Toxicology PDF

Richard Summers Intended learning outcomes  Understand and describe the use of antidotes and other therapies used in modern drug management in toxicology  Review gastro decontamination and antidotes for use in acutely poisoned patients  Be knowledgable about antivenoms and other manageme...

Richard Summers Intended learning outcomes  Understand and describe the use of antidotes and other therapies used in modern drug management in toxicology  Review gastro decontamination and antidotes for use in acutely poisoned patients  Be knowledgable about antivenoms and other management of envenomation and common bites and stings Overview of some mechanisms Action; prevent reaching target - activated charcoal Competitive antagonism – receptor Replace substrate – N-acetylcysteine Bind and inactivate toxin – digibind Reactivate oximes Antagonise enzyme toxic alcohols Alternative sources Toxin elimination – urine alkalinisation Limitations of antidote  Not available for most poisonings  Not always 100% effective  Limited by time from exposure (eg. NAC)  Inherent toxicity – dicobalt editate  Expensive – 4 methylpyrazole History  Methridates 150BC - 120BC  Antidotum mithridaticum – universal antidote  Took daily  Sub lethal doses of poisons  Tested on slaves  Ironically – Built up tolerance and it failed when he wanted to suicide Epidemiology – Vic Poisons information Centre – VPIC  Australia 240,000 calls/yr ( about 600/day)  Accidental exposure (66%), therapeutic error (14%) and intentional exposure (16%) (others ADRs, enviro)  Health professional and public access service  30,000/yr (60% paediatric)  Severe toxicity < 1% of calls  Poisons information centre; national network 24/7, 7 days a week from four centres (Qld, NSW, Vic, WA) Phone 131126  Victorian; VPIC; www.austin.org.au/poisons  Dextrose 50%, 50mL IV – hypoglycaemia  Naloxone 50 – 400mcg – opioid toxicity (pinpoint pupils)  Thiamine 100mg IV – ethanol abuse (to avoid Wernekes encephalopathy)  Atropine  Ca Gluconate  Physiological antagonist to effects of hyperkalaemia & hypermagnesaemia on cardiac conduction & skeletal muscle  NAC  Glucagon in B blocker toxicity  ? No evidence Poisoned patient  Deliberate self-poisoning  Frequently involve benzodiazepines, antidepressants & paracetamol  Recreational drug abuse  Occupational poisoning  Envenomation  Management tailored to individual patient Pharmacists role  Asked for assistance (often 1st point of contact)  Need to understand potential risks and complications associated with acute poisoning  Appropriate management  Role early in assessment and management by providing first aid, contacting emergency medical services and seeking or providing advice (poisons information centre)  Contacting emergency services (dial 000)  Collapse, stopped breathing, anaphylactic reaction or seizure Risk assessment  Quantitative  Take in account:  Agent  Dose  Time of ingestion  Clinical features  Progress  Patient factors (wt, age, co-morbidities) Poisoning  Note;  Often associated with exacerbation of psychiatric, social or drug and alcohol problem  Leading cause of death in patients < 40yrs Resuscitation  Resuscitation in poisonings – good neurological outcomes following prolonged CPR  Priority is resuscitation (before decontamination of GIT or skin) and ? Aim to increase elimination or antidote  Airway, breathing, circulation  Altered conscious state => loss of airway protective reflex  Seizures (benzodiazepines first-line)  Hypoglycaemia (check BSL if altered mental state)  Hyper-/hypothermia Initial decontamination A Airway B Breathing C Circulation D Decontamination GIT E Elimination  Specific intervention Seizure management  Clinical determination - GCS – Glasgow Coma Scale often doesn’t apply in poisonings  Seizures; venlafaxine, bupropion, tramadol, amphetamines  Tx benzodiazepines, barbiturates, pyridoxine (phenytoin CI in Mx of seizures related to poisonings)  ? Any issues with benzodiazepine management?  ED presentations  Deliberate self-poisonings  Paracetamol, analgesics, psych drugs,  Recreational –  methamphetamine, GHB (gamma hydroxybuteric acid or fantasy), opioids  http://www.druginfo.adf.org.au/drug-facts/ghb  Mental health disorders  Morbidity higher, but in hospital fatality rates remain low. Common pharmaceutical poisons  Often involves one or more and frequently in association with alcohol  Benzodiazepines;  CNS depressant effects, ataxia, lethargy, slurred speech, drowsiness, resp depression  Hypothermia, bradycardia & hypotension (V. large doses)  Ethanol;  rapid dose related CNS depression.  Acute toxicity; disorientation, tachycardia, hypotension, hypothermia, resp depression (risk increases with other drugs) & coma. (NB also in MW, food extracts, cough and cold preps, perfumes) Common pharmaceutical poisons  NSAIDs; widespread availability (esp ibuprofen 2/3)  Not significant clinical effects 400mg/kg => shock, coma, seizure ARF, metabolic acidosis  Paracetamol;  Most common call to PIC, supra-therapeutic dosing or acute OD (>10g in adults or 200 mg/kg children within 8hrs or less).  GI Sx – early clinical signs => progressive liver injury Common pharmaceutical poisons  Quetiapine;  dose-dependent CNS depression. 3g mild sedn and tachycardia, >3g CNS depression, hypotension, seizures, coma. Onset 2-4hrs  Management supportive  SSRIs;  low risk of severe toxicity unless taken with serotonergic agents => increase risk of life-threatening serotonin toxicity  Progressive muscle rigidity & hyperthermia => rhabdomyolysis, RF, death Hypoglycaemia  Hypoglycaemia causes neurological injury  Associated with insulin, sulfonylurea agents, beta- blockers, quinine, chloroquine, salicylates and valproic acid Hyper-/hypothermia  Temp >38.5’C  Temp > 39.5 C => organ failure and neurological injury  Neuromuscular paralysis with intubation reduces temp from muscle-generated heat production  Hypothermia => cause or mimic MI  Coma, bradycardia, hypotension Antidote administration  Sometimes in resuscitation  IV sodium bicarbonate in TCA poisoning  Atropine in organophosphate intoxication  Digibind in digoxin toxicity  Acute poisoning is a dynamic process  TCAs – within 6 hrs (usually within 2hrs)  Rapid onset CNS, cardiovascular toxicity (blockade of inactivated fast sodium channels)  Intubation, hyperventilation & sodium bicarbonate  CCB – SR formulation later onset of toxicity  Screening tests  ECG; paracetamol level Paracetamol  Deliberate self-poisoning is common, 15% of adult poisoning presentations in Australia  Timely administration of NAC