Drug metabolism Flashcards
define Drug metabolism
biochemical modification of pharmaceutical substances by living organisms usually through specialized enzymatic activity
Where are drugs usually metabolised
The liver
What happens to lipid soluble drugs instead of excretion
passively reabsorbed from renal filtrate and absorbed back into the blood
What is the purpose of drug metabolism and
what else can occur from the process that can cause an adverse reaction
increase water solubility to aid excretion
deactivate compounds
Toxic metabolites
What are pro drugs (example)
drugs activated following metabolism e.g. codeine
What is the most important metabolising enzyme family in the liver
Cytochrome P450
What are the two ways metabolising enzymes can be expressed
constitutively -continuously
or Induced in the presence of substrate
What process occur in phase 1 metabolism and what is the purpose of the processes
Oxidation Reduction Hydrolysis
To increase polarity
How is drug specificity determined in the liver
isoform of cytochrome P450
What are the three isoforms of cytochrome P450
CYP1A2
CYP2D6
CYP3A4
What are the drug substrates for
CYP1A2
CYP2D6
CYP3A4
CYP1A2 - theophyline - respiratory diseases
CYP2D6 - codeine - pain relief
CYP3A4 - cyclosporine - immunosuppressant drug
What is the purpose of CYP2D6 and what induces the enzyme
metabolises antidepressant
smoking
What would happen if someone who smokes and takes antidepressants stops smoking
Induced levels go away but level of drug concentration remains this causes an accumulation of the drug resulting in toxicity
What would happen to people that don’t have CYP2D6 enzyme and take codeine
Cant metabolise to morphine so don’t receive any pain relief
What enzyme is a major constitutive enzyme
CYP3A4
How is it easy to cause toxicity giving smoking patients theophlyine
As smoking induces enzyme CYP1A2, therefore if patient was to stop smoking the concentration of the drug would be to high as enzymes level decrease, the accumulation causes toxicity
What are the factors affecting metabolism
Other drugs/herbals/natural substances Genetics Hepatic blood flow Liver disease Age Sex Ethnicity Pregnancy
What are the most common enzyme inducers
alcohol and smoking
What is enzyme induction and
how long does it take to take an effect
Increase synthesis of enzymes therefore increases the metabolism of a drug
Is a slow process = progressive loss of drugs affect
How long does it take for enzyme inhibition to occur
Immediate response
What ar common enzyme inhibitor drugs
cimetidine - inhibits stomach acid production erythromycin - antibiotic clarithromycin - antibiotic ketoconazole - fungal infections grapefruit
what is pharmacogenetics and what is the problem
A branch of pharmacology concerned with effects of genetic factors
You will over treat or under treat some patients
wha is the consequences genetic variation in pharmacology
therapeutic failure or an adverse drug reaction
How is genetic variation tackled
Wide variability in the response to drugs between individuals
Drug metabolising enzymes are often expressed in multiple forms
Gene mutations resulting in lack or decreased activity of an enzyme results in what
Increased drug toxicity
Gene varriation or mutation resulting in multiple expressions of a particular metabolising enzyme results in what
enhanced metabolism and reduced drug effect or drug resistance
What are the Four phenotype subpopulations of metabolizers
Poor metabolizers (PM) Intermediate metabolizers (IM) Extensive metabolizers (EM) Ultrarapid metabolizers (UM)
When is the rate of metabolism the best in humans
at puberty
What are the levels of drug metabolising enzymes in children
deficient or reduced
What happens to metabolising in pregnancy
is induced
What are the factors that effect drug metabolism in elderly patients
plasma protein, lean body mass decreased liver weight More likely to have chronic disease so on multiple drug therapy renal functions aren't as efficient
How might ethnicity effect drug metabolism
due to racial differences in the genetic expression of cytochrome P-450 isoforms.
