) 12. (b) 13. (d) 14. (c) 15. (d) 16. (b) 17. (c) 18. (b) 19. (c) 20. (c)
21. (c) 22. (a) 23. (a) 24. (d) 25. (d) 26. (b) 27. (d) 28. (d) 29. (d) 30. (d)
31. (C) 32. (a) 33. (b) 34. (b) 35. (c) 66. (b) 37. (a) 38. (d) 39. (d) 40. (a)
41. (b) 42. (b) 43. (b) 44. (b) 45. (a) 46. (d) 47. (d) 48. (a) 49. (b) 50. (b)
51. (b) 52. (a) 53. (c) 54. (d) 55. (b) 56. (a) 57. (b) 58. (b) 59. (?) 60. (a)
61. (a) 62. (c) 63. (d) 64. (d) 65. (c) 66. (c) 67. (d) 68. (b) 69. (b) 70. (b)
71. (a) 72. (d) 73. (a) 74. (a) 75. (d) 76. (d) 77. (c) 78. (b) 79. (a) 80. (b)
81. (b) 82. (?) 83. (a) 84. (c) 85. (d) 86. (d) 87. (a) 88. (b) 89. (d) 90. (b)
91. (a) 92. (c) 93. (a) 94. (d) 95. (c) 96. (a) 97. (d) 98. (a) 99. (d) 100. (a)
a s a
Model Paper-4
1. The profile of expected adverse effects What is the minimum time interval
associated with the thiazide diuretics necessary for the drug to reach the
during heart failure therapy include: plasma steady state?
(a) cardiac dysrhythmia, (a) 200 hours (b) 8 hours
gastrointestinal disturbances, (c) 40 hours (d) 15-30 minutes
nausea and vom iting, visual
5. Prior to administering a due dose of
disturbances
digoxin, a client's pulse rate is found
(b) hypotension, a non-productive to be 55 bpm. What is the most
cough and hyperkalaemia appropriate course of action?
(c) hypotension, hypokalaemia and (a) administer the dose as directed by
dehydration the medication order
(d) hypotension, bradycardia, (b) treat the client for digoxin
dizziness, headache and overdose
gastrointestinal upsets
(c) determ ine the client's blood
2. The cardiac glycosides produce which potassium level
of the following effects? (d) do not administer the dose and
(a) Negative chronotropic and indicate this on the medication
positive inotropic effects chart
(b) Positive chronotropic and negative 6. In general the means by which
inotropic effects antidysrhythmic agents control cardiac
(c) N egative chronotropic and dysrhythmias can involve:
inotropic effects (a) enhancing automaticity
(d) Positive chronotropic and (b) reducing the effective refractory
inotropic effects period
3. The use of ACE inhibitors in heart (c) decreasing the rate of
failure is directed towards: depolarization
(a) enhancing glomerular filtration (d) increasing impulse conduction
rate speed
(b) decreasing heart rate 7. The antidysrhythmic drug group that
(c) peripheral vasodilation acts by shortening the duration of the
(d) increasing cardiac output cardiac action potential belong in
4. The half-life of the cardiac glycoside class:
digoxin is approximately 40 hours.
366 □ □ Drug Inspector Exam
17. The calcium channel antagonists are 22. Which action below is affect ,d by an
not indicated in the treatment of: antihistamine?
(a) cerebral ischaemia (a) blood vessel dilation
(b) dysrhythmias (b) phagocytosis of antigens
(c) angina pectoris (c) MHC presentation by
(d) hypotension macrophages
(d) the secondary immune response
18. A common adverse effect of
spironolactone in men is due its 23. Which cells and which signaling
intrinsic sex hormone activity. What molecules are responsible for initiating
is thought to be the mechanism of an inflammatory response?
action of spironolactone here? (a) phagocytes: lysozymes
(a) its oestrogenic activity (b) phagocytes: chemokines
(b) its progestagenic activity (c) dendritic cells: interferons
(c) its antiandrogenic activity (d) mast cells: histamines
(d) its antigonadotrophic activity 24. Inflammatory responses may include
20. Both the eye and the respiratory tract which of the following?
are protected against infections by (a) clotting proteins migrating away
which of the Following? from the site of infection
(a) the mucous membranes that cover (b) increased activity of phagocytes in
their surface an inflamed area
(b) the secretion of complement (c) reduced permeability of blood
proteins vessels to conserve plasma
(c) the release of slightly acidic (d) release of substances to decrease
secretions the blood supply to an inflamed
(d) the secretion of lysozyme onto area
their surface 25. A bacterium entering the body
21. Which statem ent about the through a small cut in the skin will
complement system is true? do which of the following?
