Pharmacogenetics Flashcards
____ catalyzes the acetylation of isoniazid and other drugs
N-acetyltransferase 2 (NAT2) catalyzes the acetylation of isoniazid and other drugs
patients treated with isoniazid can be classified as which 2 groups?
slow acetylators = metabolize isoniazid slowly and have high blood drug levels
fast acetylators = metabolize isoniazid rapidly and have low blood drug levels
what is the inheritance of the slow acetylators of isoniazid (NAT2)?
homozygous for an autosomal recessive allele
isoniazid toxicity may cause which 2 symptoms?
neuropathy
hepatotoxicity
hydralazine and procainamide toxicity may cause ____
hydralazine and procainamide toxicity may cause SLE
sulfonamides toxicity may cause which 3 conditions?
hypersensitivity reactions
hemolytic anemia
SLE
succinylcholine is a ____ neuromuscular blocker
succinylcholine is a depolarizing neuromuscular blocker
succinylcholine binds to the ___ receptor and acts like ___ to cause ___ of the end plate
succinylcholine binds to the nicotinic receptor and acts like ACh to cause depolarization of the end plate
describe the normal metabolism of succinylcholine
succinylcholine is not metabolized effectively at the synapse and therefore the membrane remains depolarized and unresponsive to additional impulses –> flaccid paralysis results
describe the breakdown of succinylcholine
rapid hydrolysis by plasma butyrylcholinesterase; duration of the neuromuscular blockade is 5-10 min.
how are patients with genetic variations in butrylcholinesterase affected?
decreased rate of metabolism of succinylcholine, and therefore prolonged paralysis
butyrylcholinesterase polymorphisms are caused by defects in the ____ gene; what is the inheritance of this gene?
\butyrylcholinesterase polymorphisms are caused by defects in the BCHE gene
transmission = autosomal recessive trait
____ metabolizes a large number of drugs, including antidepressants, antiarrhythmics, and analgesics
CYP2D6 metabolizes a large number of drugs, including antidepressants, antiarrhythmics, and analgesics
describe the CYP2D6 enzyme inheritance and enzyme activity for:
poor metabolizers
extensive metabolizers
ultrarapid metabolizers
poor metabolizers = homozygous for recessive alleles coding for enzymes with low activity
extensive metabolizers are heterozygous or homozygous for the “wild type“ allele
ultrarapid metabolizers have multiple copies of the CYP2D6 gene (can have up to 13 copies of the gene)
CYP2D6 metabolizes:
the B-blocker ____
CYP2D6 metabolizes:
the B-blocker metoprolol
CYP2D6 metabolizes:
the antipsychotic ____
CYP2D6 metabolizes:
the antipsychotic haloperidol
CYP2D6 metabolizes:
the opioids ____
CYP2D6 metabolizes:
the opioids codeine and dextromethorphan
TPMT catalyzes the ___ of the anticancer thiopurines ___ and ___
TPMT catalyzes the S-methylation of the anticancer thiopurines 6-mercaptopurine and azathioprine
thiopurines have a narrow ___ and some patients suffer from life-threatening ____ when levels get too high
thiopurines have a narrow therapeutic index and some patients suffer from life-threatening myelosuppression when levels get too high
patients with mutations in the ____ of the ___ domain of the receptor bind better to ____
patients with mutations in the ATP-binding site of the tyrosine kinase domain of the receptor bind better to gefitnib
how does the CYP2C9 gene affect warfarin metabolism?
patients who carry the variant alleles require decreased doses of warfarin to achieve an anticoagulant effect and they have increased risk for hemorrhage during warfarin therapy
