Exam 1 - Metabolism and Excretion Flashcards
redistribution
drug moves away from its site of action; reducing its active concentration at the target site
biotransformation (metabolism)
drugs are chemically alterd, usually in the liver, to inactive metabolites that are easier to excrete
What are the two major effects of biotransformation?
- usually converts substances to more hydrophilic compounds that are more readily excreted
- usually converts substances to compounds that are less pharmacologically active
What is Phase I of biotransformation?
introduction of small polar groups on the drug
* reaction classes: oxidations and hydrolysis
* product is usually more polar (hydrophilic)
Phase I oxidations
- mixed functions oxidases
- monoamide oxidases
explain the reaction of mixed function oxidases
drug + oxygen molecule –> drug-OH + water
* cytochrome P450s or CYPs
* metabolize wide variety of xenobiotics and endogenous compounds
explain CYPs
- 3 families: CYP1, CYP2, CYP3
- each family has subfamilies
explain the reaction of monoamine oxidases
monoamine (NH2) drug + oxygen molecule –> drug metabolite
* mainly impacts drugs affecting neurotransmission
Phase I hydrolysis
cholinesterases (add a water)
* acetylcholinesterase
* plasma cholinesterase
- differ in molecules they prefer to metabolize
- differ in location in the body
What is Phase II of biotransformation?
adding a larger polar molecule (glucuronic acid, sulfate) to a hydroxyl (-OH) group on the drug
* reaction classes: transferases
* products usually very polar
Phase II enzymes
- glucuronyl transferases (UGTs)
- sulfotransferases (STs)
- catechol-O-methyltransferase (COMT)
glucuronyl transferases (UGTs) reaction
drug-OH + activated glucose –> drug-glucuronide
sulfotransferases (STs) reactions
drug-OH + activated sulfate –> drug-sulfate
catechol-O-methyltransferase (COMT) reactions
mainly impacts monoamine drugs affecting neurotransmission
active metabolite
drug metabolite that has significant activity (sometimes greater than parent compound)
prodrug
inactive or relatively inactive precursor that is converted to a more active compound
reactive metabolite
very toxic compound produced by biotransformation of a relatively inert substance (often reacts with protein or DNA)
Where are common sites of biotransformation?
liver, GI tract, lungs, skin, kidneys, plasma
Inhibitors of drug metabolism
- imidazoles
- macrolide antibiotics
- bioflavonoids (grapefruit)
What are important points about drug metabolism inhibitors?
- decreased metabolism leads to increased drug levels
- each inhibtors affects different CYPs
- common site of drug-drug interaction
factors influencing drug metabolism
- genetic (pharmacogenetics)
- disease states
pharmacogenetics
the study of how an individual’s genetic makeup influences their response to drugs
excretion
the drug and its metabolites are removed from the body; primarily through the kidneys or the liver
What will a deficiency in an excretion route result in?
increased plasma concentration with subsequemt enhanced drug effects, unless the drequency or dose of a drug administered is reduced
