Pharmacology- Elementary Drug Metabolism

Question 1

What is the most important drug-metabolising organ?

Answer 1

The liver

• kidney, gut mucosa, lungs and skin also contribute

Question 2

What does metabolism in liver/gut do?

Answer 2

reduces bioavailability of drugs when administered via the enteral route

Question 3

Where are hepatic drug-metabolising enzymes/ microsomal enzymes found?

Answer 3

Embedded in the SER of the liver hepatocytes

Question 4

Phase one metaboism

Answer 4

Change in the drug by oxidation, reduction or hydrolysis

Question 5

Oxidation in phase one

Answer 5

accomplished by cytochrome P450 enzymes (microsomal haem proteins)

the drug incorporates one 02 atm to form hydroxyl group

Question 6

which type of bonds are susceptible to hydrolysis?

Answer 6

ester and amide bonds

Question 7

Which type of metabolites may be formed in phase one?

Answer 7

pharmacologically active and/ or toxic ie harmful

Question 8

How is P450 activity determined?

Answer 8

Genetically

lack activity-> high drug plasma levels (adverse actions)

high levels of activity-> lower plasma levels (reduced drug action)

Question 9

Phase 2 reactions

Answer 9

Involve the combination of the drug with a polar molecule to form a water soluble metabolite

usually involves reactive group from phase one

Question 10

What happens to conjugated products from phase 2

Answer 10

readily excreted via the kidney