CNS Poisons: Alcohol, Barbiturates & Opioids
Forensic Medicine · Toxicology · lean revision notes
CNS Poisons: Alcohol, Barbiturates & Opioids
Central-nervous-system depressant poisons dominate forensic toxicology MCQs. This chapter consolidates the three highest-yield CNS depressants — ethyl alcohol (and the lethal methyl alcohol), barbiturates, and opioids — with their medico-legal levels, toxidromes, antidotes, and postmortem appearances.
Overview & Classification
CNS poisons act primarily by depressing the cerebral cortex and brainstem, producing a continuum of excitation → inebriation → narcosis → coma → death as dose rises. The unifying examiner theme is respiratory-centre depression as the cause of death, with each agent having signature pupils, smell, and a specific antidote (or lack thereof).
| Poison | Pupils | Classic clue | Antidote |
|---|---|---|---|
| Ethyl alcohol | Normal/dilated | Smell of liquor, congestion | Supportive (thiamine, glucose) |
| Methyl alcohol | Dilated, fixed | Blindness, metabolic acidosis | Fomepizole / ethanol + folate |
| Barbiturates | Constricted early → dilated late | "Barb blisters", bullae | Alkaline diuresis (no specific antidote) |
| Opioids | Pinpoint (miosis) | Pulmonary oedema, froth | Naloxone |
High-yield: The classic toxidrome triad of opioid overdose = pinpoint pupils + respiratory depression + coma (depressed consciousness). Reversed by naloxone.
Ethyl Alcohol (Ethanol)
Pharmacology & metabolism
- Absorbed rapidly from stomach (20%) and small intestine (80%); peak blood levels in 30–90 min (delayed by food).
- Metabolised mainly in liver: alcohol dehydrogenase (ADH) → acetaldehyde → (aldehyde dehydrogenase, ALDH) → acetate. A minor microsomal pathway (MEOS/CYP2E1) is induced in chronic drinkers.
- Metabolism follows zero-order (fixed-rate) kinetics — about 15–20 mg/100 mL per hour is removed regardless of concentration (the "β" of Widmark ≈ 0.015%/hr).
High-yield: Alcohol elimination is zero-order — a constant amount per hour, NOT a constant fraction. This is the basis of back-calculation in drunk-driving cases.
Stages of acute alcoholic intoxication (clinical)
| Blood alcohol (mg/100 mL) | Stage | Features |
|---|---|---|
| 30–50 | Subclinical / euphoria | Mild, talkative, disinhibited |
| 50–100 | Excitement | Emotional lability, impaired judgment |
| 100–200 | Confusion | Disorientation, slurred speech, ataxia |
| 200–300 | Stupor | Marked incoordination, vomiting |
| 300–400 | Coma | Anaesthesia, hypothermia, depressed reflexes |
| >400–500 | Death | Respiratory failure |
Medico-legal blood alcohol levels (must memorise)
| Context | Level (mg/100 mL) |
|---|---|
| Driving offence (India, Motor Vehicles Act) | > 30 mg/100 mL (0.03%) |
| Clinical drunkenness ("under the influence") | ~150 mg/100 mL |
| Surgical anaesthesia level | ~250–300 mg/100 mL |
| Fatal / lethal level | ~400–500 mg/100 mL |
High-yield: In India the legal driving limit is 30 mg per 100 mL of blood (0.03 g%). This is the single most repeated forensic alcohol MCQ.
The Widmark formula
Used to back-calculate the amount of alcohol consumed or the blood level at a given time:
A = p × r × c
where A = amount of alcohol in body (g), p = body weight (kg), r = Widmark factor (~0.6 in men, 0.5 in women, reflecting body water distribution), c = blood alcohol concentration (g/L or mg/mL).
Time correction: Ct = Co − (β × t), where β ≈ 0.015%/hr.
High-yield: Widmark r factor is 0.6 (males) and 0.5 (females) — women reach higher levels per unit dose due to lower body water.
Specimens & preservative for blood alcohol
- Best ante-mortem sample: venous blood; cleanse skin with non-alcoholic antiseptic (e.g., aqueous benzalkonium / mercuric chloride — never spirit/tincture).
