Poisoning

Question 1

What is biochemical toxicity?

Answer 1

Drug/ active metabolite that causes cellular damage

Question 2

Most drugs have been thoroughly tested before they reach the market. What is the most common way a patient can experience biochemical toxicity?

Answer 2

Overdose - the safe metabolism pathway has been saturated, so the drug is metabolised in a different pathway which produces a harmful metabolite

Question 3

What is the harmful metabolite produced when paracetamol is taken as an overdose, and what are its effects?

Answer 3

NAPQI

Causes oxidative damage to hepatocytes

Question 4

What is the treatment of paracetamol overdose, and what is the MoA of the treatment?

Answer 4

Acetylcysteine - replenishes glutathione levels to be able to neutralise the NAPQI

Question 5

What is the harmful metabolite produced when cyclophosphamide is taken, and what are its effects?

Answer 5

Acrolein

Eliminated in the urine but can cause haemorrhagic cystitis

Question 6

What is given to patients on cyclophosphamide to minimise the risk of haemorrhagic cystitis?

Answer 6

MENSA

Question 7

What are the three principles of managing overdose?

Answer 7

• Prevention of absorption
• Enhancement of elimination
• Antidotes

Question 8

State a method of preventing the absorption of drug in an overdose

Answer 8

Activated charcoal - binds to things in the gut

Gastric lavage

Question 9

State two methods of enhancing the elimination of drug

Answer 9

Activated charcoal

Sodium bicarb - raises the pH of urine to encourage the elimination of aspirin

IV fluids - force diuresis

Haemodyalysis - used for drugs with a small Vd

Question 10

State two principles for the MoA of antidotes

Answer 10

Competitive antagonists - e.g. naloxone in opioid overdose

Chelating agents - bind to things e.g. lead, mercury

Mannipulating drug metabolism - e.g. acetylcysteine in paracetamol

Antibodies - e.g. antivenom for snake bites, digoxin-specific antibody