Chapter 8 - Individual Variation in Drug Responses Flashcards
In the very young patient, heightened drug sensitivity is the result of
organ immaturity
in older adults, heightened sensitivity results largely from
decline in organ function
Recall that, because of pH partitioning, if there is a difference in pH on two sides of a membrane, a drug will accumulate on the side where
the pH most favors its ionization
if liver function declines, the rate of metabolism will
decline, causing drug levels to climb
Tachyphylaxis?
a reduction in drug responsiveness brought on by repeated dosing over a short time
The most serious toxicity of digoxin is production of
potentially fatal dysrhythmias
The tendency of digoxin to disturb cardiac rhythm is related to levels of
potassium
When potassium levels are low, the ability of digoxin to induce dysrhythmias
greatly increased
Pharmacodynamic tolerance is the result of
adaptive processes that occur in response to chronic receptor occupation.
How is metabolic tolerance brought about?
by the ability of certain drugs (eg, barbiturates) to induce synthesis of hepatic drug-metabolizing enzymes, thereby causing rates of drug metabolism to increase
Diarrhea can _____ absorption by accelerating transport of drugs through the intestine.
reduce
Pharmacogenomics
the study of how genetic variations can affect individual responses to drugs
What two drugs require genetic testing before use?
maraviroc [Selzentry] and trastuzumab [Herceptin
Variants in the gene that codes for cytochrome _____ can greatly reduce the benefits of tamoxifen [Soltamox, Nolvadex-Dimage], a drug used to prevent breast cancer recurrence
CYP2D6
Variants of the gene that codes for ______ can greatly reduce the benefits of clopidogrel [Plavix], a drug that prevents platelet aggregation
CYP2C19
About 1 in 14 people of European heritage have a form of ______ that is unable to convert codeine into morphine, the active form of codeine.
CYP2D6 — As a result, codeine cannot relieve pain in these people.
Variants in the gene that codes for _______ can increase the risk of toxicity (bleeding) from warfarin [Coumadin], an anticoagulant with a narrow TI.
CYP2C9
Variants in the genes that code for the beta1-adrenergic receptor (ADRB1) produce receptors that are
hyperresponsive to activation
The most common mechanism by which genetic variants modify drug responses is by
altering drug metabolism
The most serious adverse effect of MAO inhibitors is ______ , which can be triggered by foods that contain
malignant hypertension ; tyramine, a breakdown product of the amino acid tyrosine. Accordingly, patients taking MAO inhibitors must rigidly avoid all tyramine-rich foods (eg, beef liver, ripe cheeses, yeast products, Chianti wine).
The most serious adverse effect of MAO inhibitors is ______ , which can be triggered by foods that contain_____
malignant hypertension ; tyramine, a breakdown product of the amino acid tyrosine. Accordingly, patients taking MAO inhibitors must rigidly avoid all tyramine-rich foods (eg, beef liver, ripe cheeses, yeast products, Chianti wine).
Kidney disease can _________ drug excretion
Reduce
If liver function declines, the rate o metabolism will _______
Decline, causing drug levels to climb
Recall that because of PH partitioning, if there is a difference in pH on two sides of a membrane, a drug will accumulate in the side where_____
The pH most favors ionization
The most serious toxicity of digoxin is production of______
Potentially fatal dysthymias
The tendency of digoxin to disturb cardiac rhythm is related to levels of
Potassium.
When potassium levels are low, the ability of digoxin to induce dysthymias ______
Greatly increases
Pharmacodynamic tolerance is the result of ________
Adaptive process that occur in response to chronic receptor occupation
Metabolic tolerance?
Tolerance resulting from accelerated drug metabolism.
The most common mechanism by which genetic variants modify drug response is by _____
Altering drug metabolism