(a) These proteins are involved in (a) inactivate the erythrocytes
innate immunity and not acquired (b) stimulate apoptosis of nearby body
immunity. cells Study Guide for Lecture
(b) These proteins are secreted by Exam II for BIOL1407 Page 2
cytotoxic T cells and other CD8 (c) stimulate release of interferons
cells. (d) activate a group of proteins called
(c) This group of proteins includes complement
interferons and interleukins.
26. An invertebrate, such as an insect, has
(d) These proteins are one group of innate immunity that can be
antim icrobial proteins acting nonspecific about which pathogens
together in cascade fashion. are prevented from harming its
metabolism. Which of the following
368 □ □ Drug Inspector Exam
(a) His cells would lack class I MHC (c) flat shaft curved needle
molecules on their surface. (d) straight pointed scissor
(b) His humoral immunity would be gg Tensile strength testing is done for
missing. which of the following?
(c) Genetic rearrangement of antigen (a) belladonna plaster
receptors would not occur.
(b) salicylic acid plaster
(d) His T cells would not mature and
(c) zinc paste bandage
differentiate appropriately.
(d) both (a) and (b)
34. Clonal selection implies that
39 Which are the different types of
(a) brothers and sisters have similar
forceps?
immune responses.
(a) tissue forcep
(b) antigens increase mitosis in
specific lymphocytes. (b) haemostatic forcep
(c) only certain cells can produce (c) bone cutting forcep
interferon. (d) all of the above
(d) B cell has multiple types of antigen 40. What are the different type of scissors?
receptors. (a) straight blunt scissors
35. Which of the following cell types are (b) straight pointed scissors
responsible for initiating a secondary (c) lister's bandage scissors
immune response? (d) all of the above
(a) memory cells What is the use of
(b) macrophages sphygmomanometer?
(c) stem cells (d) B cells (a) to measure heart rate
36. Which of the following differentiates (b) to measure bp
T cells and B cells? (c) to measure pulse
(a) T cells but not B cells are (d) none of the above
stimulated to increase the rate of ^ What does ct scan stand for?
their cell cycles.
(a) computer topography
(b) Only B cells are produced from
(b) computed tomography
stem cells of the bone marrow.
(c) computerized transfer
(c) T cells but not B cells can directly
attack and destroy invading (d) none of the above
pathogens. 43. What does MRI stand for ?
(d) T cells but not B cells have surface (a) magnetic resonance imaging
markers. (b) magnetic resonance index
37. Which one of the following is not a (c) magnetic resonance impulse
type of surgical needles? id) none of the above
(a) straight needle 44. C rystallization is an example of
(b) round shaft curved needle ................... Incompatibility.
370 □ □ Drug Inspector Exam
(a) Immediate (b) Delayed 51. The most common site of chronic
(c) Instantaneous gastric peptic ulcer is:
(d) Both (a) and (b) (a) lesser curvature at antral-body
junction
45......................... Compatibility may be
corrected by changing the order of (b) anterior wall at duodenal verge
mixing. (c) greater curvature in mid-antrum
(a) Delayed (b) Immediate (d) esophago-gastric junction
(c) Tolerated (d) Adjusted 52. The most frequent complication of
46. Effective ulcer treatment which works chronic duodenal ulcer is:
without any action on gastric acid (a) hemorrhage (b) obstruction
secretion is: (c) perforation (d) malabsorption
(a) Lactulose 53. What is the predominant p-
(b) Aluminium hydroxide adrenoceptor in bronchial smooth
(c) Sucralfate (d) Lactitol muscle?
