Haemopoietic

Pharmacology
SYLLABUS
Haemostatics: (P. 789)
Classification, their actions and uses
Therapy of Thromboembolic Disorders: (P. 789)
Anticoagulants: (P. 789)
Introduction, general principle, Classification, Mechanism of action, indications, adverse effects and
contraindications.
Thrombolytics: (P. 792)
Preparations,Pharmacological basis for their actions and related usefulness.
Flibrinolytics (P. 793)
Antiplatelet agents: (P. 794)
Classification, Mechanism of action, indications, adverse effects and contraindications.
Therapy of Iron Deficiency Anaemia: (P. 795)
Introduction, iron Preparations, indications, adverse effects, treatment of overdose.
Therapy of Megaloblasticanaemia (P. 796) with/without neurological Involvement, Pernicious Anaemia:
Folic acid (P. 797) and vitamin B12: (P. 796)
III
Preparations, actions, uses, inter-relationship between folic acid and vitamin B12
Therapy of Parasitic Infections: (P. 797)
Anti-Malarial drugs: (P. 797)
Introduction, general principle, Classification, Mechanism of action, indications, adverse effects and
contraindications.
Drug therapy for Leishmaniasis: (P. 801)
Classification of drugs, uses of urea Stibogluconate and pentamidine.
Drug therapy for Filariasis: (P. 801)
Classification of drugs, uses of Diethylcarbamazine citrate and Ivermectin.
Anticancer Drugs: (P. 802)
Introduction, general principle, Classification (P. 802), Mechanism of action, indications, adverse effects and
contraindications.
General adverse effects (P. 803) of anti-cancer drugs.
Therapy of shock: (P. 803)
Drugs used in different types of shock, rationale for using these
Drugs adverse effects, precautions

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 Pharmacology

III

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 Haemopoietic

PHARMACOLOGY

HAEMOSTATIC AGENTS d. Liver disease

 Drugs which arrest blood loss and promote e. Newborns
coagulation are called haemostatics. f. Overdose of oral anticoagulants
Classification Deficiency of Vitamin K
i. Vitamin K Bleeding disorders like
- K1 (from plants, fat - soluble): Phytonadione a. Haematuria
- K3 (synthetic) b. Epistaxis
 Fat soluble: Menadione, Acetomenaphthone c. Ecchymoses

 Water soluble: Menadione sodium bisulfite, d. GI bleeding

menadione sodium diphosphate
THERAPY OF THROMBOEMBOLIC
ii. Miscellaneous
DISORDER
- Fibrinogen
- Antihaemophilic factor ANTICOAGULANTS
- Desmopressin
Past Questions:
- Adenochrome monosemicarbazone
1. Give the pharmacological basis for:
- Rustin, ethamsylate
a. Mechanism of action of heparin [3][02 Dec]
Vitamin k
b. Heparin as anticoagulant [3][02 June] III
 Fat soluble vitamin 2. Write short notes on:
 Total daily requirement: 50 - 100 g/day a. Low molecular weight heparin [3][05 June]
 Dietary source: Green leafy vegetables such as b. Heparin [3][04 June, 09 July]
cabbage, spinach and liver, Cheese etc.
c. Warfarin [3][10 July]
Mechanism of Action:
 These are the group of drugs used to reduce
- Vitamin K helps in -carboxylation of coagubility of blood.
glutamate residue of coagulation factors
Classification
(prothrombin and factor VII, IX, X)
- The  - carboxylation helps those coagulation 1. Used to Vivo
factors interact with calcium and get bind to A. Parenteral anticoagulants
phospholipid surface of platelets. - Heparin, low molecular weight heparin
- Unless carboxylated, coagulation factors - Heparinoids - Heparan sulfate
cannot bind to phospholipid surface and - Danaparoid, Lepirudin, Ancrod
coagulation process can't occur.
B. Oral anticoagulants
Uses of Vitamin K prophylaxis
i. Coumarin derivatives: Bishydroxy coumarin
a. Dietary deficiency (dicumarol), Warfarin sodium, Acenocoumarol,
b. Prolonged antimicrobial therapy Ethyl biscoumacetate
c. Obstructive jaundice or malabsorption ii. Indandione derivative: Phenindione
syndromes
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 Pharmacology

2. Used in Vitro Note:

A. Heparin - Monitoring of heparin therapy is done by testing
- 150 U to prevent clotting of 100 ml blood blood partial thromboplastin time with kaolin.
B. Calcium complexing agents Adverse effect
i. Sodium citrate (1.65 g for 350 ml blood) - Haemorrhage
ii. Sodium oxalate (10 mg for 1 ml blood) - Thrombocytopenia
iii. Sodium edetate (2mg for 1 ml blood)i.Sodium oxalate\
- Transient and reversible alopecia
Heparin [KU 02, 04, 09] - Osteoporosis
 It is glycosaminoglycan - Hypersensitivity rxns like - urticaria, rigor, fever
 Natural heparin is usually stored in secretory and anaphylaxis
granules of mast cells. - Hyperkalaemia
 It is strongest organic acid in body and has highest Contraindication
negative charge density of any known biological
- Bleeding disorders like haemophilia, purpura
molecule.
etc
 Heparin contains polymer of 2 sulfated
- Chronic alcoholics, cirrhosis, renal failure
disaccharides.
D - Glucosamine - L - iduronic acid - Severe hypertension, threatened abortion,
piles, GI ulcers
+
- Subacute bacterial endocarditis, large
D - Glucosamine - D - glucuronic acid
malignancies, tuberculosis
Mechanism of action
- Ocular and neurosurgery, lumbar puncture
Heparin - Hypersensitivity to drug
III Uses
1. Deep vein thrombosis and pulmonary
Binds with Antithrombin III, Provides Scaffolding for
induces conformational clotting factors and
embolism
change that accelerates Antithrombin III to bind 2. Myocardial infarction
action of antithrombin - III and interact with each 3. Unstable angina
(1000 fold than normal) other
4. Rheumatic heart disease, atrial fibrillation
Antithrombin inactivates 5. Cerebrovascular disease
coagulation factors (Xa, IIa, IXa, XIa, 6. Vascular surgery, prosthetic heart valves,
XIIa, XIIIa) retinal vessels thrombosis, extracorporeal
circulation, hemodialysis
Inhibition in clotting 7. Defibrination syndrome
(Anticoagulation)
Low molecular weight Heparin (LMWH) [05]
- Molecular weight 3000 - 7000 [Natural being
Pharmacologic actions about 10,000 - 20,000]
1. Anticoagulation
- Isolated from standard heparin by Gel
2. Antiplatelet action: filtration chromatography
- Heparin in higher dose inhibits platelet Examples of low molecular weight Heparin
aggregation and prolongs bleeding time
- Enoxaparin, Reviparin, Nadroparin, Daltepari,
3. Hypolipidimic action: Heparin releases lipoprotein
Pamparin, Ardeparin
lipase from various tissues so decreases blood lipid.

