Drug Metabolism

Question 1

Define drug metabolism and its conditions

Answer 1

Drug metabolism: preparing drugs for excretion and conversion of lipophilic chemicals to polar and reducing toxicity drug. Drugs needs to be lipohilic to achieve therapeutic effect and access tissue. They also need to be water soluble in order to be retained in blood and delivered to excretion site.

Question 2

Describe the first phase of metabolism m

Answer 2

Introduce a reactive group to the drug to increase polarity. Via oxidation (creating new functional group, resulting in an electrophile) or Hydrolysis (which unmasks the new functional groups, resulting in nucleophile).

In the liver various different enzymes that metabolise different drugs eg cytochrome p450 (LOOK AT MM)

Question 3

Describe the second phase of metabolism

Answer 3

Main aim is to add a water soluble conjugate to the reactive group

1. Glucoronidation: low affinity and high capacity = more likely to occur at high drug doses
2. Sulfation: high affinity and low capacity and most likely to occur at low doses
3. Glutathione conjugation: drug needs to be electrophilic to be conjugated. However electrophiles are extremely reactive and can react to produce other toxic metabolites in liver..
4. Acetylation, methylation and amino acid conjugation.

Question 4

Describe the metabolism of paracetamol

Answer 4

Something about NAPQI (LOOK AT TUTORIAL NOTES ALISTAISPR)