lehne ch 8: Individual variation in drug response Flashcards
Intensity of the response to a drug is determined in large part by the concentration - the higher the concentration, the more intense the response. If you gave the same dose to a large and small person, which will have more intense effects?
Smaller.
Why is using BSA (Body Surface Area - mg per m2) an accurate way to adjust a dosage?
BSA determinations account for weight AND for how fat or lean the person is. The percentage of body fat can change distribution thereby changing concentration.
What affect does age have on drug sensitivity?
Infants are sensitive because of organ immaturity.
Elderly are sensitive due to organ degeneration and first pass effect decreases.
T or F: Abnormal pathophysiology does not affect drug response.
False! Kidney disease, liver disease, acid-base imbalance and altered electrolyte status can affect drug response.
Kidney disease, such as nephrosclerosis, can reduce ________, causing drugs to accumulate in the body (potentially to a toxic level).
Excretion. The dosage must be reduced when this is happening.
If liver function declines, rates of ______ will decline too, and drug level will climb.
metabolism
T or F: Changes in acid-base status can alter absorption, distribution, metabolism, and excretion of drugs.
True. Drugs accumulate on the side where the pH most favors its ionization (remember acid ionizes in alkaline, alkaline ionizes in acid).
What is an example of altered electrolyte status affecting drug response?
Digoxin, a drug for heart disease can cause dysrhythmias when potassium levels are depressed.
NOT IN PPT: Tolerance resulting from accelerated drug metabolism…
Metabolic Tolerance; dosage must be increased to maintain therapeutic levels.
NOT IN PPT: ________ is a form of tolerance that can be defined as a reduction in drug responsiveness brought on by repeated dosing over a short time. An example is leaving a transdermal nitroglycerin patch on for 24 hours. Must be removed and fiven intermittently to allow cofactors to be replenished.
tachyphylaxis
NOT IN PPT: __________ refers to the ability of a drug to reach the systemic circulation from its site of administration.
bioavailability; different formulations can alter bioavailability, and can thereby make drug responses variable.
What is CYP2D6?
An enzyme; a member of the cytochrome P450 family of enzymes involved in the oxidative metabolism of drugs. CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs.
If a person inherited a deficiency in the CYP2D6 gene, and the drug requires activation by the CYP2D6 enzyme what happens to metabolism?
Metabolism of the drug slows AND toxicity may occur. The dosage may need to be adjusted. The FDA does not require testing for this deficiency but a test is available.
What happens if a person takes two drugs requiring CYP2D6?
They have a drug-drug interaction.
Does ethnicity change the likelihood of having a CYP2D6 Deficiency?
Yes. African Americans and Middle Eastern people have highest risk of deficiency. Asians have the lowest.
