PHARMACO GENETICS

Prof. CB Choudhary
NMCTH
Prof. Dr. CB Choudhary
Pharmacology
NMCTH
Personalized Medicine
Is Medicine a science or an art?
 The differences in response are most commonly due to variations in the amount of
metabolising enzymes. The production of these enzymes is genetically controlled.

Use of genetic information to guide the choice of drug & dose on an individual basis.
Intends to identify individuals who are either more likely or less likely to respond to a drug on
an individual basis.
 Pharmacogenetics
1. The rate of drug acetylation differs among individuals
who may be fast or slow acetylators.E.g. INH ,
Sulfonamides & Hydralazine metabolized by
acetylation. The acetylator status of an individual
significantly affects the nature of adverse effects with
drugs which are mainly metabolized through acetylation.
– Slow acetylators treated with Hydralazine more likely to
develop lupus erythematosus.
– In slow acetylators INH get accumulated after repeated doses
leading to neurotoxicity.
– In fast acetylators INH metabolizes faster providing higher
concentration of metabolic product acetyl hydrazine causing
hepatotoxicity.
– Dapsone therapy in slow acetylators may lead to haemolysis.
2. Atypical pseudocholine esterase results in
prolonged succinylcholine apnoea. Some
people inherit an atypical pseudocholine
esterase which can not quickly metabolize
succinylcholine.
3. G6PD deficiency responsible for haemolysis with
Primaquine & other oxidizing drugs. This X-linked
monogenic trait is more common in the Mediterranean,
African & Southeast Asian races. Haemolysis largely dose
related.

• Important drugs to cause haemolysis in G6PD

deficiency are:
– Primaquine, Chloroquine, Quinine, Proguanil, Pyrimethamine,
Dapsone, Sulfonamides, Sulfasalazine, Thiazide diuretics,
Aspirin, Nalidixic acid, Chloramphenicol, Probenecid
4. Malignant Hyperthermia: Halothane & Succinyl
choline can trigger malignant hyperthermia in some
genetically predisposed individuals.
5. Hepatic Porphyrias: Some people lack an enzyme
for Heme synthesis, and this results in accumulation
of porphyrin containing Heme precursors.
– Drugs like Barbiturates, Carbamazepine, Griseofulvin
induce the enzyme required for porphyrin synthesis
resulting in accumulation of porphyrins. Neurological,
Gi& behavioral abnormalities can occur due to excess
porphyrins.
 Contd….
6. Attack of closed angle glaucoma is
precipitated by mydriatrics in individuals with
narrow iridocorneal angle.
7. Inability to hydroxylate Phenytoin results in
toxicity at usual doses.
8. Low activity CYP2C9 variants metabolize
warfarin at a slower rate and are at higher
risk of bleeding.