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17 Cards in this Set
- Front
- Back
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Anticoagulants |
These are drugs used to reduce the coagulability of blood. |
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classification of anticoagulants |
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heparin chemistry |
- Heparin is a non uniform mixture of straight chain mucopolysaccharides with MW 10000 to 20000 |
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heparin occurrence |
It occurs in mast cells as a much bugger molecule (mw ~ 75000) loosely bound to a granular protein. - heparin is present in all tissues containing mast cells, richest sources are lung, liver and intestinal mucosa. |
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Anticoagulant action of heparin |
- powerful and instantaneously acting anticoagulant - acts indirectly by activating plasma antithrombin III (AT III, a serine proteinase inhibitor) - heparin AT III complex binds to clotting factors of intrinsic and and common pathways and inactivates them. - the anticoagulant action is exerted mainly by inhibition of factor Xa and thrombin mediated conversion of fibrinogen to fibrin. |
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heparin enhances the action if AT III how? |
- the long heparin molecule provides a scaffolding for the clotting factors on one hand and AT III on the other so they interact with each other - heparin induces conformational change in AT III to expose it's interactive sites * inhibiton of IIa requires both mechanisms but Xa inhibition can occur by mechanism "2" |
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antiplatelet effect of heparin |
Heparin in higher doses inhits platelet aggregation and prolongs bleeding time |
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Lipaemia clearing by heparin |
-Injection of heparin clears turbid post prandial lipaemic plasma by releasing a lipoprotein lipase from the vessel wall and tissues which hydrolyses TGs of chylomicra and VLDL into FFA. -The FFAs then pass into tissues and the tissue looks clear. |
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Pharmacokinetics of heparin |
- large, highly ionized molecule - injection by iv acts instantaneously - sc injection takes over 60 mins to develop - heparin doesn't cross BBB or placenta (used during pregnancy) - metabolised in liver by heparinase and fragments are excreted through urine |
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Adverse effects of heparin |
- bleeding due to overdose is the most serious complication, since heparin interfere w secondary haemostasis, bleeding from deeper organs is common. hematuria is first sign!! - heparin induced thrombocytopenia (HIT) : mild and transient, occurs due to aggregation of platelets. in some patients, ABs are formed to heparin-platelet complex and marked depletion of platelets occurs - heparin should be discontinued in this case - transient and reversible alopecia - osteoporosis - hypersensitivity reactions are rare |
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contraindications of heparin |
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LOW MOLECULAR WEIGHT HEPARINS : mode of action |
- heparin has been fractionated into LMW forms (MW 3000 to 7000) by different techniques. - they selectively inhibit factor Xa with little effect on IIa. they act by inducing conformational change in AT III and not by providing a scaffolding for interaction of AT III with thrombin - smaller effect on aPTT and whole blood clotting time than UFH - eliminated primarily by renal excretion , not to be used in patients with renal failure |
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advantages of LMW heparin |
- better subcutaneous bioavailability compared to ufh - longer and more consistent T1/2, making it possible for once daily administration - aPPT/clotting times are not prolonged - risk of osteoporosis is lesser than in ufh |
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indications of LMW heparins |
- prophylaxis of DVT and PE in high risk patients - treatment of DVT - replaced continuous infusion of ufh in unstable angina and mi - maintain patency of cannula and shunts in dialysis patients |
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Fondaparinux |
- pentasaccharide with specific sequence that binds to AF III with high affinity, induces an irreversible conformational change to selectively inactivate factor Xa without binding thrombin (factor IIa) - produced synthetically - bioavailability of fondaparinox injected sc is 100 percent, peak effect is produced in 2 hours - minimal metabolism, excreted unchanged by kidney (not used by renal failure patients) - less likely to cause thrombocytopenia - risk of bleeding and osteoporosis is less - does not require laboratory monitoring of aPTT - longer acting alternative to LMW heparins |
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Direct thrombin inhibitors |
Recently developed anticoagulants which bind directly to thrombin and inactivate it without the need to combine with and activate AT-III example - bivalirudin |
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Bivalirudin |
- synthetically prepared 20 amino acid peptide congener of the larger polypeptide anticoagulant hirudin secreted by salivary glands of leech - binds firmly to catalytic as well as the substrate recognition sites of thrombin and inhibits it directly - bivalirudin is cleared from plasma by both proteolysis as well as renal excretion, conferring a short T1/2 of 25 minutes in subjects with normal renal function. - specific and reversible DTI with quick onset and short lasting anticoagulant function - indicated as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI) for STEMI - used as an antiplatelet drug viz. aspirin and/ or clopidogrel - adverse effects : bleeding , headache , back pain and hypotension |
