Toxicology Flashcards

Question

Amanita Phalloides - signs, symptoms, prognosis, management

Answer 1

High source of cyclopeptides 1 mushroom cap can cause fulminant liver failure and death while other mushrooms need more then 10 Typically, asymptomatic for 6-18hrs. GI symptoms: Abdo pain, N/V, watery diarrhoea Dehydration/AKI/electrolyte derangement/metabolic acidosis from above Mildly elevated LFTs in first 24hrs Over next 1-7 days: progressive liver failure, coagulopathy, multiorgan failure (mortality 10-30%) >7 days: complete resolution over weeks to months OR chronic hepatitis POOR PROGNOSTIC FACTORS: - Worse prognosis with earlier onset symptoms - lactate >5 or progressive rise in context of hepatitis - Rising ALT (may take up to 24hrs) - AKI with acute liver injury - Rising INR 3 days post ingestion or INR>6 on day 4 Onset of diarrhea 6-10hrs or INR>6 from day 4 indicate possible need for liver transplant MANAGEMENT Amatoxin has significant enterohepatic recycling, benefits from charcoal and MDAC even if presenting after 2days from ingestion Antidote silibinin 5mg/kg over 1hr then 20mg/kg/24hrs for 4 days or benpen 3g (60mg/kg) q4hrly or rifampacin + NAC 200mg/kg over 4hrs and 100mg/kg over 16hrs fro hepatoprotection

Answer 2

Home brew, paints, varnishes, rocket and race car fuel, solvents/cleaners, embalming fluid, windshield wiper fluid Metabolised to formaldehyde and then to formic acid (neurotoxic to retina and optic nerves) by ALDH Ingestion > 0.1ml/kg signficiant toxicity in children 30g (30ml of 100%) will cause coma and blindness Effects at 12-24 hours CNS depression - Intoxicated, coma, seizure later due to acidosis Retinal toxicity - blurred vision, scotomata, papilloedema, loss of light reflex, blindness Cardio - hypotension secondary to acidosis HAGMA (low pH best predictor of severe toxicity) High osmolar gap (Serum osmo - 2xNa+Ur+Glucose+1.2xETOH>10) NORMAL CALCIUM (low in ethylene glycol) Normal renal function and no urinary calcium oxalate crystals (found in ethylene glycol Brain imaging (CT/MRI): bilateral putamen necrosis, basal ganglia haemorrhages and necrosis of the caudate nucleus with atrophy of the optic chiasma and lesions in the occipital cortex and subcortical white matter.

Answer 3

Antifreeze, radiator coolant, brake fluid, degreasing agents, foam stabilizers, metal cleaners Metabolized to glycolaldehyde and then via ALDH glycolic acid. Then oxalic and glycoxylic acid. Oxalic acid combines with serum calcium and deposits in renal tubules leagding to ARF as well hypocalcemia (QT prolongation and ventricular arrhythmia) Ingestion > 1ml/kg fatal CNS depression - intoxicatClincial - Coma and seizures (secondary to acidosis) GI - N/V and abdo pain Cardio - hypotension secondary to acidosis (12-24hrs) ARF, oligouria, flank pain (24-72hrs) HAGMA (high anion gap best predictor of severe toxicity) High osmolar gap (Serum osmo - 2xNa+Ur+Glucose+1.2xETOH>10) HypoCa Calcium oxalate crystals in urine Lactate gap (glycolate interfering with POC lactate and artificially raising)

Answer 4

IVF and correct hyperK No role for charcoal (too rapidly aborbed) NaHCO3 for severe acidosis Ethanol and fomepizole inhibit ADH and prevent toxic metabolites Fomepizole has easier dosing regime and better side effect profile but costs more Ethanol worsens sedation and agitation leading to higher rates of intubation and ICU admissions but more readily available Should be commenced in any pt - confirmed ingested toxic dose of methanol or ethylene glycol toxic dose - unexplained metabolic acidosis - High osmolar gap ETHANOL - Needs ETOH level prior - IV or NG - Aim ETOH level 22-44mmol/L and continue until methanol/ethylene glycol <20mg/dL (6.24 mmol/L for methanol, 3.23 mmol/L for ethylene glycol). - Ethanol 10% 6ml/kg loading dose (if not already intoxicated) Then Ethanol 10% 1-2ml/kg/hr (100ml/hr) thereafter. - If dialysis then double 0.6g/kg followed by 0.1g/kg/hr (10g/hr) if using spirits Alcohol volume= (required ethanol g)/(alcohol concentration %) x 100 FOMEPIZOLE - 15mg/kg IV loading then 10mg/kg q12hrly - Give q4hrly if dialysis continue until methanol/ethylene glycol <20mg/dL (6.24 mmol/L for methanol, 3.23 mmol/L for ethylene glycol) DIALYSIS (intermittent hemodialysis preferred) - Confirmed toxic dose ingestion - Metabolic acidosis - AKI - Serum level > 50 mg/dL (15.6 mmol//L for methanol, 8.07 mmol/L for ethylene glycol) EXTRA Folate for methanol - calcium folinate/folic acid 50mg IV QID Vit B in Ethylene Glyco - Pyridoxine (B6) 50mg IV QID or thiamine (B1) 100mg IV QID

Answer 5

Surgical spirits - disinfectant, solvents, window cleaners 4ml/kg can cause coma Supportive as per ETOH intoxication Only toxic alcohol that causes ketosis without acidosis

Answer 6

RISK FOR TOXICITY - Propranolol (coma, seizures, Na channel blocker/QRS prolongation) and sotalol (cardiac K channel blocker/QT prolongation) most toxic - Children 1 dose can be toxic - >1g propanolol toxic - Modified release (metoprolol only) - Older Age - Medical conditions (heart disease, cirrhosis) - Co-ingestion with other cardiovascular drugs (CCB, diogxin, ACE etc) CLINICAL - within 1-2 hrs Cardiovascular - Hypotension due to myocardial depression and bradycardia - Sinus brady most common arrhythmia BUT PR prolongation earliest sign of toxicity - 1st/2nd/3rd HB, junctional brady, ventricular brady and asystole in severe - QRS widening in propranolol - QT prolongation in sotalol CNS - Seizures, delirium and coma in lipophilic betablockers (propanolol) Resp - Bronchospasm and APO Metabolic - Hypo/hyperglycemia (interferes in gluconeogenesis and glycolysis but uncommon in adults) - HyperK

Answer 7

Charcoal as soon as possible for severe overdose Otherwise 2hrs in IR adn 4hrs in MR Early intubation in refractory cardiovascular instability or decreased LOC with pretreatment of Atropine 600microg to prevent vagal mediated bradycardia during laryngoscopy Hypotension with IVF first line - TTE can be helpful in determining cardiogenic shock vs vasodilatory shock Bradycardia with hypotension - 1st line: Atropine 600microg q15min - 2nd line: Adrenalin 10-20microg (0.1microg/kg) q3min followed by infusion 0.1microg/kg/min - Isoprenaline 20microg (0.1microg/kg) q3min followed by infusion can also be used for bradycardia but may worsen hypotension IN VASOPLEGIC SHOCK Norad 0.05-0.5microg/kg/hr second line vasopressor IN CARDIOGENIC REFRACTORY SHOCK High dose insulin euglycemic therapy 1unit/kg actrapid with 50ml 50%glucose (2.5ml/kg of 10%) Followed by 1unit/kg/hr (MAX 10unit/kg/hr) with 50% glucose 20ml/hr or 10% 100ml/hr (10g/hr) - 2.5ml/kg/hr of 10% in children Aim BSL 4-5 and check every 30min K replacement and aim K 4-4.5. Check every 2-4hrs Intralipid controversial but can be considered if still refractory - 20% 1.5ml/kg bolus q5min for 2-3 doses if in asystole otherwise infusion 0.25ml/kg/min for 30-60minutes Hemodialysis only effective in sotalol and atenolol VA ECMO if available but not after intralipids as clots circuit. Evidence in cardiogenic shock but no vasoplegic shock Sodium Bicab 1-2mmol/kg q3minutely (6mmol/kg) if refractory hypotension or cardiac arrest as acidosis decreases effectiveness of inotropes OR in Na channel blockade QT prolongation management Seizures - Glucose first line (intracellularly deplete despite normal BSL) - benzos second line Glucagon no longer recommended as short half life and dose required quickly exhausts hospital supply