can prevent hepatic failure and death  Screen for others? Often clinical picture will dictate management (some false +ves and –ves)  What if have drowsy patient; what else could we do to eliminate a cause? GI Decontamination Gastric lavage – rare now http://www.youtube.com/watch?v=XSU4ho7ybjc Only given within 1st hour > 20mg/kg of TCA No evidence for efficacy May push tabs further down GIT ? Stimulation of vagus nerve => arrhythmia Very difficult to monitor patient during procedure GI decontamination – Induced emesis  Traditional in toxicology  Syrup of ipecac – (plant extracts) induce vomiting within 18minutes  Amount of toxin removed unreliable – don’t know ingestion time  Considered only for an agent with a dose likely to cause significant toxicity that doesn’t involve rapid onset of altered consciousness/seizures or if AC (activated charcoal) unavailable or doesn’t bind  ED no longer stock and not recommended – no benefit (esp if presentation delays)  ? Reserved where risk assessment predicts severe or life-threatening toxicity  Where supportive care or antidote Tx insufficient  Pharmacists - Knowledge of absorption kinetics important  Most absorption complete within 1hr  Caution; Avoid pulmonary aspiration  Complications;  prolonged vomiting (10-20% vomit> 1hr) leading to physical injury (Mallory Weiss tear, gastric perforation), diarrhoea (20-30%), lethargy (10%), pulmonary aspiration, corrosive ingestion Gastric lavage  Sequential administration and aspiration of small volumes of fluid from stomach – orogastric tube  Now mainly abandoned  Amount removed unreliable and negligable unless given < 1hr  CI if impaired consciousness (need airway protection), corrosive ingestion, hydrocarbon  Pulmonary aspiration; hypoxia, laryngospasm, mechanical injury, water intoxication, hypothermia GI Decontamination Activated charcoal (small particles) – achieved by burning charcoal and then steam carbonaceous substance (super-heating distilled wood pulp) => fine porous particles – made from wood peat Enormous surface area; reversibly adsorbs toxins => preventing GI absorption  Suspended in water or sorbitol prior to oral or nasogastric administration Doesn’t produce constipation with single dose; if needing repeat procedure then consider addition with sorbitol (no additional benefit and could cause hypovolaemia or electrolyte disturbance – Carbosorb XS) Binds => passes harmlessly Good but poor with heavy metals and alcohols  Useful where toxin remains in GIT within 1st hr Dose 50g – child 1g/kg in 250mL  Mixing with ice cream improves palatability for children  Intubated patients – give oro or nasogastric (dilute with water first) Well tolerated < 5% vomit (Complications; vomiting (30% within 1hr) Chilled, drink through straw (covered container or eyes shut) Avoid if semi-conscious state Risks charcoal pulmonary aspiration (from impaired consciousness or seizures) Misplaced nasogastric tube (directly into lungs – fatal) Impaired absorption of oral antidotes Messy !!!!! GI Decontamination  Timing  < 25% of patients in ED present < 1hr (10% receive AC)  No evidence that it changes outcomes  Evidence for efficacy is limited to volunteer studies  Not a benign intervention – process involved GI Decontamination  Theophylline  Carbamazepine  Phenobarbitone  Quinine  Dapsone  GI Dialyser effect so consider if 4-6 hrs after for SR preparations or with anticholinergic drugs (that slow transit time) such as TCAs Activated Charcoal  Not for agents poorly bound  Examples of poorly bound agents  Hydrocarbons and alcohols  Ethanol, isopropyl alcohol, ethylene glycol, methanol  Metals  Lithium, Iron, Potassium, Lead, Arsenic, Mercury  Corrosives  Acids, Alkalis Whole bowel irrigation - WBI PEG – Poly ethylene glycol – go lytely®, colonlytely® Wash through Adults 2L/hr Kids 500mL/hr Used for: Iron Lithium Lead SR calcium channel blockers (severe toxicity) Whole bowel irrigation - WBI Paint Lead toxicity (eating paint from old home) – WBI (whole bowel irrigation) “Body Packers” – packets of drugs ingested with constipating agent; condoms – now latex packs (sealed airtight) inserted Ingestion – transit time 2 days – 3 weeks Commonly present toxic Cocaine heroin – 50 – 100 packets 5-10g and lethal dose 1g Whole bowel irrigation  Aggressive – labor-intensive  Cleanse entire bowel with large volumes of PEG electrolyte solutions  SR or EC preparations or agents that do not bind to AC (activated charcoal)  Iron overdose  SR potassium chloride  SR verapamil, diltiazem  Lead ingestion  “Body packers”  Complications; NV, abdo bloating, non-anion gap metabolic acidosis, pulmonary aspiration;  PEG nasogastric 2L/hr (children 25mL/kg/hr)  Metoclopramide to minimise vomiting and enhance gastric emptying  May take 6hrs to get clear effluent  Cease if abdominal distension or loss of bowel sounds Enhanced elimination  Multiple-dose activated charcoal (MDAC)  Interruption of entero-hepatic circulation  Charcoal binds drug in small intestine preventing reabsorption  Limited to drug with small Vdist and undergoes hepatic circulation  Carbamazepine, phenobarbitone, dapsone  Complications; constipation, charcoal bezoar formation (mass trapped in GIT), bowel obstruction, perforation  Urinary alkalinisation – (sodium bicarbonate)  Promotes ionisation of highly acidic drugs => prevents reabsorption  Renally excreted, small Vdist and be a weak acid  Salicylates (normally hepatic but is saturated in OD)  Phenobarbitone (MDAC superior)  Complications; alkalaemia, hypokalaemia, hypocalcaemia  Correct hypokalaemia if present  Monitor 4hrly, regularly dipstick aim pH>7.5 Haemodialysis or haemofiltration  Intermittent or continuous (intermittent preferred)  Haemoperfusion  Plasmapheresis  Exchange transfusion  Specialised and reserved for life-threatening poisonings where good outcome unlikely with other means  Toxic alcohol poisoning; methanol, ethyene glycol  Theophylline  Salicylate severe toxicity  Lithium intoxication  Phenobarbitone coma  Metformin lactic acidosis  Carbamazepine OD  Potassium salt OD Mushroom poisoning  Most are benign => self-limited GI disturbance  Some toxic syndromes – lethal hepatotoxicity  Sx; acute GI toxicity  Cyclopeptide hepatotoxic poisoning accounts for majority of mushroom- related deaths (rare in Australasia).  