(e) Magnesium trisilicate (a) pi-adrenoceptor
47. Chagas' disease may be suspected if a (b) p2-adrenoceptor
patient has: (c) p3-adrenoceptor
(a) Constipation (b) Dysphagia (d) p4-adrenoceptor
(c) Heart failure (d) Jaundice 54. What is the main clinical use for
(e) Option (a), (b) & (c) agonists of the p2-adrenoceptor?
48. Captopril causes: (a) Treatment of angina.
(a) Hyperkalemia (b) Treatment of hypertension.
(b) Hypernatremia (c) Treatment of asthma.
(c) Hypokalemia (d) Treatment of pain.
(d) Hypercalcemia 55. What is the main clinical use for
antagonists of the pl-adrenoceptor?
49. Patient after an ischemic attack has
ventricular Tachycardia. Drug of (a) Treatment of glaucoma.
choice is: (b) Treatment of hypertension.
(a) Amiodrone (b) Metoprolol (c) Treatment of asthma.
(c) Lidocaine (d) Verapamil (d) Treatment of pain.
50. Which one of the following is a feature 56. Which one of the following laxatives
of the Zollinger-Ellison syndrome? is a lubricant?
(a) hypoglycemic attacks (a) Senna (b) Decussate
(b) obesity (c) castor oil (d) liquid paraffin
(c) gastric hyperchlorhydria 57. Which of the following antiemetics is
(d) diabetes least likely to cause an oculogyric
(e) fainting spells crisis?
Model Paper-4 □ □ 371
(b) Intrastrand cross linking of DNA 74. Tick the drug for trematodosis (fluke
results from the action of the invasion) treatment:
agent. (a) Bithionol (b) Ivermectin
(c) Base pairing between adenine and (c) Pyrantel (d) Metronidazole
thymine is disrupted by the agent.
75. Tick the drug, a benzim idazole
(d) The compound acts as a derivative:
metallating agent
(a) Praziquantel (b) Mebendazole
68. All of the following Anticancer agents (c) Suramin (d) Pyrantel
cause bone marrow depression
76. Tick the broad spectrum drug for
except?
cestodosis, trem atodosis and
(a) Chlorambucil
cycticercosis treatment:
(b) Daunorubicin
(a) Piperazine (b) Ivermectine
(c) Doxorubicin (d) Flutamide
(c) Praziquantel (d) Pyrantel
69. Which people are said to be fastest
77. Dose of Gentamicin is reduced in the
acetylators because they metabolize
elderly due to:
isoniazid by the process of acetylation
very quickly (a) Liver failure
(b) Reduced renal function
(a) Canadian Eskimos
(c) Decreased GI absorption
(b) Indians
(d) Decreased metabolism
(c) Asiatic Jews (d) Chinese
(e) Europeans (f) all the above 78. The iim portant side effect of
gentamicin is
70. Tick the drug, inhibiting oxidative
(a) Ototoxicity
phosphorylation in some species of
helminthes: (b) Nephrotoxicity
(a) Niclosamide (b) Piperazine (c) Neurmuscular dysfunction
(c) Praziquantel (d) Mebendazole (d) Teratogenic
(e) all of the above
71. Tick the drug for neurocysticercosis
treatment: 79. The antileprotic drug,dapsone act by
(a) Praziquantel (b) Pyrantel (a) inhibition of incorporation of
(c) Piperazine (d) Bithionol PABA in folic acid
(b) inhibition of protein synthesis
72. Tick the drug for nem atodosis
(c) inhibition the cell wall synthesis
(roundworm invasion) treatment:
(d) inhibition of ergosterol synthesis
(a) Niclosamide (b) Praziquantel
(c) Bithionol (d) Pyrantel 80. Which of these is a thiourea derivative
used as antipeprotic dtug?
73. Tick the drug for cestodosis
(a) dapsone (b) clofazimene
(tapeworm invasion) treatment:
(c) thiambutosine
(a) Piperazine (b) Praziquantel
(d) solapsone
(c) Pyrantel (d) Ivermectin
Model Paper-4 □ □ 373
81. The permission for cultivation of any (b) Merck & Co.,Inc.Rahway,New
coca plant was given by Jersy,USA
(a) State government (c) Merck & Co,UK
(b) Dristic Magistrate (d) Merck & Co,Germany
(c) District Judge 88. What is Amalaki?
