Metabolism Flashcards
What is the definition of metabolism?
- conversion of drug to a more polar, water soluble, ionized substance usually with reduced pharmacological activity and toxicity
What are the sites of metabolism?
- bloodstream
- kidneys
- brain
- muscle tissue
- wall of GI tract (e.g. bacteria)
- lungs
The liver is the main organ of ________
biotransformation
What are the three chemical processes of phase 1 hepatic metabolism?
oxidation. reduction and hydrolysis
What are the three chemical process of phase 2 metabolism?
glucuronidation, acetylation and sulfation
What metabolic processes do barbiturates undergo in the body?
- glucuronidation
- oxidation
What metabolic processes do benzodiazepines undergo in the body?
- N-dealkylation
- hydroxylation
- glucuronidation
What are the metabolic processes that morphine undergoes in the body?
- glucuronidation
- morphine 6-glucuronide
- morphine 3-glucuronide
10% of codeine is demethylated to _____
morphine
The majority of anti-psychotic agents undergo the process of _____, but some also undergo glucuronidation
oxidation
What is the metabolic process that ethanol typically undergoes?
oxidation
What is the most prevalent phase 1 metabolism process?
oxidation
What are the chemical requirements to carry out an oxidation reaction?
requirement of NADPH, molecular oxygen and heme protein
Where in the cell are many of the phase 1 oxidation processes carried out?
in the smooth endoplasmic reticulum
Key element in the oxidative process is the hemeprotein cyctochrome _______
cytochrome P450 enzyme system
What families of the CYP enzyme is drug metabolism carried out by?
- carried out my families 1, 2 and 3
How many major P450 isoenzymes is the metabolism of drugs dominated by?
6
What are the drug substrates for enzyme CYP1A2?
phenacetin and theophylline
What are the drug substrates for enzyme CYP2C8/9/10?
hexobarbital, phenytoin
What are the drug substrates for the enzyme CYP2C18/19?
diazepam, mephenytoin
What are the drug substrates for the enzyme 2D6?
imipramine, propranol
What are the drug substrates for the enzyme CYP2E1?
acetaminophen
What are the drug substrates for the enzyme CYP3A4?
erythromycin and cyclosporin
Smoking _____ the enzyme CYP1A2, resulting in the activation of benzopyrene, a carcinogen in the cigarette smoke
induces
In what enzyme is there quite a bit of genetic polymorphism?
CYP2C9, CYP2C19
5% of caucasians and 20% of asians are poor metabolizers
There is an inhibition of S-Warfarin metabolism by _____
amiodarone