• Anti-Snake Venom (ASV) — indications: Neurotoxicity (ANY); haemotoxicity; local necrosis > 5 cm; coagulopathy; AKI; cardiovascular involvement
• 20-min Whole Blood Clotting Test (WBCT20) — place 2 mL blood in glass tube; if no clot at 20 min = coagulopathy → ASV needed; repeat q1h to monitor response
• Dosing: 8–10 vials (polyvalent ASV) IV initially; repeat based on clinical response; premedicate with SC adrenaline and IV antihistamine
• DO NOT: Incise/suck the wound; tourniquet; electric shock therapy; traditional remedies
• Classification of venom effects: neurotoxic (cobra, krait) - ptosis, diplopia, bulbar palsy, respiratory paralysis, minimal local effects; haemotoxic (viper) - local swelling, blistering, necrosis, spontaneous bleeding, coagulopathy, AKI; cytotoxic - local tissue destruction.
• Clinical features: local - pain, swelling, fang marks, blistering, necrosis; systemic - neurotoxicity (descending paralysis starting with ptosis), coagulopathy (spontaneous bleeding, non-clotting blood), AKI, hypotension, rhabdomyolysis.
• Investigations: WBCT20 (whole blood clotting test - primary field test); PT/APTT, fibrinogen and D-dimer (coagulopathy); serum creatinine and urine for haemoglobinuria (AKI); neostigmine test (reverses cobra neurotoxicity post-synaptic).
• ASV - administration and monitoring: dilute 8-10 vials in 250 mL saline over 1 hour IV; premedicate with SC adrenaline 0.25 mg + chlorpheniramine; repeat every 6 h if WBCT still abnormal; give neostigmine + atropine for neurotoxicity.

• Pathophysiology: chronic alcohol upregulates NMDA glutamate receptors and downregulates GABA receptors; abrupt cessation → CNS hyperexcitability, catecholamine excess, autonomic instability.
• Delirium tremens (DTs): peaks 48-72 h after last drink; confusion, vivid hallucinations, extreme agitation, hyperthermia, profuse diaphoresis, autonomic instability; mortality 5-15% if untreated.
• Treatment in detail: long-acting benzodiazepines (diazepam or chlordiazepoxide) titrated to CIWA-Ar score; IV thiamine before any dextrose; correct electrolytes (Mg, K, PO4 are typically depleted); phenobarbital or propofol for refractory DTs; consider ICU for severe withdrawal.
• Long-term management: motivational interviewing, alcohol liaison nurse referral, and pharmacotherapy for relapse prevention - naltrexone (blocks reward), acamprosate (reduces craving), disulfiram (aversion).

▶ Intoxication treatment: IV Naloxone (μ-opioid receptor antagonist) 0.4–2 mg IV/IM/IN every 2–3 min until RR > 12 and GCS improves; SHORT half-life (30–60 min) — may need infusion for long-acting opioids (fentanyl, methadone ); monitor for re-narcotisation; O2; airway management

▶ Withdrawal treatment: Methadone substitution (opioid maintenance therapy); Buprenorphine + Naloxone (Suboxone) (partial agonist — safer; preferred); Clonidine (α2 agonist — suppresses autonomic symptoms ); symptomatic (loperamide, NSAIDs)

• Opiate toxidrome recognition: miosis (pinpoint pupils), respiratory depression and coma are the classic triad; bradycardia and hypotension may also occur; check oxygen saturations and respiratory rate.
• Naloxone - practical: short half-life (30-90 min) much shorter than most opioids; repeat doses or infusion needed to avoid re-narcotisation; titrate to respiratory rate > 12 breaths/min without fully reversing analgesia; IM or intranasal routes available for community use.
• Opioid use disorder: buprenorphine/naloxone (Suboxone) is the preferred maintenance therapy; methadone is an alternative under supervised dispensing; psychosocial support is essential for relapse prevention.
• Pharmacology of opioids: activate mu, kappa, and delta opioid receptors; mu-receptor activation mediates analgesia, euphoria, respiratory depression, miosis, constipation, and physical dependence; tolerance develops rapidly to the euphoric effect but more slowly to respiratory depression.
• Opioid-induced respiratory depression: the most life-threatening effect; mediated by mu-receptors in the pre-Botzinger complex; respiratory rate falls before consciousness; give naloxone promptly; buprenorphine (partial agonist) causes a ceiling effect on respiratory depression unlike full agonists.

CARBON MONOXIDE POISONING

CO poisoning = odourless, colourless gas (silent killer); CO binds Hb with 240× affinity compared to O2 → COHb (carboxyhaemoglobin) → impaired O2 delivery + cytochrome c oxidase inhibition. Sources: car exhaust, generators, heaters, fires.

