Opioid overdose is a critical medical emergency resulting from excessive use of opioid drugs such as morphine, heroin, tramadol, oxycodone, and methadone. With increasing availability and misuse of prescription opioids, overdose cases have become a major clinical concern. Rapid identification and prompt management are essential to prevent complications such as respiratory failure, hypoxia, and death.
Mechanism of Toxicity
Opioids exert their effects by binding to stereospecific opioid receptors—mu, kappa, and delta—located in the central nervous system and peripheral tissues. These receptors normally interact with endogenous peptides such as enkephalins and endorphins. In overdose, excessive stimulation of mu receptors leads to profound CNS depression, respiratory suppression, altered thermoregulation, and impaired cardiovascular function.
Toxicokinetics
Opioid absorption and distribution vary depending on the drug and route of exposure. Many opioids are highly lipid-soluble and cross the blood–brain barrier rapidly. They undergo hepatic metabolism and renal excretion, but long-acting opioids such as methadone and sustained-release formulations may produce prolonged toxicity.
Clinical Features of Opioid Toxicity
The classic triad of opioid overdose consists of:
- CNS depression – ranging from drowsiness to deep coma
- Miosis – pinpoint pupils
- Respiratory depression – slow, shallow, or absent breathing
Central Nervous System
- Impaired consciousness
- Slurred speech
- Confusion and decreased responsiveness
- Seizures in certain opioid exposures (e.g., meperidine, tramadol)
Respiratory System
- Slow respiratory rate (< 12/min)
- Shallow breathing
- Cyanosis due to oxygen deprivation
- Non-cardiogenic pulmonary edema
Cardiovascular Effects
- Bradycardia
- Hypotension
- Arrhythmias with drugs like propoxyphene
- ECG abnormalities similar to TCA toxicity in some cases
Complications
- Aspiration pneumonia
- Rhabdomyolysis
- Acute respiratory distress syndrome (ARDS)
- Tetanus and infections in IV drug use
- HIV and hepatitis from needle sharing
Diagnosis and Investigations
Diagnosis is largely clinical and based on characteristic signs. Laboratory investigations help assess complications and co-ingestions.
Investigations Include:
- Chest X-ray – for aspiration or pulmonary edema
- ECG – especially in methadone or propoxyphene overdose
- Electrolytes and arterial blood gases – to detect acidosis
- Toxicology screen – to identify other substances
- Serum paracetamol and salicylate levels – in suspected mixed overdose
Urine drug screens may confirm opioid exposure but do not guide acute management.
Management of Opioid Overdose
1. Initial Stabilization
- Ensure airway patency
- Provide oxygen supplementation
- Initiate assisted ventilation if respiratory depression is severe
2. Naloxone Administration
Naloxone is a competitive opioid antagonist that rapidly reverses CNS and respiratory depression.
- Administered IV, IM, SC, or intranasally
- Initial doses range from 0.04 mg to 2 mg depending on severity
- Repeat dosing may be required for long-acting opioids
- Monitor for acute withdrawal symptoms (agitation, hypertension, vomiting)
3. Supportive Care
- Maintain ventilation until patient regains adequate respiratory effort
- Treat pulmonary edema with oxygen and ventilatory support
- Correct hypotension with IV fluids
- Monitor for rhabdomyolysis with CK levels
4. Complication Management
- Manage seizures with benzodiazepines
- Treat infections in IV drug users appropriately
- Address co-ingested toxins
Prevention and Public Health Considerations
Widespread misuse of opioids has led to increased mortality. Education, controlled prescribing practices, availability of naloxone kits in the community, and early rehabilitation programs are critical strategies for prevention.
Detailed Notes:
For PDF style full-color notes, open the complete study material below:
PATH: PHARMD/ PHARMD NOTES/ PHARMD FOURTH YEAR NOTES/ CLINICAL TOXICOLOGY/ OPIATES OVERDOSE.