Anticoagulants

Question 1

Outline the mechanisms of action for aspirin.

Answer 1

Irreversible, non-selective cyclooxygenase inhibitor. Reduced production of thromboxane-A2 in platelets, causing reduced platelet adhesion and aggregation, reduced vasoconstriction. Reduced prostaglandin synthesis in tissues, giving anti-inflammatory effects, analgesic, anti-pyretic effects.

Question 2

Describe the pharmacokinetics of aspirin

Answer 2

• Well absorbed in stomach and intestine, reaches peak plasma levels in 1-2hrs
• Absorbed in an acidic environment because aspirin is a weak acid
• 49% protein-bound, small Vd
• Saturable hepatic metabolism, zero-order kinetics in high doses over 2g
• Urinary alkalization increases the excretion
• Half-life 15 minutes (parent drug to salicylates by plasma esterases), 3hrs (breakdown of salicylates in doses 100-600mg / day), 10hrs (doses over 2g)

Question 3

Outline the adverse effects of aspirin.

Answer 3

GI upset, GI bleed from ulceration or gastritis, hepatotoxicity, hypersensitivity reactions (asthma, angioedema, rash), prolonged bleeding time from platelet inhibition.

Question 4

How does heparin act?

Answer 4

Heparin binds endogenous antithrombin, and enhances its activity, to inhibit factors IIa, IXa and Xa.

Question 5

How can heparin be administered?

Answer 5

IV or subcutaneous. Continuously (after a bolus) or intermittently. Therapeutic vs prophylactic.

Question 6

What are the potential adverse effects of heparin?

Answer 6

Bleeding, HIT, allergy, alopecia, osteoporosis, mineralocorticoid deficiency.