(d) Central government (a) Phyllanthus embilica
82. The narcotic drugs & Psychotropic (b) Withania somnifera
substance consultative committee is (c) Brahmi (d) Berberis aristata
headed by
89. Which one of these has phytoestrogen
(a) State government activity?
(b) Dristic Magistrate (a) Phyllanthus embilica
(c) Distic Judge (d) chairman (b) Withania somnifera
83. Opium can be manufactured by (c) Brahmi
(a) central governm ent at opium (d) Azadirachta indica
factories
90. What is the source of Aesculetin used
(b) private factories for the treatment of dysentery?
(c) on loan licience (a) Frazinus rhychophylla
(d) none of the above (b) Adonis vemalis
84. Various substance & preparation have (c) Aesculus hippocastanum
been declared to be manufactured (d) Andrographis paniculata.
drugs in
91. The latin term'tussi urgent' indicates
(a) 1985 (b) 1857
(a) when cough is troublesome
(c) 1993 (d) 1865
(b) immediately
85. In 1925 India participate in second (c) when pain is severe
international opium conference held
(d) frequently
at
(a) Geneva (b) jaipur 92. Supercription indicates
(c) Delhi (d) U.S.A (a) direction to patient
(b) direction to physician
86. Who has published the National
(c) symbol Rx
Formulary
(d) none of the above
(a) Indian Pharmaceutical Association
(b) American Phcirmaceurical 93. Subcription is directed to
Association (a) patient (b) pharmacist
(c) British society of Pharmaceutical (c) doctor (d) all of the above
Association 94. In hospital, the most of the
(d) None of the above contamination is caused by free living
87. Who has published Merck index? opportunistic pathogens like
(a) Merck&Co.India
374 □ □ Drug Inspector Exam
ANSWERS
1. (c) 2. (b) 3. (d) 4. (c) 5. (c) 6. (c) 7. (d) 8. (c) 9. (b) 10. (c)
11. (?) 12. (b) 13. (d) 14. (c) 15. (d) 16. (b) 17. (c) 18. (b) 19. (c) 20. (c)
21. (c) 22. (a) 23. (a) 24. (d) 25. (d) 26. (b) 27. (d) 28. (d) 29. (d) 30. (d)
31. (c) 32. (a) 33. (b) 34. (b) 35. (c) 36. (b) 37. (a) 38. (d) 39. (d) 40. (a)
41. (b) 42. (b) 43. (b) 44. (b) 45. (a) 46. (d) 47. (d) 48. (a) 49. (b) 50. (b)
51. (b) 52. (a) 53. (c) 54. (d) 55. (b) 56. (a) 57. (b) 58. (b) 59. (?) 60. (a)
61. (a) 62. (c) 63. (d) 64. (d) 65. (c) 66. (c) 67. (d) 68. (b) 69. (b) 70. (b)
71. (a) 72. (d) 73. (a) 74. (a) 75. (d) 76. (d) 77. (c) 78. (b) 79. (a) 80. (b)
81. (b) 82. (?) 83. (a) 84. (c) 85. (d) 86. (d) 87. (a) 88. (b) 89. (d) 90. (b)
91. (a) 92. (c) 93. (a) 94. (d) 95. (c) 96. (a) 97. (d) 98. (a) 99. (d) 100. (a)
101. (c) 102. (b)
cm
Model Paper-5
1. Tick the main approach of peptic ulcer 6. Choose the drug which is a H2-
treatment: receptor antagonist:
(a) Neutralization of gastric acid ((a) Omeprazole
(b) Eradication of Helicobacter pylori ((b) Pirenzepine
(c) Inhibition of gastric acid secretion ((c) Carbenoxolone
(d) All the above ((d)Ranitidine
2. Gastric acid secretion is under the 7. All of the following drugs are proton
control of the follow ing agents pump inhibitors EXCEPT:
