14: Pharmacogenetics Flashcards
If we have a mutation in a gene then the enzyme is different and drug either does _____ work or works _____.
If we have a mutation in a gene then the enzyme is different and drug either does not work or works slower.
It has been estimated that _____% of all adverse drug reactions (ADRs) are due to genetic anomalies.
It has been estimated that 50% of all ADRs are due to genetic anomalies
Drug trials work on _____ to benefit the majority.
There is _____ information on genotype- phenotype connection and drug reactions.
Drug trials work on averages to benefit the majority.
There is little information on genotype- phenotype connection and drug reactions.
ADME core markers are genes involved in drug _____ absorption, distribution, metabolism, excretion.
ADME core markers are genes involved in drug metabolism absorption, distribution, metabolism, excretion.
CYP2D6 is a cytochrome _____ gene
On chromosome _____
Involved in metabolism of about 100 drugs.
CYP2D6 is a cytochrome p450 gene
On chromosome 22
Involved in metabolism of about 100 drugs.
Poor metabolizer has _____ genes for CYP2D6 so has low or nonexistant enzyme activity. At risk for toxicity in cells. For these individuals we switch drugs to bypass CYP2D6.
Intermediate metabolizer = _____ functional CYP2D6 allele, other allele mutated Intermediate heterozygotes take longer to metabolize drug since less enzyme present so give smaller dose of drug.
Extensive metabolizer = normal has _____ functional CYP2D6 alleles (group to which most drug trials are targeted)
Ultra metabolizer has _____ than 2 alleles of CYP2D6. More enzyme is present & they metabolize drug more rapidly. We must increase the dose so drug can actually work before it is broken down.
Poor metabolizer has no genes for CYP2D6 so has low or nonexistant enzyme activity. At risk for toxicity in cells. For these individuals we switch drugs to bypass CYP2D6.
Intermediate metabolizer = 1 functional CYP2D6 allele, other allele mutated Intermediate heterozygotes take longer to metabolize drug since less enzyme present so give smaller dose of drug.
Extensive metabolizer = normal has 2 functional CYP2D6 alleles (group to which most drug trials are targeted)
Ultra metabolizer has more than 2 alleles of CYP2D6. More enzyme is present & they metabolize drug more rapidly. We must increase the dose so drug can actually work before it is broken down.
CYP2D6 converts codeine (a prodrug) to _____ (active form).
 _____ metabolizers cannot convert the drug thus have a limited therapeutic benefit from it.
_____ metabolizers may become intoxicated with even low doses of codeine (morphine overload intoxication).
CYP2D6 converts codeine (a prodrug) to morphine (active form).
Poor metabolizers cannot convert the drug thus have a limited therapeutic benefit from it.
Ultra metabolizers may become intoxicated with even low doses of codeine (morphine overload intoxication).
TPMT is thiopurine methyltransferase.
6 mercatopurine used in cancer treatment.
TPMP breaks 6 mercatopurine _____.
Extensive metabolizers do _____ with it.
_____ metabolizers (homozygous recessive) do not do well and get bone marrow failiure due to toxicity due to buildup of 6MP.
Hererozygote, intermediate metabolizes take longer so they need _____ doses to avoid toxicity.
TPMT is thiopurine methyltransferase.
6 mercatopurine used in cancer treatment.
TPMP breaks 6 mercatopurine down.
Extensive metabolizers do fine with it.
Poor metabolizers (homozygous recessive) do not do well and get bone marrow failiure due to toxicity due to buildup of 6MP.
Hererozygote, intermediate metabolizes take longer so they need lower doses to avoid toxicity.
G6PD reduces oxidative stress in cells.
Glucose 6 phosphate dehydrogenase (G6PD) _____ patients are susceptible to drug induced hemolysis. G6PD deficiency is found in _____ and _____ american populations.
Oxidant drugs (e.g., primaquine-antimalarial) deplete the cell of reduced glutathione and lead to oxidative damage and hemolysis.
G6PD reduces oxidative stress in cells.
Glucose 6 phosphate dehydrogenase (G6PD) deficiency patients are susceptible to drug induced hemolysis. G6PD deficiency is found in Mediterranean and african american populations.
Oxidant drugs (e.g., primaquine-antimalarial) deplete the cell of reduced glutathione and lead to oxidative damage and hemolysis.
Favism – oxidants in the fava _____ can lead to severe hemolytic anemia in individuals with G6PD deficiency. Not everyone with a G6PD defficiency will react negativley with fava _____.
Favism – oxidants in the fava bean can lead to severe hemolytic anemia in individuals with G6PD deficiency. Not everyone with a G6PD defficiency will react negativley with fava beans.
Malignant _____ thermia is associated with mutations in genes RYR1, CACNL1A3, and 4 other loci.
Malignant _____ thermia has negative response to _____ anesthetics (high fever, sustained contractions, hypercatabolism) due to elevation of ionized calcium in the muscle. A person could live with this their whole life & not know. It is fatal.
Malignant hyperthermia is associated with mutations in genes RYR1, CACNL1A3, and 4 other loci.
Malignant hyperthermia has negative response to inhalation anesthetics (high fever, sustained contractions, hypercatabolism) due to elevation of ionized calcium in the muscle. A person could live with this their whole life & not know. It is fatal.
Warfarin _____ blood clots in the human body (coumadin is natural form). Dose changes from one individual to the next.
Warfarin acts on Vtamin K _____. Reduced vitamin K is cofactor important for clotting factors. If you do not have vitamin K reductase you do _____ have Reduced vitamin K and you do _____ have clotting factors so you do not have clots - anticoagulation.
Warfarin is acted on by CYP _____ which degrades Warfarin.
To give Warfarin, we start off with a _____ dose & we build it up. We do this to avoid extreme anticoagulability issues. Also, clinically, it is difficult to genotype for all of the genes involved in Warfarin metabolism.
Warfarin eliminates blood clots in the human body (coumadin is natural form). Dose changes from one individual to the next.
Warfarin acts on Vtamin K Reductase. Reduced vitamin K is cofactor important for clotting factors. If you do not have vitamin K reductase you do not have Reduced vitamin K and you do not have clotting factors so you do not have clots - anticoagulation.
Warfarin is acted on by CYP2C9 which degrades Warfarin.
To give Warfarin, we start off with a small dose & we build it up. We do this to avoid extreme anticoagulability issues. Also, clinically, it is difficult to genotype for all of the genes involved in Warfarin metabolism.
There are many drugs that have been _____ out in clinical trials phase because it caused ADRs in some populations. However, this drug could be useful to the people who did not develop ADRs—so why do we not keep these drugs around and label them for specific populations.
The same thing goes for drug _____.
There are many drugs that have been thrown out in clinical trials phase because it caused ADRs in some populations. However, this drug could be useful to the people who did not develop ADRs—so why do we not keep these drugs around and label them for specific populations.
The same thing goes for drug dosages.
GINA = genetic information nondiscrimination act is a federal law that prohibits _____ in health coverage and employment based on genetic information.
GINA = genetic information nondiscrimination act is a federal law that prohibits discrimination in health coverage and employment based on genetic information.
