L4 Pharmacokinetics 2 - drug metabolism and excretion Flashcards
what is the definition of drug metabolism
the chemical alteration to foreign substances or drugs by enzymes in the body
what are the three main drug biotransformation reactions in the human body
glucuronidation, oxidation and sulfation
what is the most important CYP in human metabolism
CYP3A4, handling about 1/2 of all drug substrates
what are the clinical problems associated with using multiple drugs with reference to CYP isoforms
1) Drug B can induce CYP450 causing increased metabolism of another drug (i.e. drug A) into it’s metabolite causing a lack of clinical benefit.
2) Drug B could inhibit the action of CYP450 on metabolism of another drug causing increases in plasma concentration of drug A and toxicity
3) may inhibit a CYP450 that causing activation of a drug into it’s metabolites–> therefore causing lack of clinical benefit
give an example of a CYP3A4 inhibitor
grapefruit- contains furocoumarins compounds that competitively inhibit CYP3A4.
what are some of the drugs affected by grapefruit juice
statins, calcium, benzodiazepines etc.
What are the three processes that happen in the glomerulus that contribute to excretion of drugs?
renal filtration, renal secretion and renal absorption
What are the two molecules/transporters involved in first-pass clearance in the GI-tract and the Liver? How do they do this?
CYP3A4 and P-gp (p-glycoprotein)
Cooperatively minimize drug absorption; P-gp is an efflux pump that pumps lipid soluble drugs back into the intestinal lumen, reducing their absorption, while CYP3A4 oxidises these drugs. This results in less than 30% of a drug making it to the liver.
Following first pass clearance in the liver by both of these molecules, only about 15% of the drug continues into systemic circulation
If a drug is renally cleared, will it undergo chemical transformation in the liver?
No, only in the kidneys. If a drug is handled by the liver, it is called a ‘hepatically cleared drug’.
What are the major classes of transporters that eliminate drugs in renal excretion?
ABC transporters - cross the apical membrane
SLC transporters - cross the basolateral membrane
