Pharmacokinetics II: Metabolism and Excretion. Flashcards
Define drug metabolism.
The enzymatic conversion of one chemical entity to another, primarily to make drugs more water-soluble for excretion.
Where does drug metabolism predominantly occur?
In the liver, but also in the gut, lungs, and plasma.
Name the two phases of drug metabolism and their functions.
Phase I: Catabolic reactions that may make products more chemically reactive (e.g., oxidation, reduction).
Phase II: Conjugation reactions attaching chemical groups (e.g., glucuronyl, sulfate) to make compounds more water-soluble.
What is the role of CYP450 enzymes in drug metabolism?
They metabolize drugs in the liver and are involved in many drug interactions regulated by inducers and inhibitors.
How can genetic variation affect drug metabolism?
People can be poor metabolizers (PM), extensive metabolizers (EM), or ultra-rapid metabolizers (UM), affecting drug efficacy and safety.
What is first-pass metabolism?
A process where drugs administered orally are metabolized in the liver and gut wall, reducing the concentration reaching systemic circulation.
How can first-pass metabolism be overcome?
By using alternative routes of administration, such as inhalation for salbutamol or sublingual for glyceryl trinitrate (GTN).
What are active metabolites?
Products of drug metabolism that may have pharmacological effects, e.g., prodrugs like enalapril or long-lived metabolites of benzodiazepines.
What are toxic metabolites?
Harmful by-products of metabolism, such as the toxic metabolite of paracetamol, which can cause damage if detoxification pathways are overwhelmed.
What is drug excretion?
The removal of drugs from the body, primarily via the kidneys through processes like glomerular filtration, active tubular secretion, and passive diffusion.
Name drugs excreted unchanged via the kidneys.
Excreted unchanged: The drug is not chemically altered by the body and is removed through urine.
Up to 100%: Furosemide, gentamicin, atenolol.
Up to 75%: Benzylpenicillin, oxytetracycline.
What is enterohepatic recycling?
A process where drugs excreted into bile are reabsorbed into the bloodstream after being released in the intestine, creating a drug reservoir.
Give examples of drugs that undergo enterohepatic recycling.
Morphine, rifampicin.
Define the half-life of a drug.
The time taken for the plasma concentration of a drug to decrease by 50%.
Why is half-life important?
It influences dosing intervals and residual drug effects in the body.
