Heme Drugs Flashcards
Heparin
Activates antithrombin-> decreases thrombin and factor Xa; short half life
Use: immediate anticoagulation for PE, acute coronary syndrome, MI, DVT,
Used in pregnancy; Follow PTT
Tox: bleeding, thrombocytopenia (HIT), osteoporosism drug-drug interaction
Antidote for tox: Protamin Sulfate (positively charged bind neg charged Heparin)
Enoxaparin, Dalteparin (LMWH) and fondaparinux
Act on Factor Xa, better bioavailability, longer half life than Heparin
No need lab monitoring, administered SubQ
HIT
IgG antibodies against Heparin bound platelet factor 4. This complex activates platelets -> thrombosis and thrombocytopenia
Argatroban, bivalirudin, dabigatran
leeches; inhibit thrombin directly
Alternative to Heparin if have HIT
Warfarin
Interefers with gamma carboxylation of Vitamin K dependent clotting factors (Factor 2, 7, 9, 10, C and S)
Labs: follow PT (increased) - extrinsic and common pathway. Long half life
Use: anticoagulation (venous thromboembolism prophylaxis), prevent stroke in A fib
CI: pregnant women
Warfarin toxicity
Bleeding, teratogenic, skin/tissue necrosis due to small vessel microthrombosis, drug-drug interaction
Protein C and S have shorter half lives -> early transient hypercoagulability with warfarin use
Warfarin antidote
Vitamin K
Rapid reversal: Fresh frozen plasma
Heparin bridging - to prevent transient hypercoaguable state and skin/tissue necrosis
Heparin V. warafarin
Heparin - large, anionic molecule; IV or SC; site of action: blood, onset: rapid - seconds, MOA: activates antithrombin -> decrease Xa and thrombin action; Duration: hours - acute; Reversal agent: protamin sulfate; follow PTT
Warfarin: small molecule, oral route, liver - site of action, onset of action: slow; MOA: inhibit activation of Vit K dependent factors; duration: chronic (days), reversala gent: Vitamin K, fresh frozen plasma; follow PT; teratogenic
Apixaban, Rivaroxaban
Direct Factor Xa inhibitors
Use: Tx and prophylaxis for DVT and PE, Stroke prophylaxis in A fib patients
No monitoring needed;
Tox: bleeding (no reversible agent)
Thrombolytics
Alteplase, tPA, streptokinase, tenecteplase
Direct or indirect conversion of plasminogen to plasmin-> cleaves thrombin and fibrin clots -> increased PT and PTT; no change in PC
Use: early MI, early ischemic stroke, severe PE
Toxicity of Thrombolytics and toxicity reversal
Bleeding, CI in patients with active bleeding, hx of intracranial bleed, recent surgery, bleeding diathesis or severe HTN
Toxicity tx: Aminocaproic acid (inhibits fibrinolysis), fresh frozen plasma and cryoprecipitate (to correct factor deficiencies)
Aspirin
Irreversible inactivates COX1 and 2 by covalent acetylation. Effect last until new platelets are produced-> increased BT, decreased TXA2 and PGs. No PT and PTT effects
Use: antipyretic, analgesic, anti-inflamamtory and anti-platelet
Tox: Gastric ulceration, tinnitis (CNVIII). Chronic use: Acute renal failure, interstitial nephritis and upper GI bleeding
Reye syndrome.
Overdose initially causes hyperventilation and respiratory alkalosis => mixed metabolic acidosis and respiratory alkalosis
ADP receptor inhibitors
Clopidogrel, prasugrel, ticagrelor (reversible), ticlopidine
Inhibit platelet aggregation by IRREVERSIBLY blocking ADP receptors and prevent GpIIb/IIIa receptors on platelets
Use: ACS, coronary stenting. decrease recurrence of thrombotic stroke
Tox: neutropenia, TTP
Cilostazol, Dipyramidole
Inhibits PDEIII -> increases cAMP in platelets -> inhibits platelet aggregation; vasodilators
Use: intermittent claudication, coronary vasodialtion, prevent stroke or TIA (combined with Aspirin), angina prophylaxis
Tox: Nausea, HA, facial flushing, hypotension, abdominal pain
GpIIb/IIIa inhibitors
Abciximab, eptifibatide, tirofaban
Prevent aggregation by direct inhibition of activated platelets
Abciximab - from monoclonal Ab Fab fragments
Use: unstable angina, coronary angioplasty
Tox: Bleeding thrombocytopenia