EXCEPT: (a) Pantoprozole
(a) Histamine (b) Omeprazole
(b) Acetylcholine (c) Famotidine
(c) Serotonin (d) Rabeprazole
(d) Gastrin 8. Indicate the drug belonging to M l-
3. Indicate the drug belonging to proton cholinoblockers:
pump inhibitors: (a) Cimetidine
(a) Pirenzepine (b) Ranitidine
(b) Ranitidine (c) Pirenzepin
(c) Omeprazole (d) Omeprazole
(d) Trimethaphan 9. Which of the following drugs may
4. All of the following agents intensify cause reversible gynecomastia?
the secretion of gastric glands (a) Omeprazole
EXCEPT: (b) Pirenzepine
(a) Pepsin (c) Cimetidine
(b) Gastrin (d) Sucralfate
(c) Histamine
11. Tick the drug forming a physical
(d) Carbonate mineral waters barrier to HCL and Pepsin:
5. Which of the following drugs is an (a) Ranitidine
agent of substitution therapy? (b) Sucralfate
(a) Gastrin (c) Omeprazole
(b) Hydrochloric acid (d) Pirenzepine
(c) Hystamine
12. Which drug is an analog of
(d) Carbonate mineral waters prostaglandin El?
376
Model Paper-5 □ □ 377
25. Tick a hypnotic agent - a barbituric 31. Which of the following hypnotic drugs
acid derivative: is more likely to cause cumulative and
(a) Flurazepam residual effects?
(b) Zaleplon (a) Zolpidem
(c) Thyopental (b) Temazepam
(d) Triazolam (c) Phenobarbital
26. Select a hypnotic drug, which is an (d) Triazolam
imidazopyridine derivative: 32. Which of the following hypnotic drugs
(a) Pentobarbital increases the activity of hepatic drug-
(b) Temazepam metabolizing enzyme systems?
(c) Zolpidem (a) Phenobarbital
(d) Chloral hydrate (b) Zolpidem
(c) Flurazepam
27. Which of the following hypnotic
agents is absorbed slowly? (d) Zaleplon
(a) Phenobarbital 33. Hepatic microsomal drug-
(b) Flurazepam metabolizing enzyme induction leads
(c) Triazolam to:
(d) Temazepam (a) Barbiturate tolerance
(b) Cumulative effects
28. Which of the following barbiturates
(c) Development of physical
is an ultra-short-acting drug?
dependence
(a) Secobarbital
(d) "hangover" effects
(b) Amobarbital
(c) Thiopental 34. Hypnotic benzodiazepines are more
(d) Phenobarbital powerful enzyme inducers than
barbiturates.
29. Indicate the barbituric acid derivative, (a) True
which has 4-5 days elimination half-
(b) False
life:
(a) Secobarbital 35. Indicate the hypnotic drug, which
(b) Thiopental does not change hepatic drug-
metabolizing enzyme activity?
(c) Phenobarbital
(a) Flurazepam
(d) Amobarbital
(b) Zaleplon
30. Indicate the hypnotic benzodiazepine, (c) Triazolam
which has the shortest elimination
(d) All of the above
half-life:
(a) Temazepam 36. Barbiturates increase the rate of
metabolism of:
(b) Triazolam
(c) Flurazepam (a) Anticoagulants
(d) Diazepam (b) Digitalis compounds
Model Paper-5 □ □ 379
82. This drug reduces blood pressure by (a) Labetalol (b) Clonidin
acting on vasomotor centers in the (c) Enalapril (d) Nifedipine
CNS:
91. Pick out the diuretic agent for
(a) Labetalol (b) Clonidine hypertension treatment:
(c) Enalapril (d) Nifedipine (a) Losartan (b) Dichlothiazide
83. All of the following are central acting (c) Captopril (d) Prazosin
antihypertensive drugs EXCEPT:
92. Which action below is affected by an
(a) Methyldopa (b) Clonidine antihistamine?
