Table 19-2
- MC1r Gene (codes for the melanocortin-1 receptor)
- Involved in the regulation of skin and hair pigmentation and immunomodulation
- Specific mutations in this gene cause a phenotype of red hair; fair, freckled skin; and an increase in µ-opioid analgesia
- Redheads require more midazolam and inhalational anesthetics compared with blond and dark-haired individuals.
- Genetic Variability in the Gene Coding for CYP2D6
(clinically most important)
- Rate of opioid metabolism of (ultra-rapid to poor) depends on the number of copies a subject expresses
- Important for drugs that rely on CYP2D6 to convert an inactive precursor (codeine as a prodrug) into the active component of pain therapy (for codeine, this is morphine)
- Patients without an active gene will have no benefit from treatment with codeine
- Dangerous circumstances may occur when a patient is an extensive metabolizer and produces large amounts of the active component (codeine intoxication caused by ultra-rapid CYP2D6 metabolism).
- Variations in the ABCB1 Gene (gene coding for P-glycoprotein, a protein involved in the efflux of xenobiotics from the brain) cause variations in the toxicity of fentanyl
- Lesser efficacy of the variant P-glycoprotein to transport fentanyl from the brain