- Preservative: sodium fluoride (anti-glycolytic) + potassium oxalate (anticoagulant).
- Postmortem: blood from peripheral (femoral) vein preferred over heart blood (avoids diffusion/neoformation artefact). Vitreous humour and urine corroborate.
High-yield: Preservative for a blood-alcohol sample = sodium fluoride + potassium oxalate. Fluoride stops microbial fermentation that would otherwise raise (or lower) alcohol falsely.
Tests for sobriety / breath analysis
- Breath analysers use potassium dichromate (turns green) or fuel-cell/IR technology; blood:breath ratio ≈ 2100:1.
- Romberg, finger-nose, walk-the-line, dictation = clinical drunkenness tests.
Postmortem findings (acute ethanol death)
- Smell of alcohol in stomach/brain cavity; congestion of gastric mucosa ("alcoholic gastritis").
- Generalised visceral congestion, cerebral oedema; bladder often full of urine.
- Death may be from aspiration of vomitus, hypothermia, or hypoglycaemia (especially in malnourished/children).
Chronic alcoholism & withdrawal
- Delirium tremens (DT): the most severe withdrawal syndrome, appears 2–4 days (peak ~72 h) after the last drink. Features: coarse tremors, vivid visual hallucinations (classically Lilliputian — small animals/insects, "rats and snakes"), disorientation, autonomic storm (fever, tachycardia, sweating), seizures.
- DT mortality is significant; treat with benzodiazepines (chlordiazepoxide/diazepam/lorazepam), thiamine, fluids.
- Wernicke encephalopathy: thiamine (B1) deficiency → triad of confusion + ophthalmoplegia + ataxia. Always give thiamine BEFORE glucose to avoid precipitating Wernicke.
High-yield: Delirium tremens peaks at ~72 hours after the last drink; drug of choice = benzodiazepines. Always give thiamine before glucose in a suspected alcoholic.
Mnemonic for Wernicke = "COAT" → Confusion, Ophthalmoplegia, Ataxia, Thiamine.
Methyl Alcohol (Methanol) — the lethal impostor
Worth a dedicated note because "hooch tragedy" / illicit liquor questions are common.
- Found in methylated/denatured spirit, varnishes, antifreeze; consumed in spurious country liquor.
- Toxicity is from metabolites: methanol → (ADH) → formaldehyde → (ALDH) → formic acid → severe high anion-gap metabolic acidosis and optic nerve / retinal damage.
- Clinical: latent period 12–24 h, then headache, vertigo, blurred vision → blindness ("snowfield" vision), abdominal pain, Kussmaul breathing, coma. Dilated, fixed, non-reacting pupils are a bad prognostic sign.
High-yield: Methanol blindness is caused by formic acid (its toxic metabolite), which injures the optic disc/retinal ganglion cells. Pupils are dilated and fixed.
Management flow: secure airway → IV bicarbonate for acidosis → block ADH with fomepizole (DOC) or ethanol → folinic/folic acid (enhances formate clearance) → haemodialysis for severe acidosis, level >50 mg/dL, or visual symptoms.
| Feature | Ethanol | Methanol |
|---|---|---|
| Toxic metabolite | Acetaldehyde (mild) | Formic acid (severe) |
| Pupils | Normal | Dilated, fixed |
| Vision | Spared | Blindness |
| Acidosis | Mild | Severe high-anion-gap |
| Antidote | Supportive | Fomepizole/ethanol + folate + dialysis |
Barbiturates
Classification by duration
| Duration | Examples | Use |
|---|---|---|
| Ultra-short | Thiopentone | IV anaesthesia induction |
| Short | Pentobarbitone, secobarbitone | Hypnotic (most abused) |
| Intermediate | Amylobarbitone, butobarbitone | Hypnotic |
| Long-acting | Phenobarbitone, barbitone | Antiepileptic |
Mechanism
Barbiturates potentiate GABA-A receptor activity, increasing the duration of chloride-channel opening (cf. benzodiazepines increase frequency) → CNS depression. High doses directly open Cl⁻ channels → profound depression and death.
