An overdose Flashcards
Overdose: Paracetamol Pathophysiology
- paracetamol is well absorbed from the stomach and small intestine
- mainly inactivated by the liver by conjugation leading to two metabolites: glucuronide or sulfate. It is then renally excreted through urine.
- in overdose the liver conjugation becomes inundated, causing paracetamol to be metabolised by an alternative pathway.
- This results in a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is itself inactivated by glutathione, rapidly preventing any harm.
- When glutathione stores are depleted to less than approximately 30%, NAPQI reacts with nucleophilic aspects of the cell, leading to necrosis. Necrosis occurs in the liver and in the kidney tubules.
Overdose: Paracetamol
Management
- Resuscitation: maintain ABCDs
- Obtain more information: NPIS, Toxbase, MIMS Colour Index
•Decontamination if appropriate •Decrease absorption: - Single-dose activated charcoal - Gastric emptying - Whole bowel irrigation
•Increase elimination:
- Multiple doses of activated charcoal
- Forced diuresis
- Haemoperfusion and acid/alkaline diuresis
- Haemodialysis
•Specific antidote: N-acetylcysteine (NAC) treatment
Overdose: Paracetamol
Toxicity
Risk of severe liver damage (peak ALT more than 1000 IU/L)
Based on the dose of paracetamol ingested (mg/kg body weight):
Less than 150 mg/kg - unlikely.
More than 250 mg/kg – likely
More than 12 g total - potentially fatal
Overdose: Salicylates
Two main toxic effects of salicylate overdose
- direct central stimulation of the respiratory centres
2. uncoupling of oxidative phosphorylation inhibiting ATP-dependent reactions
Overdose: Salicylates
Two main toxic effects of salicylate overdose
- direct central stimulation of the respiratory centres
2. uncoupling of oxidative phosphorylation inhibiting ATP-dependent reactions
Overdose: Salicylates
Toxicity
The ingested dose
- > 125 mg/kg body weight: likely toxicity is mild
- > 250 mg/kg body weight: likely toxicity is moderate.
- > 500 mg/kg body weight: likely toxicity is severe, possibly fatal
Salicylate concentration:
- intoxication associated with plasma concentrations greater than 350 mg/L (2.5 mmol/L)
- Most adult deaths occur in patients whose concentrations exceed 700 mg/L (5.1 mmol/L).
Overdose: Salicylates
Clinical Grading of Toxicity
Mild (nausea, vomiting, tinnitus).
Moderate (hyperventilation and confusion)
Serious (hallucinations, seizures, coma, cerebral oedema or pulmonary oedema)
Overdose: Salicylates
Clinical Grading of Toxicity
Mild (nausea, vomiting, tinnitus).
Moderate (hyperventilation and confusion)
Serious (hallucinations, seizures, coma, cerebral oedema or pulmonary oedema)
Overdose: Salicylates
Effect on Acid- Base
Stage I: blood pH >7.4, urine pH >6.0 - respiratory alkalosis, increased urinary excretion of bicarbonate.
Stage II: blood pH >7.4, urine pH <6.0 - metabolic acidosis with compensating respiratory alkalosis, urinary hydrogen excretion, intracellular potassium depletion
Stage III: blood pH <7.4, urine pH <6.0 - severe metabolic acidosis and hypokalaemia.
Overdose: Salicylates
Management
- General measures for poisoning
- Consider oral activated charcoal (50 g for an adult, 1 g/kg for a child) if ingested more than 125 mg/kg body weight salicylate less than one hour previously.
- A second dose of charcoal may be required in patients whose plasma salicylate level continues to rise or who have taken enteric-coated preparations (absorption may be slower).
- Gastric lavage if the patient has ingested more than 500 mg/kg body weight salicylate within one hour.
- Aggressive rehydration.
- Urinary alkalinisation : optimum urine pH is 7.5-8.5.
Overdose: Salicylates
Management
- General measures for poisoning
- Consider oral activated charcoal (50 g for an adult, 1 g/kg for a child) if ingested more than 125 mg/kg body weight salicylate less than one hour previously.
- A second dose of charcoal may be required in patients whose plasma salicylate level continues to rise or who have taken enteric-coated preparations (absorption may be slower).
- Gastric lavage if the patient has ingested more than 500 mg/kg body weight salicylate within one hour.
- Aggressive rehydration.
- Urinary alkalinisation : optimum urine pH is 7.5-8.5.
- Haemodialysis is the treatment of choice for severe poisoning
- Mechanical ventilation: indicated for deteriorating mental status or acute lung injury
Overdose: Salicylates
Management
Indicates for Haemodialysis
- Plasma concentrations greater than 700 mg/L (5.1 mmol/L)
- Acute kidney injury
- Congestive cardiac failure
- Non-cardiogenic pulmonary oedema
- Coma
- Convulsions
Overdose: Tricyclic Antidepressants
Mechanism of Tricyclics
TCAs act by blocking reuptake of noradrenaline and serotonin leading to increased brain amine concentration. (also anticholinergic effect, Na blockade, alpha 1 blockage)
TCAs are extensively tissue-bound and have a predilection for cardiac tissue (MCQs: therefore dialysis unhelpful). Active elimination by haemoperfusion and haemodialysis is ineffective as only a small amount of the drug remains in the vascular compartment.
Overdose: Tricyclic Antidepressants
Toxicity
Severe toxicity can occur at doses >1000 mg (in a 70 kg adult).
Overdose: Tricyclic Antidepressants
Main toxic effects
• Cardiovascular system (quinidine-like effect): TCAs competitively inhibit the myocardial fast sodium channels resulting in slowed cardiac conduction (e.g. increased QRS duration, prolonged QTc, increased PR interval, AV block) and ventricular dysrhythmias.
- TCAs also inhibit peripheral alpha-adrenergic receptors, resulting in vasodilation and orthostatic hypotension.
- Neurologic toxicity (seizures and anticholinergic stigmata) results from CNS receptor blockade