Suspected if GI symptoms develop > 6hrs after ingestion  Thousands of species  Acute gastroenteritis; cholinergic syndrome secondary to muscarine (doesn’t cross BBB)  Glutaminergic toxicity due to muscimol – resembles GABA and stims central GABA receptors  Ibotenic acid resembles glutamic acid - stims central glutaminergic receptors  Gyromitrin is activated to monomethylhydrazine – similar action to isoniazid; it inhibits pyridoxin-dependent synthesis of GABA  Psilocybin – resembles lysergic acid diethylamide (LSD)  Coprine inhibits acetaldehyde dehydrogenase (similar to disulfiram)  Amatoxins – inactivate RNA polymerase II and inhibit protein synthesis. (Amanita phalloides) – liver failure (50% die)  Mushroom poisoning  http://www.abc.net.au/news/2012-06-08/woman-dies-after-eating-death-cap-mushrooms/4061254  http://www.health.vic.gov.au/media/poison-mushroom-warning.htm History:  Death cap mushrooms are considered the most poisonous in the world - one is enough to kill an adult.  At least six people have died and at least 12 made sick from eating death cap mushrooms in Australia in the past decade.  Death caps have been involved in the majority of deaths around the world from mushroom poisoning, including that of Roman emperor Claudius. Appearance:  Death cap mushrooms are similar in appearance to several species of edible mushrooms commonly used in cooking, such as paddy straw mushrooms and caesar's mushroom.  http://www.anbg.gov.au/fungi/deathcap.html  Death caps may be white but are usually pale green to yellow colour, white gills and a white or pale green stalk up to 15cm long.  The entire mushroom is poisonous and cooking or peeling the mushroom does not remove toxicity. Symptoms:  Death caps are said to taste pleasant and symptoms can occur six to 24 hours after consumption.  Initial symptoms can include abdominal pain, diarrhoea, vomiting, hypotension and jaundice, followed by seizures, coma, renal failure and cardiac arrest. Habitat:  Death cap mushrooms can be found in parts of south eastern Australia, particularly ACT and parts of Victoria.  They are commonly found near established oak trees and some other hardwood trees and are most common during later summer to early winter after heavy rain or irrigation.  It is thought death caps were introduced to Australia with the importation of different hardwoods. Treatment:  Death caps are extremely poisonous and if consumed it is a medical emergency.  Anyone who suspects they have eaten a death cap should seek immediate medical attention and where possible take a mushroom sample for identification. Mushroom poisonings  Clinical features: early  GIT; NV, abdo pain, malaise, diarrhoea (lots)  Cholinergic; vomiting, diarrhoea, lacrimation, salivation, incontinence, miosis, bronchospasm (within 30min to 2hr – muscarine)  Hallucinogenic; ataxia, tachycardia, delirium (minutes – psilocybin)  Disulfiram- like reaction; flushing, sweating, chest pain, NV (ethanol consumption < 2hrs – Coprine)  Glutaminergic; dizziness, drowsiness, delirium hallucinations, seizures (30min to 2hr – Ibotenic acid, muscimol)  Epileptogenic; NV, diarrhoea, headache, ataxia, fatigue tremor, seizures rare ( < 6hrs – gyromitrin) Mushroom poisoning  Aminita Muscaria (hallucinogenic)  https://www.mja.com.au/journal/2011/195/11/mushroo m-poisoning-personal-vignette  never eat any mushrooms with white gills nor any wild mushrooms, and even more simply — do not eat any mushrooms that you do not positively know Mushroom poisonings  Delayed onset (6 to 24hr)  Hepatotoxic; NV, abdo cramps, increased transaminases; severe gastroenteritis with fulminant hepatic failure & pancreatitis (2-6 days) (Amatoxins, Phallotoxins, Virotoxins)  Erythromelalgia; burning pain, redness oedema of hands and feet; exacerbated by heat and relieved by cold ( onset 24- 72hr; resolves 8days to 5mths) (Acromelic acids)  Greatly delayed (> 24hrs)  Nephrotoxic; anorexia, headache, NV, flank pain, interstitial nephritis, ARF (24-36hrs; Orellanine)  Rhabdomyolysis; fatigue, myalgias, muscle weakness & myocarditis rarely; (24-72hr; Tricholoma and Russula sp) Anti-dotes  Cyclopeptide hepatotoxic mushroom poisoning (very rare poisoning)  Tx:- High dose benzyl penicillin, cimetidine, NAC, silibinin  Atropine in pts with peripheral cholinergic signs and symptoms  Pyridoxine for seizure management from monomethylhydrazine (Gyromitra mushrooms)  Any mushrooms or fungi that have a cup at the base of the stalk should never be eaten. Any mushrooms with a redness to them are also highly toxic. Any type of fungus that you are not sure about is best left alone and should definitely not be eaten. Plant poisonings  Serious poisoning from plant exposure is rare  Most asymptomatic or cause minor Sx  Some plants cause local irritation Plant poisonings  Delphinium spp. (Aconite) => tachycardia, GI upset, lactic acidosis  Angel’s trumpet (belladona) => anticholinergic poisoning, tachycardia, delirium, agitation, ileus  Digitalis spp, Nerium spp pink oleander (cardiac glycosides) => bradycardia, GI disturbances, hyperkalaemia  Morning glory (Ipomea spp; psychotropic alkaloids) => acute psychosis, visual hallucinations  Castor beans Ricinus (ricin; GI disturb; multi organ failure)  Seed kernels (apricots, plum, pear, cherry, almond) cyanogenic glycosides; => tachycardia, bradycardia, coma, acidosis, multi organ failure Plant poisonings  Physostigmine – reverse severe anticholinergic poisoning  Cyanide antidotes  Digibind – for oleander poisoning Plants  Some contain needle-like calcium oxalate crystals => mechanical injury to mucosal membranes if ingested  Pain & swelling, lips, tongue, oral cavity and pharynx; even upper airway obstruction, profuse salivation; can take days for Sx to subside; cold dairy, yoghurt, ice- cream=> soothing  Nettles; deliver irritant chemicals to skin; contact dermatitis from sap of certain plants (eg Mango tree; rarely serious) Cleaning agents  Detergents;  GI Sx (vomiting, diarrhoea)  Give fluids to dilute  Corrosive dishwasher tablet or pdw; give fluids and observe for corrosive effects (difficulty swallowing, vomiting abdo or oral pain, drooling, persistent coughing)  Disinfectants  Most will only cause GI Sx  Window cleaners contain glycol but not often enough ingested to cause ethanol effects  Others (eg oven cleaners) check for corrosive effects Others  Essential oils, including eucalyptus and vapouriser solutions (Sx 30 mins; CNS depression or coma, also chemical pneumonitis (aspiration))  Herbicides; glycophosate (corrosive) and hypotension, RF, seizure  Hypotension, pulmonary oedema, renal failure, seizures, cardiac arrest  Perfumes, colognes, aftershave (ethanol up to 60%); CNS depression & hypoglycaemia => seizures (check for delayed hypo)  Rodenticides; anticoagulants (warfarin & related cpds)  