Flashcards in Pharmacokinetics II Deck (16):
What is the purpose of metabolism (biotransformation)?
- decrease lipid solubility (i.e., make a drug more water soluble)
- increase ionization
What event is caused by biotransformation?
increased body excretion
What are three mechanisms/purposes of biotransformation?
- lipophilic --> hydrophilic
- active drug --> metabolite
(metabolites can act as an active drug, active toxicant, or be inactive)
- pro-drug --> active drug
How does metabolism occur?
- reactions include oxidation (CYP 450), reduction, deamination, and hydrolysis
- reactions that involve addition (i.e., conjugation) of subgroups to -OH, -NH2, and -SH functional groups on a drug molecule
What is biotransformation?
- process by which chemicals (drugs) are modified by the organism
- usually occurs by enzymatic reaction
- present for endogenous as well as exogenous substrates (vitamins, steroids, hormones, drugs, etc.)
What are three mechanisms of metabolism (alteration of drug)?
- lipophilic to hydrophilic
- first pass effect (oral administration)
- cytochrome P450
Why is biotransformation necessary?
If no biotransformation, drugs/substances will stay in body for much longer; biotransformation can eliminate them from the body in hours
How does the first-pass effect, and subsequent liver passes, affect a drug?
the drug passes through the liver several times, more and more gets metabolized and eventually eliminated
What is path of blood circulation (first-pass)?
Oral administration --> GI Tract --> absorbed into portal vein --> Liver --> Hepatic Vein --> heart --> aorta:
-->hepatic artery --> liver -->....
--> i) celiac artery; ii) superior & inferior mesenteric arteries --> GI Tract -->....
What is the importance of biotransformation?
- a key determinate of therapeutic half-life
- may produce "active metabolite"
- site of "drug-drug interaction" (drugs can increase half life of another drug/increase metabolism, inhibit other drugs, etc.)
- produces toxic metabolites for intermediates
What are the results of biotransformation?
- stops pharmacological effect (of parent drug); with the exception of production of an active metabolite
- restricts distribution (remains in plasma, filtered by kidney)
- facilitates excretion
What are the key organs involved in biotransformation - high capacity?
What are the key organs involved in biotransformation - medium capacity?
intestine, lung, kidneys
What are the key organs involved in biotransformation - low capacity?
skin, testis, placenta, adrenals
*not that significant relative to liver
Is the brain involved in biotransformation?
functional activity of enzymes for metabolism in brain is not clear right now - don't know much