Answer 8

Most concerning are diltiazem and verapamil 2-3x normal dose (10 tabs, > 15ml/kg) toxic Can be immediate release - first 2-4 hours or delayed 4-16 up to 24 hours Bradycardia, 1-3 HB, hypotension, ACS, CVA, ischaemic gut, hyperglycaemia, lactic acidosis, shock, seizures

Answer 9

- Charcoal (up to 4 hours slow release) - Expect bradycardia and hypotension - IVF, pacing (rather than drugs), adrenaline, ECMO/bypass - High dose insulin glucose therapy Calcium glutinate 10-20mls 10% IV repeated with monitoring of Ca levels

Answer 10

Drugs, toad toxin, oleanders 10 x daily dose toxic, lethal > 10mg (4mg children) GI early - n+v, abdo pain CVS later 8-12 hours - bradycardia, slow AF, HB, increased automaticity, bigeminy, SVT, VT, hypotension CNS - leathery, confusion, seizure Dig levels at 4 hours < 1 therapeutic 2-3.2 potentially toxic > 3.2 toxic Often hyperkalaemia - poor sign if > 5.5 early ECG - reverse tick ST depression lateral leads, shortened QTc

Answer 11

- Cardiac arrest - 20 amps digibind - Life threatening arrhythmia, refractory hypotension, refractory hyperK, significantly symptomatic then give digibind - dose digibind vials = ingested dose in mgx0.8x2 - if unknown start 2-5 - atropine 0.6mg, pacing - arrhythmia - magnesium, lignocaine - hyperK - insulin/dextrose, bicarb NOT calcium

Answer 12

Usually intercurrent illness (sepsis, NSAIDs etc) so renal impairment and delayed elimination GI upset, bradycardia, syncope Lower levels than acute cause problems - bradycardia alone with level 2.5 50% toxic - GI alone with level 2.5 60% toxic - bradycardia and GI level 2.5 90% - automaticity + others level 2.5 100% - cardiac arrest 5 amps - digibind 1-2 amps

Answer 13

Aspirin Oil of Wintergreen (can be 98% methyl salicylate and 1 tsp=7000mg) Topical gels for teething and skin peeling (choline salicylate and salicylic acid) Alternative medicines (Willow bark) Dose dependent toxicity and other salicylates should be converted to aspirin equivalents Methyl salicylate conversion factor 1.4 (4mls of Wintergreen lethal in small child) <150mg/kg mild toxicity (6hrs monitoring) 150-300mg/kg Mild to moderate but can evolve to severe (primary respiratory acidosis and salicylism) and so need admission and management 300-500mg/kg Severe (confusion, coma, seizures, mixed resp acidosis and metabolic acidosis) >500mg/kg lethal Chronic salicylate toxicity occurs with regular doses >100mg/kg/day More likely in older pts and chronic liver or kidney disease

Answer 14

First respiratory alkalosis though direct stimulation of medulla respiratory centers causing hyperopnoea Second high anion gap metabolic acidosis through uncoupling of oxidative phosphorylation causing inhibition of electron transport chain in mitochondria causing lactic acidosis as well as the mild effects of the salicylic acid itself Third is respiratory acidosis as preterminal event secondary to respiratory exhaustion, ARDS or severe CNS dysfunction

Answer 15

6-12hrs to manifest but deterioration is rapid Early GI distress -N/V/epigastric pain Tinnitus or altered hearing Dizziness Hyperventilation and respiratory alkalosis Antiplatetlet effects Late Altered mental status/Coma Seizures Fevers Hypoglycemia/hyperglycemia with intracellular hypoglycemia Hypokalemia ARDS AKI Chronic intoxication is nonspecific cause of delirium, confusion, fever with unexplained metabolic acidosis Cerebral oedema and ARDS more common in acute

Answer 16

Activated charcoal within 6hrs of ingestion of >150mg/kg and second dose 4hrs after if serum levels still rising Correct hypoK 10-20mmol/hr, aim K 3.5-4 BEFORE Urinary Alkalization - Check 2hrly on gas and formal EUC 2-4hrly Urinary alkalinization to prevent penetration of salicylate into tissues and enhance urinary excretion by preventing tubular reabsorption Sodium bicarb 1mmol/kg bolus followed by 25mmol/hr infusion (Add 15ml to 850ml of 5% glucose and run at 166ml/hr) - Serum pH 2hrly aim 7.45-7.5 - Urine pH 2hrly aim pH7.5-8.0 and UO 1-2ml/kg/hr Glucose 50ml of 50% or 2.5ml/kg of 10% with: - hypoglycemia - Altered LOC (likely cerebral hypoglycemia) - Seizures (glucose first line then benzos) - Check 2hrly and aim BSL 4-8 Avoid intubation but if needed pretreat with sodium bicarb, Ventilate through apneic period and set high MV (high TV and RR) Hypotension often responds to fluids Hemodialysis last line. Consider with: - Altered LOC - ARDS - ARF - Worsening acidosis (pH<7.2) or electrolyte disturbance - Serum salicylate level >7.2 or rising despite medical management (check 4-6hrs to determine peak concentration and effectiveness of elimination/ongoing absorption)

Answer 17

Altered LOC ARDS ARF Worsening acidosis (pH<7.2) or electrolyte disturbance Serum salicylate level >7.2 or rising despite medical management (check 4-6hrs to determine peak concentration and effectiveness of elimination/ongoing absorption) Rarely needed as most pts respond to medical therapy Intermittent hemodialysis preferred

Answer 18

At least 6hrs AND - Serum salicylate <2.2 and falling - Acid base disturbances have resolved - Pt asymptomatic

Answer 19

Triad - miosis, resp depression, CNS depression Aspiration, hypothermia, hypoxic brain injury, rhabdo Pethidine - serotonin syndrome Dextropropoxyphene - seizures Naloxone 100-400mcg bolus 2 x boluses needed then start infusion at 2/3 initial dose required/hr and titrate

Answer 20

20-60mg/kg moderate, 60-90mg/kg requires decontamination, > 130 potentially fatal Vomiting within 80 mins in 90%, direct GI irritation Hypotension, acidosis, myocardial damage, inhibition coagulation, confusion, coma 0-3 hrs GI symptoms 12-48 hrs systemic symptoms 2 weeks strictures Iron level at 4 hours Hyperglycaemia, acute tubular necrosis, hepatoxicity, prolonged INR/APTT, elevated WCC, metabolic acidosis CXR/AXR for FB Resonium, gastric lavage, whole bowel irrigation, scope Desferioxamine if coma, acidosis, peak level > 90. Can promote infection - stop if fever, give abs

