Drug Metabolism Flashcards
Drug metabolism
Biochemical modification of pharmaceutical substances by living organisms usually through specialised enzymatic activity
How does drug metabolism limit life of substance in the body?
Rendering lipid soluble compounds water soluble to be excreted
Lipid soluble drug reabsorption
Passively from renal or extra renal back into blood
Where are most drugs metabolised before excretion?
Liver, lining of gut, kidneys, lungs
Pro drugs
Some drugs are pro drugs and only become active after metabolism eg codeine
What are some effects of toxic metabolites
Direct toxicity
Carcinogenesis
Teratogenesis
Metabolising enzymes
- wide substrate specificity and many metabolise a drug
- Expressed constantly or when needed
Phase 1 metabolism steps
- Oxidation
- reduction
- hydrolysis
What does phase 1 metabolism do?
Increases polarity and provides an active site
Introduce or expose polar groups
Cytochrome p450
Enzymes in liver which are important in oxidative drug metabolism
Isoform determines drug specifity
CYP 1
CYP1A2 induced by smoking so a higher dose of theophylline needed
CYP2
CYP2D6 metabolise antidepressants and codeine and are reduced in 5-10% of population and are induced by smoking q
CYP3A4
Major liver enzyme works on a wide range of drugs eg cyclosporine and also found in gut for pre systemic metabolism
Phase 2 reactions
Conjugation - Eg acetate, sulphate attached to metabolite from phase 1
What does phase 2 reactions do?
Increase water solubility and enhance secretion of metabolised compound
Mostly inactivation although sometimes activation
