Drug Overdose (Paracetamol, Opiates, Benzos, TCAs & SSRIs)

Question 1

What is the pathophysiology behind salicylate (aspirin) poisoning?

Answer 1

• Pathophysiology
  
  • Usually aspirin.
  • Uncouples oxidative phosphorylation causing metabolic acidosis.
  • Also directly stimulates CNS respiratory centre causing ↑RR and respiratory alkalosis.

Question 2

What are the common signs and symptoms of salicylate poisoning?

Answer 2

• ASA-DOSE:
  
  • Agitation or delirium.
  • Sweating
  • Auditory symptoms: tinnitus or deafness.
  • Dizziness
  • Overbreathing: ↑RR due to CNS effect or response to metabolic acidosis.
  • Seizures and coma.
  • Emesis

Question 3

Which investigations should be done in suspected salicylate poisoning?

Answer 3

• Investigations
  
  • Plasma salicylate levels. Repeat every 2 hours until it peaks, which can take up to 6 hours.
  • U+E: ↓K+, AKI if severe.
  • ↓Glucose
  • ABG and HCO3-: initially alkalosis, later acidosis.

Question 4

How is salicylate poisoning managed?

Answer 4

• ABCD:
  
  • Activated charcoal ± MDAC.
  • Sodium Bicarb for urine and serum alkalinisation: ionises salicylates so they can’t cross blood-brain barrier, and can’t escape renal tubules so are eliminated from circulation.
  • Correct glucose and K+ deficits.
  • Dialysis if: ↓pH, ↑↑salicylates, AKI.

Question 5

What is the background of TCA poisoning?

Answer 5

• TCA overdoses are rare – as the drug is not widely used now – but very dangerous.
  
  • In contrast, SSRI overdoses are commoner, but much less likely to be fatal.

Question 6

What signs and symptoms might be seen in TCA overdose? What effects are these symptoms due to?

Answer 6

• Anticholinergic effects:
  
  • Hot dry skin.
  • Mydriasis: dilated pupils.
  • ↑HR
  • Urinary retention.
  • Agitation and delirium.
  • Neurological: seizures, coma, hypertonia, hyperreflexia.
• Anti Na+ channel effects:
  
  • Arrhythmias, including VT and VF.
  • Cardiac arrest.
  • Heart block.
• Anti α-adrenergic effects:
  
  • ↓BP

Question 7

Which investigations should be performed in TCA overdose?

Answer 7

• ECG: wide QRS, long QT, increased PR. Continue to monitor if large OD or initial abnormality found.
  
  • U+E
  • Glucose
  • ABG: metabolic acidosis secondary to seizures and/or tissue hypoxia from ↓cardiac output.

Question 8

How can TCA overdose be managed?

Answer 8

• Activated charcoal (± MDAC) if <2h since ingestion.
  
  • Sodium bicarbonate to reverse Na+ channel blockade if QRS >100 ms or there is ventricular arrhythmia.
  • DC cardioversion, lidocaine, or MgSO4 if bicarb fails. Most other anti-arrhythmic drugs are contraindicated.
  • Benzodiazepines if there are seizures.
  • Lipid emulsion if peri-arrest.

Question 9

What are the signs and symptoms of benzodiazepine poisoning?

Answer 9

• Drowsy. In severe cases, coma.
  
  • Neurological impairment, including motor impairment, diplopia, slurred speech, and ataxia.
  • Anterograde amnesia.
  • Rarely, paradoxical symptoms: anxiety, delirium.
  • ↓RR, which would suggest a combined OD.

Question 10

How is benzodiazepine poisoning managed?

Answer 10

• Supportive treatment, especially airway.
  
  • Activated charcoal only if BZD taken in combo with something else.
  • Flumazenil is the antidote.

Question 11

What are the indications for giving flumazenil? How does it work and how is it given?

Answer 11

Mechanism:
* BZD receptor antagonist, which mainly acts to reverse CNS depression.

• Indications:
  
  • Severe OD – with marked impairment of consciousness or respiratory distress – in a first time or infrequent user.
  • In practice, it is most likely to be used for iatrogenic overdoses, when we can be sure that they are not long-term users and it is not a mixed overdose.
• Contraindications due to seizure risk:
  
  • BZD-dependant patients.
  • Mixed TCA OD.
  • Epilepsy history.
• Dose and administration:
  
  • Use the minimum effective dose.
  • Apply ECG monitoring when giving flumazenil as it may unmask an arrhythmia, especially if patient on TCA or carbamazepine.
• Half life is less than BZD, so may wear off first.

Question 12

What are the signs and symptoms of iron poisoning?

