Katzung 12th ed - Chapter 4 - Biotransformation (1) Flashcards
What happens in Phase I reactions?
There is a simple alteration of the drug, and it is usually an oxidation-reduction reaction.
What happens in Phase II reactions?
The drug becomes conjugated with one of various endogenous acids.
True or false: All drugs are metabolised with both Phase I and Phase II reactions before elimination.
False. Some drugs, after a Phase I reaction, become sufficiently polar and are rapidly excreted. Some drugs are excreted unchanged.
Explain briefly what cytochrome P450 does to drugs.
Cytochrome P450 is an enzyme that, with the help of flavoprotein, oxidises drugs. This is a Phase I reaction.
Name at least one drug that is an inhibitor of cytochrome P450.
Cimetidine. Amiodarone.
Name at least three drugs that are inducers of cytochrome P450.
Rifampicin, Carbamazepine, Phenytoin, Barbiturates, St John’s Wort.
Paracetamol overdose: Give an overview of the pharmacology.
At toxic doses, the three different Phase II reactions in the metabolism of paracetamol are saturated. This results in accumulation of a toxic Phase I metabolite, which leads to hepatotoxicity and death.
What is “genetic polymorphism”, in reference to drug metabolism in different populations?
Across genetically varied populations, many enzymes involved in Phase I and Phase II drug metabolism will have different levels of functionality. This means that different people will metabolize drugs to differing degrees.
Name two or three drugs that will enhance the metabolism of warfarin.
Rifampicin, Barbiturates, St John’s wort.
What is meant by the term “distribution half-life”? What is another name for this?
This is also called the “alpha half-life”. It refers to the initial fate of drugs injected intravenously. After initial injection, the serum levels rapidly fall, primarily due to the redistribution of the drug into the tissues. The distribution half-life is the time take for half of the drug to leave the plasma during this initial “alpha phase”.
What is meant by the term “elimination half-life”? What is another name for this?
This is also called the “beta half-life”. It refers to the time taken for a drug to be metabolized / excreted from the blood. If the drug was given intravenously, this “beta phase” follows an initial “alpha phase”, during which the drug is much more rapidly removed from the bloodstream, although the primary mechanism is redistribution rather than metabolism.
