Introduction
Response to drugs varies widely between individuals in efficacy, toxicity, dose requirements and risk of severe adverse reactions, and genetic variation is a major contributor. This topic covers pharmacogenetics and pharmacogenomics, rare monogenic pharmacogenetic defects (malignant hyperthermia, atypical butyrylcholinesterase), polymorphic defects (G6PD, TPMT, DPYD, NAT1/NAT2, ADH/ALDH), CYP450 variants (CYP2D6, CYP2C9, CYP2C19, CYP3A4) and pharmacogenetics in individuals with genetic diseases (FGD).
Pharmacogenetics
Pharmacogenetics is the study of how inherited genetic differences in a single gene affect an individual's response to a specific drug. It focuses mainly on drug-metabolizing enzymes, drug transporters and drug targets (receptors, ion channels).
Key concept: a single gene variant can markedly alter drug metabolism or action, leading to exaggerated drug effect, lack of therapeutic response or serious adverse reactions.
Mechanisms of pharmacogenetic variation
- Reduced or absent enzyme activity.
- Increased enzyme activity (ultrarapid metabolism).
- Altered drug receptor sensitivity.
- Abnormal ion channel function.
Pharmacogenomics
Pharmacogenomics is the study of how multiple genes across the genome influence drug response, using genome-wide approaches.
Clinical importance of pharmacogenomics
- Individualized drug therapy.
- Optimized drug selection and dosing.
- Reduced adverse drug reactions.
- Basis of personalized / precision medicine.