Some Heritable Conditions Causing Decreased Drug Responses

Resistance to coumarin anticoagulants. Subjects of this rare inherited abnormality possess a variant of the enzyme that coverts vitamin K to its reduced and active form, which enzyme the coumarins normally inhibit; patients require 20 times or more of the usual dose to obtain an adequate clinical response. A similar condition also occurs in rats and has practical importance as warfarin, a coumarin, is used as a rat poison (rats with the gene are dubbed 'super-rats' by the mass media).

Resistance to heparin. Patients with antithrombin deficiency require large doses of heparin therapy for anticoagulant effect. (The action of heparin is dependent on the presence of antithrombin in the plasma.)

Resistance to suxamethonium. This rare condition is characterised by increased pseudocholinesterase activity and failure of normal doses of suxamethonium to cause muscular relaxation (cf Cholin-esterase deficiency, above).

Resistance to vitamin D. Individuals develop rickets which responds only to huge doses of vitamin D, i.e. x 1000 the standard dose.

Bacterial resistance to drugs is genetically determined and is of great clinical importance.

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