Antiplatelets/Anticoagulants

Question 1

Endogenous anticoagulant antithrombin III inhibits?

Answer 1

factors IIa, IXa, Xa, Xia and XIIA

Question 2

Endogenous protein C and S inhibit?

Answer 2

factors Va and VIIIA

Question 3

pharmacodynamics of Aspirin

Answer 3

Irreversible non-selective COX inhibitor (COX-1 and COX-2)

In platelets, irreversible inhibition of COX-1 results in reduction of thromboxane A2 and inhibition of platelet aggregation for life of platelet (10 days)

In tissues, inhibits PG synthesis (COX-2), resulting in antiinflammatory, antipyretic and analgesic effects:
Duration of action 6-12 hours before synthesis of new COX enzyme

Question 3

pharmacokinetics of aspirin

Answer 3

Weak acid, pKa 3.5
Rapid absorption from stomach and upper small intestine
Peak plasma level 1-2 hours
High protein binding

Metabolism:
Rapid hydrolysis to acetic acid and salicylate by esterases in tissue and blood
Salicylate is non-linearly bound to albumin
Saturable metabolism and excretion with increasing dose,
switch from first to zero order kinetics at higher doses
Serum half-life 15 minutes

Excretion:
Renal – pH dependent reabsorption
Urinary alkalinisation increases excretion of free salicylate and its water-soluble conjugates

Question 4

relationship between aspirin and gout

Answer 4

Aspirin has a bimodal effect on renal handling of uric acid
High doses > 3 g / day are uricosuric thus reduce uric acid levels
Low doses 1-2 g / day cause uric acid retention and increase levels
Therefore aspirin is contraindicated in treatment of pain and inflammation associated with gout

Question 5

Pharmacodynamics of Clopidogrel

Answer 5

Reduce platelet aggregation by inhibiting ADP pathway of platelets
Irreversibly inhibits ADP P2Y12 receptor on platelets for life of platelet
Unlike aspirin, no effect on prostaglandin metabolism

Question 6

Pharmackinetics of clopidogrel

Answer 6

Prodrug
Hepatic metabolism to active and inactive metabolites
80% of platelet activity inhibited within five hours of loading dose of 300mg

Effects lasts for life of platelet, duration of anti-platelet effect 7-10 days
Elimination half-life 30-60 minutes

Following oral dose, 50% excreted in urine and 46% in faeces in next five days