Drug Metabolism Flashcards
(26 cards)
What is metabolism
Biochemical modification of pharmaceutical substances through enzyme activity
What happens to lipid soluble substances instead of getting excreted?
Passively reabsorbed from renal or extra renal excretory sites back into the blood
What are the important sites of metabolism
Liver
Gut lumen
Kidney
Lungs
Purpose of metabolism?
To increase water solubility and so aid excretion
or to deactivate compounds (may involve a number of steps).
What are prodrugs?
Drugs activated by metabolism
What are the effects of metabolism
Loss of pharmological activity
Production of toxic metabolite
What are phase 1 reactions of metabolism?
OXIDATION
REDUCTION
HYDROLYSIS
What does phase 1 metabolism involve
Increased polarity of compound provides active site for Phase 2
Cytochrome P450 metabolising enzymes
P450 determines drug specificity
What are the functions of CYP1
CYP2
CYP3
CYP1- metabolises theophylline
CYP2- metabolism of antis, converts codeine-> morphine
CYP3- Enzyme in liver, gut, presystemic metabolism of many drugs
What is the main role of the CYP1-3 families (contained within the P-450 family)
Important in oxidative drug metabolism
Where are enzymes found that are responsible for the breakdown of SOME drugs
CYP3A4 - Liver + Gut
Omeprazole
Why may 5-10% of the population may be immune to the analgesic actions of codeine?
Reduced expression of the enzyme responsible for conversion of codeine to morphine
Why do smokers require a higher dose of theophylline than non-smokers?
Enzyme responsible for the metabolism of theophylline is induced by smoking
What does phase 2 metabolism involve?
Conjugation
Attachment of glucoronic acid, glutathione, sulphate or acetate to the metabolite generated by phase 1 metabolism
Usually results in inactivation
What does conjugation increase
Water solubility
Excretion of metabolised compound
What factors affect metabolism?
Hepatic blood flow Age Liver disease Other drugs/herbals/natural substances Pregnancy Ethnicity Genetics Sex
What is the effect of induction of drug metabolising enzyme on metabolism?
Increased enzyme synthesis
increased activity
Decreased drug effect
What is the effect of inhibition of drug metabolising enzyme on metabolism?
Reversible or irreversible binding to the enzyme
Metabolism decreased
What is the effect of decreased enzyme activity on drug metabolism?
(can be as a result of genetic polymorphism)
Increased drug toxicity
What are the four phenotype subpopulations of metabolizers?
Poor metabolizers (PM) Intermediate metabolizers (IM) Extensive metabolizers (EM) Ultrarapid metabolizers (UM)
Describe the prevalence of drug metabolising enzymes in the fetus or premature infant?
Deficient or reduced
renal function deficient so drug metabolites rapidly build up to toxic levels.
Who metabolises drugs faster - a teenager at puberty or an adult?
At puberty
What can affect the metabolism of drugs in a pregnant woman?
The trimester she is in
Hormonal changes
What factors brought about in old age alter drug metabolism?
Plasma protein
Lean body mass
Liver weight
DECREASE
Other drugs taken to treat chronic illness
