18B20: Exam Report
Describe the pharmacology of heparin highlighting important differences between unfractionated and fractionated (low molecular weight) heparin.
71% of candidates passed this question.
Better answers were tabulated and included sections on pharmaceutics, indications and an explanation on how the difference in molecular weight influenced pharmacodynamics and pharmacokinetics. Knowledge of adverse effects was limited to bleeding and HITTS, often without consideration of relative risk from LMWH. Many candidates did not know the t1/2 of UFH or LMWH.
17B05: Exam Report
Compare and contrast unfractionated heparin with low molecular weight heparin.
68% of candidates passed this question.
This question was generally well answered and lent itself well to a tabular format. Expected information included an approximation of the molecular weights / significance of the differences in size and therefore its mechanism of action.
Other pertinent areas to mention included pharmacokinetic differences and its use in renal failure, side effect profiles, monitoring, predictability of response and reversibility for the two agents.
Q2i / 18B20 / 17B05: Describe the pharmacology of heparin highlighting the important differences between unfractionated and fractionated heparin
Long chain bridging when on ATIII
But does not affect Thrombin bound to Fibrin; already enzymatically active & protected from inactivation
By binding ATIII inhibits Xa activity
So reduced formation of Thrombin
Xa:IIa activity ratio
2:1 or 4:1
Via thrombin inhibition
Moderate plat inhibition
Prevents cross-linking due to Thrombin inhibition
Inhibits formation of Fibrin Stabilising Factor
Factor V, VIII, XI, XIII
Via Thrombin inhibition
Time to peak effect
Time to normal hemostasis on cessation
Predictability of effect
(remember it is like a refined selection of the heparins)
Binds many proteins \large interpatient variability
Much less PPB
Great 100% bioavailability after sc injection
Heparinases of liver, kidney, RES
Desulfation +/- depolymerisation in liver
Metabolites excreted renally
(no dose adj w renal impair)
Majority of dose renally cleared as active/inactive metabolites
Needs dose adjustment in renal impairment
ACT (high dose)
But variable, up to 60% of dose
May rebound due to cont subcut depot after protamine dose
SC injection twice daily
Excellent bioavailability -> predictable dosing od
Daily monitoring for Tx dose
Predictable, no monitoring for prophylactic/Tx dose
Not easily used for outpatients
Outpatients can use much easier
Plat dysfn; reduce count or HITS
Lower incidence of HITS
Risk of bleeding
Less risk of bleeding
Less risk of osteoporosis
Fully reversible w Protamine
Up to 60% reversibility w Protamine
Can be used in renal impairment
Accumulates in renal impairment
Rapid onset & clearance
Delayed Clearance – need to wait 12-24h post dose for CNB