(c) Moxonidine (d) Minoxidil (a) blood vessel dilation
84. A ganglioblocking drug for (b) phagocytosis of antigens
hypertension treatment is: (c) MHC presentation by
(a) Hydralazine macrophages
(b) Tubocurarine (d) the secondary immune response
(c) Trimethaphan 93. Which cells and which signaling
(d) Metoprolol molecules are responsible for initiating
85. Pick out the sympatholythic drug: an inflammatory response?
(a) Labetalol (a) phagocytes: lysozymes
(b) Prazosin (b) phagocytes: chemokines
(c) Guanethidine (c) dendritic cells: interferons
(d) Clonidine (d) mast cells: histamines
86. Tick the drug with nonselective beta- 94. Inflammatory responses may include
adrenoblocking activity: which of the following?
(a) Atenolol (b) Propranolol (a) clotting proteins migrating away
(c) Metoprolol (d) Nebivolol from the site of infection
(b) increased activity of phagocytes in
87. Choose the selective blocker of beta-1
an inflamed area
adrenoreceptors:
(c) reduced permeability of blood
(a) Labetalol (b) Prazosin
vessels to conserve plasma
(c) Atenolol (d) Propranolol
(d) release of substances to decrease
88. Pick out the drug - an alpha and beta the blood supply to an inflamed
adrenoreceptors blocker: area
(a) Labetalol (b) Verapamil 95. A bacterium entering the body
(c) Nifedipine (d) Metoprolol through a small cut in the skin will
89. This drug inhibits the angiotensin- do which of the following?
converting enzyme: (a) inactivate the erythrocytes
(a) Captopril (b) Enalapril (b) stimulate apoptosis of nearby body
(c) Ramipril (d) All of the above cells Study Guide for Lecture
Exam II for BIOL1407 Page 2
90. This drug is' a directly acting
vasodilator: (c) stimulate release of interferons
384 □ □ Drug Inspector Exam
(d) activate a group of proteins called (c) reducing the response of the
complement periphery to released adrenal
96. Which of the following cell types are ' medulla hormones
responsible for initiating a secondary (d causing an increase in systemic
immune response? vascular resistance (SVR)
(a) memory cells 99. The angiotensin II receptor
(b) macrophages antagonists:
(c) stem cells (a) induce a cough as a cohrtmon
(d) B cells adverse reaction
(b) act by inhibiting the formation of
97. Which of the following does not play
angiotensin II
an important role in blood pressure
(c) do not appear to produce any
(a) endothelin-1
clinical hyperkalaemic state
(b) rennin
(d) are used in the management of
(c) the carotid bodies
angina pectoris
(d) prolactin
100. What crucial feature of penicillin is
'8. Diuretics help reduce blood pressure involved in its mechanism of action?
by
Carboxylic acid
(a) producing a decrease in vascular (b) p-lactam ring
voiume
(c) Acyl side chain
(b) reducing sympathetic outflow
(d) Thiazolidine ring
from the CNS
ANSW ERS
1. (d) 2. c) 3- (c) 4. (a) 5. (b) 6. (d) 7. (c) 8. (c) 9. (c) 10. (?)
11. (b) 12. (a) 13. (c) 14. (a) 15. (a) 16. (a) 17. (b) 18. (c) 19. (b) 20. (a)
21. (b) 22. (c) 23. (b) 24. (b) 25. (c) 26. (c) 27. (d) 28. (c) 29. (c) 30. (b)
31. (c) 32. fa) 33. (a) 34. (b) 35. (d) 36. (d) 37. (b) 38. (d) 39. (c) 40. (a)
41. (b) 42. (b) 43. (c) 44. (d) 45. (d) 46. (a) 47. (b) 48. (a) 49. (b) 50. (c)
51. (d) 52. (a) 53. (c) 54. (a) 55. (b) 56. (a) 57. (c) 58. (b) 59. (c) 60. (b)
61. (b) 62. (a) 63. (d) 64. (d) 65. (b) 66. (c) 67. (b) 68. (d) 69. (a) 70. (b)
71. (c) 72. (c) 73. (a) 74. (d) 75. (b) 76. (a) 77. (c) 78. (b) 79. (d) 80. (b)
81. (?) 82. (b) 83. (d) 84. (c) 85. (c) 86. (b) 87. (c) 88. (a) 89. (d) 90. (d)
91. (b) 92. (a) 93. (d) 94. (b) 95. (d) 96. (a) 97. (d) 98. (a) 99. (c) 100.(b)