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 Haemopoietic

LMWH in comparison with high molecular weight Adverse effect

heparin - Haemorrhage
1. Doesn't bring antithrombin III and thrombin - Dermatitis
together. It acts only by inducing confirmational - Diarrhoea
change in Antithrombin III. So it selectively inhibits
- Transient purpura
factor Xa.
- Alopecia
2. Produce equivalent anticoagulant effect as
standard heparin but has lower risk of bleeding. - Teratogenicity
3. It has longer T1/2 so single dose a day is sufficient - Liver damage (hepatitis)
4. Since prothrombin time/clotting time are into Uses
prolonged laboratory monitoring is not required. - Established venous thromboembolism
5. No report of thrombocytopenia and osteoporosis - Secondary prophylaxis of vanous thrombosis
Warfarin [KU 10] and pulmonary embolism
- Warfarin is the most common oral - Prosthetic heart valve thromboembolism
anticoagulant used in vivo and not in vitro - Mitral stenosis
- Bioavailability is nearly 100% - Atrial fibrillation
- It can cross placental barrier so it is teratogenic - Thyrotoxic heart disease
drug. - Unstable angina
Mechanism of action - Stroke prophylaxis
- Warfarin acts indirectly by inhibiting the Note:
synthesis of vitamin K dependant clotting factors.
- Monitoring of warfarin therapy is done by
- It interferes with regeneration of active
prothrombin time.
hydroquinone form of vitamin k which carries out III
the final step of carboxylating glutamate residue Contraindication
of prothrombin and factors VII, IX, and X - Recent trauma, injury
- This carboxylation is essential for the ability of - Active internal bleeding e.g. peptic ulceration
clotting factor to bind Ca++ and to get bound to - Severe HTN
phospholipid surface, necessary for - Non thromboembolic strokes
coagulation sequence to proceed.
- Major surgery (brain, spinal cord)
Decarboxy prothrombin Prothrombin - Pregnancy (teratogenicity)
(or factor VII,IX,X) (or factor VII, IX, X)
- Lactating mother (appears in milk)
- Severe liver and renal disease
- Hypoprothrombinemia
Vitamin K Vitamin K Note: Fetal warfarin syndrome
Hydroquinone Epoxide - Warfarin given in early pregnancy causes skeletal
abnormalities like hypoplasia of nose, eye socket,
hand bones and growth retardation
NAD NADH - Warfarin given later in pregnancy causes CNS
defects, foetal haemorrhage, foetal death and
Blocked by anal
anticoagulants accentuates neonatal hypoprothrombinemia.

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 Pharmacology

Heparin V/S Warfarin THROMBOLYTIC/ FIBRINOLYTICS

Heparin Warfarin Past Questions:
Large anionic Small lipid soluble 1. Role of thrombolytic agent in acute attack of
Structure
polymer, acidic molecule myocardial infarction [3][02 Dec]
Route given Parenteral (IV, SC) Oral 2. Streptokinase is used in myocardial infarction
Site of action Blood Liver [3][09 July, 08 July]
Impairs synthesis 3. Low dose aspirin [3][07 July, 06 Dec]
and carboxylation 4. Low dose Aspirin in therapy [3][10 July]
Activates
of vitamin K- 5. Use of small doses of aspirin for prevention of
antithrombin III
dependent of
Mechanism which decrease myocardial infarction [3][02 June, 05 June]
factors II, VII, IX and
of action the action of 6. Aspirin (low dose) in myocardial infarction
X and protein C and
thrombin (IIa) and
protein C and [3][05 Dec]
Xa
protein S (vitamin K 7. Aspirin in low dose in prophylaxis of MI [3][10 Jan]
antagonist)
 These are the drugs used to lyse thrombi/clot to
Slow, limited by recanalise occluded blood vessels mainly coronary
Onset of Rapid (within
half-lives of clotting
action seconds) artery.
factors
 They act by activating natural fibrinolytic system.
Duration of
Acute (hours) No  Venous thrombi lysed easily than arterial and
action
recent thrombi respond better.
Inhibits
coagulation Yes No  Clinically important thrombolytics/fibrinolytics are
in vitro - Streptokinase
III Treatment of - Urokinase
Protamine IV vitamin K and
acute - Alteplase
sulphate fresh frozen plasma
overdose
- Reteplase
PTT (intrinsic PT/INR (Extrinsic
Monitoring - Tenecteplase
pathway) pathway)
EXTRINSIC INTRINSIC

Streptokinase Factor XIIa

Urokinase ACTIVATORS Kallikrein
Alteplase (rt-PA) t-PA
Tenecteplase FIBRIN
(Insoluble)

PLASMINOGEN PLASMIN
(profibrinolysin) (Fibrinolysin)

FIBRIN FRAGMENTS
EACA Antiplasmin (Soluble)
Tranexaemic acid INHIBITORS Macroglobulin

