Hepatic drug metabolism Flashcards
What are prodrugs?
Drugs administered in an inactive form, but they undergo metabolism in the body to become active drugs
What are the 4 phases of pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
What is codeine converted into once inside the body?
Morphine
What is first-pass metabolism?
Orally-administered drugs, absorbed by the GI tract, are transported via the portal system to the liver where they are metabolised to an extent before entering the systemic circulation
What is formed from a phase I reaction?
Intermediate metabolite
What is formed from a phase II reaction?
Conjugated metabolite
What are the 3 types of reactions involved in a phase I reaction?
Oxidation
Reduction
Hydrolysis
What are the 5 chemical groups involved in phase II conjugation reactions?
Glucuronide / glucuronyl
Sulphate
Acetate / acetyl
Methyl
Glutathione
During a phase I reaction, what is attached to the drug?
A functional group
What 2 things does adding a functional group to a drug in a phase I reaction achieve?
Increases the polarity of the drug, making it more water-soluble
Provides a site for phase II reactions
Which enzymes are involved in phase I reactions?
Cytochrome P450
Where in the hepatocytes are cytochrome p450 enzymes located?
Smooth endoplasmic reticulum
Why is it essential that cytochrome p450 enzymes contain haem?
To capture oxygen
What 3 things do cytochrome p450 enzymes need to function?
Oxygen
NADPH
Cytochrome p450 reductase
What are the 2 most relevant cytochrome p450 enzymes?
CYP3A
CYP2D6
What is the basic chemical reaction for oxidation by cytochrome p450 enzymes?
DH + O2 + NADPH + H+
gives
DOH + H2O + NADP+
Ethanol is metabolised by which enzyme?
What is the location of this enzyme in hepatocytes?
Alcohol dehydrogenase
Cytosol
When prescribing medication to children, dosages are often calculated based on which 2 factors?
Age
Body surface area
What is the effect of St. John’s Wort on cytochrome p450 enzymes and what does this mean for drug efficacy?
Induces cytochrome p450 enzymes
Increased metabolism of drugs, reduced plasma concentration - reduced therapeutic efficacy
Describe why taking omeprazole with warfarin increases the risk of internal bleeding.
Omeprazole is an inhibitor of cytochrome p450 enzymes - reduced metabolism of warfarin, increased plasma concentration and therapeutic effect
Where can guidelines concerning drug interactions and metabolism be found?
British National Formulary
How does hypoproteinaemia in liver disease affect the therapeutic efficacy of drugs?
Increases the therapeutic efficacy of drugs since there is more unbound and pharmacologically active drug
