Flashcards in Drug metabolism and Pharmacokinetics Deck (12)
Define drug metabolism
• Drug metabolism is biochemical modification of pharmaceutical substances by living organisms usually through specialized enzymatic activity. Metabolism is divided into two phases (I and II)
• Is an essential pharmacokinetic process, which limits the life of a substance in the body, by rendering lipid soluble and non-polar compounds to water soluble and polar compounds so that they can be excreted.
What is the purpose of drug metabolism?
• To increase water solubility and so aid excretion
• Or to deactivate compounds (may involve a number of steps)
Describe some possible effects of metabolism,
• Loss of pharmacological activity.
• Decrease in activity, with metabolites that show some activity.
• Increase in activity, more active metabolites.
• Activation of a prodrug.
• Production of toxic metabolites.
• Direct toxicity
Describe some phase I reactions and what their role is
Increases the polarity of a compound by introducing or revealing a polar group to provide an active site for phase II metabolism,
Describe the action of CYP3A4
Major metaboliser of a wide range of drugs, including diazepam and methadone
Describe the action of CYP2D6 and any implications
Metabolises some antidepressants, antipsychotics and the conversion of prodrug codeine to morphine.
Reduced or absent expression in 5-10% of population, making them immune to analgesic effect of codeine
Induced by smoking - problem in psychiatric patients
Describe the action of CYP1A2 and any implications
Important in the metabolism of theophylline (COPD drug), which is induced by smoking, meaning smokers require higher doses
What types of reactions occur in phase II metabolism, and what effect do they have on the drugs?
Conjugation reactions to increase their water solubility and therefore aid in their secretion
What groups can be added in conjugation reactions?
What effect does enzyme induction have on drug metabolism?
Causes increased metabolism, which results in the decreased effect of the drug, meaning higher doses may be needed.
What effect does enzyme inhibitors have on drug metabolism?
Causes decreased metabolism, meaning drugs accumulate in the body and may cause a variety of toxic side effects