EXTRINSIC INTRINSIC

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Mechanism of action
- All the thrombolytics activate plasminogen
molecules causing its limited proteolysis to
plasmin
- Thus formed plasmin is a non - specific
protease which degrades coagulation factors
into fragments and makes them soluble. As a
result thrombus dissolves
Streptokinase [KU 08, 09]
- It is obtained from -haemolytic Streptococci
group C
- Streptokinase combines with circulating
plasminogen to form an activation complex
which then causes limited proteolysis of other
plasminogen molecules to plasmin. Plasmin
causes hydrolysis of fibrin plugs.
Adverse effect:
- Causes hypersensitivity and anaphylaxis as it is
antigenic
- Fever is common, hypotension
arrhythmias
Dose:
- MI: 7.5 - 15 lac IU infused iv over 1 hr
- For deep vein thrombosis and pulmonary
embolism  2.5 lac IU
Urokinase
- Enzyme isolated from human urine.
- Now prepared from cultured human kidney cells
- It activates plasminogen directly
- It is non-antigenic but fever occurs during
treatment
- Indicated in patient in whom streptokinase has
been used for earlier episode.
Alteplase (Recombinant tissue-
plasminogen activator rt - PA)
- Produced by recombinant DNA technology
from human tissue culture
- It activates gel phase plasminogen already
bound to fibrin and has little action on
circulating plasminogen.
- Non- antigenic but nausea, mild hypotension
and fever may occur.
FAST TRACK BASIC
Haemopoietic
Uses of Fibrinolytics
1. Acute myocardial infarction
2. Deep vein thrombosis
3. Pulmonary embolism
4. Peripheral arterial occlusion
5. Stroke
ANTIFIBRINOLYTICS
 These are drugs which inhibit plasminogen
activation and dissolution of clot.
 Clinically used antifibrinolytics are
1. Epsilon amino - caproic acid (EACA)
2. Tranexaemic acid
3. Aprotinin
Epsilon Amino - Caproic Acid (EACA)
Mechanism of Action
- It combines with lysine binding sites of
and plasminogen and plasmin.
- As a result, plasminogen and plasmin cannot
bind to fibrin and lyse it.
Use
- Overdose of fibrinolytics III
- To prevent recurrence of subarachnoid and G.I.
haemorrhage
- Certain traumatic and surgical bleeding
- Abruptio placentae, Post Partum Hemorrhage
and menorrhagia
Adverse effect
- In haematuria, it can cause ureteric obstruction
- Intravascular thrombosis
- Rapid I.V. injection results in hypotension,
bradycardia, arrhythmias
- Myopathy (rare)
Note:
- Tranexaemic acid is similar to EACA but 7 times
more potent.
- Aprotinin has serine protease inhibitory activity i.e.
trypsin, chymotrypsin, kallikrein, plasmin are
inhibited.
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 Pharmacology
ANTIPLATELET DRUGS
Past Questions:
1. Give the pharmacological basis for:
a. Antiplatelet drugs used in prevention of
thromboembolic disorder [3][08 July]
b. Antiplatelet drugs [3][03 Dec]
 These are the drugs which interfere with platelet
function and are useful in prophylaxis of
thromboembolic disorders.
 Clinically important antiplatelet drugs are
- Aspirin
- Clopidogrel
- Dipyridamole
- Abciximab
- Ticlopidine
- Glycoprotein IIb/IIa receptor antagonist
1. Aspirin [KU 05, 07, 10]
- It acetylates and inhibits enzyme, cyclo-
oxygenase-1 and thromboxane A2 synthase
inactivating them irreversibly.
- Platelets are exposed to aspirin in portal
III
circulation before 1st pass metabolism so
inhibition of TXA2 occurs even in small dose.
- Since platelets have no nuclei, they cannot
synthesize fresh enzyme so TXA2 formation is
supressed till new platelets are formed
(Approx. 7 - 10 days)
- Aspirin at low dose (75 - 150 mg/day) inhibits
only TXA2 formation but at higher dose (> 900
mg/day) inhibits both TXA2 and PGI2 formation.
- Though PGI2 is inhibited, vascular intimal cells
can synthesize fresh enzyme and activity
returns rapidly [PGI2 also inhibits platelet
activation]
- Aspirin also inhibits release of ADP from
platelets. [ADP is necessary for platelets to
stick with each other]
- Thus platelet aggregation and formation of
haemostatic plug is inhibited.
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2. Dipyridamole
- It blocks Phosphodiesterase. Thus, uptake of
cAMP by phosphodiesterase is inhibited and
platelet cAMP level increases.
- This, cAMP potentiates PGI2 action i.e.
interferes in platelet aggregation.
- But levels of TXA2 or PGI2 are not altered.
3. Ticlopidine
- It alters surface receptors on platelets and
inhibits ADP as well as fibrinogen induced
platelet aggregation.
- It irreversibly blocks Gi Coupled receptors, so
adenylyl cyclase is not inhibited; cAMP
formation increases, potentiates PGI2 and
inhibits platelet aggregation.
- It prevents fibrinogen binding to platelets
without modifying GP II b/ III a receptor
- There is no effect on platelet TXA2
4. Clopidogrel
- Newer congener of ticlopidine
- Has similar mechanism of action and
therapeutic efficacy but appeared to be safer
and better tolerated.
5. Glycoprotein (GP) IIb/IIIa receptor
antagonists
- GP IIb/IIIa is an adhesive receptor for fibrinogen
and vWF through which agonists like collagen,
thrombin, TXA2, ADP etc induce platelet
aggregation.
- These drugs inhibit GP IIb/IIa receptor and thus
platelet aggregation is inhibited.
6. Abciximab
- It is a Fab fragment of monoclonal antibody
against GP IIb/IIIa receptor.
- Thus, it also inhibits platelet aggregation.
Uses of Antiplatelet drugs
- Coronary artery disease i.e. MI, unstable
angina etc
- Cerebrovascular disease
- Coronary angioplasty, stents, by pass implants
SCIENCE MBBS
 Haemopoietic

