Lab 5: Induction/inhibition Of Drug Metabolism In Vivo Flashcards
What is a pharmacokinetic drug interaction?
When one drug interferes with the absorption, distribution, metabolism or excretion of another
What are two drugs that result in the altered metabolism of pentobarbitone?
Cimetidine which is an antigastric ulcer drug. This will inhibit pento metabolism.
Phenobarbitone which is an anticonvulsant. This will induce pento metabolism
How was phenobarbitone administered?
Via the drinking water of the mouse for 6 days prior to injection with pentobarbitone
This is because it takes longer for the body to synthesise enzymes for induction.
How was cimetidine administered?
Via IP injection 30 minutes before injecting the mice with pentobarbitone.
This is because inhibition of metabolism is much quicker than induction.
What is the effect of inhibition or induction of metabolism on the onset of pentobarbitone ?
There does not seem to be any significant effect on the onset of pento with altering the metabolism of the drug
What is the effect of inhibition on the duration of pento?
Inhibiting the metabolism of pento by injecting cimetidine 30 minutes prior resulted in a much longer duration of action of pento.
This is because inhibition of the metabolising enzymes results in a lower elimination rate of pento, leaving more of the active drug available to exert its effect.
What is the effect of inducing metabolism on the duration of pento?
This resulted in a much shorter duration of action as pre treatment with phenobarbitone resulted in the synthesis of more metabolising enzymes. This leaves very little of the active drug left to exert its effect, resulting in a shorter duration of action.
What are the results of giving several drugs to a patient at the same time?
An altered response compared to when the drug was given on its own. This arises from pharmaceutical, pharmacodynamic or pharmacokinetic interactions
What is a pharmaceutical interaction?
Interaction which arises when drugs are mixed in appropriately in syringes and infusion fluids prior to administration
What are pharmacodynamic interactions?
Interactions which arise between drugs acting on the same receptors or sites of action or physiological systems
What are examples of two clinically important pharmacokinetic interactions ?
The induction
And inhibition
Of hepatic microsomal drug oxidation
What is the potential result of inhibition of drug metabolism.
Exaggerated, prolonged responses with an increased risk of toxicity
What can induction if metabolism potentially result in?
Therapeutic failure.
What is the potential effect which can occur with the withdrawal of an enzyme inducing agent from an established and stabilised regimen?
Toxicity may occur with other drugs eliminated by the hepatic microsomal system when the enzymes revert to a lower level of activity due to the withdrawal of the enzyme inducing drug.
