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Abstract -56- Pharmacogenetics concerns itself with a special type of inborn error of metabolism, the response of individual to drugs.,The aberrant response may be manifested only in a need for a dose di fferent from that usually given to achieve a desired theraputic effect or may be responsible for marked deviations from normal that may have mild, moderate, or serious untoward effects, including death. A number of mendel ian disorders habe been identified and are discussed. One of the most informative loci in the human ~p.ne~. tics is the X-linked gene determining the red blood cell enzyme glucose-6-phosphate dehydrogenase., Over 90 mutant alleles are known, many of which determine enzyme deficiencies, resulting in a haemolytic response to more than 20 drugs,as. well as infection. It is likely that further genetic differences influencing responses to drugs will be foun d, thus pe rmt t t , ing increasing accuracy in determining doses, choosing appropriate drugs, and avoi ding undesirable side reaction. For example, of a man prepared to do an surgical operation under general anaesthesia with a family hi~- tory of a death under unaesthesia is least likely to develop succinyl apnoea due to paralysis of striated -57- muscle which may be prolonged and the patient may stop voluntary breathing for an hour or more. Also this patient may develop malignant hyperthermia which may be fatal. Another example is the hypersensitivity. involving a defective enzyme wh ich cause s a borderline Ieve lr o r act ivj tY wit h b0 r der lin e sy m ptom s 0 fen zy me de f ic ien cy when the adminstered chemical is the primary toxic agent. Example of this condition involve the primaquine-” induced haemolytic anaemia in which there is a genetic~ ally altered stability of reduced ’glu!a~~hione and an altered glucos-6-phosphate dehydrogenase activity. Additional examples are the abnormal haemoglobins in which there is an altered ability of the haemoglobin to remain in the reduced state. and the sulfonamide and barbiturate-induced porphyrias which are involved with the deficiency of the inhibitor system which normally controls the level ofa(-amino livulinic acid synthetase. Th~ example~’ given here. besides domenstrating the’ truth of the adage that one me n ’s medicine is another man1s poison. remained us that our genes make us unique pharmacelogially. as in so many other ways. the pharma- 58- cogenetic differences may make it desirable to screen high risk families and high risk populations before exposing them to certain agents and that patients being treated with drugs should be regarded as individuals, not just as so many kilograms uf body mass. |