- Prosthetic heart valves and ateriovenous  Ferrous fumarate: (33% iron)

shunts  Colloidal ferric hydroxide: (50% iron)
- Venous thromboembolism - Other forms of iron present in oral
- Peripheral vascular disease formulations are:
Adverse effect  Ferrous succinate (35% iron)
- Bleeding  Iron choline citrate
- Thrombocytopenia  Iron calcium complex (5% iron)
- Nausea, vomiting, epigastric distress  Ferric ammonium citrate (scale iron)
- Hypersensitivity and Idiosyncrasy
 Ferrous aminoate (10% iron)
- Acute salicylate poisoning
 Ferric glycerophosphate
THERAPY OF IRON DEFICIENCY  Iron hydroxy polymaltose
ANEMIA Adverse effect of oral iron [KU 08]
Past Questions: - Epigastric pain
1. List the drugs used in iron deficiency anemia. - Heartburn
Mention the important differences between oral - Nausea, vomiting
iron preparations and adverse effects of oral iron
- Staining of teeth
preparations. [2+3+2=7] [08 Jan]
- Metallic taste
2. List oral iron preparations. Write indications of
parental iron preparations and their adverse - Blotting
effects. [1+1+2=4] [05 June] - Colic
3. Drugs used in microcytic hypochromic anaemia. 2. Parenteral preparation III
What instructions you will give to your patients.
- Iron dextran  50 mg elemental iron/ml
[2+2=4][02 Dec]
- Iron sorbitol - citric acid complex  50 mg
4. Write short notes on:
iron/ml
a. Iron preparation and their important
Indication of parenteral iron therapy [KU 05]
differences. [3][07 July]
b. Ferrous fumarate in therapy [3] [11 July] - When oral iron is not tolerated; bowel upset is
c. Differences in iron preparations [3][10 July] too much

 Iron is major constituent for hemoglobin - When there is failure to absorb oral iron eg
synthesis. malabsorption, inflammatory bowel disease
 Decreased hemoglobin synthesis due to deficiency - Non - compliance to oral iron
of iron results into microcytic hypochromic state - In presence of severe deficiency with chronic
of RBC called as iron deficiency anaemia. bleeding
Iron Preparations [KU 07, 10] - Along with erythropoietin as oral iron may not
1. Oral preparation be absorbed at sufficient rate to meet the
- Some simple oral preparations are: demands of induced rapid erythropoiesis
 Ferrous sulfate: (Hydrated salt- 20% iron, Formula for total iron requirement
dried salt- 32% iron) Iron requirement (mg) = 4.4 × Body wt. (kg) × Hb
 Ferrous gluconate: (12% iron) deficit (g/dl)

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 Pharmacology

Adverse effect of parenteral iron [KU 07] Treatment

1. Local: a. To prevent further absorption of iron
 Pain at site of I.M. injection  Induce vomiting or perform gastric lavage
 Pigmentation of skin with sodium bicarbonate
 Sterile abscess  Give egg yolk and milk orally that forms
2. Systemic complex with iron
 Fever, headache, joint pain, flushing, b. To bind and remove the already absorbed iron
palpitation, chest pain, dyspnea, lymph  Desferrioxamine (iron chelating agent) is
node enlargement. injected I.M. 0.5 - 1 gm (50mg/kg) repeated
 Iron sorbitol should be avoided in patient 4 - 12 hourly as required till serum iron falls
with kidney disease below 300 g/dl
Treatment of Iron deficiency anaemia [KU 02] c. Supportive measure
1. Non pharmacological  Fluid and electrolyte should be maintained
- Food rich in iron such as meat, green leafy  Acidosis should be corrected
vegetables, and pulses general should be taken  BP and respiration should be maintained
more.
- Practice of walking bare foot should be avoided THERAPY OF MEGALOBLASTIC
2. Pharmacological ANAEMIA
- Ferrous sulfate 200 mg 8-hrly till normal Past Questions:
haemoglobin is attained and 2-3 months
1. Folic acid in megaloblastic anaemia [3][06 Dec]
III thereafter to replenish the stores.
2. Folic acid [04 June, 09 July]
- If oral is intolerable parenteral therapy should
3. Therapy of megaloblastic anaemia [2] [09 Jan]
be started.
Acute Iron poisoning Vitamin B12
- 10 - 20 iron tablets or equivalent liquid Preparations
preparation (> 60 mg/kg iron) may cause - Cyanocobalamin
serious toxicity in infants and children. - Hydroxocobalamin
- It is very rare in adults - Methyl cobalamin
Clinical manifestation Uses
- Abdominal pain - Treatment of Vit B12 deficiency
- Haematemesis - Prophylaxis when there are predisposing factor
- Diarrhoea for development of deficiency
- Dehydration - Neuropathies, psychiatric disorder, cutaneous
- Convulsion sarcoid
- Acidosis - Tobacco amblyopia (hydroxocobalamin mainly)
- Lethargy ADR
- Cyanosis - Usually safe, Anaphylactoid reaction on
- Shock, cardiovascular collapse, death i.v. injection may occur.

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 Haemopoietic

Folic acid [KU 04, 09] 4. Give the pharmacological basis for:
a. Chloroquine and Primaquine in P. vivax
Preparations
[3][04 June]
- Folic acid
b. Primaquine after chloroquine in P. vivax
- Folinic acid
malaria [3][10 July, 11 July]
Uses
5. Write short notes on:
- Magaloblastic anaemia
a. Treatment of acute attack of malaria [3][05 Dec]
- Prophylaxis of folate deficiency
b. Radical cure of malaria [3][08 Jan]
- Methotrexate toxicity
c. Treatment of drug resistance falciparum
Treatment of magaloblastic anaemia [4][06 June]
1. Supportive therapy d. Uses and adverse effects of chloroquine
- Blood transfusion: in significantly symptomatic [3][02 June]
and severely anaemic patient e. General toxicity of cytotoxic drugs [3][09 Jan]
- Treatment of infections f. Chloroquine resistant malaria [3][03 Dec]
- Treatment of cardiac failure
2. Specific therapy
- Treatment of underlying causes of vit B12 or
Classification of antimalarials (A/C to
folic acid deficiency.
parasitic stage)
A. Primary tissues schizonticides (causal
- Vitamin B12 therapy
prophylaxis)
 Inj. hydroxocobalamin 1000 g i.m, in five
1. Primaquine: Most effective
doses 2 or 3 days apart
2. Proguanil and Tetracyclines: Less effective
 Maintenance therapy of 1000 g every 3 III
months B. Erythrocytic Schizonticides (Suppressive
prophylaxis)
- Folic acid therapy
1. Highly effective and rapidly acting:
 Tab folic acid 5 mg daily for 3 weeks
Chloroquine, Halofantrine, Quinine,
 Maintenance therapy: Tab folic acid 5 mg
Artemisinin derivatives, Mefloquine,
one weekly.
Mepacrine
THERAPY OF PARASITIC 2. Less effective and slowly acting:
INFECTIONS Pyrimethamine, suphamethoxazole, Proguanil,
Tetracycline
MALARIA
C. Exo-erythrocytic schizonticides (Radical cure)
Past Questions:
1. Primaquine
1. Write regimen for treatment of acute attack of
malaria due to plasmodium falciparum. D. Gametocidals (Prevent transmission)
[2+3+2=7] [05 Dec] 1. Chloroquine
2. Write on suitable regimen for: [2+2=4] [02 Dec] 2. Proguanil
a. Treatment of acute attack of malaria 3. Primaquine
b. Prophylaxis of malaria
4. Artemisinin derivatives
3. Uses and adverse effects of chloroquine
[3] [02 June] 5. Pyrimethamine