Superwarfarins (long acting & toxic at lower doses)  brodifacoum, bromadiolone, chlorphanicone, difenacoum, diphacinone and floumafen)  Most have taste deterrent  Anticoag effect delayed and large ingestion (last wks – mths) need large doses of vit K Poisons & toxins – potential Toxicity in children in low doses for severe toxicity Acids (hydrochloric, hydrofluoric) Amphetamines Arsenic Beta-blockers Colchicine Cyanide Calcium Channel Blockers Digoxin Diphenoxylate and atropine Ethylene glycol Lead Iron tablets Methanol Opioids Methotrexate Organophosphorous agents Phenothiazines Paraquat Sulfonylureas Plant toxins Potassium Tricyclic antidepressants Quinine Salicylates Strychnine Venlafaxine and desvenlafaxine Coma  Direct altered mental status where patient cannot be roused  Common manifestation of many agents  Direct toxic effect on CNS (eg affecting neurotransmitter systems)  Secondary; hypoxaemia, hypoglycaemia, hyponatraemia, hypotension, seizures, cerebral oedema  Most agents produce relatively benign and temporary alteration in mental status => good prognosis with supportive care Resuscitation  Airway and ventilation – priority  Bag and mask  Endotracheal intubation  Poisoning – dynamic process; ability to ventilate effectively changes in a short period  TCAs rapid decline within 2hrs  Patients - difficult to protect airway irrespective of GCS – so need intubation esp if delay to presentation  Some poisonings associated with metabolic acidosis and compensatory hyperventilation to achieve respiratory alkalosis (salicylate, methanol, ethylene glycol) Considerations  Hypotension  Assessed and managed in resuscitation phase  Seizures  Generalised and self-limiting (control with benzodiazepines)  Caused by venlafaxine, bupropion, tramadol, amphetamines, TCAs, propranolol, salicylates, theophylline  Prolonged => associated with irreversible CNS injury  Tx if refractory with Phenobarbitone or thiopentone or pyridoxine as 3rd line if associated with isoniazid or other hydrazines Considerations  Delirium & agitation  Altered conscious state with impaired cognition  Transient direct effect  Alcohol, anticholinergic syndrome, antiepressants, atypical antipsychotics (olanzapine), benzos, cannabis, hallucinogenics, nicotine, theophylline, serotonin syndrome Serotonin syndrome  Excessive stimulation of serotonin receptors in CNS  Accumulation in CNS from;  Inhibition of serotonin metabolism (MAOI)  Prevention of serotonin reuptake in nerve terminals (SSRI)  Serotonin release or increased intake of serotonin precursors (tryptophan)  Features; triad;  mental status changes,  autonomic stimulation  neuromuscular excitation Serotonin syndrome Mental status changes Autonomic stimulation Neuromuscular excitation Apprehension Diarrhoea Clonus (ocular, ankle) Anxiety Flushing Hyperreflexia Agitation, psychomotor Hypertension, Increased tone (lower acceleration and delirium tachycardia, sweating limbs> upper) Confusion Hyperthemia, Mydriasis Myoclonus, rigidity, tremor Serotonin syndrome  Spectrum of severity; very mild to life-threatening (generalised rigidity, hyperthemia)  Without intervention => rhabdomyolysis, renal failure, DIC (disseminated intravascular coagulation) and death  Symptoms rapid in onset (within hrs of medication changes or OD)  Resolves over hours (24 – 48 hrs) Agents  Analgesics and antitussives  MAOIs  Dextromethorphan  Moclobemide  Fentanyl  Phenelzine  Pethidine  SSRIs  Tramadol  Citalopram,  TCAs escitalopram  Drugs of misuse  Fluoxetine  Amphetamines  Paroxetine  Methylenedioxymethampheta  Sertraline mine (MDMA, ecstasy)  SNRIs  Herbals  Bupropion  St John’s wort  Venlafaxine  Lithium  Tryptophan Management  Resuscitation,  Hyperthermia > 39.5 C (needs neuromuscular paralysis, intubation and ventilation) muscle-generated heat production => multi organ failure  Tx benzodiazepines (IV titrated) gentle sedation  Hypertension and tachycardia also responds to sedation (alternative managed with nitroprusside or GTN)  Antidote Tx for mild to moderate  Cyproheptadine 8mg (oral or nasogastrically); alternatives chlorpromazine or olanzapine  Aggressive supportive care in severe form Anticholinergic  Agitated delirium (central signs)  Fluctuating mental status  Confusion  Fidgeting  Visual hallucinations  Mumbling slurred speech  Disruptive  Muscarinic blockade signs (peripheral)  Mydriasis  Tachycardia  Dry mouth, skin  Flushing  Hyperthermia  Urinary retention  Absence of bowel sounds Anticholinergic  Benzodiazepine (correct seizure and sedation)  Antidotes; Physostigmine – central acting anticholinesterase inhibitor  Reduces need for massive doses of benzodiazepines and risk of aspiration  Needs careful titration  May be of benefit in persistent delirium from TCA OD recovery Cholinergic Syndrome  Acetylcholinesterase inhibition or direct agonist action at muscarinic or nicotinic receptors (acetylcholine agonists)  Organophosphate or carbamate pesticide poisoning  Copious secretions; vomiting, diarrhoea and altered mental status; => death from respiratory failure and excess respiratory secretions CNS Neuromuscular PS – muscarinic effects Sympathetic nicotinic effects Agitation Fasciculation Abdominal cramps hypertension Respiratory Muscle weakness Bradycardia, Mydriasis depression bronchoconstriction Coma Diarrhoea Sweating Confusion Lacrimation, miosis Tachycardia (2’ to hypoxia) Lethargy Salivation Seizures Urination, vomiting Cholinergic Syndrome  Control seizures with benzodiazepines  Antidote; Atropine or pralidoxime  Fluid replacement (monitor fluid balance until patient drinking)  ?Decontamination of patient (GIT – risk assess) Neuroleptic Malignant Syndrome  Rare; potentially lethal  Neuromuscular rigidity;  altered mental state;  autonomic instability  Deficiency of dopaminergic neurotransmission  Nigrostriatal, mesolimbic, hypothalamic-pituitary pathway  ADR in 0.2 to 2.5% patients on neuroleptics  Onset 24 – 72hrs; recovery days to months Neuroleptic Malignant Syndrome CNS Autonomic instability Neuromuscular Confusion Hyperthermia Lead-pipe rigidity Delirium Tachycardia Bradykinesia or akinesia Stupor Hypertension Mutism and staring Coma Respiratory irregularities or Dystonia and abnormal postures cardiac dysrrhythmias Abnormal involuntary movements Incontinence Neuroleptic Malignant Syndrome - management  Bromocriptine (dopamine agonist) moderate to severe cases  ADRs; hypotension, headache, NV, dyskinesia  Treat 1-2 weeks then taper  Dantrolene (2-3mg/kg/d)  If severe muscle rigidity and fever  ECT – refractory to other Tx  ? Improve fever; sweating and conscious level  ? Increases central dopaminergic activity  A 32-year-old woman was admitted for the first episode of suspiciousness, irrelevant speech and violent behaviour for one month. There was no history of any organic illness in the patient.  