Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Mechanism of action

Compared with unfractionated heparin, LMWHs are more effective at inhibit-

ing factor Xa and less effective at promoting the formation of the inactive ‘anti-

thrombin–thrombin’ complex.

Protamine is not fully effective in reversing the effects of LMWH.

Monitoring heparin therapy

The activated partial thromboplastin time (APTT) measures the intrinsic system

factors (VIII, IX, XI and XII) in addition to the factors common to both systems.

Phospholipid, a surface activator (e.g. kaolin) and Ca^2 +are added to citrated blood.

The clotting time varies between laboratories but is about 28–35 seconds.

Monitoring LMWH is difficult as its main effects are inhibiting factor Xa, so the

APTT is not altered.

Protamine

Protamine is a basic protein prepared from fish sperm. Its positive charge enables

it to neutralize the anticoagulant effects of heparin by the formation of an inactive

complex that is cleared by the reticulo-endothelial system. It is also used in the

formulation of certain insulins.

Itis given intravenously, 1 mg reversing 100 i.u. heparin.

Side effects


Cardiovascular – hypotension (due to histamine release), pulmonary hypertension

(complement activation and thromboxane release), dyspnoea, bradycardia and

flushing follow rapid intravenous administration.


Allergic reactions – patients having previously received insulin containing pro-

tamine and those allergic to fish may be at increased risk of allergic reactions.


Anticoagulation – when given in excess it has some anticoagulant effects.

Oral anticoagulants

Warfarin

Uses

Warfarin is a coumarin derivative and is used for the prophylaxis of systemic

thrombo-embolism in patients with atrial fibrillation, rheumatic valve disease or

prosthetic valves. It is also used in the prophylaxis and treatment of DVT and PE.

Mechanism of action

Warfarin inhibits the synthesis of the vitamin K-dependent clotting factors: II (pro-

thrombin), VII, IX and X. The precursors of these clotting factors are produced in