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 Pharmacology

Blood
vessel
Enter liver
Maturation Sporozoites

Zygote Erythrocytic RBC

Schizogony Pre-erythrocytic
schizogony
Primaquine
Proguanil
Tetracycline
Exo-erythrocytic
Male & schizogony
Chloroquine
Quinine female
Mefloquine gametes
Halofantrine
Artemisinin Primaquine
Mepacrine
Atovaquone Primaquine
Sulfadoxine-pyrimethamine Chloroquine
Proguanil Quinine
Tetracyclines

Chloroquine [KU 02, 10, 11] - Infectious mononucleosis

- Chloroquine is a synthetic 4 - amino quinoline. - Photogenic reactions
- Giardiasis
III - It is rapidly acting erythrocytic schizontocide
against all species of Plasmodia. [@My RED LIP Girl]
MOA Adverse effects
- Exact mechanism is not known With oral administration
- As chloroquine is slightly basic, it accumulates - Nausea, vomiting, anorexia, epigastric pain,
in acidic lysosomal vacuoles of Plasmodia headache
- It then raises the pH of vacuoles and thereby Parenteral administration
interferes with degradation of hemoglobin by - May cause hypotension, cardiac depression,
parasitic lysosomes. arrhythmias and CNS toxicity including convulsions
- Polymerization of toxic haeme to nontoxic Prolonged use
hemozoin is inhibited by formation of - Retinal damage, loss of hearing, rashes, photo
chloroquine - heme complex allergy, mental disturbance, myopathy, graying
of hair etc
- Haeme (as it is toxic) itself or its complex with
chloroquine then damages plasmodial membrane. Note: Criteria for developing retinal damage
Use - Dosage > 6.5 mg/kg
- Duration of Use > 5 years
- Malaria
- High fat level
- Rheumatoid arthritis
- Presence of renal/liver disease
- Extraintestinal amoebiasis
- Presence of concomitent retinal disease
- Discoid lupus erythematous - Age > 60 years
- Leprae reactions
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Contraindication
- Psoriasis
- Porphyria
- Retinal or visual field abnormality
- Myopathy
- Cautious use in patient with history of liver
disease, neurologic and hematologic disorders
Primaquine [KU 10, 11]
 Synthetic 8 - aminoquinoline
 Most effective tissue schizonticide but poor
erythrocytic schizonticide
 Active against hepatic stage of all human malaria
parasites
 Also highly active against gametocytes and
hypnozoites
 Mechanism of antimalarial action is unknown,
postulated mechanism is disruption of plasmodial
mitochondria.
ADR
- Abdominal pain, G.I. upset, nausea vomiting,
chest uneasiness
- Hemolytic anaemia in G6PD deficiency
- Methaemoglobinemia in NADH
methemoglobin reductase deficiency
- Leucopenia occurs rarely with large dose
- CNS and cardiovascular symptoms are
infrequent.
Use
- Radical cure of Relapsing (vivax and ovale)
malaria
- Chemoprophylaxis of malaria
- Gametocidal action
- Penumocystis jiroveci infection
Mefloquine (4 - quinoline methanol)
 Fast acting erythrocytic schizontocide
 Effective against chloroquine sensitive as well as
chloroquine resistant Plasmodia
 One of the recommended chemoprophylactic
drugs for used in most malaria endemic regions
with chloroquine resistant strains
FAST TRACK BASIC
Haemopoietic
MOA
- Structural analog of quinine, exact mechanism
unknown, acts as a blood schizonticide
- May increase intravesicular pH in parasites
- It appears to bind to haem and the complex
damages membrane of parasite
ADR
- Dizziness, nausea, vomiting, diarrhoea,
abdominal pain, sinus bradycardia
- Neuropsychiatric reactions like disturbed sense
of balance, ataxia, anxiety, hallucination,
strange dreams and rarely convulsions
- Hematological, hepatic and cutaneous toxicity
are rare.
USE
- Multi-resistant P. falciparum
- Prophylaxis of malaria among travelers
Contraindication
- In patient with a history of epilepsy, psychiatric
disorders, arrhythmia, cardiac conduction
defect or sensitivity to related drugs.
Quinine III
-
 Levo - rotatory alkaloid obtained from cinchona bark
 Erythrocytic schizonticide
 Gametocidal against P. vivax and P. ovale
 Inactive against liver stage parasite
MOA
- Exact mechanism is unknown
- Like chloroquine, it a weak base; gets
concentrated in the acid vacuoles of the blood
schizonts and causes pigment changes; inhibits
polymerization of heme to hemozoin; free
heme or heme - quinine complex damages
parasite membranes and kills it.
Adverse reaction
1. Cinchonism
- Large single dose or higher therapeutic doses
taken for a few days produce syndrome called
cinchonism.
SCIENCE MBBS -799-
 Pharmacology