Her physical examination was normal and her psychiatric examination revealed a fearful incongruent mood, formal thought disturbances and auditory hallucinations.  She was diagnosed as acute schizophrenic episode and put on injection haloperidol 5 mg i.m. every 8 hours. The dose was increased to 5 mg every 6 hours after two days. Three days later the patient became confused and febrile. Haloperidol was discontinued and the patient was closely monitored.  During the next two days she was noted to have alteration in consciousness, marked rigidity and diaphoresis. Her vital signs showed significant fluctuations -temperature: 100-1030F, pulse rate: 80-120 beats/minute, blood pressure: 120/70-150/110 mm of Hg and respiratory rate: 43/minute. Her investigations revealed WBC count of 24,100/min and serum CPK levels of 1950 IU/L. Her X-ray skull and chest, CSF study, EEG, ECG, liver and renal function tests, serum electrolytes and blood gases were within normal limits.  She was diagnosed as a case of NMS and started orally on bromocriptine 2.5 mg t. d. s. and lorazeparn 2 mg t. d. s. along with nutritional support and serial monitoring of serum CPK and urine myoglobin.  Over the next seven days the patient became alert and afebrile and her vital signs stabilised. The serum CPK levels and WBC count fell concomitant with clinical recovery.  The recovery was complete at the end of two weeks without any recurrence of psychotic symptoms.  Bromocriptine was tapered off and the patient was discharged on lorazepam 2 mg b. d. after a month's stay in the hospital. During a follow-up period of six months the patient maintained her recovery even after discontinuing lorazepam thus obviating the introduction of neuroleptics. Substance abuse  Alcohol  Opioid  Sedative-hypnotic  Solvent abuse Alcohol  Dependence; affecting multiple neurotransmitter systems;  Down regulation of neuro-inhibitory GABA => GABA excess in withdrawal  Inhibits excitatory NMDA glutamate receptor therefore withdrawal removes inhibition  Get increased dopaminergic and noradrenergic neurotransmission Alcohol  Autonomic excitation  Tremor, anxiety/agitation, sweating, tachycardia, hypertension, NV, hyperthermia  Neuro-excitation  Hyperreflexia, nightmares, hallucinations, seizures generalised tonic- clonic  Delirium tremens  Hallucinations, confusion, disorientation,  Respiratory and cardiovascular collapse and death  Co-morbidities  Wernicke’s encephalopathy  Dehydration  Electrolyte abnormalities  GI bleeding, pancreatitis, alcoholic liver disease, hepatic encephalopathy  Alcoholic ketoacidosis  Diazepam regular 5-20mg orally  Thiamine 100mg IV or orally daily  Hydration  Electrolyte balance  Nutrition Toxic alcohol poisoning Ethylene glycol (colorless) – slightly sweet Antifreeze – coolants and solvents Lethal dose approx 100mL Methanol (colorless) – Lethal 60mL Blind 20 – 30mL Metabolites are toxic rapid methanol => formaldehyde => formalin » Ethanol glycol Toxic alcohol poisoning 1940 – ethanol infusion; aim 100 to 150mg/dL Serum [ ] must be monitored frequently 1-2hrly until steady Dosing is challenging 66mg/kg/hr ADRs hypoglycaemia 4MP – 4 methylpyrazole (Antizol®) Antidote Tx for methanol or ethylene glycol toxicity Potent inhibitor of alcohol dehydrogenase – predictable p’kinetics – no TDM needed Methanol metabolized to formaldehyde => then oxidation via formaldehyde dehydrogenase to formic acid => metabolic acidosis and visual disturbances. Ease of administration - load 15mg/kg => 10mg/kg bd Well tolerated with no CNS depression $$$ cost about $20,000 per patient Opioid  Naloxone (competitive antagonist at mu, kappa and delta receptors) => reverses opioid effects  Tx life-threatening Respiratory depression  CNS depression  Empiric Tx for coma thought to be secondary to opioids  Avoid in opioid-dependent individual unless significant respiratory depression (RR withdrawal Sx (so may not want to completely reverse) Opioid withdrawal  Intense craving, dysphoria, autonomic hyperactivity, GI disturbance  Sx; anxiety, restlessness, dysphoria  Insomnia, yawning, lacrimation,  Salivation, rhinorrhoea,  Anorexia, NV, intense craving  Abdominal cramps & diarrhoea  Mydriasis  Piloerection (cold turkey)  Diaphoresis (Xs sweating)  Flushing  Myalgia and arthralgia  Hypertension and tachycardia Opioid  Opioid replacement therapy  (methadone, buprenorphine)  Abstinence programs  Detoxification with antagonist  (naltrexone)  Symptomatic therapy  Correct dehydration  Tx nausea (metoclopramide, prochlorperazine)  Abdominal cramps (hysocine)  Myalgia (paracetamol)  Anxiety, dysphoria, insomnia (diazepam)  Clonidine – alpha2 agonist (centrally acting) manage physical and psychological Sx. Caution hypotension esp if dehydrated or with bradycardia Solvent abuse  Glues (toluene), household cleaners, thinners, paints, cosmetics, pesticides  Aliphatic, cyclic, aromatic and halogenated hydrocarbons, ethers, esters, glycols, ketones, aldehydes and amines  Volatile hydrocarbons (fuels) => alter mental status  Peak effects seen in 15 to 30mins  High lipid solubility => CNS (depressants)  Toxicity correlates to volatility (aspiration)  Myelin toxicity – neuropsychiatric consequence from long-term abuse and myocardial sensitisation to catecholamines ? Arrhythmias and sudden death  “Huffing” – poured in bag or cloth and held to face  “bagging” – poured into bag and held over head  Sniffing or snorting ; inhaled directly from container Solvent abuse - Clinical features  Solvent neurotoxicity; CNS (altered cognition) bit like drunk  Impaired psychomotor function – altered reaction time, dexterity, co-ordination, balance  Disinhibited, lethargic, ataxic, slurred speech  Severe => confusion, altered consciousness, seizures, coma  Irritation of eyes, nose, throat  Sudden death (butane, propane); asphyxiation, dysrhythmias (sensitised to catecholamines) Solvent abuse  Chronic abuse (toluene)  Persistent neurotoxicity; structural and functional brain abnormalities  White matter (lipid rich myelinated structures) – lipid- dependent distribution  Impaired cognition; poor memory (tests)  Not known if long-term abstinence gives significant improvement in neuropsychological function  Metabolic acidosis => hyperchloraemia, hypokalaemia (can be profound) - from