Drug metabolism Flashcards
What is ADME of drugs?
Absorption
Distribution
Metabolism
Elimination
What is the function of drug metabolism?
Deactivates the drug (Usually)
Eliminates the drug
What is the pathway of drug metabolism?
Goes through Phase I then Phase II.
Some drugs go straight into Phase II.
What does Phase I of drug metabolism do?
It adds or exposes a reactive group by Oxidation, reduction or hydrolysis
What does Phase II of drug metabolism do?
Conjugation, the altered drug molecule is combined with a water soluble group
What are the main sites for Phase I drug metabolism?
Liver - Microsomes on ER of herpatocytes
Kidney
GI Tract
What is the Phase I drug metabolism system called?
Cytochrome P450 enzyme system
What is the main sites for Phase II drug metabolism?
Liver - Cytosolic enzymes
What can effect drug metabolism?
Genetics - Gene delitions so enzyme deficiencies
Environment - Enzyme inhibition/induction
What is the normal pathway for Paracetamol metabolism?
Straight to Phase II metabolism
What is the metabolism pathway in Paracetamol overdose?
Phase II is saturated so it goes through Phase I too which makes NAPQI (toxic)
What is the reaction for Alcohol breakdown?
Alcohol –> Acetaldehyde (toxic) –> Acetic acid
What enzymes allow alcohol breakdown?
Alcohol dehydrogenase and CHYP2E1 aids step 1, Aldehyde dehydrogenase aids step 2
How does chronic alcohol toxicity effect the liver?
Excess NADH stimulates fat deposition
Acetaldehyde damages liver cells
causes alcoholic hepatitis and cirrhosis
How can alcoholism be treated?
Disulfiram - Aldehyde dehydrogenase inhibitor