Answer 12

• Signs and symptoms
  
  • Early (0-6 hours): GI symptoms including nausea, vomiting, diarrhoea, and abdo pain.
  • Delayed (2-72 hours): black stools, circulatory collapse, and CNS symptoms including drowsiness, seizures, and coma.
  • Late (2-4 days): liver and kidney failure.
  • Very late (2-5 weeks): gastric stricture.

Question 13

Which investigations should be done in suspected iron poisoning?

Answer 13

• Establish amount of elemental iron from history.
  
  • Fe level, taken at least 4 hours after ingestion, then repeated 2-hourly.
  • ↑WBC
  • ↑Glucose
  • U+E and LFT.
  • Daily monitoring: clotting, HCO3-.

Question 14

How is iron poisoning managed?

Answer 14

• Gastric lavage.
  
  • Desferrioxamine is the antidote.
• Desferrioxamine (aka deferoxamine)
  
  • Chelates Fe, which is then excreted as red urine.
  • Indicated in severe OD, characterized by ↓consciousness, seizures, shock, metabolic acidosis, GI bleed.
  • Contraindicated in kidney failure.
  • Can cause ↓BP and pulmonary oedema.

Question 15

What is the pathophysiology/background behind organophosphate poisoning?

Answer 15

• Relatively common suicide method in developing world, taken in the form of fertilizer. Also used as chemical weapon (sarin, VX).
  
  • Percutaneous or oral entry → cholinesterase inhibition → ↑acetylcholine (ACh) levels → parasympathetic activation, NMJ depolarization, and CNS dysregulation.

Question 16

What are the signs/symptoms of organophosphate poisoning?

Answer 16

• DUMBELLS:
  
  • Diarrhoea
  • Urination
  • Miosis
  • Bradycardia, Bronchospasm, Bronchorrhea. The ‘killer Bs’ most likely to cause death.
  • Emesis
  • Lacrimation
  • Lethargy
  • Salivation
• Other symptoms:
  
  • Muscle: fasciculations and weakness.
  • Blurred vision.

Question 17

Which investigations may be done in organophosphate poisoning?

Answer 17

• ↓Serum and RBC cholinesterase.

* Atropine therapeutic trial.

Question 18

How is organophosphate poisoning managed?

Answer 18

• Decontaminate patient, while wearing personal protective equipment.
  
  • Atropine IV.
  • Contact public health authorities.
  • Pralidoxime – a cholinesterase reactivator – is the antidote. Use in severe poisoning.

Question 19

What is the pathophysiology of paracetamol overdose?

Answer 19

• The usual paracetamol metabolism pathways – glucuronidation or sulfation – are rapidly saturated.
  
  • The other pathway – via the cytochrome P450 isoenzymes CYP2E1 and CYP3A4 – generates toxic NAPQI. The body can only detoxify a small amount with endogenous glutathione.
  • Risk is increased by malnutrition, concomitant enzyme inducer use (enzyme-inducing anti-epileptics, rifampicin), or chronic alcoholism (also causes enzyme induction). Reduces potentially toxic level from 12 g to 7.5 g.

Question 20

What are the signs and symptoms commonly seen in paracetamol overdose?

Answer 20

• Symptoms takes up to 3 days to develop.
  
  • Early features: non-specific abdo pain, nausea and vomiting, altered clotting.
  • Later features: jaundice, RUQ pain, ALF, encephalopathy.
  • Presentation is often pre-symptomatic, among those who have regretted their OD (or been brought in by others).

Question 21

Which investigations can be done in paracetamol overdose?

Answer 21

• Basic bloods: FBC, LFTs, U+E, coag, albumin, glucose.
  
  • Serum paracetamol levels should be measured ≥4 hours post-ingestion, as they take time to peak.
  • ABG: lactic acidosis if severe, due to NAPQI inhibition of aerobic respiration and ↓hepatic clearance of lactate.

Question 22

How is paracetamol managed?

Answer 22

• N-acetylcysteine (NAC) IV is the antidote, and is most effective within 8 hours. Usually a 24 hour infusion.
  
  • Methionine PO is 2nd-line.
  • Activated charcoal if <1 hour from ingestion.
  • Transplantation indications (King’s College Criteria): pH <7.3 24h post ingestion, or all 3 of {INR >6.5 (PT >100 sec) and creatinine >300 μmol/l (3.4 mg/dL) and grade 3-4 encephalopathy}.
  • Correct any hypoglycaemia, but seek specialist advice before correcting INR.

Question 23

What are the complications of paracetamol overdose?

Answer 23

• Acute liver failure.
  
  • AKI: develops at 3-7 days.
  • Death: usually occurs 3-6 days post-ingestion. Occurs in <1%, but in 50% of those who develop ALF.
  • Poor prognostic indicators: ↑ or rising PT, ↓pH, ↑lactate, ↑BR, grade 3/4 encephalopathy, ↑creatinine.