Opioid posing
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I now have comprehensive information from multiple authoritative sources. Here is a complete overview of opioid poisoning.
Opioid Poisoning - Complete Overview
1. Definitions & Classification
Opiates are drugs derived directly from the opium poppy (Papaver somniferum): morphine, codeine, thebaine. Opioids is the broader term covering all agents that bind to opioid receptors, including opiates, synthetic drugs, and endogenous peptides (enkephalins, endorphins, dynorphins).
| Category | Examples |
|---|---|
| Natural (opiates) | Morphine, Codeine |
| Semi-synthetic | Heroin, Hydrocodone, Hydromorphone, Oxycodone, Oxymorphone |
| Synthetic | Fentanyl, Methadone, Pethidine (meperidine), Tramadol, Diphenoxylate, Dextropropoxyphene |
2. Mechanism of Action
Opioid receptors belong to the GPCR (G protein-coupled receptor) family. There are three classical types:
| Receptor | Location/Effects |
|---|---|
| Mu (μ, MOR) | Supraspinal & spinal analgesia, euphoria, respiratory depression, miosis, GI dysmotility, dependence, prolactin release |
| Kappa (κ, KOR) | K1: spinal analgesia, miosis; K2: psychotomimesis, dysphoria; K3: supraspinal analgesia |
| Delta (δ, DOR) | Modulates mu receptor effects, analgesia |
Activation of mu receptors causes inhibition of adenylyl cyclase (AC) and downstream neuronal inhibition - this is the core mechanism behind both therapeutic effects and toxicity.
Endogenous ligands: β-Endorphin (mu-preferring), Dynorphins (kappa), Enkephalins (delta > mu).
3. Pharmacokinetics
- Absorption: Well absorbed from the GI tract and all parenteral routes. Oral bioavailability of morphine ~25% (significant first-pass metabolism).
- Metabolism: Morphine is conjugated with glucuronic acid to form the active metabolite morphine-6-glucuronide (M6G), and excreted as morphine-3-glucuronide (M3G) by the kidneys.
- Drug interactions: Effects are enhanced by alcohol, barbiturates, tricyclic antidepressants, and phenothiazines.
Duration of action:
| Drug | Duration |
|---|---|
| Fentanyl, Alfentanil, Sufentanil | Minutes to 1 hour |
| Pentazocine, Pethidine | 2-4 hours |
| Morphine, Codeine, Heroin | 4-8 hours |
| Methadone, Buprenorphine | 8+ hours |
4. Opioid Toxidrome - Clinical Stages
Opioid poisoning classically progresses through three stages:
Stage 1 - Excitement (often brief or absent with large doses)
- Euphoria, elated mood, talkativeness, reduced anxiety
- Flushed face, restlessness
- In severe/rapid onset: hallucinations, seizures (especially in neonates), rhabdomyolysis, hyperkalemia
Stage 2 - Stupor
- Giddiness, drowsiness, headache
- Nausea, vomiting
- Pruritus (histamine release)
- Pupils constricted, conjunctival congestion
- Cyanosed face/lips
- Pulse and BP still relatively normal
Stage 3 - Narcosis/Coma (Life-threatening)
- Unresponsiveness, deep coma
- Pin-point (miotic) pupils - hallmark sign
- Decreased BP, feeble pulse
- Facial pallor, cold clammy skin
- Flaccid muscles
- Terminal: facial flushing, progressive hypotension
- Death from respiratory failure
The classic triad of opioid overdose: coma + respiratory depression + miosis
5. Fatal Doses
| Opioid | Therapeutic Dose | Fatal Dose |
|---|---|---|
| Raw Opium | - | 2 g |
| Morphine | 10-15 mg | 200 mg |
| Heroin | - | 50 mg |
| Methadone | 5-10 mg | 100 mg |
| Codeine | 10-60 mg | 800 mg |
| Pethidine | 50-150 mg | 1 g |
6. Adverse Effects (Therapeutic Doses)
- Respiratory depression
- Nausea, vomiting, vertigo, dysphoria
- Miosis (pin-point pupils)
- Hypotension
- Urinary retention
- Constipation
- Pruritus
- Priapism
7. Differential Diagnosis
Other causes of coma/toxidrome to exclude:
- Alcohol intoxication (smell + labs)
- Barbiturate poisoning (labs)
- Carbolic acid/phenol poisoning (characteristic smell, urine analysis)
- Intracranial hemorrhage
- Cerebral malaria (Falciparum)
- Carbon monoxide poisoning (spectroscopy of blood)
- Diabetic coma, epilepsy, uremia, meningitis, heat stroke
8. Laboratory Diagnosis
- Marquis test: Suspect sample + Marquis reagent (5 mL of 40% formaldehyde in 100 mL sulfuric acid) → fine purple-red color, changing to violet then blue.
