Lecture 27+28 Flashcards
N-acetyltransferase 2 (NAT2)
Polymorphism
catalyzes the acetylation of isoniazid and other drugs
can be a slow or fast metabolizer
slow: high isoniazid levels in the blood
fast: low isoniazid levels in the blood
homozygous for an autosomal recessive allele
Butyrylcholinesterase Polymorphism
neuromuscular blockers such as succinylcholine (binds to the nicotinic receptor and acts like Ach)
not metabolized efficiently - flaccid paralysis
prolonged paralysis due to defect in BCHE gene
auto recessive trait
CYP2D6 Polymorphism
member of the cytochrome P450 family of drug-metabolizing enzymes
metabolizes a large number of drugs, including antidepressants, antiarrhythmics, and analgesics
homozygous for recessive alleles (poor metabolizers)
Extensive metabolizers are heterozygous or
homozygous for the “wild type” allele
ultrarapid metabolizers have multiple copies
of the CYP2D6 gene
examples of CYP2D6 metabolized drugs
metoprolol
haloperidol
codeine and dextromethorphan
fluoxetine, imipramine, & desipramine, etc
Thiopurine S-methyltransferase Polymorphism
TPMT catalyzes the S-methylation of the
anticancer thiopurines 6-mercaptopurine and azathioprine
methylation deactivates these drugs
They are at increased risk for myelosuppression
what drugs cause oxidative stress in those with G6PD deficiency?
sulfonamides, antimalarial’s, and chloramphenicol.
will develop hemolytic anemia
Malignant Hyperthermia
Triggered in susceptible individuals by volatile inhalation anesthetics (eg halothane) and depolarizing skeletal muscle relaxants, such as succinylcholine
auto dom trait
one of the main causes of death due o anesthesia
symptoms: • Tachycardia • Hypertension • Severe muscle rigidity • Hyperthermia • Hyperkalemia • Acidosis
what causes malignant hyperthermia
results from altered control of Ca2+ release from the SR.
caused by a defect in the ryanodine receptor gene (RYR1) which codes for the ryanodine receptor, which when dysfunctional, leads to unregulated Ca release.
