What is drug metabolism?
Biochemical modification of pharmaceutical sibstances by living organisms usually through specialised enzymatic activity
What does metabolism limit?
The life of a substance in the body by rendering lipid soluble and non-polar compounds to water soluble and polar compounds than can be excreted
What substances are excreted?
What substances are reabsorbed back into the blood from renal sites?
What are some sites of drug metabolism?
Lining of gut
What is the purpose of drug metabolism?
Increase water solubility and aid excretion
What are prodrugs?
Drugs that may be activated following metabolism
What are examples of prodrugs?
What are the effects of metabolism?
Loss of pharmacological activity
Decrease in activity, with metabolites that show some activity
Increase in activity, more active metabolites (activation of prodrug)
Production of toxic metabolites
What can different kinds of toxic metabolites do?
Carcinogenesis (formation of a cancer)
Teratogenesis (congenital malformations produced in an embryo)
What is carcinogenesis?
Formation of a cancer
What is teratogenesis?
Congenital malformations produced in an embryo
What happens to a prodrug during metabolism?
Inactive chemical compound is coverted into its active metabolite
What controls the metabolism of drugs?
What can you say about the specificity of enzymes that metabolise drugs?
They have a wide range of specificity so individual drugs are often metabolised by more than one
How can different enzymes be expressed?
Constitutively (constant amounts)
In the presence of particular substance
What are the 2 phases of metabolism?
Phase 1 (activation/inactivation)
Phase 2 (conjugation products)
What are different phase 1 reactions?
What happens during phase 1?
Polar groups are introduced to the molecule
What does increasing the polarity of compounds during phase 1 do?
Provides an active site for phase 2 metabolism
What is the most important superfamily of metabolising enzymes?
What does drug specificity of an enzyme depend on?
Which isoform of cytochrome P-450 is being used
What are the 3 families of the cytochrome P-450 super family used in oxidative drug metabolism?
What is CYP1A2 important in the metabolism of?
What is CYP1A2 induced by?
What is CYP2D6 important for the metabolism of?
Some antidepressants, antipsychotics and conversion of codeine to morphine
What is CYP2D6 induced by?
Where is CYP3A4 found?
In the liver and the gut
What is CYP3A4 important for?
Pre-systematic (first pass) metbaolism of several drugs
What are examples of drugs that CYP3A4 is important for the metabolism of?