Pharmacology for Anaesthesia and Intensive Care

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23 Drugs affecting coagulation

Inactive precursors Active clotting factors

γ-carboxylation of

glutamic acid residues

NAD+ NADH

Inhibited by warfarin

Reduced

vitamin K

Oxidised

vitamin K

Figure 23.3.Mechanism of action of warfarin.

the liver and are activated byγ-carboxylation of their glutamic acid residues. This

process is linked to the oxidation of reduced vitamin K. Warfarin acts by preventing

the return of vitamin K to the reduced form (Figure23.3).

Circulating factors will not be affected by the actions of warfarin, which therefore

takes up to 72 hours to exert its full effect.

Side effects


Haemorrhage


Ter atogenicity – this is more common and serious in the first trimester. Dur-

ing the third trimester it crosses the placenta and may result in foetal haemor-

rhage.


Drug interactions – drugs that impair other aspects of coagulation (NSAIDs and

heparin) will potentiate the effects of warfarin. Competition for plasma bind-

ing sites (NSAIDs) and inhibition of metabolism (cimetidine, alcohol, allopuri-

nol, erythromycin, ciprofloxacin, metronidazole and TCAs) lead to potentiation

of warfarin’s effects. Barbiturates, rifampicin and carbemazepine induce hep-

atic enzymes and antagonize the effects of warfarin. Cholestyramine interferes

with the absorption of fat-soluble vitamins and thereby potentiates the action

of warfarin. The effects of warfarin are rapidly reversed by fresh frozen plasma.

Vitamin K (1 mg) will also reverse its effects but more slowly, while 10 mg

vitamin K will prevent anticoagulation for a number of days. Spinal and

epidural anaesthesia is contraindicated in patients anticoagulated with warfarin.