- Amphetamines give yellow-orange with the same test.
- Urine drug screen: Metabolites appear 3-6 hours after use. Morphine, heroin, codeine, hydrocodone detectable in urine.
9. Treatment
Step 1 - Supportive/ABC
- Support respiration with bag-valve mask before antidote if needed
- Endotracheal intubation rarely needed in isolated opioid poisoning (naloxone reverses it), but may be required in polysubstance overdose or co-occurring trauma
Step 2 - Decontamination (oral ingestion)
- Gastric lavage with potassium permanganate (leave 250-300 mL in stomach due to enterohepatic circulation)
- Oral sodium sulfate 30 g + twice-daily enema (prevent reabsorption)
- Activated charcoal
Step 3 - Antidote: Naloxone (Narcan)
| Aspect | Details |
|---|---|
| Mechanism | Competitive mu-opioid receptor antagonist |
| Starting dose (IV) | 0.04 mg IV (titrate up); 0.4 mg in children |
| Repeat doses | Repeat/increase until normal respiration restored |
| Max dose concern | No response after 10 mg → question the diagnosis |
| Long-acting opioid overdose | Start naloxone infusion at 2/3 of effective reversal dose per hour |
| Alternate routes | Intranasal, IM, endotracheal, intraosseous (higher doses needed) |
| Caution | Excess naloxone precipitates acute opioid withdrawal in dependent patients |
Naloxone reversal is virtually diagnostic for opioid involvement - Goodman & Gilman's
10. Opioid Use Disorder (OUD)
OUD is a problematic pattern of opioid use leading to clinically significant impairment or distress. Note: tolerance or dependence from prescribed opioids alone does not equal OUD.
Medications for OUD (mOUD)
| Drug | Type | Dosing | Notes |
|---|---|---|---|
| Buprenorphine (sublingual/IM) | Partial mu agonist, very high receptor affinity | 4-32 mg/day | Can be prescribed in acute care without DEA waiver |
| Methadone | Full mu agonist, high affinity | 30-150 mg/day | Must be dispensed daily at methadone clinic |
| Naltrexone IM (Vivitrol) | Antagonist | 380 mg monthly | Requires 7-14 days opioid abstinence first; doesn't treat cravings/withdrawal |
mOUD produces sustained remission, prevents relapse and overdose, improves quality of life, and prevents premature death.
Opioid Withdrawal Symptomatic Management
- Clonidine 0.1 mg PO q8h PRN - reduces anxiety, psychomotor agitation, autonomic symptoms
11. Special Situations
- Fentanyl overdose: Extremely potent (50-100x morphine), very short duration - may need repeated or continuous naloxone infusions
- Pulmonary edema: Non-cardiogenic pulmonary edema can occur with morphine, heroin, codeine, methadone, or fentanyl overdose (first described by Osler with morphine overdose; seen in ~95% of opioid-associated pulmonary edema cases)
- Neonates: More susceptible to seizures and rhabdomyolysis
- Buprenorphine: Ceiling effect on respiratory depression; relatively resistant to naloxone reversal due to very high receptor affinity
Sources: The Essentials of Forensic Medicine and Toxicology (36th ed.) | Goodman & Gilman's The Pharmacological Basis of Therapeutics | The Washington Manual of Medical Therapeutics | Fishman's Pulmonary Diseases and Disorders | Kaplan & Sadock's Comprehensive Textbook of Psychiatry
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