GENETIC FACTORS ::
The effect of drug may be altered by influence of heridity The branch of pharmacology dealing with the influence of heridity on pharmacokinetic and pharmacodynamic responses to drugs is pharmacogenetics Various examples of genetic variation as follows ::
(1) Acetylation ::
Several drugs are acetylated by hepatic enzyme N- acetyl transferase The differences have been found in population regarding ability of acetylation and accordingly there may be slow acetylators and fast acetylators Patients with slow acetylation -ability will show increased blood levels of drugs like isoniazid hydralazine procainamide dapsone and some sulfonamides Reverse will be true for fast acetylation
Like N-acetyl transferase genetic differences have been found for enzyme hydroxylase (metabolizing phenytoin and phenformin ) and pseudocholinesterase for succinylcholine )
(2) Glucose-6-phosphate dehydrogenase (G6PD) ::
Lack of G6PD in red blood cells may result in hemolysis This has been observed in many patients specially in Sephardic Jews (50%) and negros (10-20%) The hemolysis occurs with many drugs like primaquine phenacetin nitrofurantoin probenecid and sulfonamides
Genectical variations have also been observed for enzyme glutathione reductase and methhemoglobin reductase
(3) Coumarin and vit -D resistance ::
Genetic differences have been noticed with respect to the effectiveness of coumarin and Vit -D The precise mechanism of the genetic effect is not known
(4) porphyria and malignant hyperthermia ::
porphyria the abnormality in haem biosynthesis may be increased if $ aminolaevulinic acid synthase enzyme activity in increased Some drugs like ethanol barbiturates chloroquine etc may precipitate porphyria as genetic disorder
Drugs like halothane succinylcholine etc may produce malignant hyperthermia in about 1 in 20000 anaesthetized patients The cause is genetic The characteristics of malignant hyperthermia are rise in body temperature to 40-41 .C. muscle stiffness tachycardia sweating cyanosis and tachypnoea
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