Overdose

Question 1

N-AcetylCysteine (NAC)

Common indications

Answer 1

1. Antidote for paracetamol poisoning
2. Prevent renal injury due to radiographic contrast material (Contrast nephropathy)
3. To reduce the viscosity of respiratory secretions (acting as a mucloytic)

Question 2

NAC

MOA

Answer 2

• In therapeutic doses, paracetamol is metabolisde mainly by conjugation with glucuronic acid and sulfate
• A small amount is converted to N-acetyl-q-benzoquinone (NAPQI), which is hepatotoxic
• Normally, this is quickly detoxicified by conjugation with glutathione
• However, in paracetamol poisoning, the body’s supply of glutathione is overwhelmed and NAPQI is free to cause liver damage
• NAC replenishes the body’s supply of glutathione. It also has antioxidant effects, which may contribute to it’s effect in preventing contrast nephropathy, although this is not completely understood.
• If acetylcysteine is brought into contact with mucus, it causes it to liquefy
• For patients who have tenacious respiratory secretions (e.g. bronchiectasis), this may aid sputum clearance

Question 3

NAC

Important adverse effects

Answer 3

• When administered IV can cause anaphylactoid reaction
• This is similar to an anaphylactic reaction (presenting with nausea, tachy, rash and wheeze) but involves histamine release independent of IgE Abs
• Therefore, once the reaction has settled (by stopping the NAC and giving antihistamine), it is usually safe to restart NAC, but a lower rate of infusion.
• When administered in nebulised form as a mucolytic, NAC may cause bronchospasm. Therefore a bronchodilator is often given prior to adminstration

Question 4

NAC

Warnings

Answer 4

• History of anaphylactoid reactions to acetylcysteine does not contraindicate its future use if still needed
• It is important that such reactions are not labelled as allergic, which may lead to effective treatment for paracetamol poisoning being inappropriately denied
• However, it is essential to obtain specialist advice if there is any doubt

Question 5

Interactions

Answer 5

• No significant adverse drug reaction

Question 6

NAC prescription

Answer 6

• Paracetamol overdose (IV infusion, 3 components, over 21 hours)
• Prophylaxis of contrast nephropathy (600-1200mg PO 12hrly for 2/7)
• Respiratory secretions (2.5-5mL of 10% solution 6H)

Question 7

Activated charcoal

Common indications

Answer 7

• A single dose of activated charcoal may be used to reduce absorption of certain poisons (including drugs in overdose) from the gut
• Multiple doses of activated charcoal may also be used to increase the elimination of certain poisons

Question 8

Activated Charcoal

MOA

Answer 8

• Van der Waals forces are responsible for the MOA.
• Molecules are adsorbed onto the surface of the charcoal as they travel through the gut, reducing the absorption into the circulation
• However, activated charcoal is only useful in cases where the poison ingested is likely to be absorbed onto it
• The affinity of a substance of activated charcoal is determined by its ionic status and its solubility in water
• Weakly ionic, hydrophobic substances (e.g. BZ, MTX) are well absorbed. Hydrophillic (Li, Fe, alcohols, acid/base) not well absorbed
• Multiple administrations cause more rapid diffusion back into the gut, by causing a concentration gradient (high in circ, low in gut)

Question 9

Activated charcoal

Adverse effects

Answer 9

• Aspiration of activated charcoal can lead to pneumonitis, bronchospasm and airway obstruction
• It can also precipitate intestinal obstruction
• Most common: Black stools and vomiting

Question 10

Activated Charcoal

Warnings

Answer 10

• Activated charcoal should not be used in patients with a reduced level of counsciousness, unless their airway is protected via intubation
• Caution is required when prescribing activated charcoal to patients with persistent vomiting, as there is a risk of aspiration
• Those with reduced GI motility have an increased risk of intestinal obstruction

Question 11

Activated Charcoal

Interactions

Answer 11

• Prevents absorption of many drugs (mainly hydrophobic)

Question 12

Activated charcoal

Prescription

Answer 12

• Only for patients presenting within 1 hours of ingestion of clinically significant amount of substance that is absorbed by charcoal
• For drugs that delay gastric emptying (Aspirin, Opioids, TCA) AC can be administered upto 2hrs following ingestion
• AC should be prescribed on the once-only section of the drug chart
• For multiple doses 50g 4H with pre-emptive anti-emetic and laxatives