• Clinical: Headache (most common + earliest); nausea/vomiting; confusion; cherry-red discolouration of skin (classic but rare in real life); coma; pulse oximetry NORMAL (false negative ) — SpO2 reads COHb as oxyhaemoglobin; ABG COHb level is diagnostic; cardiac arrhythmias; delayed neurological syndrome

▶ 100% O2 via non-rebreather mask — reduces COHb half-life from 5 hours (room air) to 1 hour; Hyperbaric O2 (HBO) (if available: COHb > 25%, cardiac complications, neurological symptoms, pregnancy; reduces half-life to 20 min); continue until COHb < 5%

• CO poisoning - pathophysiology: CO binds Hb with 240x greater affinity than O2 forming carboxyhaemoglobin (COHb) which neither carries oxygen nor releases it (left shift of dissociation curve); also binds myoglobin and cytochrome oxidase causing cellular hypoxia.
• CO investigations: ABG (co-oximetry measures COHb - pulse oximetry falsely normal because SpO2 cannot distinguish oxHb from COHb); ECG (ischaemia, arrhythmia); troponin and CK; neurological assessment; head CT if altered consciousness.
• Hyperbaric oxygen indications: COHb > 25%, any loss of consciousness, neurological deficit, ECG changes/cardiac involvement, pregnancy; reduces risk of delayed neuropsychiatric sequelae.
• Salicylate - investigations and monitoring: plasma salicylate level (4-6 h post-ingestion for peak); ABG showing the characteristic mixed respiratory alkalosis and metabolic acidosis; glucose (hypoglycaemia); INR and LFTs for hepatotoxicity with large doses.

SALICYLATE (ASPIRIN) POISONING

• Mechanism: Uncouples oxidative phosphorylation; stimulates respiratory centre → hyperventilation → respiratory alkalosis (initially); then metabolic acidosis (salicylic acid) + lactic acidosis → mixed disorder
• Clinical: Tinnitus (earliest; pathognomonic ); hyperventilation (compensatory); hyperthermia; non-cardiogenic pulmonary oedema; bleeding (antiplatelet); hypoglycaemia

▶ Activated charcoal (if < 1 hr); IV fluids; urinary alkalinisation (IV NaHCO₃ — maintains urine pH 7.5–8.5; ↑ ionisation of salicylate in tubule → ↓ reabsorption → ↑ excretion ); Haemodialysis (salicylate > 700 mg/L; coma; pulmonary oedema; severe acidosis; renal failure)

Ethylene glycol = antifreeze; toxic metabolites: glycolaldehyde → glycolate → oxalate (by alcohol dehydrogenase ) → oxalate nephropathy + CNS toxicity + cardiac toxicity. Osmolar gap ↑ (early) → Anion gap metabolic acidosis (late).

• Phases:

• Phase 1 (0–12 hrs): Inebriation without odour of alcohol ; nausea; vomiting; CNS depression
• Phase 2 (12–24 hrs): Cardiopulmonary failure (tachycardia, hypertension, CHF, pulmonary oedema)
• Phase 3 (24–72 hrs): AKI (oxalate crystals in renal tubules → flank pain + haematuria); calcium oxalate crystals in urine (monohydrate — needle-shaped; dihydrate — envelopes )

• Investigations: Anion gap metabolic acidosis; ↑ osmolar gap; hypocalcaemia (oxalate binds Ca²⁺); urine oxalate crystals; serum ethylene glycol level; urine fluorescence (car antifreeze contains fluorescein )

▶ Fomepizole (4-MP; alcohol dehydrogenase inhibitor) — antidote of choice ; 15 mg/kg IV loading → 10 mg/kg q12h; blocks conversion to toxic metabolites; preferred over ethanol

▶ Ethanol (competitive ADH inhibitor — if fomepizole unavailable); Haemodialysis (for severe AKI, acidosis, ethylene glycol > 8 mmol/L); Thiamine + Pyridoxine (cofactor supplementation)

• Source and mechanism: antifreeze (ethylene glycol) and brake fluid; metabolised by alcohol dehydrogenase to glycolaldehyde, glycolate (causes acidosis) and finally oxalate (forms calcium oxalate crystals in renal tubules).
• Investigations: anion gap metabolic acidosis with raised osmolar gap (early, before metabolism); urine fluorescence under Wood lamp (fluorescein additive in some antifreeze); urine oxalate crystals; hypocalcaemia; serum ethylene glycol level.
• Fomepizole: the antidote of choice - blocks alcohol dehydrogenase and prevents formation of toxic metabolites; given as loading dose 15 mg/kg IV then 10 mg/kg every 12 h; haemodialysis removes ethylene glycol and corrects acidosis.

Methaemoglobinaemia (MetHb) = iron in Hb oxidised from Fe²⁺ (ferrous) → Fe³⁺ (ferric) → Hb cannot carry O2 + left shift of O2-dissociation curve (↑ affinity for remaining O2 → impaired O2 delivery to tissues). Normal MetHb < 1%.