Answer 21

Narrow therapeutic index 0.8-1.2 Toxicity with intercurrent illness Acute > 40mg/kg, symptoms over 3-5 days < 1.5 Lethargy, fine tremor, memory deficits < 2.5 confusion, visual disturbances, ataxia, coarse tremor, hyperactive reflexes < 3.5 myoclonic twitches, nystagmus, stupor > 3.5 seizure, flaccid paralysis, coma T wave flattening or inversion, prolonged PR/QRS/QT Hypokalaemia, abnormal TFTs Gastric lavage Diuresis with IVF Dialysis Supportive

Answer 22

CAUSES Acute - inhalation of arsine gas (metal refineries) - Ingestion of INORGANIC arsenic compounds in older pesticides/insectiscides, wood treatment or metal refineries - Arsenic trioxide in treatment in acute promyelocytic leukemia Chronic - Usually >10yrs to develop - long term exposure to environmental arsenic (well water, industrialized areas, landfill/wastesites) Organic arsenic in seafood, shellfish, organic rice relatively nontoxic DOSES/CONCENTRATION <0.05mg/kg mild Gi symptoms Lethal dose of inorganic arsenic 1-3mg/kg 24hr urine concentrations >1000microg/L indicated acute poisoning Raised urine levels on spot collection indicated recent exposure in symptomatic pts only. Nontoxic Organic arsenic raises urinary concentration for up to 2 weeks EFFECTS Binds to numerous cellular enzymes and interferes with cellular respiration. Also produces reactive oxygen intermediates causing lipid peroxidation RAPID/IMMEDIATE EFFECTS Classic - Hypersalivation and garlic odor GI (rapid onset) - N/V, severe watery diarrhoea, abdo pain, GI hemorrhage Metabolic acidosis Within hours: CVS - hypotension (peripheral vasodilation), QT prolongation, ventricular arrhythmias, acute heart failure (myocardial depressions), cardiovascular collapse CNS - Encephalopathy, seizures ARDS, ARF, hepatic injury Acute severe hemolysis with arsine gas DELAYED EFFECTS Bone marrow suppression in 24-72hrs (lasts 2-3 weeks) Ascending peripheral neuropathy 1-3weeks (predominately motor, mimic GBS but sensory component so can be painful) Bone marrow suppression (leukopenia, anemia) Hepatitis Pigmented skin lesions Chronic toxicity - constitutional symptoms, painful peripheral neuropathy (glove and stocking), hyperkeratosis of palms and soles, hyperpigmentation, hair loss, nail mees lines, malignancy of skin/ bladder/lung/liver/kidney, headache, confusion, haemolytic anemia MANAGEMENT ETT as needed IVF and inotropes (dehydration + peripheral vasodilation and myocardial depression) Optimize electrolytes and avoid bradycardia for QT prolongation WBI if radioopaque material on Xray NAC 200mg/kg over 4hrs then 100mg/kg over 16hrs for hepatoprotection, enhancing excretion of arsenic in acute poisoning and prevent arsenic binding to cellular proteins Chelation (risk of micronutrient deficiency such as Fe, Zn, Cu. Need blood levels +arsenic checked weekly) - PO Succimer 10mg/kg q8hr preferred but can cause abdo pain, neutropenia, elevated aminotransferase, neutropenia - IV DMPS 5mg/kg QID OR dimercaprol and calcium EDTA

Answer 23

Fumes, FB retention, contaminated drinks, improper storage foods in pewter, leaded glass, paint, batteries Myalgia, hypo chromic microcytic anaemia, painless wrist drop, encephalopathy, HTN, gout, nephritis, abdo pain, infertility Lead levels represent last 3-5 weeks Children > 0.5 act on, symptomatic > 2.9 Chelation BAL or CaEDTA

Answer 24

Inorganic - batteries, vinyl, acetaldehyde, embalming, cosmetics Ashen grey MM, metallic taste, stomatitis, abdo pain, poor muscle tone, red/oedmatous soles and palms, tachycardia, high/low BP Organic - contaminated foods, paper/wood preservatives Over days/weeks Scotoma, ataxia, parasthesia, hearing loss, dysarthria, tremor, cognitive defects, paralysis Mercury blood or urine levels Xray Decontamination Can dialyse Chelation - BAL, penicillamine

Answer 25

CaEDTA - lead, zinc Penicillamine - copper, second line lead, iron, zinc, mercury, arsenic. CI in pregnancy, renal disease, penicillin allergy BAL - acute inorganic mercury, lead CI in peanut allergy DMSA - mercury, lead

Answer 26

Large ingestions mean P450 pathway needed to metabolise which produced NAPQI - hepatic, renal, cardiac, neuro toxic Increased risk hepatoxicity: - depletion glutathione - malnutrition, HIV, chronic hepatic - induction P450 - ETOH, anticonvulsants etc Toxic doses: > 10g or > 200mg/kg Very large > 50g or > 1000mg/kg or > 3 x above nomogram Repeated: > 12g or > 300mg/kg (>150mg/kg children) over single 48 hour period OR > 4g or > 60mg/kg per 24 hour period for 48 hours with associated abdo pain/nausea/vomiting

Answer 27

Level taken at 4 hours Nomogram validated to 16 but extrapolated to 24 Check baseline ALT in all If massive or features hepatoxicity then full LFTs, coats, electrolytes (hypokalaemia common), blood gas (for metabolic acidosis), glucose (hypogylcaemia common)

Answer 28

Charcoal if within 2 hours then NAC 200mg/kg IBW over 4 hours then 100mg/kg over 16 hours - if level is > 2 x nomogram then second bag is at double dose (so 200mg/kg over 16 hrs) Check ALT 2 hours before stopping - if > 50 or rising then need to continue Check paracetamol 2 hours before stopping only if initial level was > 2 x normogram - if > 66 then need to continue If continuing then can only stop when: ALT/AST decreasing INR < 2 Patient clinically well 100% protection if started by 8 hours Adverse effects - vomiting, fever, allergy - stop infusion, give antihistamine, restart at 1/2 rate for 30 mins then increase to normal rate

Answer 29

IV paracetamol overdose Very large overdose - > 50g or > 1g/kg or > 3 x nomogram level Initial hepatotoxicity ALT > 1000 Liver unit: INR > 4.5 anytime or > 3 at 48 hours Oliguria or creat > 200 Acidosis pH < 7.3 despite treatment Persistent hypoglycaemia SBP < 80 despite resus Severe thrombocytopenia Encephalopathy Survival < 10% without transplant

Answer 30

8-24 hours Start NAC immediately Check paracetamol and ALT levels If under nomogram and ALT < 50 - no further treatment If above line or > 50 then NAC as per protocol, recheck at 2 hours prior to stopping as per acute ingestion > 24 hours Start NAC and check levels If paracetamol < 66 and ALT < 50 then stop If either elevated continue as per acute ingestion

Answer 31

Measure paracetamol and ALT Start NAC if paracetamol > 120 or ALT > 50 Repeat at 8 hours If paracetamol < 66 and ALT < 50/static can stop If elevated then continue NAC and recheck levels every 12 hours - stop when meets criteria above

Answer 32

If < 10g or 200mg/kg - paracetamol level 4 hours post ingestion (start NAC if above line) - further level 4 hours after this (start NAC if above line) - if both below, d/c If > 10g or 200mg/kg - charcoal up to 4 hours and consider more than 1 dose - start NAC and complete 20 hours regardless of initial paracetamol level - check level and ALT 2 hours before stopping, stop if meets usual criteria