distal renal tubular acidosis  Management; resuscitative supportive; benzodiazepines Mx behaviour, avoid secondary complications of hypoxia, hypoglycaemia, seizures  Correct electrolytes (if long-term abuse) Cyanide Sources – industrial accidents Fire/smoke inhalation Deliberate suicidal ingestion Sodium nitroprusside (plants, cyanogenic glycosides) Cyanide gas inhalation – Rapid onset (seconds – minutes) rapidly fatal Cn Salt – Slow onset Cyanide  Binds cytochrome oxidase – inhibits aerobic metabolism  => Lactic acidosis  => left shift oxyHb  => CNS, cardiac Respiratory depression Cyanide  Decontamination  Resuscitation  Intubate  Oxygenation  Supportive  Correct metabolic acidosis with 8.4% sodium Bicarbonate Cyanide antidotes Sodium thiosulphate metabolised to thiosulphate Slow conversion of Cn and thiocyanate Well tolerated/ SE N&V headache Can give repeat doses Meth-haemaglobulin => forms less toxic Has increased affinity for cyanide Cobalt – Dicobalt edetate – severe ADRs bronchospasm, rashes, periorbital/ laryngeal oedema, convulsions Severe poisoning => coma Cyanide antidotes Vitamin B12 70mg/kg = 7L/min 2.5 – 5g preparation Binds to form nontoxic cyanocobalamin 72% survival rate in smoke victims Ref; boron Amm Emerg Med 2007 ADRs – hypertension, red discoloration, skin, urine Cyano kit Given 10mL saline – repeat Dose may be repeated up to 10g ?? Cost effective Tx in the field Other toxicities  CCB => severe toxicity in overdose  Resistant to atropine  calcium CCB toxicity  Hyperinsulinaemia/ Euglycaemic Therapy (HIET)  Rationale – myocardium relies on FFA for energy but during shock, glucose is an important substrate  CCB decreases pancreatic insulin release and decreases myocardial glucose????? CCB toxicity Regimen; Commence Tx by administering; glucose 25 g (50mL D50W) IV bolus then short-acting insulin (actrapid) 1 unit/kg IV bolus; then continue therapy with glucose 25 g/hr IV and insulin 0.5 to 1 units/kg/hr IV Maintain euglycaemia with 10% dextrose HIET CCA poisonous – animal studies Use early on High dose insulin dextrose is well tolerated – no significant hypos/ hypokalaemia Ref; Greene et al Critical Care 2006. Lipid emulsion therapy Lipid emulsion therapy IV 20% formulation 1.2% eggyoke phos Lipid sink  CCB – lipophilic  ? Lipid sink maybe option  ? In refractory cases LA partition into lipid globules A newly created intravascular compartment Biochemical mechanism http://lipidrescue.squarespace.com/post-your-cases/post/511419 http://journals.lww.com/anesthesiology/Fulltext/2012/07000/Li pid_Emulsion_Infusion__Resuscitation_for_Local.31.aspx Lipid emulsion therapy Evidence; bupivacaine – cardiac toxicity Accident given IV => cardiac arrest Now an accepted anaesthetic practice to have lipid emulsion available on trolleys ED other setting – evidence questionable? No RCT – not good evidence in non-LA setting ADRs – increased risk fungal infection Allergies/ anaphylaxis Lipid emulsion therapy  Severe propranolol and ethanol overdose with wide complex tachycardia treated with intravenous lipid emulsion: A case report.  Jovic-Stosic J, Gligic B, Putic V, Brajkovic G, Spasic R.  Source  Clinic for Emergency and Clinical Toxicology, Military Medical Academy , Belgrade , Serbia.  Abstract  Background. Propranolol is a highly lipid-soluble beta-blocker. We describe a case of severe propranolol overdose, with atypical dysrhythmia - wide complex tachycardia - which was successfully treated with lipid emulsion. Case report. A 31-year-old woman ingested approximately 3.6 g of propranolol along with ethanol. Clinical manifestations of poisoning included coma, seizures, respiratory failure, hypoglycaemia, circulatory shock, and dysrhythmias. An ECG revealed nonspecific intraventricular conduction delay, followed by wide complex supraventricular tachycardia. Toxicological analysis of blood showed ethanol 2.42 g/L and propranolol 4.21 mg/L. The patient responded poorly to conventional therapy, so intravenous lipid emulsion was used. Apart from IV dopamine, the only treatment after the onset of wide complex tachycardia was 20% Intralipid. Transient improvement was noticed after the initial dose of 500 mL; during the infusion of further Intralipid, blood pressure returned to normal and sinus rhythm was re-established. Conclusion.  We believe that lipid emulsion had a beneficial effect in the treatment of propranolol toxicity Specific toxins – therapies  Resources; Toxicology Handbooks Bites and Stings  Bees and wasps  Multiple (10 in adult or 5 in child)  Anaphylaxis; severe allergic reaction 20 mins of exposure  Sx; difficult or noisy breathing, tongue swelling, swelling or tightness in throat, difficult talking, hoarse, wheeze or persistent cough, fainting, collapse  Sting removed ASAP  Pain = ice/cold pack (swelling can persist for several days)  Antihistamine if persistent or severe swelling or itch  Adrenalin auto-injector (EpiPen, Anapen). Admin IM into mid- lateral thigh, Different admin techniques.  https://www.epipen.ca/en/about-epipen/how-to-use  http://www.youtube.com/watch?v=ZR5c5VP2rOs  Avoid movement  Observe breathing whilst awaiting ambulance  Epidemic of misuse  http://www.medscape.com/viewarticle/838198 Caterpillars & insects  Some caterpillars cause painful, itchy and inflamed skin reactions  They shed hairs – embedded in skin (can break off)  Remove hairs; tweezers or adhesive tape  Cold pack  Antihistamine or cortisone cream if persistent Sx  Ants, centipedes, mosquitoes, earwigs  Wash area  Cold pack  Antihistamine if persistent or severe swelling or itching Jellyfish  Box jellyfish stings – lethal venom  Severe localised pain  Severe; Collapse / resp failure or cardiac arrest (5-30min)  Dermatonecrotic components => patches of full thickness skin necrosis; permanent scarring  CPR  Tentacles removed carefully  Inactivate nematocysts (sting cells containing venom) with 3-5% acetic acid (vinegar)  Ice packs  Pressure immobilisation  Bluebottles  Painful; rarely life-threatening  Tentacle (10m); localised skin lesions (“string of beads”) discrete red welts;  Systemic Sx uncommon (?headache, N&V, abdo pain)  Remove tentacles; Vinegar (NOT pressure immobilisation)  Immerse area in hot water  Cold packs or topical anaesthetics  Irukandji jellyfish (2.5cm)  Sting moderately painful but can have syndrome => generalised pain (back, abdo, limb or joint) and sweating agitation and paraesthesia or hypertension & tachycardia  Analgesia needed Leeches & Scorpions  Leeches  Caution if infected or allergic reaction develops  Removal – salt, vinegar  