- Features  Doxycycline 100 mg BD for 7 days

 Nausea, vomiting, headache, mental
confusion, vertigo, difficulty in hearing and
visual defects, diarrhoea, flushing and
marked perspiration
 Still higher dose results in delirium, fever,
tachypnoea followed by respiratory
depression, marked weakness, protration
can occur
2. Hypersensitivity: Purpura, rashes, itching,
angioedema of face, bronchoconstriction.
3. May cause haemolysis
Use
1. Malaria
a. Uncomplicated resistant P. falciparum malaria
b. Complicated and servere malaria including
cerebral malaria
2. Arrhythmia
3. Babesiosis
4. Nocturnal muscles cramps
III 5. Diagnosis of myasthenia gravis
6. Varicose veins
Treatment of acute attack of malaria
[KU 02, 05]
1. For acute attack of P. vivax, P. ovale, P malariae
and chloroquine sensitive P. falciparum
- Oral Chloroquine is drug of choice
- Chloroquine
 600 mg base (10mg/kg) stat
 300 mg base 6 hours later on first day
 300 mg base on second day (24 hr after 1st
dose)
 300 mg base on third day (48 hr after 1st
dose)
2. For chloroquine resistant P. falciparum infection
- Quinine sulphate 600 mg (10 mg/kg) orally TDS
for 3- 7 days with either

-800- FAST TRACK BASIC
Or
Clindamycin 600 mg BD for 7 days
Or
Pyrimethamine 25 mg + sulphadoxine 500 mg
(Fixed dose combination) three such tablets as a
single oral dose
Radical cure of malaria [KU 08]
- Total eradication of parasite from patient's
body is termed as radical cure.
- It is achieved by administration of drug which
inhibit exo-erythrocytic cycle (hypnozoites)
along with the drugs given for clinical cure
Regimen
I. Chloroquine:
600 mg base (10 mg/kg) stat
300 mg base 6 hours later
300 mg base - second day (24 hrs of 1st dose)
300 mg base - third day (48 has of 1st dose)
II. Primaquine: Given at a dose of 15 mg base orally
daily for 14 days only to individual who test
negative for G6PD deficiency after chloroquine
Treatment of chloroquine resistant P.
falciparum [KU 03]
- Artesunate 100 mg BD (4mg /kg /day) × 3 days
+ sulfadoxine 1500 mg (25 mg/kg) +
Pyrimethamine 75 mg (1.25 mg /kg) stat
OR
- Artesunate 100 mg BD (4mg/kg/day) × 3 days +
mefloquine 750 mg (15 mg/kg) on 2nd day and
500 mg (10 mg/kg) on 3rd day
OR
- Artemether 80 mg + Lumefantrine 480 mg twice
daily × 3 days (child 25 -35 kg BW 3/4 dose; 15-25
kg BW 1/2 dose; 5-15 kg BW 1/4 dose)
OR
- Arterolane (as maleate) 150 ml + Piperaquine
750 mg once daily × 3 days
OR
- Quinine 600 mg (10 mg/kg) 8 hourly × 7 days +
Doxycycline 100 mg daily × 7 days or +
clindamycin 600 12 hourly × 7 days.
SCIENCE MBBS
 Haemopoietic

DRUG THERAPY FOR Adverse effect

LEISHMANIASIS - It caused histamine release which is
Past Questions: responsible for
 Sharp fall in BP
1. Write short notes on: (Each question carries 3
marks unless specified)  Cardiovascular collapse
a. Treatment of kala-azar [07 July]  Dyspnoea
b. Stibogluconate in therapy [3] [11 July]  Palpitation
c. Sodium stibogluconate [04 Dec]  Fainting
 Vomiting
Classification [KU 05]
- Other adverse effects are rashes, mental
- Antimonal: Sodium stibogluconate (SSG) confusion, kidney and liver damage, ECG
- Diamide: Pentamide changes and rarely cardiac arrhythmias.
- Antifungal drugs: Amphotericin B (AMB), Treatment of kala-azar [KU 06]
Ketoconazole (KTZ) 1. Blood transfusion to correct anaemia and
- Others: Miltefosine, Paromomycin, Allopurinol treatment of bacterial infections with antibiotics
Sodium Stibogluconate [KU 04, 11] 2. Drug therapy
- Drug of choice for Kala-azar - Pentavalent antimonials: Sodium
MOA stibogluconate 20 mg/kg for 28 days
- Blocks glycolytic and fatty acid oxidation - Pentamidine: 4 mg/kg i.m. on slow iv for 5 - 25
pathways weeks on alternate days
- SH dependent enzymes are inhibited and - Antifungal: Amphotericin B 0.75 - 1.0
bioenergetics of parasite is interfered. mg/kg/day for 15 - 20 days
- An enzyme present in amastigotes reduces [For post kala-azar dermal leishmaniasis III
pentavalent - antimony of SSG to the toxic (PKDL), prolonged treatment for 3 - 4 months is
trivalent form, which then promotes efflux of required]
glutathione and other reduced thiols from
parasite exposing it to oxidative damage. DRUG THERAPY FOR FILARIASIS
ADR Past Questions:
- Nausea, vomiting, metallic taste, cough, pain
1 Diethylcarbamazine citrate (3) [02 June]
abdomen, pain and stiffness of injected
2. Give the pharmacological basis for:
muscles, sterile abscess
- Pancreatitis, liver and kidney damage, myelo a. Diethylcarbamazine in therapy [3][10 July]
suppression, ECG changes are possible. 2. Write short notes on: (Each question carries 3
Pentamidine marks unless specified)
MOA a. Diethylcarbamazine in therapy [3][11 July]
- Interacts with kinetoplast DNA and inhibits b. Diethylcarbamazine citrate
topoisomerase II or interferes with aerobic [3][10 Jan, 07 July, 09 Jan, 02 June]
glycolysis and utilization of polyamines c. Mechanism of action of Diethylcarbamazine
Uses [3][06 June]
- Kala-azar Drugs commonly used are
- Pneumocystis jiroveci pneumonia - Diethylcarbamazine citrate (DEC)
- Trypanosomiasis - Ivermictin

