Missed out drug mechanisms Flashcards
Resins
Bind bile acids in the interstinal lumen, preventing reabsorption, and increasing bile acid excretion in the faeces. Endocgenous cholesterol metabolism into bile acids is increased to compensate. LDL clearance from plasma is increased by the liver to recover cholesterol.
Ezetimibe
Blocks a transport protein located at the brush border of the duodenum (NPC1L1) preventing absorption of sterold wiithout affecting fat-soluble vitamines, TG or bile acids. Leads to a reactive up-regulation of LDL uptake from bloos, lowering plasma LDL.
Unfractionated heparin cellular mechanisms
Is a catalyst. It binds to ATIII and changes its conformation which increases its sensitivity and accelerates its action.
LMWH cellular mechanisms
LMWH increases the action of ATIII on Xa only. This is because, in order to increase the action of ATIII on other serine proteases, heparin needs to bind to other substances, requiring long chains. To speed ATIIIs effect on Xa is need only bind ATIII so shorter chains, such as LMWH are effective.
Initiation of warfarin therapy
Onset of therapeutic action is slow, as warfarin only slowly production - the circulating factors are not affected. Circulating factors have a long half life, however, protein C has a relatively short half life (6 hours). So, while warfarin inhibits production of both, protein C levels in plasma will drop relatively faster creating a thrombolic period for the first few days.
Heparin antidote
UFH: protamine sulphate
LMWH: FFP
Dabigratran cellular mechanisms
Reversibly inhibits both free and fibrin-bound thrombin (factor IIa). Prevents conversion of fibrinogen to fibrin, amplification of the coagulation cascade and activation of platelets.
Clopidogrel cellular mechanisms
Irreversibly binds platelet ADP receptors (P2Y12) decreasing the release of Ca2+ from intracellular stores, required for GPIIb/IIIa receptor expression.
Pharmacokinetics clopidogrel
Is a prodrug activated in the liver, so polymorphisms in P450 enzymes can mean some patients do not repsond as well and so are at risk of adverse CVD outcomes. Genertic testing is available but expensive.
Abciximab cellular mechaniss
Monoclonal antibody which binds and blocks the glycoprotein IIb/IIIa receptor thus blocking all pathways to platelet activation.
AMI management
Streptokinase + aspirin best practice in AMI (ISIS2).
Alteplase > streptokinase (GUSTO) .
Tenecteplase > alterplase in stroke (Parsons et al, 2012)
However, tPA are 10x more expensive.
Streptokinase cellular mechanisms
Non-selective and also complexes with plasma plasminogen, cleaving off plasmin which digests not only fibrin, but also fibrinogen, coagulation factors and other protteins. Circulating plasmin is normally inactivated by alpha2-antiplasmin though therapeutic doses of fibrinolytics overwhelm this system.
