Question

briefly discuss the mechanism of action of heparin and it's indication

Answer 1

heparin, also called unfractionated heparin (ufh), is medicinal drug that's used as an anticoagulant. particularly it's far used to treat and save you deep vein thrombosis, pulmonary embolism, and arterial thromboembolism. it's also used inside the treatment of coronary heart attacks and volatile angina. it's far given via injection right into a vein. other uses encompass inside take a look at tubes and kidney dialysis machines.

heparin binds to the enzyme inhibitor antithrombin iii (at), causing a conformational exchange that effects in its activation via an increase inside the flexibility of its reactive website loop. the activated at then inactivates thrombin, issue xa, and different proteases. the price of inactivation of those proteases through at can boom with the aid of as much as one thousand-fold because of the binding of heparin. heparin binds to antithrombin via a particular pentasaccharide sulfation series contained inside the heparin polymer:

glcnac/ns(6s)-glca-glans(3s,6s)-idea(2s)-glans(6s)
the conformational exchange in at on heparin-binding mediates its inhibition of issue xa. for thrombin inhibition, however, thrombin need to additionally bind to the heparin polymer at a site proximal to the pentasaccharide. the fairly bad rate density of heparin contributes to its very robust electrostatic interaction with thrombin. the formation of a ternary complex between at, thrombin, and heparin outcomes in the inactivation of thrombin. for that reason, heparin's hobby against thrombin is size-dependent, with the ternary complicated requiring at least 18 saccharide units for efficient formation.in assessment, anti-factor xa activity calls for best the pentasaccharide-binding site.

this length difference has led to the development of low-molecular-weight heparins (lmwhs) and, greater lately, to fondaparinux as pharmaceutical anticoagulants. lmwhs and fondaparinux goal anti-factor xa activity as opposed to antithrombin hobby, with the aim of facilitating an extra subtle law of coagulation and a progressed healing index. the chemical shape of fondaparinux is shown above. it's far an artificial pentasaccharide, whose chemical shape is almost identical to the at binding pentasaccharide series that can be discovered inside polymeric heparin and heparan sulfate.

with lmwh and fondaparinux, the hazard of osteoporosis and heparin-prompted thrombocytopenia (hit) is reduced. monitoring of the activated partial thromboplastin time is likewise now not required and does not replicate the anticoagulant effect, as aptt is insensitive to changes in issue xa.

danaparoid, an aggregate of heparan sulfate, dermatan sulfate, and chondroitin sulfate can be used as an anticoagulant in sufferers having evolved hit. due to the fact, danaparoid does no longer include heparin or heparin fragments, go-reactivity of danaparoid with heparin-caused antibodies is suggested as less than 10%.

the outcomes of heparin are measured within the lab by the partial thromboplastin time (aptt), one of the measures of the time it takes the blood plasma to clot. partial thromboplastin time should no longer be pressured with prothrombin time, or pt, which measures blood clotting time via a different pathway of the coagulation cascade.

heparin is the drug of choice for the preliminary remedy of deep venous thrombosis, pulmonary embolism, and acute arterial occlusion. for these indicators the administration of high doses of standard heparin is the guideline (i.v. or subcutaneous); the efficacy of lmwh preparations for venous thromboses has also been verified. oral anticoagulation is stated to start on the primary or 2d day of heparin remedy already. for the prophylaxis of deep venous thromboses and pulmonary embolism low doses are used. in relation with orthopedic surgical operation (mainly hip joint operations) the lmwh at the moment are taken into consideration advanced. it has no longer been correctly hooked up if this additionally applies for different surgical interventions or subjects with inner risks.

after an acute myocardial infarction (with or without thrombolysis) the preliminary anticoagulation is executed with heparin, even though the cost of the drug is not actually described. its use for risky angina pectoris desires to be researched similarly; heparin additionally serves for the prevention of thromboses in surgical procedure with extracorporeal move and in hemodialysis, in addition to for the renovation of open venous catheters.