Acute Poisoning Management

Study Notes

Management of Acute Poisoning

Introduction

Acute poisoning: toxic effects from single or multiple exposures to a substance in a short period
Individualized approach recommended for patient assessment and management in emergency care
Factors to consider for a rational therapeutic plan:
- Ingested amount
- Time since ingestion
- Clinical presentation
- Patient factors
- Geographical site
- Available resources

Paracetamol

Contained in > 100 over-the-counter products and many prescription drugs
Overdose common, often for suicidal intent
Acute oral overdose ≥ 150 mg/kg (> 12 g in adults) within 24 hours can cause toxicity
Overdoses < 150 mg/kg unlikely to result in toxicity

Pathophysiology of Paracetamol

At therapeutic doses, paracetamol metabolized by hepatic conjugation to non-toxic metabolites
< 5-10% of paracetamol metabolized by hepatic CYP enzymes to N-acetyl-p-benzoquinone imine (NAPQI), a highly reactive intermediate metabolite responsible for toxicity

Diagnosis of Paracetamol

Rumack-Matthew nomogram plots serum concentration of acetaminophen against time since ingestion to predict possible liver toxicity and guide N-Acetylcysteine (NAC) treatment

Poor Prognostic Indicators for Paracetamol

pH < 7.3 after adequate resuscitation
International normalized ratio (INR) > 3
Serum creatinine > 2.6 mg/dL
Hepatic encephalopathy grade III (confusion and somnolence) or IV (stupor and coma)
Hypoglycemia
Thrombocytopenia

Treatment of Paracetamol

Activated charcoal: not well adsorbed by activated charcoal
Oral or IV N-Acetylcysteine (NAC):
- Antidote for paracetamol poisoning
- Equally effective given orally or IV
- Decreases paracetamol toxicity by increasing hepatic glutathione stores
- Inactivates toxic metabolite NAPQI before it can injure liver cells

Aspirin and Other Salicylates

Acute ingestion > 150 mg/kg can cause severe toxicity
Salicylate tablets may form bezoars, prolonging absorption and toxicity
Chronic toxicity can occur after several days of high therapeutic doses, especially in elderly patients

Pathophysiology of Salicylates

Weak acids that cross cell membranes easily, more toxic when blood pH is acidic
Impair cellular respiration, stimulating respiratory centers in the medulla (hyperventilation)
Cause respiratory alkalosis, reduction in serum levels of K+ and phosphate, and possible reduction in free Ca2+

Symptoms of Salicylates

Early symptoms: nausea, vomiting, tinnitus, and hyperventilation
Later symptoms: hyperactivity, fever, confusion, and seizures
Hyperventilation → hypocapnia → respiratory alkalosis → compensatory metabolic acidosis → rhabdomyolysis → acute kidney injury and respiratory failure

Iron

Treatment:
- IV/IM deferoxamine: severe toxicity
- IV hydration to aid in eliminating chelated iron and preventing hypotension

Organophosphates/Carbamates

Common causes of poisoning and poison-related deaths
Those most often implicated in human poisoning:
- Carbamates: Aldicarb and methomyl
- Organophosphates: Chlorpyrifos, diazinon, dursban, fenthion, malathion, and parathion

Pathophysiology of Organophosphates/Carbamates

Absorbed through GI tract, lungs, and skin
Inhibit plasma and red blood cell cholinesterases, preventing breakdown of acetylcholine
Carbamates: reversible inhibition of acetylcholinesterase, cleared spontaneously within 48 hours
Organophosphates: reversible or irreversible inhibition of acetylcholinesterase

Symptoms of Organophosphates/Carbamates

Acute muscarinic manifestations: salivation, lacrimation, urination, diarrhea, emesis, bronchorrhea, bronchospasm, miosis, bradycardia, hypotension
Acute nicotinic symptoms: muscle fasciculations and weakness
Neuropathy: can develop days to weeks after exposure
Weakness, particularly of proximal, cranial, and respiratory muscles: may develop 1 to 3 days after exposure

Diagnosis of Organophosphates/Carbamates

Diagnosis based on muscarinic toxidrome in patients with prominent respiratory findings, pinpoint pupils, muscle fasciculations, and weakness
Reversal or abatement of muscarinic symptoms after atropine supports the diagnosis
Measurement of red blood cell acetylcholinesterase level can monitor effectiveness of therapy

Treatment of Organophosphates/Carbamates

Supportive therapy
Atropine: for respiratory manifestations, given in amounts sufficient to relieve bronchospasm and bronchorrhea
Pralidoxime: given with atropine to relieve neuromuscular weakness (nicotinic receptors on skeletal muscles), contraindicated in carbamate poisoning
Decontamination: conducted as soon as possible after stabilization, with activated charcoal for ingestion within 1 hour of presentation

Description

This quiz covers the management of acute poisoning, including pathophysiology, symptoms, diagnosis, and treatment of specific substances such as paracetamol, salicylates, iron products, and organophosphates/carbamates. It's a great resource for pharmacy students and healthcare professionals.

Acute Poisoning Management

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Questions and Answers

What is the primary difference in the inhibition of acetylcholinesterase between organophosphates and carbamates?

What is the typical time frame for the development of neuropathy after exposure to organophosphates or carbamates?

What is the primary indication for the use of pralidoxime in the treatment of organophosphate poisoning?

What is the contraindication for the use of pralidoxime?

What is the primary goal of atropine administration in the treatment of organophosphate poisoning?

What is the recommended timeframe for decontamination after ingestion of organophosphates or carbamates?

What is the measurement used to monitor the effectiveness of therapy in organophosphate poisoning?

What is the typical presentation of acute muscarinic manifestations in organophosphate poisoning?

What is the typical duration of treatment with atropine in organophosphate poisoning?

What is the recommended treatment for acute nicotinic symptoms in organophosphate poisoning?