Examples of Pharmacogenetic Variations

Acetylation, fast

Need for higher or more frequent doses of medications that are acetylated (eg, isoniazid) to produce the desired therapeutic responseNeed for higher or more frequent doses of medications that are acetylated (eg, isoniazid) to produce the desired therapeutic response

Acetylation, slow (medication inactivation by hepatic N-acetyltransferase)

Increased susceptibility to adverse effects of medications that are acetylated (eg, isoniazid causing peripheral neuritis; hydralazine or procainamide causing drug-induced lupus)Increased susceptibility to adverse effects of medications that are acetylated (eg, isoniazid causing peripheral neuritis; hydralazine or procainamide causing drug-induced lupus)

Aldehyde dehydrogenase-2 deficiency

With alcohol ingestion, marked elevations of blood acetaldehyde, causing facial flushing, increased heart rate, diaphoresis, muscle weakness, and sometimes catecholamine-mediated vasodilation with euphoria

CYP2C19 genetic polymorphisms

Reduced enzymatic activation of clopidogrel, resulting in reduced antiplatelet effect and increased risk of Reduced enzymatic activation of clopidogrel, resulting in reduced antiplatelet effect and increased risk ofthrombosis in high-risk patients

G6PD deficiency

With use of oxidant medications, such as certain antimalarials (eg, chloroquine, primaquine), increased risk of With use of oxidant medications, such as certain antimalarials (eg, chloroquine, primaquine), increased risk ofhemolytic anemia

Genetic polymorphisms of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1)

Increased action of warfarin, increasing risk of bleeding eventsIncreased action of warfarin, increasing risk of bleeding events

HLA-B*1502

Increased risk of adverse reactions to carbamazepine, including serious dermatologic reactions (eg, Increased risk of adverse reactions to carbamazepine, including serious dermatologic reactions (eg,Stevens-Johnson syndrome)

Plasma pseudocholinesterase deficiency

Decreased succinylcholine inactivationDecreased succinylcholine inactivation

With conventional succinylcholine doses, prolonged paralysis of respiratory muscles and sometimes persistent apnea requiring mechanical ventilation until the medication can be eliminated by alternate pathwaysWith conventional succinylcholine doses, prolonged paralysis of respiratory muscles and sometimes persistent apnea requiring mechanical ventilation until the medication can be eliminated by alternate pathways