Phamracology - Hematology

Platelet Aggregation Inhibitors

• Aspirin (ASA):
  • Inhibits platelet aggregation and thromboxane A2 synthesis
  • Effects last for the life of the platelet (7-10 days)
  • Cumulative effect with repeated administration
  • Only antiplatelet agent that irreversibly inhibits platelet function
  • Therapeutic uses: prophylaxis of transient cerebral ischemia, reduce incidence of recurrent MI, primary and secondary prevention of MI
  • Dosing: 81 mg and 325 mg
  • Pharmacokinetics: absorbed by passive diffusion, quickly hydrolyzed to salicylic acid in the liver, half-life: 15-20 minutes, salicylic acid half-life: 3-12 hours

P2Y12 Receptor Antagonists

• Ticlopidine:
  • Irreversible inhibitor, max effect in 3-4 days
  • Therapeutic use: prevention of atherosclerotic events in patients with recent MI or stroke, and in those with established peripheral arterial disease
• Clopidogrel:
  • Irreversible inhibitor, max effect in 3-5 days
  • Therapeutic use: prevention of atherosclerotic events in patients with recent MI or stroke, and in those with established peripheral arterial disease
• Prasugrel:
  • Irreversible inhibitor, max effect in 2-4 hours
  • Therapeutic use: decrease thrombotic cardiovascular events in patients with acute coronary syndromes
• Ticagrelor:
  • Reversible inhibitor, max effect in 1-3 hours
  • Therapeutic use: prevention of arterial thromboembolism in patients with unstable angina and acute MI
• Cangrelor:
  • Injectable only, reversible inhibitor, max effect in 2 minutes
  • Therapeutic use: adjunct during PCI to reduce thrombotic events in select patients

Glycoprotein IIb/IIIa Inhibitors

• Abciximab:
  • Inhibits GP IIb/IIIa receptor complex
  • Therapeutic use: adjunct to PCI for prevention of cardiac ischemic complications
• Eptifibatide:
  • Inhibits GP IIb/IIIa receptor complex
  • Pharmacokinetics: administered as IV infusion, rapidly cleared from plasma, metabolites excreted by the kidney
• Tirofiban:
  • Inhibits GP IIb/IIIa receptor complex
  • Pharmacokinetics: administered as IV infusion, rapidly cleared from plasma, excreted largely unchanged by the kidney and to a lesser extent in the feces

Dipyridamole

• Mechanism of action: coronary vasodilator, increases intracellular cAMP, decreases thromboxane A2 synthesis
• Therapeutic use: stroke prevention (in combination with aspirin)
• Pharmacokinetics: variable bioavailability, highly protein bound, hepatic metabolism, excreted primarily in the feces
• Adverse effects: may worsen ischemia in patients with unstable angina, causes headache and dizziness, orthostatic hypotension (especially with IV administration)

Cilostazol

• Mechanism of action: phosphodiesterase type III inhibitor, increases cAMP levels in platelets and vascular tissues
• Therapeutic use: antiplatelet agent with vasodilating activity
• Pharmacokinetics: oral administration, metabolism by CYP3A4, elimination: renal

Parenteral Anticoagulants

• Heparin:
  • Administered subcutaneously or intravenously
  • Dosing: bolus followed by infusion, titrated to target aPTT or anti-Xa level
  • Pharmacokinetics: binding to plasma proteins is variable, metabolism: taken up by the monocyte/macrophage system, elimination: renal, half-life: approximately 1.5 hours
• Low molecular weight heparins (LMWHs):
  • Administered subcutaneously
  • Onset: maximum anti-factor Xa activity about 4 hours after subcutaneous injection
  • Monitoring: factor Xa levels only in special populations (renally impaired, pregnant, obese)
  • Elimination: renal, needs renal dosing, half-life: 3-12 hours
• Adverse effects: bleeding, HIT (heparin-induced thrombocytopenia), osteoporosis (with long-term therapy)

Argatroban

• Mechanism of action: direct thrombin inhibitor
• Therapeutic use: prophylaxis or treatment of venous thromboembolism in patients with HIT, use during PCI in patients who have or are at risk of developing HIT
• Pharmacokinetics: anticoagulant effects are immediate, metabolized in the liver, half-life: about 39-51 minutes, dose reduction recommended for patients with hepatic impairment
• Adverse effects: bleeding

Bivalirudin

• Mechanism of action: selective direct thrombin inhibitor, reversibly inhibits the catalytic site of both free and clot-bound thrombin
• Therapeutic use: alternative to heparin in patients undergoing PCI who have or are at risk of developing HIT, patients with unstable angina undergoing angioplasty
• Pharmacokinetics: half-life: 25 minutes, dosage adjustments required in patients with renal impairment
• Adverse effects: bleeding

Fondaparinux

• Mechanism of action: selectively inhibits factor Xa
• Therapeutic use: treatment of DVT and PE, prophylaxis of VTE in orthopedic and abdominal surgery
• Pharmacokinetics: predictable pharmacokinetic profile, requires less monitoring than heparin, elimination: renal, half-life: 17-21 hours
• Adverse effects: bleeding, no available reversal agent, HIT is less likely than with heparin but is still a possibility