Do not attempt to pull them off (skin tear, leeche’s jaw partly attached => infection)  Wash site  Cold pack +/- pressure if bleeding  Scorpions  In Australia not dangerous  Pain and redness/swelling  Risk of infection is main concern  Ticks  Attach to warm-blooded animals as brush against foliage  Feed on host; remain attached for 4 days  Cause range of illnesses; some even paralysis  Can transmit infectious diseases and infect bite site  Some have allergic reaction  Ticks; Removal of whole tick important! (attempts can result in head or mouthpiece embedded)  More handled = more toxin released  pry off (tweezers or forceps on either side of mouth parts). Do not hold by body, Straight steady firm movement no rotation  Aerosol insect repellent (pyrethrin) or lyclear (permethrin). Hydrocarbons and pyrethrin act as narcotic and toxicant => prevents tick injecting saliva (repeat 1 min later, leave 24hrs to drop off or physical remove)  Irritation; alcohol, flame => agitated tick more toxin released  https://www1.health.gov.au/internet/main/publishing.nsf/Content/EA2FA455F96F36F1C A257C3700786BCB/$File/Preventing-treating-tick-bites.pdf  https://www1.health.gov.au/internet/main/publishing.nsf/Content/ohp-tick-bite- prevention.htm  Seek assistance – paralysis, numbness, swelling rash and area does not clear, Sx of infection  Double vision, weakness, unsteady  Difficult breathing or swallowing ? allergic  After removal wash & antiseptic, bandage Some spiders  White tail  Mouse spider – ground dwelling  Funnel web  Red-back First aid  Red back (latrodectus hasselti) and other spiders (except funnel web or mouse)  Reassure patient – life is not at major risk  Medical treatment is NOT always required many only cause local reaction.  Localised pain, redness and swelling and heat  Was bite area with soap and water, apply cold pack and analgesia  Can be incredibly painful; systemic effects, sweating shivering, fever, N&V, headache and even paralysis  If untreated Sx => worsen over 24hrs and wks – mths to resolve  Apply ice pack to bite area  Do NOT use a pressure immobilisation bandage (worsens pain)  Antivenom if redback & if systemic Sx Antivenom  Best treatment – usually only needed if there is significant systemic envenoming.  Signs  Pain spreading from bite and not relieved  Painful swollen glands in affected limb (armpits or groin)  Shivering  Tremors  Stomach upset – NV, cramps  HR increased  Ptosis (drooping of eyelid), dysarthria (difficult talking), weakness, persistent bleeding from bite site (eg coagulopathy), dark urine (to myoglobin – myolysis), haematuria  Profuse sweating (red back),  Salivation, lacrimation, piloerection with muscle twitching (funnel web)  Any bite – could be source of secondary infection  watch for cellulitis,  Check tetanus immunisation status Funnel-web (atrax robustus)  Coastal and mountain regions of eastern and southern Australia  Extremely toxic  Sheltered burrows in ground or stumps, tree trunks & ferns  Opaque white silk lined burrow  Males nocturnal wander  Clinical features; tingling around lips, tongue twitching, profuse salivation, lacrimation, sweating, piloerection muscle twitch/spasm, hypertension, tachycardia, resp depression (lethal)  Do not wash or apply arterial tourniquet (use pressure immobilisation to restrict lymphatic flow); start above fingers or toes and move upward as far as possible; splint  Funnel-web spider antivenom is systemic Sx  Victorian Funnel-Web (hadronyche modesta)  Venom only causes general symptoms as headache and nausea Necrotising Arachnidism  Syndrome of blistering and ulceration of the skin following spider bite  White-tailed spider ?, black house spider and fiddle-back spider  Interaction between spider venom and victim’s immune system  ? Sole cause  Sx; spider bite (few definite Hx)  Develops over 2-3 days  Considerable localised pain  Bite site; upper or lower limb => red, blistering superficial ulceration (+/- satellite lesions close to site)  Generalised illness rare – could have N&V after bite  Tx; conservative; Sx resolve 2-3 wks (recurrences known)  Swab; micro testing => antibiotics (which one??)  Debride dead tissue  ? Skin graft after necrotising process ceased  ? Hyperbaric oxygen in some cases benefit  Steroids or cytotoxic drugs (dapsone) ? Efficacy (no RCT) Necrotising Arachnidism  Treatment of Necrotising Arachnidism  no definitive treatment for necrotising arachnidism.  Tried antibiotics, corticosteroids, hyperbaric oxygen therapy, surgical debridement +/- skin grafting (early or late) and (for loxoscelism) cytotoxics such as colchicine and cyclophosphamide.  Antibiotics that have been used include dapsone (particularly in the United States), erythromycin and doxycycline, as well as penicillin , flucloxacillin and cephalosporins. None of the above treatments has been systematically trialled.  Alternative treatments such as L-cysteine and aloe vera have also been used. There are anecdotal reports of success in healing ulcers, including ulcers thought to be related to spider bites, with hyperbaric oxygen therapy, but no organised trials have been conducted. White tail spider bite  There is no specific first aid recommended for bites by white- tailed spiders (lampona cylindrata).  Ice packs can be used to try and relieve acute local pain.  Medical advice should be sought if local changes are causing concern.  No antivenom is available for white-tailed spider bites, as most of these bites only cause the mild local effects seen with most mildly venomous spider bites.  Medical Treatment  Medical treatment is usually not required for white-tailed spider bites. The incidence of skin ulceration after bites by these spiders is unknown, but is likely to be extremely low. Local changes (typically redness, itch and pain) usually resolve within a few days.  The bite site may be painful; a red mark with associated itchiness, pain or lump may persist for up to 12 days. An antihistamine may help control any pain, swelling or itch.  In cases of ongoing ulceration or necrosis, other causes, such as infection, circulatory problems etc., should be excluded. Other spider bites  For other spider bites, the treatment is aimed at minimising pain and the risk of infection.  