• Causes: Drugs — Dapsone (#1 drug cause ); nitrites (amyl nitrite; nitroglycerin); metoclopramide ; primaquine; sulphonamides; benzocaine (topical anaesthetic); nitrates in well water (infant metHbaeaemia — 'blue baby syndrome ')
• Clinical: Cyanosis not relieved by O2 (pathognomonic — most important clinical clue); headache; dyspnoea; confusion; chocolate-brown blood (venous blood appears brown — pathognomonic ); pulse oximetry reads ~85% regardless of true SpO2 (SpO2 spuriously normal or ~85%; does NOT correlate with severity )
• Diagnosis: Co-oximetry on ABG (directly measures MetHb fraction ); levels: 10–20% = symptomatic; > 30% = severe (coma/seizures); > 70% = fatal

▶ Methylene blue 1–2 mg/kg IV over 5 min — antidote ; cofactor for NADPH-methaemoglobin reductase → reduces Fe³⁺ back to Fe²⁺; repeat at 30 min if inadequate response; CONTRAINDICATED in G6PD deficiency (may cause haemolysis; use ascorbic acid instead )

• O2 by non-rebreather mask; treat underlying cause; exchange transfusion (severe MetHb + G6PD deficiency); hyperbaric O2 (if no response to methylene blue )
• Normal physiology: methaemoglobin is produced at a low rate normally and reduced back to haemoglobin by cytochrome b5 reductase (NADH pathway, major) and NADPH-methaemoglobin reductase (minor; activated by methylene blue).
• Congenital causes: cytochrome b5 reductase deficiency (autosomal recessive); haemoglobin M variants.
• Management nuances: methylene blue requires G6PD activity to work (NADPH-dependent); it will NOT work and may worsen methaemoglobinaemia in G6PD-deficient patients - use high-dose ascorbic acid or exchange transfusion instead.

Heat stroke = life-threatening hyperthermia (core temp > 40°C ) with CNS dysfunction (distinguishes from heat exhaustion where CNS intact); failure of thermoregulation. Two types: Exertional (young, healthy athletes in hot weather); Classic (non-exertional) (elderly, infants, chronically ill, drugs impairing sweating ).

• Clinical: Hyperthermia > 40°C (rectal temperature); anhidrosis (classic type; exertional may have diaphoresis); CNS — confusion, agitation, seizures, coma; tachycardia; hypotension; hot, dry skin (classic)
• Complications: Rhabdomyolysis (CK ↑↑↑; myoglobinuria → AKI); DIC; hepatic failure; ARDS; multi-organ failure
• Investigations: Core temp (rectal); CK (rhabdo ); coagulation (DIC ); ABG; LFT; RFT; blood glucose; electrolytes

• Heat exhaustion vs heat stroke: heat exhaustion - normal or mildly elevated temperature, normal CNS, profuse sweating, responds to rest and fluids; heat stroke - core temp > 40 C, CNS dysfunction (confusion/coma), medical emergency requiring immediate cooling.
• Cooling methods: ice-water immersion (most effective, fastest cooling), evaporative cooling (fans + misted water), ice packs to groin/axillae/neck; target core temp < 39 C within 30 min; avoid antipyretics (not effective, hepatic damage risk in rhabdomyolysis).
• Complications and monitoring: rhabdomyolysis (CK, urine for myoglobinuria, treat with aggressive IV fluids to protect kidneys); DIC (clotting screen); AKI (U&E, creatinine); hepatic failure (LFTs rise after 24-48 h); multi-organ failure - ICU care.

• Organophosphate management summary: decontaminate (gloves, remove clothing, wash skin); secure airway (avoid suxamethonium - AChE-dependent); IV atropine (treat until bronchial secretions dry - not until pupils dilate) + pralidoxime (within 48 h to reactivate AChE); benzodiazepines for seizures.
• Carbamate vs organophosphate: carbamates (carbofuran, aldicarb) also inhibit AChE but the inhibition is spontaneously reversible; treat with atropine and supportive care; pralidoxime is NOT needed for carbamate poisoning.
• Pyrethroid poisoning: sodium channel toxins; cause paraesthesia, tremor, salivation and in severe cases seizures; treat supportively with vitamin E and phenobarbitone for seizures; no specific antidote.
• Organophosphate - intermediate syndrome: occurs 24-96 hours after cholinergic crisis resolves; weakness of proximal limb muscles, neck flexors, and respiratory muscles; cranial nerve palsies; caused by persistent AChE inhibition at NMJ; supportive (ventilatory support); pralidoxime less effective at this stage.
• Management priorities: decontamination and airway protection are the most urgent steps; avoid succinylcholine (prolonged paralysis due to AChE inhibition); use non-depolarising NMJ blockers if intubation needed; document the time and dose of atropine given for handover.

