Warfarin exerts its effect via inhibition of clotting factors II, VII, IX, X.

True

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Warfarin effect takes place in 6 hours after administration.

False

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Warfarin does not cross placental barrier.

False

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Warfarin's effect is potentiated with amiodarone.

True

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1. Warfarin exerts its effect by inhibiting the hepatic synthesis of vitamin K dependent clotting factors II, VII, IX and X; which is caused by the inhibition of vitamin K. The effect of warfarin is monitored with prothrombin time, which is usually kept at 2-3 times control for most therapeutic indications.

2. After oral administration, warfarin is absorbed erratically from the gastrointestinal tract, after which the molecules are almost entirely bound to plasma protein. There is a 2 to 7 days of delay between the achievement of a peak plasma level and a substantial therapeutic response. The half-life is around 37 hours. Normally a loading dose is used if early achievement of therapeutic response is desired. For Chinese, the usual maintenance dose is 2 to 3mg daily but it may vary from 1 to 20mg daily. Therefore titration of doses according to regular monitoring of the prothrombin time is essential. Patients with heart failure, liver disease and renal impairment require a lower maintenance dose. In general, PT/INR monitoring every 4-8 weeks is needed for patients on long term warfarin treatment. Patients should be reminded that warfarin should be stopped a few days before dental or surgical procedures.

Patient education is an integral part of warfarin program and patients need to know the different warfarin tablet preparations and protocol of dosage titration. They should be reminded for symptoms of bleeding tendency.

3. Warfarin, in contrast to heparin, crosses placental barrier. Since it is teratogenic to the fetus, warfarin, if indicated for the pregnant woman, is generally omitted in the first 8 weeks of pregnancy, in which heparin is used for replacement.

4. Warfarin is metabolized in the liver and its potency is markedly affected by diet as well as concomitantly administered medications. Its effects would be reduced with many dark green vegetables that are rich in vitamin K and with drugs that induce hepatic enzymes such as barbiturates, phenytoin and rifampin. On the other hand, its effects are potentiated by those drugs that inhibit the CYP 2C9 isoform of the hepatic cyotchrome P-450 system. These include amiodarone, metronidazole, co-trimoxazole, anti-fungals like fluconazole and cimetidine. Other potentiating drugs include allopurinol, propafenone and quinidine.

Patients should be reminded that they should not take any concomitant herbal medicine or drugs of uncertain nature while they are on warfarin treatment.

What is the clinical diagnosis?

The clinical diagnosis is fixed drug eruption (FDE).

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What is the typical presentation of this condition?

FDE is a relatively common and distinctive form of drug reaction. It develops in the same site with each exposure of a particular medication. The lesions are well-demarcated, round or oval patch of erythema and swelling, sometimes develop into blister. Local symptoms include pain and pruritus. Post-inflammatory hyperpigmentation is common.

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What are the commonly affected anatomical sites in this condition?

FDE commonly occurs in the oral and genital mucosa, face and acral areas although anywhere of the body may be involved.

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What are the agents implicated in this condition?

Many drugs have been implicated. These include NSAIDs (especially pyrazolone derivatives, naproxen, and mefenamic acid), sulphonamides, tetracyclines, barbiturates, salicylates, acetaminophen and phenolphthalein.

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What are the treatments?

The offending drug should be avoided as repeated challenge may cause worsening of subsequent eruption. Topical and/or systemic corticosteroid may produce clinical improvement.

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