Drug Metabolism Flashcards
What is drug metabolism?
Biochemical modification of pharmaceutical substances by living organisms through specialised enzymatic activity.
How are drugs changed to be able to excrete them?
They are made water soluble and polar so they can be excreted.
What are prodrugs?
Drugs that are activated by metabolism such as codeine.
What are three phase one reactions of metabolism and what do they do?
Oxidation
Reduction
Hydrolysis
They increase the polarity of the compound and provides an active site for phase two metabolism.
What is an important family of drugs for oxidative metabolism?
Cytochrome P-450
CYP1
CYP2
CYP3
What is the main constitutive enzyme in the liver (also found in gut) and name some drugs it metabolises?
CYP3A4
Diazepam and methadone
Why are 5-10% of the population immune to the analgesic effects of codeine?
The enzyme CYP2D6 is responsible for the conversion of codeine to morphine and reduced or absent expression of this is found in 5-10% of the population.
Why do smokers need a higher dose of theophylline than non smokers?
CYP1A2 metabolises theophylline and is induced by smoking.
What is the reaction in phase two metabolism and what does this involve?
Glucuronidation (addition of glucaronic acid)
Involves conjugation which increases the water solubility and enhances excretion.
What are some factors that affect metabolism of drugs?
Other drugs (inc herbal) Gender Ethnicity Pregnancy Hepatic blood flow Liver disease Age Genetics
What does enzyme induction do the drug?
It increases the enzymes activity so the drug gets metabolised faster so it has a decreased effect.
What are some substances that can inhibit drug metabolising enzymes?
Erythromycin
Clarithromycin
Grapefruit
What are four phenotype subpopulations of metabolisers?
Poor metabolisers (PM) Intermediate metabolisers (IM) Extensive metabolisers (EM) Ultrarapid metabolisers (UM)