Wash the bitten area with soap and water  Apply a cold pack if required to relieve pain and swelling  Medical attention is only required if the bite has not cleared up in 2-3 days or if there are signs of infection or tissue damage  For most spider bites, this is all the treatment that will be required. Some spider bites may result in mild symptoms, including headache and nausea, but usually do not require any specific treatment. Envenomations  First aid for bites and stings  Do no harm  Practical and achievable  Supported by both clinical and scientific evidence  Pressure Immobilisation Method  Developed Dr Struan Sutherland at CSL (1978 Lancet)  Lymphatic system plays key role in transport of toxins (periphery to circulation);  Lymphatic vessels at bite site compressed – bandaging, extending to as much of the rest of bitten limb as possible (improvise, pantyhose etc); could go over top of clothing rather than remove jeans.  Slow (stop) proximal movement of limb (splint), stop muscle pump  Doesn’t threaten tissue oxygenation (up to hours)  http://www.avru.org/firstaid/firstaid_pibmovie.html  Ideal for all Australian snake species, funnel web spiders, mouse spiders and bites from blue ringed octopus and cone shells.  NOT red back and other spiders, scorpions, centipedes or stings from venomous fish First aid  Keep patient still and reassure them  Maintain vital functions (ABC, Airway, breathing, cardiac function)  Immediately apply pressure and immobilise  Bring transport to them  Medical help earliest possibility  If killed snake (bring with them)  Do not wash wound  Do not use tourniquet, cut or suck  Do not give alcohol to patient  No food only clear fluids Antivenom  Snake venom detection kit  http://www.toxinology.com/generic_static_files/cslavh_svdk.html  Antivenoms - purified antibodies against venoms or venom components.  Antibodies are made by other animals.  Horse, (Sheep, rabbits and dogs are also used in Australia).  Innoculated with a non-lethal dose of venom, => their immune systems make antibodies.  Extracted and purified in the making of antivenom.  Venom is obtained from different animals in different ways. Snakes and funnel web spiders are milked for their venom. Australian Venom Research Unit  http://www.avru.org/ Unknown snake – which antivenom  Victoria:  Tiger and Brown  ???  Tasmania;  Tiger  NSW, Qld, WA, SA, NT, ACT, PNG  Polyvalent Snake antivenoms – which one to use?  Victorian venomous snakes;  Tiger,  Tiger used for tiger , copperheads, rough scaled snake, broad-headed snake, pale-headed snake, Stephen’s banded snake and red-bellied black snake (same genus) also many sea snake bites  Tiger – common cause of snakebites 2nd most common cause of snakebite deaths in Australia  Coloration may vary (also with maturity) most show banding  Black snake antivenom (species used is mulga snake (king brown), Butler’s mulga snake, Collett’s snake and Papuan black snake);  use tiger antivenene for red bellied black or blue bellied black (spotted black snake)  Mulga snake or king brown – large 2.5m (1.5 to 3m, more venom than any other Australian snake but less toxic than others)  Brown (common or eastern brown)  Think about possibility of other snakes???  polyvalent Mulga snake (king brown)  More venom than any other snake but less toxic than some  Black snake antivenom Black snake  Spotted (or blue bellied) black snake  Drier areas (rocky)  Red bellied black snake  Like water courses – rivers streams Copperhead  Copperhead Brown snake  Brown snake (eastern) Tiger snake  Black tiger snake  Mainland tiger snake  Near water courses or swamps (irrigation)  Neurotoxins, myolysins, procoagulants, 2’ kidney damage Taipan  Taipan  Inland tiapan (fierce snake)  Most toxic venom (of any snake) in world  Coastal tiapan. Death Adder  Death Adder antivenom  Northern, Common, Desert  Not normally retreat when approached Administration  ? Premedication with adrenaline to decrease allergic response (Sri Lanka study43% cf 11% placebo -Premawardhena et al., BMJ 318: 1041-1043, 17 April 1999)  Dose 0.25 to 0.3mg sc (not IV as hypertension has potential for bleeding in coagulopathic pt, not IM => haematoma)  ? Antihistamine (promethazine)  Dose; not adjusted for pt size (generally 1 vial)  May be insufficient – may need larger initial dose if evidence of severe envenomation (rapidly progressive, multiple bites, snake size)  IV dose diluted in 100mL NS or D5W or Hartmans solution  Given slowly (observe for allergy signs), administer adrenaline, plasma volume expanders or B blockers as clinical signs dictate. Antivenom serum sickness  Deposition of immune complexes,  Sx fever, rash, arthralgia and flu like illness.  Estimated: 3 out of 70 cases  Discuss possibility of serum sickness & S&S with pt so it can be recognised.  Steroids - if a large volume of antivenom, such as polyvalent snake antivenom or multiple ampoules of monovalent snake antivenom, is given or past Hx.  Both the incidence and severity of delayed serum sickness is reduced prednisolone, 50 mg for 5/7. Snake envenomation  Rhabdomyolysis  Break down of muscle; not in brown snake but not uncommon in tiger or taipan  Myolysis => renal failure (some degree)  Oliguria Tx mannitol, frusemide, adequate hydration maintained (avoid overload)  Renal toxicity (managed by antivenom)  Neurotoxicity;  Some snake venoms initially involve the cranial nerves => descending paralysis over time.  Antivenom to resolve neurotoxicity. (In other cases - treat the condition symptomatically, for instance, mechanical ventilation)  Funnelweb spider envenomations are characterised by a condition labelled "sympathetic overdrive", which may include localised sweating, piloerection and fasciculation, excessive salivation and lachrymation, tachycardia and hypertension.  Paralysis tick venom causes an ascending paralysis, with the lower limbs involved before the trunk.  Blue-ringed octopus venom typically acts initially on the VIIth cranial nerve.  Coagulopathy: procoagulant or anticoagulant  Procoagulant; brown, tiger, taipan; they use up fibrinogen supplies => blood unable to clot  Need antivenom to neutralise porcoagulant - FFP won’t work as it will just be a substrate for action of procoagulant Blue-ringed octopus  Australian coastal waters; not aggressive but sting if handled  Highly toxic venom => muscle paralysis  No sting at first but tingling in tongue or lips followed by difficulty speaking & visual disturbance, collapse within 10 mins  CPR  First aid; pressure and immobilisation (similar to snake bite) Stinging fish  Many with venomous spines  Risk infection  Booster tetanus  Severe pain, can => shock  Stonefish;  highly toxic venom (instant pain, swelling, tenderness, blue skin discoloration around site); dizziness, nausea, hypotension collapse;  Stonefish antivenom  Immerse area in hot water 1hr (heat breaks down venom)