FAST TRACK BASIC SCIENCE MBBS -801-

 Pharmacology

Diethylcarbamazine Citrate (DEC) ANTICANCER DRUGS

[KU 02, 06, 07, O9, 10, 11]
Past Question:
- Highly selective upon microfilaria (MF)
1. List the drugs used in leukemias. Write adverse
- Prolonged treatment may kill adult B. malayi
reactions of anti-cancer drugs. [4+3=7][08 July]
and probably W. bancrofti also.
MOA Classification
- Alter the microfilarial membranes so that they 1. Alkylating agents:
are readily phagocytosed by tissue fixed a. Nitrogen mustard:
monocytes (not by circulating phagocytes)  Mechlorethamine
- Muscular activity of microfilaria and adult
 Cyclophosphamide
worms is also affected causing hyper
polarization due to piperazine moiety so that  Melphatan
they are dislodged.  Chlorambucil
Use b. Alkyl sulphonate: Busulphan
1. Filariasis: Drug of choice
c. Nitrosoureas:
 A dose of 2mg/kg TDS for 7 days
 Carmustine
2. Tropical eosinophilia
 2 - 4 mg/kg TDS For 2 - 3 weeks  Lomustine
Adverse effect  Streptozocin
- Drug induced effects: Anorexia, nausea, d. Platinum - containing compounds:
vomiting, headache, tiredness and dizziness
 Cisplatin
- Parasite induced reaction: Due to release of
III proteins from dying parasites characterized by
 Carboplatin
fever, skin rashes, severe itching, cough, chest 2. Anti - metabolites:
pain, muscles and joint pain. a. Folate antagonist: methotrexate
Ivermictin: b. Purine antagonist:
MOA
 6 - mercaptopurine
- Acts via special type of glutamate gated Cl–
channel and causes tonic paralysis of parasite  6 - thiogurine
- Potentiation of GABAergic transmission in 3. Pyrimidine antagonist
worm has also been observed. - 5 - Fluorouracil
Use - Cytarabine
- Filariasis (single 10 - 15 mg oral dose annually
4. Natural products
for 5-6 years
a. Vinca alkaloids: Vinblastine, vincristine
- Strongyloidosis (single 0.15 - 0.2 mg/kg)
Adverse effect b. Taxanes: Paclitaxel, docetaxel
- Pruritus, giddiness, nausea, abdominal pain, c. Epipodophyllotoxins: Etoposide, Teniposide
constipation, lethargy and transient ECG d. Comptothecins: Topotecan, Irinotecan
changes 5. Hormones and antagonists:
- Reactions due to degeneration products of Mf a. Oestrogens: Ethinyl estradiol, Fosfestrol
which are similar to those occurring after DEC b. Antiestrogen: Tamoxifen

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 Haemopoietic

c. Progestins: Hydroxyprogesterone caproate, Current choice of drugs in malignancy

medroxyprogesterone acetate S. Second line
Malignancy First line drugs
d. Androgens: Testosterone propiionate N. drugs
e. Antiandrogen: Flutamide 1. Acute VAMP Cytarabine, 1-
f. 5 -  reductase inhibitor: Finasteride leukemia combination Asparaginase,
g. GnRH analogues: Buserelin, Goserelin, Methotrexate
Natarelin Maintenance Dounorubicin 6- Doxorubicin
h. Corticosteroids: Prednisolone and others TG, 6-MP,
General Toxicity of cytotoxic drugs [KU 08] Cyclophosphamide
These drugs have more profound effect on rapidly 2. Chronic Chlorambucil, Cytarabine,
multiplying cells because the most important lymphatic fludarabine, Doxorubicin
target of action are the nucleic acids and their leukemia cyclophosphamide
precursors: rapid nucleic acid synthesis occurs prednisolone
during cell division.
3. Chronic Busulfan, Imatinib 6 - MP, 6 - TG,
1. Bone marrow: Depression of bone marrow myeloid Mitoxantrone, Hydroxyurea
results in granulocytopenia, agranulocytosis, leukemia Interferon vincristine,
thrombocytopenia, aplastic anemia. cyclophosphamid
2. Lymphoreticular tissue: Lymphocytopenia and e, melphalan
inhibition of lymphocyte functions results in
4. Hodgkin's MOPP Bleomycin,
suppression of cells mediated as well as
disease combination procarbazine,
humoral immunity.
vinblastine, Lomustine, III
3. Oral cavity: Stomatitis Dacarbazine Ifosphamide,
4. GIT: Diarrhoea, shedding of mucosa, Doxorubicin,
hemorrhages occurs due decrease in the rate cytarabine,
of renewal of the mucosal lining prednisolone
5. Skin: Alopecia occurs due to damage to the
cells in hair follicles THERAPY OF SHOCK
6. Gonads: Inhibition of gonadal cells causes  Shock is a clinical syndrome that occurs because
oligozoospermia and impotence in males; of inability of circulatory system to provide
inhibition of ovulation and amenorrhea are adequate oxygen and nutrients to meet metabolic
common in female demand of vital organs.
7. Foetus: Abortion, foetal death, teratogenesis Causes
8. Carcinogenicity: Secondary cancers, especially - Dehydration
leukemia, lymphomas and histiocytic tumors - Haemorrhage
9. Hyperuricemia: Gout and urate stones in the - Sepsis
urinary tract may develop. - MI
- Vulvular heart disease
- Adrenal failure

FAST TRACK BASIC SCIENCE MBBS -803-

 Pharmacology

- Spinal cord injury ii. Vasodilator drugs

- Anaphylaxis  Nitroprusside: Arteries > Veins
- Trauma  Nitroglycerin: Veins > Arteries
- Poisoning etc 2. Inotropic drugs
Symptoms - Dopamine  D1/D2>> receptor
- Failure of multiple organ system - Dobutamine 1>2> receptor
- Confusion, agitation - Epinephrine  1> 2> receptor
- Respiratory distress - Milrinone  Phosphodiesterase inhibitor
- Tachycardia, tachypnea - Amrinone Phosphodiesterase inhibitor
- Hypotension, decreased urine output 3. Antibiotic
Drugs used in shock - Administered to patient in septic shock
1. Vasoactive drugs - Choice depends on most likely pathogen
i. Vasopressor drugs - 3rd generation cephalosporin, vancomycin are
 Dopamine  D1/D2>> used commonly
 Epinephrine 1 = 2> 4. Corticosteroids
 Nor epinephrine 1>>2 - Recommended in patent with catecholamine -
 Phenylephrine  selective resistant shock and suspected or proven
adrenal insufficiency.