Barbiturate poisoning = CNS depression from excess GABA-A receptor activation; now less common (benzodiazepines largely replaced). Common in elderly/chronic users (phenobarbitone); suicidal overdose.

• Clinical: CNS depression → coma; respiratory depression (most dangerous — main cause of death ); hypothermia (severe cases); bullous skin lesions (pressure blisters — 'barb blisters' ); hypotension; cardiac arrhythmias; absent reflexes (severe)
• Investigations: Serum barbiturate level; ABG (respiratory acidosis + hypoxia); urine drug screen; ECG

▶ NO SPECIFIC ANTIDOTE (unlike benzodiazepines where flumazenil is partial antidote)
Supportive care: Airway (intubate early ) + O2 + MV for respiratory failure; IV fluids + vasopressors for hypotension; maintain body temperature
Decontamination: Activated charcoal (within 1–4 hrs ); multiple-dose charcoal (MDAC ) for phenobarbitone (enterohepatic recirculation )
Alkalinisation of urine (NaHCO₃ ) for phenobarbitone (↑ ionisation → ↑ excretion )
Haemodialysis/haemoperfusion for severe/refractory phenobarbitone poisoning

• Mechanism: barbiturates enhance GABA-A receptor activity (increase duration of Cl- channel opening), causing CNS and respiratory depression; in overdose they also directly open the channel.
• Clinical grading (Reed): Grade I - drowsy but rousable; Grade II - unconscious, rousable; Grade III - unconscious, not rousable, reflexes present; Grade IV - unconscious, absent reflexes, apnoea.
• Treatment: airway protection and mechanical ventilation is the cornerstone; multiple-dose activated charcoal for phenobarbitone (enterohepatic recirculation); urinary alkalinisation increases excretion of phenobarbitone (weak acid); haemodialysis for severe phenobarbitone poisoning.
• Phenobarbitone vs short-acting: phenobarbitone has a longer half-life and more prolonged toxicity; short-acting barbiturates (thiopentone, secobarbital) cause deeper but more transient coma.

NEAR DROWNING

• Near drowning = survival (at least temporarily) after submersion/immersion; ARDS (secondary drowning ) main complication (pulmonary surfactant destruction); hypoxia; hypothermia; acidosis
• Management: Rescue; ABC; CPR if arrested; ALL should be hospitalised (secondary drowning up to 24 hrs later ); warm IV fluids (hypothermia); PEEP/CPAP for pulmonary oedema; antibiotics only if infection evidence; do NOT use prophylactic antibiotics (fresh vs salt water — similar management now)

LATHYRISM

• Lathyrism = neurotoxic disease from prolonged consumption of Lathyrus sativus (chickling vetch/khesari dal) — contains BOAA (beta-oxalyl-amino-alanine ) — excitotoxin → spastic paraparesis (UMN); irreversible; common in famine/drought conditions (India, Ethiopia, Bangladesh )
• Prevention: Avoid khesari dal; dehusk before cooking (removes BOAA); nutritional supplements (antioxidants); no effective treatment once established

BIOTERRORISM AGENTS

• Category A (highest priority — greatest public health impact):
• Near drowning - pathophysiology: aspiration of even small volumes causes surfactant washout, atelectasis and ARDS (secondary drowning - can be delayed up to 24 h); hypoxia and hypothermia drive cardiac arrest; fresh vs salt water aspiration has less clinical relevance than previously thought.
• Resuscitation: standard CPR; do NOT delay for "drainage manoeuvres"; warm the patient (remove wet clothing, warm IV fluids, warm humidified O2); treat hypothermia if present; admit all patients even if initially asymptomatic.
• Lathyrism: caused by beta-N-oxalyl-amino-L-alanine (BOAA) in Lathyrus sativus (khesari dal); neurolathyrism presents as spastic paraplegia in adults who consumed the dal excessively during famine; endemic in India, Ethiopia and Bangladesh.
• Bioterrorism - key agents: anthrax (cutaneous - painless black eschar, pulmonary - widened mediastinum, treat with ciprofloxacin); plague (bubonic/pneumonic - streptomycin/doxycycline); smallpox (deep synchronous rash on palms/soles - vaccinate contacts); botulinum toxin (descending flaccid paralysis - antitoxin).

• Anthrax (*B. anthracis*) — cutaneous (black eschar ), pulmonary (widened mediastinum ), GI; treat with ciprofloxacin/doxycycline
• Smallpox (Variola) — eradicated; deep synchronous rash involving palms/soles; highly contagious; vaccine stockpiles
• Plague (*Y. pestis*) — bubonic (bubo ); pneumonic (most contagious); treat streptomycin/gentamicin/doxycycline
• Botulinum toxin — descending flaccid paralysis; antitoxin
• Ebola/VHF