3 - Metabolism Flashcards
What is metabolism?
Conversion of a drug to a more polar, water soluble, ionized substance, usually w/ reduced pharmacological activity and toxicity (exception is a prodrug)
____ is the main organ of biotransformation
Liver
What are the sites of metabolism?
- Bloodstream
- Kidneys
- Brain
- Muscle tissue
- Walls of GI tract
- Lungs
What are the 2 types of hepatic metabolism? What are examples of each?
1) Phase 1 - oxidation, hydrolysis, reduction (in order from most to least prevalent)
2) Phase 2 - glucuronidation, acetylation, sulfation
What must happen to a drug to undergo phase 2 metabolism?
Must be activated, generally by a phase 1 reaction
What does it mean when an active drug is metabolized to an active metabolite?
Don’t have to dose as frequently
How are barbiturates metabolized?
Glucuronidation and oxidation
How are benzodiazepines metabolized?
1) N-dealkylation to biologically active metabolite
2) Hydroxylation to active metabolite
3) Glucuronidation to inactive metabolite
How is morphine metabolized?
Glucuronidation to morphine-6-glucuronide (active metabolite) or morphine-3-glucuronide (inactive metabolite)
How is codeine metabolized?
10% is demethylated to morphine
How are tranquilizing agents (anti-psychotic agents) metabolized?
Majority is oxidized, some undergoes glucuronidation
How is cocaine metabolized?
Plasma esterases
How is ethanol metabolized?
Oxidation (zero order process)
What is required for oxidation?
- NADPH
- Molecular oxygen
- Heme-protein
Important phase 1 oxidation reactions are performed by ______ found in ______
Mixed function oxidases found in smooth endoplasmic reticulum
Why is it called cytochrome P450?
Absorbs light at wavelength 450 nm
What is the key element in the oxidative process?
Hemeprotein cytochrome
What is the difference btwn ferrous and ferric iron?
- Ferrous = Fe2+
- Ferric = Fe3+
Which families of CYP enzymes are responsible for drug metabolism?
Families 1, 2, and 3
What are the 6 major CYP P450 isoenzymes responsible for the majority of drug metabolism in humans?
1) CYP1A2
2) CYP2C8/9/10
3) CYP2C18/19
4) CYP2D6
5) CYP2E1
6) CYP3A4
What are the substrates of CYP1A2?
- Phenacetin
- Theophylline
What are the substrates of CYP2C8/9/10?
- Hexobarbital
- Phenytoin
What are the substrates of CYP2C18/19?
- Diazepam
- Mephenytoin
What are the substrates of CYP2D6?
- Imipramine
- Propranolol