III

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 Haemopoietic

SPECIAL POINTS FOR MCQs

1. Maximum iron absorption occurs in duodenum and proximal jejunum.
2. Vitamin B12 is absorbed in distal ileum whereas folic acid is absorbed in proximal jejunum.
3. The antidote of acute iron poisioning is desferrioxamine (IM) whereas for chronic iron overload,
deferiprone (oral) is preferred.
4. Rise of hemoglobin level of blood by 0.5-1 g/dl per week is considered adequate response to iron
therapy.
5. Iron requirement is determined by equation.
4.3  Body weight (Kg)  Hemoglobin deficit (g/dl)
6. Iron sorbitol citrate should not be used I.V because it may rapidly saturate transferrin receptors
and can result in high concentration of free iron.
7. To raise haemoglobin level of blood by 1gm/dl, about 200mg of iron is needed.
8. If the cause of megaloblastic anaemia is not known, folic acid alone should not be given because it
will correct blood picture of anaemia but neurological deficits due to vitamin B12 deficiency may be
aggravated.
9. Posterior column sensations in lower limbs are lost in Vitamin B12 deficiency
10. Parenteral hydroxycobalamine is preferred over cyanocobalamine for treating Vit B12 deficiency
because it is highly bound to plasma so remains longer in circulation.
11. Leucovorin can be used to prevent toxicity of methotrexate. III
12. Bleeding tendency due to coumarin therapy is reversed by vitamin K injection.
13. Pre-conceptional intake of folate results in decrease in incidence of neural tube defects
14. Vitamin K is involved in post- translational modification of Glutamate.
15. Vitamin K is involved in the activation of various clothing factors like II, VII, IX and X as well as
anti- clotting proteins like proteins C and S
16. Menadione (K3) is contraindicated in patient with G-6-PD deficiency (cause hemolysis) and in
newborn (more chance of kernicterus due to competitive inhibitions of glucuronidation of
bilirubin and its displacement from plasma protein binding sites).
17. Erythropoietin is used to treat anemia associated with chronic renal failure and cancer
chemotherapy.
18. Salt of heparin used as in-vitro anticoagulant is lithium heparin.
19. Route by which heparin is never administered is intramuscular route.
20. Anti-coagulant of choice for heparin induced thrombocytopenia is Lepirudin
21. Hemorrhage secondary to heparin administration can be corrected by administration of whole
Blood. Protamine is heparin antagonist but it is used infrequently because action of heparin
disappears by itself in few hours.
22. Protamine is indicated when heparin action needs to be terminated rapidly.
23. Heparin therapy should be monitored with intermittent estimation of partial thromboplastin time.

FAST TRACK BASIC SCIENCE MBBS -805-

 Pharmacology

24. Warfarin therapy should be monitored with intermittent estimation of prothrombin time.
25. Fresh frozen plasma is treatment of choice for bleeding but to warfarin.
26. Anticoagulant that is widely used as rodenticide is warfarin.
27. In warfarin treated patient, skin necrosis is found in protein C deficiency
28. Warfarin should not be used in pregnant female because it crosses placental barrier and has
teratogenic potential.
29. Drug of choice for treating hemophilia and von willibrand’s disease is cryoprecipitate.
30. Streptokinase is contraindicated in malignancy.
31. Aspirin is preferred over NSAIDs for antithrombotic action because it is an irreversible inhibitor
of cyclo-oxygenase enzyme.
32. Anticoagulant of choice for coagulation testing is Trisodium citrate 3.2%
33. Inhibitors of Gp IIb/IIIa receptors are abciximab, tirofiban and eptifibatide.
34. Ticlopidine and clopidogrel acts as antagonists of P2Y12 type of ADP receptors.
35. Clopidogrel is preferred over ticlopidine because latter can cause thrombocytopenia. Also,
Clopidogrel is less likely to cause neutropenia.
36. Most appropriate drug used for chelation therapy in β-thalassemia major is oral deferiprone.
37. Dextran is a good plasma expander but the disadvantage is it may interfere with blood grouping
and cross matching.
38. Drug of choice for treatment and prophylaxis of non-falciparum malaria is chloroquine.
39. Drug of choice in patient with severe complicated falciparum malaria is artesunate.
40. Drug of choice for malaria during pregnancy is chloroquine.
III 41. Drug of choice for chloroqurine resistant malaria in pregnant is Quinine.
42. Antimalarial agent which is most commonly associated with acute hemolytic reaction in patients
with G6PD deficiency is primaquine
43. Bull’s eye retinopathy is seen with chloroquine.
44. Drug of choice for Chloroquine resistant malaria is Quinine.
45. Tissue schizontocide which can prevent relapse of vivax malaria is Primaquine. Thus, it is used for
radical cure.
46. Safest anti-malarial drug during pregnancy is Proguanil.
47. Antimalarial agent which can cause hypoglycemia in patient with severe cerebral malaria on
treatment is Quinine.
48. Antimalarial drug known to cause neuropsychiatric adverse reaction is mefloquine.
49. Drawback of antesunate is rapid recrudescence of malaria.
50. Antimalarial drug whose absorption increase with food intake is Lumefartrine
51. Volume of distribution of chloroquine is above 1300L. It is the drug with highest distribution.
52. Fastest acting drugs against malaria are Artemisinins.
53. Proguanil acts by inhibiting Dihydrofolate reductase ( DHFRase)
54. Artemisinin derivatives are used for treatment of multidrug resistant malaria as well as serious
form like cerebral malaria.

-806- FAST TRACK BASIC SCIENCE MBBS