L23 - Drug Overdose

Question 1

What are the products formed from the metabolism of paracetamol (APAP) that are safely secreted?

Answer 1

• glucuronide metabolite via addition of sugar molecule
• sulfate metabolite via addition of sulfate group
• NAPQI bound to GSH = glutathione metabolite

Question 2

How is NAPQI formed and what is its signficance?

Answer 2

• formed by CYP3A (and CYP1A1 CYP2E1) metabolism

- NAPQI is dangerous and causes the toxicity of paracetamol

Question 3

Why is paracetamol toxic at high doses?

Answer 3

• NAPQI production via CYP3A
• at low doses NAPQI binds to GSH = glutathione metabolite is safely excreted
• high doses = GSH becomes saturated
• NAPQI accumulates in body and binds to liver DNA
• causes liver cell death

Question 4

What are the factors that increase the toxicity of paracetamol?

Answer 4

• CYP enzyme induction by other drugs/chemicals (means paracetamol metabolised more via NAPQI production = easier to reach high levels)
• poor diet because GSH comes from diet = less protective mechanism to bind NAPQI and excrete as non-toxic metabolite

Question 5

What are the types of things that induce the CYP enzymes?

Answer 5

CYP1A1
- smoking
- aromatic hydrocarbons
CYP2E1
- ethanol, acetone
- fasting, diabetes
CYP3A4
- St John's wort (herbal remedy)

Question 6

What is the antidote for paracetamol overdose and how does it work?

Answer 6

N-acetyl Cysteine

• glutathione precursor to recover depletion by facilitating synthesis
• given IV
• useful up to 36 hours post-overdose but if given within 8 hours, can prevent hepatic injury
• requires careful monitoring as sulfur groups can cause anaphylactic reactions

Question 7

When is ibuprofen not safe to use?

Answer 7

• patient prone to stomach ulcers

- dehydration because increases change of kidney injury

Question 8

What are the 3 major classes of antidepressants?

Answer 8

• tricyclic antidepressant
• selective serotonin reuptake inhibitors (SSRIs)
• monoamine oxidase inhibitors (MAIOs)

Question 9

What do all antidepressants have drug interaction with?

Answer 9

alcohol

- because alcohol is a sedative like the antidepressants

Question 10

What are the interactions between tricyclic antidepressant and alcohol?

Answer 10

• inhibits tricyclic antidepressant metabolism = rising plasma levels
• combined sedation effect

Question 11

What are the interactions between SSRIs and alcohol?

Answer 11

• combined sedative effect with alcohol

SSRIs = selective serotonin reuptake inhibitors

Question 12

What are the drug interactions with monoamine oxidase inhibitors?

Answer 12

should not be used with cold medicines containing dextramethophan

Question 13

What is the alcohol drug interaction relevant to dentists?

Answer 13

• alcohol can decrease the time it takes to recover from local anaesthetics
• acts as a vasodilator so LA can drain away from the area faster