Drug Metabolism

Question 1

What class of drug is paracetamol?

Answer 1

Anti-Pyretic

Question 2

How is paracetamol metabolised by the body?

Answer 2

• conjugated with glucuronide or sulphate
• if toxic dose taken, pathways become saturated and paracetamol undergoes phase 1 metabolism
• toxic metabolite NAPQI which goes into phase 2 (conjugated with glutathione) produced which damages hepatocytes in the liver.
• this can cause liver failure

Question 3

What are some reasons for variation in drug metabolism?

Answer 3

• Genetic: lacking genes for certain enzymes

- Environmental: one drug affecting another drug’s metabolism (inhibition or induction)

Question 4

Where does alcohol metabolism take place?

Answer 4

• Liver (90%)
• Smaller amounts of alcohol can also oxidised by the cytochrome P450 2E1 enzyme (CYP2E1) or by catalase in brain
• Remainder is excreted passively in urine and on breath

Question 5

Describe how alcohol is metabolised

Answer 5

• Alcohol is oxidised by alcohol dehydrogenase to acetaldehyde
• Acetaldehyde oxidised to acetate by aldehyde dehydrogenase
• Acetate converted to acetyl-coA (this requires ATP)
• Complete oxidation requires NAD+ and NADH formed

Question 6

Why is accumulation of acetaldehyde dangerous and how is it kept to a minimum?

Answer 6

-toxic and can cause liver damage

Question 7

What is the effect of a low NAD+:NADH ratio on acetyl-coA oxidation?

Answer 7

-can’t be oxidised

Question 8

How can fatty liver arise from chronic alcoholism?

Answer 8

• Increased acetyl-coA
• low NAD+/NADH ratio means low rate of fatty acid oxidation
• Synthesis of fatty acids and ketone bodies
• increased sythesis of triacylglycerol
• lipoproteins not produced
• fatty liver results

Question 9

How can gout arise from high alcohol intake?

Answer 9

• inadequate NAD+ for conversion of lactate to pyruvate
• kidney’s ability to excrete uric acid is reduced
• urate crystals accumulate in tissues producing gout

Question 10

How can hypoglycemia arise from high alcohol intake?

Answer 10

• decrease in NAD+/NADH ratio

- deficit in gluconeogenesis

Question 11

How can lactic acidosis arise from high alcohol intake?

Answer 11

• decrease in NAD+/NADH ratio
• lactate not converted to pyruvate
• lactate accumulates in blood

Question 12

How does alcohol cause a decrease in liver function?

Answer 12

• Damaged cells have leaky plasma membrane
• loss of trasaminases and gamma glutamyl transpeptidase
• appearance of these in blood is indicative of liver damage

Question 13

What are the effects of decreased liver function?

Answer 13

• decreased bilirubin uptake (jaundice)
• decreaseed urea production
• decreased protein synthesis (lower albumin levels, oedema)
• decreased clotting factors
• decrease in lipoproteins

Question 14

Describe a drug that treats alcoholism

Answer 14

• Disulfiram
• Inhibits aldehyde dehydrogenase
• causes strong hangover effects