What are the mechanisms and treatments for drug overdoses?

Mechanisms and Treatment of Drug Overdoses

Drug overdoses occur through multiple distinct mechanisms that vary by drug class, with respiratory depression being the most life-threatening mechanism requiring immediate intervention with specific antidotes and supportive care. 1

Primary Mechanisms of Drug Overdose

Respiratory Depression

• Opioids: Directly suppress respiratory drive in the brainstem, causing progressive hypoventilation, hypoxemia, and potentially respiratory arrest 2
• Benzodiazepines: Cause central nervous system depression with varying degrees of respiratory suppression, particularly dangerous when combined with other CNS depressants 3
• Alcohol: Potentiates other CNS depressants and independently causes respiratory depression at high doses

Cardiovascular Effects

• Stimulants (cocaine, amphetamines, methamphetamine): Cause sympathetic overstimulation leading to hypertension, tachycardia, arrhythmias, and potential myocardial infarction or stroke 4
• Tricyclic Antidepressants: Block sodium channels causing QRS prolongation, anticholinergic effects, and potentially fatal arrhythmias 2
• Cardiac glycosides: Cause bradycardia, heart blocks, and hyperkalemia through Na+/K+ ATPase inhibition

Neurological Effects

• Seizure-inducing drugs: Isoniazid, tramadol, bupropion, and tricyclic antidepressants lower seizure threshold 5
• Hallucinogens: Cause perceptual disturbances, agitation, and psychosis 5
• ADHD medications: Produce agitation, tremor, hallucinations, and movement disorders through excessive monoamine release 4

Metabolic Derangements

• Salicylates: Cause metabolic acidosis, respiratory alkalosis, hyperthermia, and electrolyte abnormalities
• Alcohols (methanol, ethylene glycol): Metabolized to toxic organic acids causing severe anion gap metabolic acidosis
• Hypoglycemic agents: Cause profound hypoglycemia that can lead to seizures and coma

Emergency Management of Drug Overdose

Initial Assessment and Intervention

1. Activate emergency response system immediately 2, 1
2. Assess airway, breathing, circulation (ABC) 1
   • Open airway using head-tilt chin-lift maneuver
   • Check for pulse and breathing pattern
   • Provide rescue breathing or high-quality CPR as needed

Specific Antidotes for Common Overdoses

1. Opioid Overdose 2, 1

   • Administer naloxone while continuing respiratory support
     • Adult dose: 0.4-2 mg IV/IM/IN, repeat every 2-3 minutes as needed
     • Continue until spontaneous breathing returns
   • Monitor for recurrent respiratory depression after naloxone administration, as its duration of action is shorter than many opioids 2

2. Benzodiazepine Overdose 1, 3, 6

   • Consider flumazenil cautiously in selected cases
     • Adult dose: 0.2 mg IV over 30 seconds, may repeat up to cumulative dose of 3 mg
     • AVOID in patients with:
       • Benzodiazepine dependence (risk of withdrawal seizures)
       • Co-ingestion of tricyclic antidepressants (risk of seizures)
       • History of seizure disorder

3. Tricyclic Antidepressant Overdose 2

   • Administer sodium bicarbonate for QRS prolongation >100 ms
     • 1-2 mEq/kg IV bolus, followed by infusion to maintain arterial pH 7.45-7.55
   • Monitor ECG continuously for arrhythmias

Supportive Care

1. Airway Management

   • Provide supplemental oxygen
   • Consider intubation for severe respiratory depression or airway protection 1

2. Circulation Support

   • Establish IV access
   • Administer fluids for hypotension
   • Consider vasopressors for refractory hypotension

3. Decontamination (if appropriate)

   • Consider activated charcoal only for recent ingestions (within 1 hour) if airway is protected 1
   • Avoid routine gastric lavage as benefits rarely outweigh risks 7

Common Pitfalls to Avoid

1. Delayed recognition of polysubstance overdose

   • Naloxone will not reverse effects of non-opioid substances 1
   • Multiple toxidromes may be present simultaneously

2. Premature discharge after naloxone administration

   • Patients should be observed until risk of recurrent opioid toxicity is low 2
   • For long-acting opioids, repeated doses or naloxone infusion may be needed 2

3. Focusing on awakening rather than adequate ventilation

   • Primary goal is to restore adequate spontaneous breathing 1

4. Delaying CPR while searching for naloxone

   • In cardiac arrest, high-quality CPR takes priority 2, 1

5. Failing to recognize complications of specific overdoses

   • Rhabdomyolysis in stimulant overdose
   • Aspiration pneumonia in sedative overdose
   • Compartment syndrome in prolonged immobility

Evolving Trends in Drug Overdoses

The landscape of drug overdoses continues to evolve, with significant increases in deaths involving synthetic opioids (1,040% increase from 2013 to 2019) and psychostimulants (317% increase) 8. Polysubstance use is increasingly common, requiring comprehensive approaches to overdose management that address multiple toxidromes simultaneously.

Community-based overdose education and naloxone distribution programs have shown effectiveness, with studies demonstrating that people who use opioids can be trained to respond appropriately to overdoses 9. These programs should be expanded as part of a comprehensive approach to reducing overdose mortality.