Answer 33

Acute - sympathomimetic symptoms 4-6 hours Supportive, benzos, labetolol to control BP, B blockers for arrhythmia, cooling Chronic - weight loss, poor dentition, cardiomyopathy, insomnia, paranoia, psychosis, social effects Withdrawal in 85% lasting 3-5 days or up to weeks

Answer 34

Acute - sympathomimetic symptoms Myocardial ischaemia (50% thrombus, 50% vasospasm) Prolonged QRS and QTc HTN, ICH, seizures Crack lung - fever and haemoptysis Movement disorders Chronic - Cardiomyopathy, myocarditis (IV), perforated nasal septum Supportive with benzos GTN or Phentolamine 1-2.5mg IV for HTN. Avoid betablockers Sodium bicarb for QRS widening due to sodium channel blockade May need ACS treatment

Answer 35

Acute - triad CNS depression, resp depression, miosis May be aspiration, hypothermia, rhabdo, compartment syndrome, hypoxic brain injury Pethidine - serotonin syndrome Dextropropxyphene - seizures Naloxone 100-400mcg, repeat as needed, infusion if 2 x given (2/3 initial dose needed to reverse/hr and titrate) Observe 4-12 hours depending on preparation Withdrawal lasts 6hrs - 2 weeks - GI symptoms, lacrimation, salivation, anxiety, mydriasis, diaphoresis. Admit if severe/complications/intercurrent illness. Give opiates or clonidine

Answer 36

Packing - concealing drugs in planned way, large amounts so can be severe toxicity if leaks, bowel obstruction Stuffing - last minute concealment, smaller package but badly wrapped Plain films useful, CT if concerns Stuffers - observe 8 hours Packers - observe until passed and repeat imaging OK

Answer 37

Colourless and odourless Cigarettes, car exhausts, heating malfunction 240 x affinity than O2 for Hb Features correlate to end level CO exposure Headache, vertigo, ataxia, visual disturbance, confusion, seizures, coma, n+v, arrhythmias, ischaemia, pulmonary oedema, cherry red skin Long term neuropsychological symtoms (increased risk if pregnant, > 55, ischaemia, acidosis, significant LoC) Ix - elevated CO level, metabolic acidosis, hyperglycaemia, rhabdo, renal injury Rx - 100% O2 at least 8 hrs/until symptoms resolved (24hrs if pregnant) Hyperbaric O2

Answer 38

Fires, photographic/tanning/plastic industries, sodium nitroprusside, pips/seeds (almonds, peaches, apples etc) Death rapid Burning MM, SOB, vomiting, tachycardia, confusion, seizures, coma, CVS collapse, bitter almond odour, cherry red macula, miosis HAGMA with elevated lactate Gastric aspirate - litmus blue/green if cyanide Cyanide levels often delayed Rx - remove clothing, do not wash, 100% O2, hyperbaric O2, supportive Hydroxycobalamin 5g Sodium thiosulphate 50mls 25% Produce methaemoglobinaemia (not if CO poisoning also present) with sodium nitrite or amyl nitrite

Answer 39

CNS toxicity is main effect (if absent unlikely to develop significant toxicity) - Horizontal and vertical nystagmus - Ataxia - Dysarthria - Dose dependent decreased GCS (drowsiness to coma) - Resp depression - Seizures GI - N/V Cardio - Hypotension - Tachy/bradycardia - Cardiotoxic effects (Na channel blockade and QRS prolongation particularly in carbamazepine and lamotrigine) Consider serum drug concentration for carbamazepine, phenobarbitol, phenytoin and valproate Management: Intubation IVF and management of QRS prolongation Charcoal (even if delayed) MDAC (carbamazepaine, phenytoin and barbiturate) Dialysis (barbiturates, carbamazepine, lamotrigine and valproate)

Answer 40

EXAMPLES Long acting - Phenobarbital, primidone Medium - pentobarbital Thiopental DOSES Narrow therapeutic index Dose dependent sedation depends on tolerance Normal range 60-240mg daily phenobarbital and 125mg-1.5g daily primidone EFFECTS Dose dependent CNS depression (drowsiness to coma) Areflexia Resp depression and apnoea Hypotension (myocardial depression and reduced vascular resistance) Hypothermia Multiorgan failure due to hypoxica MANAGEMENT Phenobarbital level can confirm extent Early intubation IVF and inotropes (TTE can help determine which but start with adrenalin) Charcoal, even if delayed due to potential for severe toxicity Large primidone or phenobarbital overdose with coma, resp depression or hemodynamic instbailtiy can have MDAC +/- dialysis (if long acting phenobarbital, primidone) High risk of withdrawal within 48hrs so regular dose should be restarted once toxicity resolved

Answer 41

Effects of benzo overdose usually results in mild to mod sedation RISK for severe CNS depression - Coingestions of other sedatives - Extreme of age - Naive to benzos - alprazolam relatively more toxic - newer designer benzos have higher potency Flumazenil 5microg/kg (0.2mg) every minute up to 2mg (40microg/kg) can be considered - to reverse procedural sedation - avoid intubation in pts with resp disease or extreme of age - intubation and ventilation not available on site Half life <1hr, run infusion at half-2/3 bolus dose/hr Can precipitate withdrawal and seizure if - pt has hx of epilepsy - Coingested proconvulsant (TCA) - benzo dependence

Answer 42

DOSES >20mg/kg - sedation >50mg/kg - cardiovascular toxicity, GI effects and significant CNS depression Oxcarbazepine poisoning is rare but managed the same with >30mg/kg dose needing monitoring CONCENTRATIONS 5-12mg/L (21-51microg/L) - therapeutic 12-20mg/L (51-85microg/L) - nystagmus, sedation, ataxia (occurs at slightly lower concentration 10mg/L or 40microg/L on RCH) 20-40mg/L (85-170microg/L) - horizontal and vertical nystagmus, progressive sedation >40mg/L (170microg/L) - respiratory depression, coma, seizures, cardiovascular toxicity EFFECTS Delayed onset of effects and peak (>48hrs) Absorption cyclical and erratic due to intermittent ileus and bezoar formation - fluctuating serum concentration and toxic effects - serum concentrations do not indicate extent of toxicity but serial concentrations useful for progress and response to treatment CNS - horizontal and then vertical nystagmus - ataxia with increasing severity, dysarthria - agitation and fluctuating delirium - drowsiness, altered LOC and coma - Resp depression - Seizures CVS - tachycardia - hypotension (vasodilation and dehydration) - heart block - QRS prolongation +/- VF (>40mg/L serum concentration) Anticholinergic effects - Urinary retention - Intermittent ileus +/-bezoar formation from MR preparation - dry mouth - sinus tachy MANAGEMENT Charcoal if >50mg/kg within 6hrs of ingestion or intubated MDAC if bowel sounds present for >50mg/kg IVF +/- inotropes (TTE for ?cardiogenic shock) Serum alkalinization for QRS prolongation - Sodium bicarb 1-2mmol/kg (100mmol) q5min (MAX 6mmol/kg), serum pH7.45-7.55 + hyperventilation pCO2 30-35 Early intubation with airway or breathing compromise Benzos for seizures Dialysis - severe cardiovascular toxicity - serum >5x UL theraputic range (>60mg/L or 255microg/L) Consider ECMO for cardiovascular arrest or life threatening arrhythmia

