Drug Metabolism Flashcards
Define drug metabolism?
Biochemical modification of pharmaceutical substances by living organisms usually through specialised enzyme activity.
Why is drug metabolism essential?
Limits the life of a substance in the body.
Are drugs usually metabolised before or after excretion?
Before
Where are the important sites of drug metabolism?
Liver
Lining of gut
Kidneys
Lungs
What are the 2 purposes of metabolism?
Increase water solubility
Deactivate compounds
What are the 3 effects of metabolism?
Loss of pharmacological activity
Decrease of activity
Increase of activity
What are the 3 productions of toxic metabolites?
Direct toxicity
Carcinogenesis
Teratogenesis
Enzymes in drug metabolism are very specific/have a wide specificity.
Wide
How are some enzymes expressed?
Constitutively.
How are other enzymes expressed or induced?
In the presence of a particular substrate.
How many phases are there?
2
What are the phase 1 reactions?
Oxidation
Reduction
Hydrolysis
What is increased in phase 1?
Polarity of compound, providing an active site for phase 2.
What are the most important super family of metabolising enzymes?
P-450
Is specificity usually relative or absolute?
Relative
What is a major constitutive enzyme in human liver?
CYP3A4
What drug is responsible for the metabolism of antidepressants?
CYP2D6
Why are 5-10% of the population immune to analgesic actions of codeine?
Reduced or absent expression of CYP2D6
What is CYP1A2 induced by?
Smoking
What is CYP1A2 important in?
Metabolism of theophylline.
What does phase 2 include?
Conjugation
What does conjugation increase?
Water solubility, enhancing excretion of the metabolised compound.
What factors affect metabolism?
Other drugs/herbals/natural substances Genetics Hepatic blood flow Liver disease Age Sex Ethnicity Pregnancy
What happens when a drug is induced?
Increases metabolism of drugs metabolised by that enzyme.
Induction is a ______ process.
Slow
What are the 2 most common enzyme inducers?
Alcohol
Smoking
What may inhibit drug metabolising enzymes?
Commonly used drugs, herbal medicines and food stuffs.
What are common drug metabolising inhibitors?
Cimetidine
Ketoconazole
Grapefruit
What can be the consequences of genetic variation?
Therapeutic failure
Adverse drug reactions
How are pharmacogenetics often expressed?
In multiple forms
What are common differences in gene expression?
Interindividual
What does a lack/decreased activity of an enzyme result in?
Increased drug toxicity
Approx __ nucleotide polymorphisms are known?
70
What are the 4 phenotype subpopulations of metabolisers?
Poor
Intermediate
Extensive
Ultrarapid
How many drugs does CYP2C9 commonly metabolise?
16
What are 2 substrates of CYP2C9?
Warfarin
Phenytoin
What are drug metabolising enzymes are often ______ or ______ in the fetus or premature infant.
Deficient
Reduced
What builds up due to renal function being deficient in children?
Metabolites to toxic level
By what age can children metabolise drugs more than adults?
2
Who are more prone to drug toxicity?
Women
What does pregnancy induce?
Certain drug metabolising enzymes.
What factors can decrease and alter drug metabolism in the elderly?
Plasma protein
Lean body mass
Liver weight
Why are the elderly more likely to be on multiple drug therapy?
Chronic disease
Where are the difference in racial genetic expression?
Cytochrome P-450
What do steroids do to your blood sugars?
Increases it