Acute barbiturate poisoning (toxidrome)
- Progressive CNS depression: drowsiness → ataxia → coma.
- Respiratory depression (chief cause of death), hypotension, hypothermia.
- Pupils usually constricted early, may dilate terminally (hypoxia).
- Loss of reflexes; flaccidity. EEG may go flat at high levels — do not declare brain death on EEG while barbiturate is present.
- Cutaneous bullae over pressure points = "barb blisters" / barbiturate blisters (also seen in CO, benzodiazepine, tricyclic comas) — high-yield sign of prolonged coma.
High-yield: Barbiturate (coma) blisters are tense bullae over pressure areas; they are characteristic but NOT specific (also in CO, benzodiazepine, opioid, TCA poisoning). They indicate prolonged immobile coma.
Management
Airway + ventilatory support → gastric lavage if early → activated charcoal (multiple-dose for phenobarbitone) → IV fluids/vasopressors → urinary alkalinisation with sodium bicarbonate (for long-acting phenobarbitone, which is a weak acid) → haemodialysis in severe cases. No specific antidote. Forced alkaline diuresis ionises the drug and traps it in urine (ion trapping).
High-yield: Alkalinisation of urine (sodium bicarbonate) enhances elimination of phenobarbitone (a weak acid). It does NOT help short-acting, highly protein-bound barbiturates.
Medico-legal aspects
- Common agent of suicide ("signature/automatism" — patient takes a dose, becomes confused, forgets and takes more → accidental overdose).
- Postmortem: congestion, pulmonary oedema, blisters; gastric contents and viscera sent for analysis.
Opioids (Morphine, Heroin, Codeine, etc.)
Source & types
- Natural opium from Papaver somniferum (poppy); morphine is the chief alkaloid (~10%), codeine, thebaine, papaverine, noscapine.
- Heroin (diacetylmorphine) = semisynthetic, more lipid-soluble, crosses BBB faster → greater abuse potential ("smack/brown sugar").
- Synthetic: pethidine, methadone, fentanyl, tramadol.
Mechanism
Agonist at μ (mu), κ, δ opioid receptors → analgesia, euphoria, miosis (Edinger-Westphal stimulation), respiratory depression (reduced brainstem CO₂ sensitivity), GI stasis, histamine release.
Acute opioid toxidrome
The classic triad → pinpoint pupils + respiratory depression + coma.
Other features: cyanosis, hypotension, bradycardia, hypothermia, non-cardiogenic pulmonary oedema (froth at mouth/nostrils), convulsions (esp. children, pethidine, tramadol). Death is from respiratory failure.
High-yield: Pinpoint (pin-point) pupils with respiratory depression = opioid poisoning until proven otherwise. Other causes of miosis = pontine haemorrhage, organophosphates, clonidine, barbiturates.
Antidote
- Naloxone = pure competitive μ-antagonist, IV/IM/intranasal; onset 1–2 min, short half-life (~30–60 min) so repeated dosing or infusion needed (opioids outlast it → "re-narcotisation").
- Watch for acute withdrawal in dependents after naloxone.
- Naltrexone = long-acting oral antagonist used for maintenance/de-addiction.
High-yield: Naloxone's half-life is shorter than most opioids → patient can relapse into coma; repeat doses / infusion and observe. Naloxone for acute reversal, naltrexone for de-addiction.
Opioid withdrawal (vs alcohol/barb)
Not life-threatening (unlike DT/barbiturate withdrawal). Features: lacrimation, rhinorrhoea, yawning, sweating, mydriasis, piloerection ("cold turkey"), myalgia, diarrhoea, "kicking the habit" (myoclonus). Managed with clonidine, methadone/buprenorphine substitution.
Postmortem findings (opioid death)
- Fresh needle puncture marks / track marks, thrombosed veins, tattoos over them to hide.
- Pulmonary oedema with frothy fluid; visceral congestion; pinpoint pupils may persist.
- Stomach: morphine is excreted back into the stomach even after parenteral use → always preserve stomach contents.
- "Body packers/pushers" (drug mules) — concealed packets in GIT/rectum; rupture → sudden massive overdose death.