Answer 43

DOSES >4g assosciated with life threatening toxicity Drug naive children provoked siezures with small doses (>10mg/kg) EFFECTS Peak effect within 4hrs Generally resolves within 24hrs bit can be prolonged in severe CNS - Altered LOC - Ataxia and involuntary movements (choreaathetosis, myoclonus, hemiballismus) - Seizures including statis CVS - Sinus tachy and arrhythmia - QRS prolongation, heart block, Brugada like pattern - Refractory hypotension Other GI - N/V MAOI effect - serotonergic toxidrome with coingestions (neuromuscular excitation, hyperthermia, altered LOC) Eosinophilia and hepatitis in pts taking therapeutically MANAGEMENT Charcoal Intubation if depressed LOC or status compromising airway IVF +/- intropes for hypotension - Dialysis and cardiac assist devices may be needed in refractory Serum alkinisation for QRS prolongation - Sodium bicarb 1-2mmol/kg (100mmol) q5min (MAX 6mmol/kg), serum pH7.45-7.55 + hyperventilation pCO2 30-35 Benzos for seizures Management of serotonergic toxidrome as needed with cooling Dialysis in severe cases possible due to low protein binding and moderate volume of distribution

Answer 44

RISKS OF TOXICITY - Saturable metabolism that can prolong half-life (resolution can take days to weeks) - Undergoes metabolism via CP450/CYP2C9/CYP2C19 and there is increased risk of toxicity if there is concurrent use of drugs that inhibit these enzymes (amiodarone, fluoxetine, omeprazole, disulfrim etc) - Escalation of doses or rpted doses of supratherapeutic doses in chronic therapy - Acute large ingestions DOSES >20mg/kg - cerebellar toxicity (ataxia, dystharthria, nystagmus >100mg/kg - sedation/coma >10mg/kg child's usual daily dose also at risk CONCENTRATION Useful test to confirm acute ingestion and that cerebellar toxicity is related to chronic phenytoin therapy as well as guide management in se 40-80micormol/L (10-20mg/L) - therapeutic 80 - 120micromol/L (20-30mg/L) - horizontal nystagmus 120 -160micromol/L (30-40mg/L) - vertical nystagmus, diplopia, ataxia, tremor, hyperreflexia (significant cerebellar toxicity), N/V. drowsiness 160-200micromol/L (40-50mg/L) - Confusion, disorientation, lethargy, mania, respiratory depression >200micromol/L (50mg/L) - coma/seizures EFFECTS CNS effects - Cerebellar toxicity (ataxia, dysarthria, nystagmus) - confusion -seizures CVS effects - bradycardia, hypotension and ventricular arrhythmias/conduction defects from rapid infusions secondary to propylene glycol diluent GI - Nausea/vomiting - gingival hyperplasia (chronic) MANAGEMENT ETT and IVF as needed Charcoal for >20mg/kg within 4hrs or after intubation MDAC only for severe ingestions >100mg/kg as no evidence of improved outcomes Dialysis can be considered in severe cases but low evidence of benefit Can DC after 6hrs if asymptomatic, cognitive baseline and safely ambulant - If moderate to severe or persisting symptoms after 6hrs, q6hrly concentration levels

Answer 45

EFFECTS Within 1-2hrs and resolve within 12hrs Renally excreted, kidney injury prolongs toxicity Minimal effects in single drug ingestion. Worse if coingestions with other sedatives CNS depression - Pregabalin >8g or >35mg/kg in drug naive children - Gabapentin, saturable oral absorption so toxicity. >75mg/kg in drug naive children Dizziness, ataxia, tremor, myoclonus and seizures N/V with gabapentin

Answer 46

DOSES <200mg/kg - minor effects 200mg-400mg/kg - moderate CNS depression 400-1000mg/kg - Multiorgan failure >1000mg/kg - potentially life threatening, coma, multiorgan failure, cerebral oedema CONCENTRATION Check q6hrly in pts with altered LOC 50-100mg/L (350-700micromol/L) - therapeutic >850mg/L (6000micromol/L) - coma respiratory depression and metabolic acidosis EFFECTS Within 4hrs of standard prep and up to 12hrs in enteric coated GI - N/V, abdo pain, hepatotoxicity CNS - dose dependent CNS depression, ataxia, cerebral oedema, seizures, respiratory depression CVS - QT prolongation, hypotension, tachycardia METABOLIC - hypoglycemia, hypernatremia (large ingestion from sodium load), hypocalcemia, metabolic acidosis/lactatemia/hyperammonemia in severe toxicity HAEM - late onset (3-5 days) bone marrow suppression with mild-mod thrombocytopenia and neutropenia MANAGEMENT ETT as needed IVF first line hypotension Ca, Mg and K and avoid bradycardia for prolonged QT Torsades rare but MgSO4 8mmol or 0.2mmol/kg over 10 minutes then 2-3mmol/hr or 0.12mmol/kg/hr for 12-24hrs) Glucose Charcoal for >200mg/kg or intubated MDAC >500mg/kg or rising levels Dialysis for ingestions >1g/kg, concentration >1000mg/L (7000micromol/L) or signs of severe toxicity (pH<7.1, cerebral oedema, shock) Carnitine antidote: 100mg/kg bolus then 50mg/kg q8hrly until coma and acidosis resolved - low evidence but reasonable biological basis, inexpensive and low risk of harm - Consider with cerebral oedema, hepatotoxicity, hyperammonemia, severe acidosis

Answer 47

Inhibit acetylcholinesterase increasing ACh at both muscrarinic and nicotinic cholinergic receptors Can bind irreversibly in ageing (not carbamates) Inhalation - usually within 5 mins Transdermal/oral - several hours Cholinergic signs (DUMBBELLS etc), pulmonary oedema in 40%, garlic smell Delayed muscle weakness after resolution initial cholinergic signs 24-96hrs in 10-40% (resp muscles, cranial nerves, pros limb flexors) Polyneuropathy at 2-3 weeks - rare ST elevation, QTc prolongation, arrhythmias common RBC acetylcholinesterase or plasma butyryl/pseudocholinesterase (RBC correlates better with severity of exposure, take longer to recover ~120 days and improves post oxime therapy. Plasma levels sensitive biomarker for exposure but no relation to severity) PPE - universal precautions, remove clothing, soap and water Atropine 1.2mg (50microg/kg) IV Q5mins doubling dose until chest clear, secretions, dried, HR>80 SBP>80 Pralidoxime - must be given early especially for weakness/paralysis Dimenthoate - early coma, CV collapse and death within 24hrs Chlorpyrifos - early cholinergic symptoms Fenthion - few early symptoms, late onset paralysis (up to 2days)

Answer 48

Paralysis 2-4 days after apparent recovery (fenthion, diazinon, malathion) Organophosphate induced delayed neuropathy (OPIDN) rare and occurs 1-5 weeks post acute exposure (fenthion, parathion, chlorpyrifos) Ascending sensorimotor polyneuropathy secondary to ageing Chronic organophosphate induced neuropsychiatric disorder may occur following acute intoxication or chronic low level exposure

Answer 49

Atropine in escalating doses indicated with - diaphoresis - Reduced breath sounds - Wheeze - Cough - Bradycardia - hypotension 1.2mg (50microg/kg) and double every 5 miuntes until HR>80, SBP>80 and drying of secretions with clear chest sounds. Infusion 10-20% total loading dose per hour Pralidoxime can reverse neuromuscular blockade by reactivating inhibted AChE BEFORE AGEING OCCURS 1g IV then 250mg/hr for at least 24hrs Not needed in carbamate intoxication Has not shown to improve survival or reduce need for intubation but has been seen to reactivate RBC acetylcholinesterase Controversy regarding serum alkalinsation and use of nondepolorising muscle relaxants. Early evidence suggests that it may reduce delayed neuromuscular effects by protecting the neuromuscular junction

