Metabolism and excretion: the liver and kidneys
Explains the 'big problem' the liver solves: kidneys can't hold onto lipid-soluble drugs until metabolism makes them water-soluble.
Where this fitsConnects to 1 · Unlocks 2
- Connects to
- ADME: the drug's journey through the body — This zooms into M and E.
- Unlocks
- When enzymes change: induction, inhibition and genetics — Enzyme levels change — induction, inhibition, genetics.
- First-pass metabolism and prodrugs — Oral drugs meet the liver before the brain.
Orient
Elimination: the greatest amount is renal excretion (urine) through the kidneys. A big problem: lipid-soluble drugs are hard for kidneys to hold onto. Solution: metabolism – chemical changes that usually reduce the effect of drugs and increase their excretion, mostly by liver enzymes (cytochrome P450 = CYP) in Phase I and Phase II (conjugation) reactions.
Course terms
Your professor's wording, word for word from the slides. Learn the term and this definition — the explanation underneath is only there to help it make sense.
- Renal excretion
“Renal excretion (urine)”Slides 04, p. 30
By far the most common route of elimination.
- The kidney problem
“Lipid-soluble drugs are hard for kidneys to hold onto”Slides 04, p. 32
They diffuse back into circulation before being excreted — so the liver makes them less lipid-soluble.
- Active metabolite
“May produce another molecule that is still able to cross the BBB and still has psychoactive effects - an “active metabolite””Slides 04, p. 34
Metabolism doesn't always switch a drug off.
- CYP (cytochrome P450)
“Referred to as microsomal enzymes (main category = cytochrome P450 = CYP)”Slides 04, p. 35
Mostly nonspecific; CYP2D6 and CYP3A4/5 metabolize over 50% of drugs.
- Phase I
“Phase I: CYP enzymes”Slides 04, p. 36
Oxidation (most common), reduction, hydrolysis.
- Oxidative stress
“excess free radicals (reactive molecule/chemical due to missing electron) causing oxidative stress”Slides 04, p. 36
Antioxidants target excess free radicals.
- Phase II (conjugation)
“Combining drug with another molecule (e.g., glucuronidation)”Slides 04, p. 36
Makes the drug more water-soluble so it dissolves in urine.
From your course: Course slides 04, pp. 28–36
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Full lesson: Enzymes and phases of metabolism · Excretion and the kidney-liver connection