Stepwise approach to an unknown CNS-depressant coma
- A-B-C: secure airway, ventilate, oxygen, IV access, monitor.
- Check pupils: pinpoint → think opioids/OP/pontine; dilated fixed → methanol/anoxia.
- Empirical "coma cocktail": dextrose (after thiamine), naloxone (if opioid suspected), consider flumazenil (benzodiazepine — caution: seizures).
- Decontamination: gastric lavage/activated charcoal if early and airway protected.
- Enhance elimination: urinary alkalinisation (phenobarbitone), haemodialysis (methanol, severe barbiturate).
- Specific antidote where it exists (naloxone; fomepizole for methanol).
- Preserve forensic samples with correct preservatives; document.
Complications (across agents)
- Aspiration pneumonia and ARDS / non-cardiogenic pulmonary oedema (opioids).
- Rhabdomyolysis and pressure necrosis from prolonged coma (→ acute kidney injury, compartment syndrome, barb blisters).
- Hypothermia, hypoglycaemia, hypotension.
- Methanol → permanent blindness, Parkinsonism (putaminal necrosis).
- Chronic alcohol → cirrhosis, pancreatitis, cardiomyopathy, Wernicke-Korsakoff, peripheral neuropathy.
Key differentials of "comatose patient with miosis"
| Cause | Distinguishing feature |
|---|---|
| Opioids | Responds to naloxone, pulmonary oedema |
| Organophosphate | Muscarinic excess: salivation, lacrimation, fasciculations, garlic smell; ↓ cholinesterase |
| Pontine haemorrhage | Sudden coma, no naloxone response, neuro signs |
| Clonidine/imidazoline | Hypotension, bradycardia |
| Barbiturate (early) | Blisters, hyporeflexia, no naloxone response |
Recently asked / exam angle
- Legal driving limit of blood alcohol in India = 30 mg/100 mL.
- Widmark formula and r factor (0.6 male / 0.5 female); zero-order kinetics of ethanol.
- Preservative for blood alcohol sample = sodium fluoride + potassium oxalate.
- Delirium tremens time of onset (~72 h) and treatment (benzodiazepines); thiamine before glucose.
- Methanol toxic metabolite = formic acid, causes blindness; antidote fomepizole/ethanol + folate.
- Barbiturate mechanism: ↑ duration of GABA-A Cl⁻ channel opening; alkaline diuresis for phenobarbitone; barb blisters.
- Pinpoint pupils + respiratory depression + coma = opioid triad; antidote naloxone (short t½, repeat doses); naltrexone for de-addiction.
- Morphine excreted into stomach even after IV use → preserve stomach contents.
- Causes of miosis list (opioid vs OP vs pontine).
Rapid revision
- Ethanol metabolism is zero-order, ~15–20 mg/100 mL/hour (Widmark β ≈ 0.015%/hr).
- India legal driving alcohol limit = 30 mg/100 mL (0.03%); fatal ≈ 400–500 mg/100 mL.
- Widmark r = 0.6 male, 0.5 female; women get higher levels (less body water).
- Blood-alcohol preservative = sodium fluoride + potassium oxalate; clean skin with non-alcoholic antiseptic.
- Delirium tremens peaks ~72 h post-cessation; treat with benzodiazepines; Lilliputian visual hallucinations.
- Give thiamine before glucose; Wernicke = Confusion + Ophthalmoplegia + Ataxia.
- Methanol → formic acid → blindness, high-anion-gap acidosis, dilated fixed pupils; antidote fomepizole/ethanol + folate + dialysis.
- Barbiturates ↑ duration of GABA-A Cl⁻ channel opening; benzodiazepines ↑ frequency.
- Barbiturate (coma) blisters over pressure points — characteristic, not specific.
- Urinary alkalinisation (NaHCO₃) aids phenobarbitone (weak acid) elimination; no specific antidote for barbiturates.
- Opioid triad = pinpoint pupils + respiratory depression + coma; death from respiratory failure.
- Naloxone (short t½ → repeat) for acute reversal; naltrexone for maintenance; morphine excreted into stomach even after IV use.