Answer 50

Petrol, diesel, kerosene, turps, toluene, camphor CNS - ataxia, euphoria, seizures, coma, myopathy, cerebellar dysfunction, encephalopathy CVS - in severe - arrhythmias, hypotension GIT - d+v, haematemesis Pulmonary - aspiration, oedema Bone marrow suppression Metabolic acidosis Supportive, dialysis

Answer 51

Most lethal poison, small sip can kill Early - GI /corrosive injury Multiorgan failure around 48 hours If survive > 48 hours get pulmonary fibrosis Serum level >5 fatal, >2.5 90% fatal Extensive bloods to assess organ damage PPE Immediate decontamination, remove clothes, fullers earth/charcoal Dialysis O2 only is sats < 90 and aim no more than 92% Consider palliation

Answer 52

EXAMPLES Citalopram, fluoxetine, sertraline, dapoxetine, fluvoxamine, paroxetine DOSES >600mg citalopram (>2mg/kg) >300mg escitalopram (>1mg/kg) are associated with QT prolongation and torsades otherwise >50x daily dose or >5-10mg/kg for serotonergic toxicity EFFECTS Onset 4 hours, offset 12 hours Acute serotonergic toxidrome if with congestions or massive single agent ingestion (15% of SSRI poisoning) Agitation, anxiety, confusion Neuromuscular excitation (clonus, ocular clonus, tremor, hyperreflexia, hypertonia) Autonomic (hyperthermia, sweating, flushing, mydriasis, tachycardia) Seizure <2% QT prolongation +/- torsades with citalopram and escitalopram. Bradycardia citalopram, escitalopram and fluoxetine MANAGEMENT Supportive Charcoal for large doses <4hrs Adequate hydration Diazepam 5-10mg q30min Early ETT if temp >39.5 Cyproheptadine 8mg PO TDS if mild/mod

Answer 53

Central alpha2 adrenoceptor blocker increasing noradrenalin and serotonin release. Single ingestion of more 1000mg is associated with CNS depression but otherwise relatively safe. Does not need decontamination Does not cause serotonergic toxidrome

Answer 54

EXAMPLES Venlafaxine, desvenlafaxine, duloxetine, atomoxetine Tramadol and tapentadol weak SNRIs DOSES Venlafaxine >2g or 12.5mg/kg in kids associated with seizures and serotonergic toxidrome >5g 50% risk of seizures >8g cardiotoxicity (tachyarrhythmia, Takotsubo, severe hypotension) Desvenlafaxine <800mg or <8.75mg/kg in kids considered safe EFFECTS Within 4htrs but delayed up to 16hrs with SR preparations 1) Noradrenergic most prominent - HTN, Tachycardia, diaphoresis, mydriasis 2) Serotonergic effects, especially if coingested with another serotonergic drug (MAOI) - neuromuscular excitation, altered conscious state, hyperthermia 3) Seizures (50% if >5g venlafaxine) 4) Cardiotoxicity (>8g venlafaxine) - tachycardia ST or VT, takotsubo/acute and transient LV dysfunction, severe hypotension, QRS prolongation, QT prolongation with atomoxetine MANAGEMENT Charcoal (>2g) Consider WBI for massive doses (>5g) QT and QRS management as needed Sedation and cooling (Serotonin syndrome, cold IVF and diazepam) Inotropes as needed ?cardiogenic shock Seizure control Monitor for 6hrs IR, 16hrs ER, 24hrs >5g

Answer 55

EXAMPLES Amitriptyline, clomipramine, dotheipine, doxepin, imipramine, nortryptiline DOSES <5mg/kg - non toxic 5-20mg/kg - sedation and anticholinergic >20mg/kg - severe toxicity (coma, seizures, major cardiovascular toxicity EFFECTS - Rapid onset 1-2 hours, most serious effects within 6hrs - Worse effects with acidosis (altered consciousness, respiratory depression and seizures exacerbate life risk) CNS (noradrenalin and serotonin reuptake inhibition) - decreased LOC, resp depression, coma and seizures CVS - hypotension/vasodilation and tachycardia (alpha adrenoreceptor blockade). QRS prolongation +/- VT/VF myocardial depressions (fast sodium channel blockade) QRS >100-120 predictive seizures, >160 predictive VT Anticholinergic toxidrome - Mydriasis/blurred vision, dry mouth, hyperthermia, urinary retention, reduced bowel sounds/ileus, delirium MANAGEMENT Charcoal for >5mg/kg if alert and cooperative within 2hrs or intubated IVF for hypotension 20-30ml/kg Norad 0.05-1microg/kg/minute (commence at 20microg/min for severe hypotension) >10mg/kg should be considered for intubation early especially developing signs of cardiotoxicity Sodium bicarb 1-2mmol/kg bolus prior induction every 3-5 minutes (max 6mmol/kg) with continuous BVM ventilation to avoid apnoec respiratory acidosis and ongoing hyperventilation post, aim pH 7.45-7.55 and pCO2 30-35 Lidocaine (1mg/kg +/- 0.5mg/kg) IV is a third-line agent for arrhythmia (after bicarbonate and hyperventilation) once pH is > 7.5 Discharge - 6hrs of observation - Normal ECG - Normal GCS (anticholinergic delirium that can persist beyond 24 to 48 hours) - Low risk of further self-harm if deliberate ingestion

Answer 56

Irreversible nonselective MAOI (phenelzine and tranylcypromine) have narrow therapeutic window. - days of unopposed serotonin, noradrenalin, dopamine, adrenalin, phenylethylamine (serotonin and sympathomimetic syndrome) Reversible selective MAOI (moclobemide) and selective MAO - B (selegiline) have less serve effects and resolve faster. Lamotrigine and isoniazid have weak MAOI effects DOSES >1mg/kg or coingested with serotonergic/adrenergic drug needs 24hrs admission. If less, then 12hrs monitoring >2mg/kg serious toxicity >4mg/kg lethal Onset 6-12 hrs. Can be delayed up to 24 hours Last 1-4 days EFFECTS Serotonin and sympathomimetic symptoms especially if coningestants for serotonergic reaction Early - headache, agitation, tremor, sinus tachy, mydriasis, hyperreflexia and hyperventilation Later - hypertension, muscle rigidity, hyperthermia, rhabdomyolysis, clonus, confusion Severe - coma, seizures, hypotension, worsening hyperthermia, DIC, arrythmia and arrest Death - multiorgan failure MANAGEMENT Supportive with IVF and benzos Charcoal if within 2hrs Benzos first line for agitation and HTN Titratable antihypertensive (GTN, SNIP second line as large fluctuation from autonomic instability) Hypotension and severe hyperthermia (>39.5) poor prognosis and need prompt management. - eg norad and intubation ?SS need for cyroheptadine 12mg stat or 8mg TDS

Answer 57

Dietary amine found in cheese, wine, preserved meats and yeast Indirect sympathomimetic that normally is metabolized by intestinal and hepatic monoamine oxidase enzymes MAOI cause excessive tyramine and leads to sympathomimetic toxidrome Occurs within 90 minutes often with severe headache and hypertension If having tyramine reaction, needs observation for at least 4hrs after symptom resolution and then 2-week period of tyramine free diet

Answer 58

Brown (pseudonaja), Taipan (Oxyuranus), Tiger (Notechis), Hoplocephalus species, and Rough scaled snakes (Tropidechis) always cause VICC in significant envenoming. Not present in Death Adders, Sea Snakes or Black snakes but black snakes have anticoagulant in its venom and can cause mild to mod elevation in APPT and INR. Fibrinogen and D Dimer typically normal In VICC, Prothrombin activators in venom lead to consumption of major coagulation factors including fibrinogen, factor V and factor VIII.

