Drug Metabolism Flashcards
Define metabolism.
Disappearance of a drug by chemically changing it into another cmpd called a metabolite.
Define xenobiotics.
Foreign substances that are absorbed or ingested.
Define pro-drug. What are its 3 purposes?
Cmpd w/ little or no activity that is metabolized to an active species in order to 1) promote absorption, 2) prevent acid destruction, 3) minimize exposure toxicity
Define biological half-life.
that period of time in which half of the amount of a drug disappears; a function of its rate of metabolism and its rate of excretion
Define first-pass effect. What organ is usually involved?
occurs when more than half of the amount of a drug is metabolized on its 1st pass through an organ (usually the liver)
Almost all drugs are metabolized to compounds that are: (name 3)
- more polar than the parent compound
- not as well reabsorbed and therefore more efficiently excreted
- many will become inactive or less active than their parent compound
What are the three possible outcomes of hepatic metabolism of pharmacologic cmpds?
- Activation
- Degradation into active or inactive metabolites
- Degradation to a toxic metabolite, including carcinogens
What is the most important organ for elimination of drugs and their metabolites?
Kidney
What are the three processes involved in the excretion of drugs and metabolites in the urine? Which is affected most by drug metabolism? Why?
- glomerular filtration
- active tubular secretion
- passive tubular reabsorption
Passive tubular reabsorption - b/c metabolite is more polar than the drug that was administered
What is the major diff between Phase I and Phase II rxns?
Phase II needs a donor molecule, Phase I reactions act on the drug alone
Where do enzymes that participate in hydrolysis act?
Plasma & cytoplasm
What are the reaction classes of Phase I and Phase II?
Phase I - oxidation, reduction, hydrolysis
Phase II - conjugation
What order are the kinetics of drug metabolism reactions at therapeutic doses?
First order
What order are the kinetics of drug metabolism reactions at saturation?
Zero order
What organ has the highest level of drug-metabolizing activity?
Liver
What system can oxidize drugs? What are its two requirements?
Monooxygenase or cytochrome P450 system
- Reduced NADPH
- Oxygen
What drug was removed from the market due to a P450-based toxicity? What condition did it make them susceptible to?
Seldane
Cardiac arrhythmias
What chemical group is inserted in oxidation?
Hydroxyl group
What is removed in reduction?
Oxygen
What does hydrolysis involve?
Cleavage w/ addition of water
What reaction type frequently uses transferase enzymes? Phase I or II?
Phase II
What are 4 factors in neonates that makes their drug metabolism capabilities different than adults?
- Absorption - gastric pH varies
- Distribution - body water is greater
- Metabolism - p450 is developed, but functions slower; glucuronidation is immature
- Excretion - renal blood flow, GFR, tubular function are reduced
What are 5 factors in elderly that make their drug metabolism capabilities different than adults?
- Absorption - may be less efficient
- Distribution - can be altered by hypoalbuminemia, changes in drug-binding sites, changes in protein/fat mass ratio
- Metabolism - reduced hepatic mass, enzyme activity, and blood flow to liver
- Excretion - reduced renal blood flow
- Receptor sensitivity - reduced
What are the acute and chronic effects of ethyl alcohol on drug metabolism?
Acute - inhibits drug metabolism
Chronic - induces hepatic drug metabolizing activity (drugs are not effective)
How does grapefruit juice affect drug metabolism?
Flavinoids inhibit metabolism of Ca2+ channel blockers and caffeine by inhibiting CYP3A
Which of the following drugs will cause an increased metabolism of combination pill oral contraceptives?
A. ampicillin
B. ciprofloxacin
C. erythromycin
D. tetracycline
A and D
