14.4 Pharmacology: Drug detoxification pathways

Question 1

How are dietary toxins directed in the body?

Answer 1

From the small intestine to the liver by the hepatic portal vein

Question 2

What is Cytochrome P450?

Answer 2

A group of enzymes that use iron to oxidise and thus solubulise xenobiotics

Question 3

Where are CYP450s concentrated in humans?

Answer 3

Liver and small intestine

Question 4

Where in the cell are CYP450 enzymes located?

Answer 4

The ER (and mitochondria)

Question 5

What kind of molecule are CYP450s and what do they typically do (chemistry)?

Answer 5

Monooxygenases, add a hydroxyl to a xenobiotic (R)

Question 6

What do polymorphisms in specific CYP450s lead to?

Answer 6

Abberrant metabolism of some drugs

Question 7

What does inhibition of CYP450 lead to?

Answer 7

Drug-drug interactions

Question 8

What proportion does the CYP450 system in the liver oxidise?

Answer 8

50% of administered drugs

Question 9

Which is the most important CYP in humans for metabolism and for polymorphisms?

Answer 9

CYPP3A4 (metabolism, inducible)

CYP2D6 (polymorphism)

Question 10

What CYP polymorphisms occur in:
Poor metabolisers (PM)
Intermediate metabolisers (IM)
Extensive metabolisers (EM)
Ultra rapid metabolisers (UM)

Answer 10

PM- homozygous for one deficient allele, heterozygous for two different deficient alleles
IM- heterozygous for one deficient allele or carry two alleles that cause reduced activity
EM- who have two wild-type alleles
UM- who have multiple gene copies

Question 11

What polymorphism is apparent in poor metabolisers of codeine?

Answer 11

CYP2D6 (inactive in 5-10% of caucasians), get no relief from codeine

Question 12

What can make an extensive metaboliser resemble a poor metaboliser?

Answer 12

Some drugs e.g. Prozac, inhibit CYP2D6