Answer 59

Complete VICC - INR>3 - D Dimer 100 to 1000 times ULN - Fibrinogen undetectably small Partial VICC - INR<3 - D DImer 10 times ULN - Fibrinogen low but detectable Presents with major bleeding Thrombotic microangiopathy Improves 12-36hrs after bite but faster when clotting factors are given No reversal with snake antivenom. needs new clotting factors to be synthesized unlike anticoagulant coagulopathy with black snakes which is not clinically significant and reversed with antivenom

Answer 60

Taipan (Oxyuranus) and Death Adders (Acanthophis) commonly cause neurotoxicity with death adders having slower onset over hours. Tiger and Sea Snake can also cause it uncommonly with Tiger being slower onset over hours Brown can rarely cause it Not present in Black snakes

Answer 61

Insulin and sulfonylurea only Metformin causes metabolic acidosis and lactatemia but no hypoglycemia All others only cause GI effect DPP4 inhibitors (gliptins) GLP-1 agonists (glutides) SGLTs inhibitors (flozins) alph glucosidase inhibitors (acarbose) Thiazolidinediones (glatizones)

Answer 62

RISK ASSESSMENT Formulation (ulra, short, long etc) Site and number of injections (single large injection can have depot effect) Whether pt has diabetes (non diabetic will not have BSL rise post toxic effect have worn off due to endogenous insulin release and will need weaning of glucose therapy while T2DM have insulin resistance and lower risk of hypoglycemia) Duration of symptoms dose and formulation dependent EFFECTS Symptoms of hypoglycemia may be blunted in long standing diabetics - Within 1-2hrs, delayed in long acting - CNS (dizziness, confusion, headaches, decreased GCS, seizures) - Autonomic (tremor, tachycardia, sweating, nausea) MANAGEMENT Aim BSL 4-8 (q2hrly if asympomatic, q30min-1hr otherwise. q4hrly when >4hr for 4hrs) Encourage oral intake of oral glucose and complex carbs if able Bolus glucose 50% 50ml or 10% 5ml/kg THEN Glucose 50% 20ml/hr or 100ml/hr 10% (paeds 1-2ml/kg/hr 10%) Glucose 10% vs 50% - Glucose requirements - Limitations in volume (50% preferred if >250ml/hr of 10% required) - Venous access (CVC for 50% as phlebotoxic effects of concentrated glucose) HypoK Oral 14-16mmol (0.25mmol/kg) 2-4hrly IV 10-20mmol (0.4mmol/kg) 2-4hrly Aim K>3.5 Monitor 6hr short acting 18hr long acting (and dc in daylight) 8hrs post glucose therapy cessation

Answer 63

Biguanide agent - decreasing carbohydrate absorption from the gut - increasing glucose uptake in peripheral tissues in the presence of insulin - reducing hepatic gluconeogenesis DOSES AND RISK If healthy adult >20g can have severe toxicity Lower doses needed in elderly, diabetics, kidney impairment or associated with antihypertensives (CCB/BB) Even therapeutic doses can cause toxicity if acutely unwell Chronic accumulation in renal impairment <100mg/kg in children is likely safe EFFECTS NO HYPOGLYCEMIA Effects mainly from profound acidosis - Hyperlactatemia (predicts worse prognosis), metabolic acidosis, hyperK - N/V abdo pain - hypotension and tachycardia due to acidosis and dehydration +/- cardiogenic shock - sedation, coma and seizure from acidosis - Multiorgan failure (liver and renal failure) MANAGEMENT Early intubation in decreased LOC Activated charcoal (2hr IR, 4hr MR or anytime post intubation) Consider WBI if >50g of MR however high risk of ileus IVF +/- norad Sodium bicarb as bridging therapy to dialysis, aim serum pH>7.3 Dialysis (intermittent with lactate free dialysate preferred) when: - pH<7 or lactate >20 - Refractory hypotension - Rapid deterioration and AKI DC criteria Asymptomatic Normal pH and lactate Observation 6hr IR and 12hrs MR

Answer 64

EXAMPLES Glibenclamide, gliclazide, glimepiride and glipizide DOSES AND RISKS Narrow therapeutic index Single tablet 2mg can cause hypoglycemia in children Risk of hypoglycemia even at therapeutic dose in elderly, AKI and pts taking CYP2C9 inhibitors (amiodarone, fluconazole, fluoxetine etc) EFFECTS Increase pancreatic insulin secretion causing prolonged and delayed hypoglycemia (6-12hrs however can be 18hrs in children) Hypoglycemia symptoms can be blunted in long standing diabetics - CNS: dizziness, altered LOC, headache, seizures, coma - Autonomic: tremor, tachycardia, diaphoresis, nausea, anxiety MANAGEMENT Charcoal (2hrs of IR or 4hrs of MR) Manage hypoglycemia first, aim BSL 4-8 - oral glucose/complex carbs if awake - 50% 50ml or 10% 5ml/kg - Glucose infusion (1-2ml/kg/hr 10% glucose may be needed) Octreotide (long active somatostatin analogue. Blocks pancreatic insulin release). Commence for anyone with hypoglycemia following bolus glucose - 50 microg (2microg/kg) subcut q8hrly for at least 24hrs OR - 50microg (2microg/kg) IV followed by 25microg/hr (1microg/kg/hr) IV for 24hrs Can stop octreotide after 24hrs if - daylight hours - off glucose infusion >4hrs - BSLs normal with no symptoms of hypoglycemia >4hrs Needs hrly BSL for 12hrs post cessation of octreotide infusion

Answer 65

Rarely associated with accidental exposures to children due to deterrent taste Can cause delayed onset anticoagulation which lasts months Anticoagulant effects from >0.1mg/kg brodifacoum: - 2g/kg of 0.005% bait (5mg/100g) - 3x50g pellet packs (2.5mg brodifacoum each) Unintentional ingestions of <1mg and children with single ingestion do not require investigations and can be discharged Charcoal Monitor INR 6hrly, peak effect after 48hrs. Normal INR without treatment excludes toxic ingestion Superwarfarin levels confirms diagnosis Phytomenadione (Vit K1) 20 - 100mg BD PO or IV for anyone with INR>2. Needs to continue for weeks to months until superwarfarin levels drop Prothrombinex 50units/kg and FFP 15ml/kg if actively bleeding

Answer 66

Toxic dose >0.5mg/kg Increased risk if on concurrent CYP2C9inhibitor (amiodarone, fluconazole, fluoxetine etc) Charcoal Consider MDAC or colestyramine for large overdoses Phytomenadione (Vit K1) 0.25mg/kg (20mg) PO or IV if INR>2 every 6-12hrs if not taking warfarin therapeutically If taking therapeutically then follow management of supratheraputic INR NO BLEEDING INR 4.5 - 10 = phytomenadione 1-2mg orally or 1mg IV INR >10= phytomenadione 3-5mg PO/IV. Add on Prothrombinex 15-30units/kg IV if high bleeding risk (Major bleed in last 4weeks, surgery in last 2 weeks, plt<50, liver disease, concurrent antiplatelet therapy) If bleeding add on Prothrombinex 50units/kg FFP 15ml/kg

