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Pharmacology

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Question
34 out of 45
 

Antagonist of heparin is: (LQ)



A Protamine sulfate
B Phylloquinone

C Ticlopidine
D Clopidogrel

Ans. A Protamine sulphate. (Ref.: - KDT, 6th, 600.)

Protamine sulphate is the antagonist for heparin & is indicated in overdose due to heparin as well as where heparin action must be terminated rapidly – after cardiac or vascular surgery. Phylloquinone is vitamin K derivative, while ticlopidine and Clopidogrel are anti-platelet drugs useful for arterial thrombi prophylaxis.

Indirect Thrombin Inhibitors

a. This group includes UN fractionated heparin, low molecular weight heparin (enoxaparin, dalteparin) and fondaparinux.

b. Heparin is the strongest organic acid present in the body (in mast cells)

c. This group of drugs act by activating antithrombin III (AT III) in plasmA.

d. UN fractionated heparin inhibits both factor IIa and Xa whereas LMW heparins and fondaparinux inhibit only factor XA.

e. As heparin is inhibiting already activated factors, so there is no time lag between the administration and action of this drug, therefore it can be used for initiation of anticoagulant therapy.

f. Heparin is not absorbed by oral route, therefore should be given either by s.c. or i.g. route: (i.m. route is contra indicated due to more chances of hematoma formation).

g. It does not cross the placenta and is thus anticoagulant of choice during pregnancy.

h. At higher doses, heparin also exerts antiplatelet action leading to bleeding.

i. Bioavailability of UN fractionated heparin is inconsistent after s.c. route and its effects is monitored by testing aPTT

j. LMW heparin and fondaparinux have long half lives and consistent absorption; therefore do not require monitoring and once daily s.c. does are sufficient.

k. The major adverse effect of these drugs also is bleeding which is treated with fresh frozen plasma.

l. Specific antidote of heparin is protamine (highly basic drug that can cause release of histamine).

m. Other adverse effects include thrombocytopenia, alopecia, osteoporosis and hypersensitivity reactions.

n. Thrombocytopenia (HIT syndrome; Heparin induced thrombocytopenia syndrome) may occur due to formation of antibodies against platelets that can result in paradoxical thrombosis. Warfarin is contraindicated in such a case and LMW heparin or fondaparinaux should not be used.

o. Anticoagulant of choice for HIT syndrome is direct thrombin inhibitors like aragtroban or lepirudin.

p. (Remember:1 mg of protamine neutralizes approximately 100 units of heparin sulfate; maximum dose, 50 mg intravenously)

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