HEME drugs Flashcards
Argatroban
Direct thrombin inhibitor. Used instead of heparin for anti coagulating patients with HIT
Heparin
MOA: cofactor for the activation of antithrombin, decreases thrombin, and decreases factor Xa. Short half life.
USES: immediate anticoagulant for PE, acute coronary syndrome, MI, DVT. Used during pregnancy (does not cross placenta). Follow PTT.
TOXICITY: bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal (antidote), use Protamine sulfate (positively charged molecule that binds negatively charged heparin)
NOTES: low molecular weight heparins (e.g. Enoxaparin, dalteparin) act more on factor Xa, have better bioavailability and 2-4 times longer half life. Can be administered subcutaneously and without laboratory monitoring. Not easily reversible.
Heparin-induced thrombocytopenia (HIT): development of IgG antibodies against heparin bound to platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets–>thrombosis and thrombocytopenia
Bivalirudin
derivative of hirudin, the anticoagulant used by leeches; inhibit thrombin directly. Used instead of heparin for anti coagulating patients with HIT
Warfarin
MOA: interferes with normal synthesis and gamma carboxylation of vitamin k-dependent clotting factors II, VII, IX, and X and proteins C and S. Metabolized by CYP p450. In laboratory assay, has effect on extrinsic pathway and increases PT. Long half life.
USES: chronic anticoagulant (after STEMI, venous thromboembolism prophylaxis, and prevention of stroke in atrial fibrillation). Not used in pregnant women. Follow PT/INR intervals
TOXICITY: bleeding, teratogenic effects, skin/tissue necrosis, drug-drug interactions (rifampin, phenytoin, and phenobarbital are universal Enhancers of p450 pathway)
Apixaban
MOA: Direct factor Xa inhibitor
USES: treatment and prophylaxis of DVT and PE, stroke prophylaxis in patients with atrial fibrillation
TOXICITY: bleeding
Rivaroxaban
MOA: Direct factor Xa inhibitor
USES: treatment and prophylaxis of DVT and PE, stroke prophylaxis in patients with atrial fibrillation
TOXICITY: bleeding
Alteplase
TpA
MOA: directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Increases PT, increases PTT, NO change in platelet count
USES: early MI, early ischemic stroke direct thrombolysis of severe PE
TOXICITY: bleeding, contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe HTN. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies
Reteplase (rPA)
MOA: directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Increases PT, increases PTT, NO change in platelet count
USES: early MI, early ischemic stroke direct thrombolysis of severe PE
TOXICITY: bleeding, contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe HTN. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies
Tenecteplase (TNK-tPA)
MOA: directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Increases PT, increases PTT, NO change in platelet count
USES: early MI, early ischemic stroke direct thrombolysis of severe PE
TOXICITY: bleeding, contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe HTN. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies
Apirin
MOA: irreversibly inhibits COX1 and COX2 enzyme by covalent acetylation. Platelets cannot synthesize new enzyme, so effect lasts until new platelets are produced. Increases bleeding time, decreases TXA2, and prostaglandins. No effect on PT or PTT
USES: antipyretic, analgesic, anti inflammatory, antiplatelet (decreases aggregation)
TOXICITY: gastric ulceration, tinnitus. Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. Reye syndrome in children with viral infection. Overdose causes respiratory alkalosis initially, which is then superimposed by metabolic alkalosis.
Clopidogrel
MOA: ADP receptor blocker. Inhibits platelet aggregation by blocking ADP receptors. Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
USES: acute coronary syndrome, coronary stenting. Decreases incidence or reoccurrence of thrombotic stroke
TOXICITY: neutropenia. TTP/HUS may be seen
Ticlopidine
MOA: ADP receptor blocker. Inhibits platelet aggregation by blocking ADP receptors. Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
USES: acute coronary syndrome, coronary stenting. Decreases incidence or reoccurrence of thrombotic stroke
TOXICITY: neutropenia (fever) and mouth ulcers. Rarely used anymore. TTP/HUS may be seen.
Prasugrel
MOA: ADP receptor blocker. Inhibits platelet aggregation by blocking ADP receptors. Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
USES: acute coronary syndrome, coronary stenting. Decreases incidence or reoccurrence of thrombotic stroke
TOXICITY: neutropenia. TTP/HUS may be seen
Ticagrelor
MOA: ADP receptor blocker. Inhibits platelet aggregation by blocking ADP receptors. Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
USES: acute coronary syndrome, coronary stenting. Decreases incidence or reoccurrence of thrombotic stroke
TOXICITY: neutropenia. TTP/HUS may be seen
Cilostazol
MOA: phosphodiesterase III inhibitor. Increases cAMP in platelets, thus inhibiting platelet aggregation; vasodilators.
USES: intermittent claudication, coronary vasodilation, prevention of stroke in TIAs (combined with aspirin), angina prophylaxis
TOXICITY: nausea, headache, facial flushing, hypotension, abdominal pain