Answer 67

Narrow therapeutic index and block adenosine receptors that cause smooth muscle relaxation and increased cardia output Raise catecholamine concentration Theophylline >10mg/kg can cause toxicity. >50mg/kg lethal (200mg MR release tablet toxic in 10kg child) Caffeine >15mg/kg mild to mod. >100mg/kg life threatening. Dose depends on tolerance with regular use. Caffeine tablets 100mg. Coffee is roughly 1-2 tablets RISK FOR TOXICITY Hypokalemia Hyperglycemia Age>60 (predictor of severity and poor outcome in chronic theophylline poisoning) Effects of acute toxicity due to catecholamine excess (sympathomimetic) Chronic theophylline has poorer outcomes and present with vomiting, tachycardia, seizures and dysrhythmia GI - N/V CVS - tachycardia, ectopics - refractory hypotensoin due to beta2 adrenergic stimulation - MI - SVT, VT/VF rare and only with serum concentration >100mg/L (550microg/L) CNS -agitation, tremor, seizure Metabolic (severity worse in acute) - hyperglycemia - hypercalcemia - hypokalemia (can be refractory) - hypophosphatemia - hypomagnesemia - metabolic acidosis

Answer 68

Measure serum concentration 2-4hrly Chronic theophylline poisoning can have severe effects with lower concentrations Charcoal if <2hr IR or <4hr MR) + antiemetic MDAC if theophylline >30mg/kg and caffeine >50mg/kg Consider WBI if >30mg/kg theophylline MR Seizure control imperative - Cerebral vasoconstriction and hypoxia from blocked adenosine receptors in CNS - Cerebral hypoxia and brain injury worsened with increased metabolic demand in seizures - Significant morbidity and mortality - Can be refractory - Treat with Benzos Midazolam 0.15mg/kg (10mg) IV/IM q5minute. 0.3mg/kg buccal/intranasal Phenobarbitone 20mg/kg (2g, 1g in kids) second line (Phenytoin ineffective and increased sodium channel blockade) Consider ETT IVF +/- norad Correct electrolytes Hemodialysis increases clearance 1.5-2 fold but same as MDAC Hemoperfusion 2-5 fold but more adverse effects (coagulopathy and eletrolyte disturbances) Indicated if - Serum theophylline >100mg/L (550microg/L) in acute - Serum theophylline >60mg/L (330microg/L) in chronic - Severe toxicity (dysrhythmia, hypotension, seizures)

Answer 69

EXAMPLES Sedating (H1 antagonists +central, alpha adrenergic, anticholinergic, serotinergic, Na channel blockade) - promethazine, diphenhydramine, dimenhydrinate, doxylamine, cyclizine, cyprohepatidine, dexchlorpheniramine Nonsedating (peripheral H1 antagonists) - desloratadine, loratadine, fexofenadine, cetrizine DOSES >3x max daily doses of sedating antihistamines Dimenhydrinate and diphenhydramine >300mg or 7.5mg/kg in kids (dimenhydrinate slower onset as needs to dissociate to diphenhydramine, 50mg=29mg) Diphenhydramine >1g severe effects (cardiotoxicity) Promethazine anticholinergic delirium dose dependent 31% 250mg 42% 500mg 55% 1g Tolerances can develop if taking regularly Non-sedating antihistamines normally benign EFFECTS Look out for coingestions (paracetamol, caffiene, etc) CNS - Dose dependent sedation Sedation early, masking anticholinergic delirium Sedation lasts 12-24hrs then delirium major effect Anticholinergic delirium (particularly promethazine) Seizures (pheniramine, dimenhydrinate, diphenhydramine) indicate severe toxicity, increased risk of cardiac events and worsen acidosis Dystonia CVS - Tachycardia and postural hypotension most common QRS/QT prolongation and torsades in diphenhydramine, dimenhydrinate and loratadine but rare Rate dependent BBB with doxylamine Other - Urinary retention Rhabdo with doxylamine and diphendramine MANAGEMENT Charcoal in 2hrs or after ETT (particularly promethazine to prevent delirium) ETT as needed IVF +/- norad QRS management (serum alkalization) QT management (electrolyte replacement and keeping rate >90) Benzos for persistent or recurrent seizures Anticholinergic Delirium - physostigmine 0.5mg (0.01mg/kg) IV q15min. Max 2mg in 60min. May need more after 1-2 hrs as short acting Monitor for bradycardia and bronchospasm (cholinergic overdose) Can then have oral diazepam 5-20mg q30min (0.2mg/kg) MAX 120mg in 24hrs for ongoing sedation Droperidol 0.1mg/kg 2nd ling, then midaz 0.1mg/kg

Answer 70

GABA analogue used in muscle spascitiy, alcohol dependence and GHB withdrawal DOSES >200mg/kg in naive pts causes severe toxicity EFFECTS CNS effects - Altered LOC/coma/resp depression - Myoclonus and seizures (early due to reduced presynaptic GABA release and late due to baclofen withdrawal - Delirium (lasts 1-3 days following resolution of coma) - Hypotonia, hyporeflexia, mydriasis, hypothermia - loss of brainstem reflexes in massive overdoses lasts 1-2 days CVS effects - Bradycardia, tachycardia, hypertension - Hypotension less common Skin - Morbilliform rash rare MANAGEMENT ETT IVF +/- inotropes Charcoal within 2hrs or after ETT Seizures generally self limiting. Benzos first line Delirium: benzos or droperidol. Can try low dose baclofen for suspected withdrawal. Needs EED to rule out nonconvulsive status epilepticus

Answer 71

DOSES Risk of seizures is dose dependent ~50% risk in >4.5g >9g severe cardiovascular toxicity (hypotension, QRS prolongation and arrhythmia) >10mg/kg in children needs assessment EFFECTS Can be delayed up to 24hrs (admit >4.5g or 10mg/kg for 24hrs with cardiac monitoring. Less needs at least 12hrs monitoring) CNS - severe agitation and aggression (characteristic), hallucination, tremor, seizures CVS - hypertension and tachycardia (most common), hypotension/QRS widening/arrhythmia with >9g GI - N/V MANAGEMENT ETT as needed Charcoal within 4hrs or if intubated IVF +/- inotropes for hypotension Serum alkanisartion for QRS prolongation (1-2mmol/kg sodiuum bicarb with hyperventilation aiming pH 7.45-7.55 and etCO2 30-35) Benzos for agitation and seizures if not self limiting or recurrent

Answer 72

PRESENTATION Severe envenoming more common in Eastern Australia Commonly present with localized pain and bleeding from bite mark and hx of bite Rapidly developing symptoms 10min-4hrs Pathognomonic presentation is abrupt onset sweating, piloerection, coma and fasciculations ANS - cholinergic and adrenergic excess (diaphoreiss, hypersalivation, lacrimation, piloerection, hypertension, brady/tachycardia, miosis/mydriasis NMS - parasethesia (local, distal, perioral), fasciculations (tongue common), spasms CVS - Adrenergic excess (hypertension and tachycardia followed by bradycardia and hypotension with myocardial injury) CNS - agitation, anxiety, altered LOC/coma Resp - APO Nonspecific - abdo pain, N/V, headache FIRST AID AND MANGEMENT Pressure bandage with immobilisation of limb and pt within 4hrs Broad (15cm) elastic bandage starting at bite site then distally to proximally to cover entire limb Only removed once antivenom administered Antivenom in all suspected funnel web bites with signs of severe envenoming 2 vials 4 vials in arrest OTHER MEASURES Tetanus booster Analgesia - panadol/nurofen/oxycodone NIV/ETT Alpha blockers for hypertension/tachycardia IVF, inotropes, atropine for hypotension CPAP/ETT for APO