Toxicology Flashcards
Ethylene Glycol
> 1ml/kg potentially lethal
Severe High Anion Gap Metabolic Acidosis Elevated Osmolar Gap Elevated Lactate Hypocalcaemia - calcium oxalate crystals AKI
Clinical:
CNS - EOTH like effects, coma, seizures
Cardiopulmonary - SOB, tachycardia, tachypnoea, HTN, shock
Renal - flank pain and oliguria
Mx: Sodium Bicarb Intubation and hyperventilation Treat seizures with IV BZD Ethanon - competitive inhibitor of ADH Haemodialysis if: -Large ingestion with Osmolar gap >10 -acidaemia pH <7.3 -AKI -Ethylene glycol level > 8mmol/L
Methanol
> 0.5ml/kg of 100% methanol is potentially lethal
metabolised to formic acid
Severe HAGMA
Elevated Osmolar Gap
elevated Lactate later due to inhibition of cellular oxidate metabolism
CT BRAIN may demonstrate ischaemic or haemorrhagic injury to basal ganglia
Clinical:
Initially ETOH like effects
Latent onset of headache, dizziness, vertigo, visual changes/blindness, Seizure/comas
Mx: Sodium Bicarb INtubation and Hyperventilation Seizures - IV benzos correct hypoglycaemia (cofactor therapy) Folic acid 50mg IV every 6 hours ETOH: 3x 40ml shots 40% vodka then 40ml shot per hour, aim BAL of 100-150mg/dL Haemodialysis: -if treating with ETOH -pH < 7.3 -visual symtpoms -renal failure -Methanol level > 16mmol/L
Amisulpride
Atypical Antipsychotic
Risk > 4g
QT Prolongation, Torsades
Bradycardia - increases risk of torsades
Hypotension
CNS depression
16 hours observation, cardiac monitoring if abnormal ECG
Amphetamines / Sympathomimetics
MDMA/ecstasy, speed/methamphetamines
Severe Hyperthermia ACS / APO / Hypertension Cardiac Dysrhythmias Aortic Dissection Intracranial haemorrhage/SAH Rhabdomyolysis, renal failure SIADH / Hyponatraemia / Cerebral oedema Seizures
mx: AVOID Betablockers titrated Benzodiazepines IV for aggitation/seizures/HTN Refractory HTN: -Phentolamine 1mg IV every 5 minutes -GTN or SNIP infusion -Treat hyponatraemia <120 with 3% saline Manage Hyperthermia with cooling
Children, One Pill Kills
Methamphetamines - agitation, hypertension, hyperthermia Opioids - resp depression, coma CCBs - hypotension, bradycardia BBs - hypoglycaemia TCAs - arrythmias, seizures Chloroquines - prolonged QRS/VT Sulfonylureas - hypoglycaemia Theophylline - SVT, seizures
Serotonin Syndrome - diagnostic criteria
The Hunter diagnostic criteria requires the presence of one of the following categories in the setting of ingested serotonergic medication:
- spontaneous clonus
- inducible clonus + (agitation or sweating)
- occular clonus + (agitation or sweating)
- tremor + hyper-reflexia
- hypertonia and T > 38C + clonus
Anticholinergic Syndrome
•warm, dry skin •mild hyperthermia •dry mucous membranes •mydriasis •tachycardia •urinary retention •absent bowel sounds •central anti-cholinergic syndrome -confusion -hallucinations - usually visual
Common sources •antimuscarinics -benztropine -hyoscine -scopolamine -Trumpet lily / Angel's trumpet / (Brugmansia) -Jimsonweed (Datura stramonium) •antihistamines •tricyclic antidepressants •amanita muscaria mushrooms
Neuroleptic Malignant Syndrome
•idiosyncratic reaction to neuroleptic drugs:
- haloperidol
- fluphenazine
- chlorpromazine
- metoclopramide
- prochlorperazine
Fever Generalised muscle rigidity •catatonia, stupor, coma •Parkinsonian rigidity present in > 90% •often with associated tremor •reflexes decreased or absent •characteristically unresponsive to anticholinergics Autonomic instability •tachycardia •sweating •sialorrhoea •labile BP -pupils usually normal Altered conscious state •ranging from confusion to coma •seizures uncommon
Treatment:
Supportive - cooling, hydration, I+V
Bromocriptine
•dopamine agonist
•2.5 mg orally or via NGT 8 hourly
•increase up to max of 5 mg every 4 hours according to response
•has been useful when combined with dantrolene
Dantrolene
•2-3 mg/kg per day IV up to 10 mg/kg maximum total dose
•probably of little use in neuroleptic malignant syndrome (controversial)
Sympathomimetic Toxidrome
•CNS excitation -agitation -tremor -seizures •hypertension •tachycardia •sweating •mydriasis
Common sources
- amphetamines
- cocaine
- LSD
- caffeine
- theophylline
- phencyclidine
- methylphenidate
Drugs with toxicity on withdrawal
•ethanol •benzodiazepines / barbiturates -tremor -sleep disturbance -depression -seizures •opioids •amphetamines •GHB •beta blockers -hypertension -angina •clonidine -hypertension •SSRIs (short acting only) •valerian •steroids -adrenocorticoid deficiency
Drug Withdrawal toxidrome
•diarrhoea •mydriasis •piloerection -“cold turkey” •tachycardia •lacrimation •abdominal pain •agitation •hallucinations
Serotonin Syndrome Causes
Drugs most commonly responsible
•sertraline (the most common) •other SSRIs •lithium •moclobemide and other MAOI -including methlyene blue and linezolid •LSD •imipramine
Other agents associated with serotonin toxicity
- amphetamines and synthetic stimulants
- pethidine
- fentanyl
- tramadol
- sumatriptan
- dextromethorphan
- chlorpheniramine (chlorphenamine)
- sibutramine (anti-obesity agent)
- citalopram
- tryptophan
- St John’s wort
Serotonin Syndrome Clinical Features
Early features
•agitation
•akathisia
•tremor
•hyper-reflexia
•shivering
•inducible clonus
-especially ocular clonus (distinguishable from nystagmus as no fast component)
- includes a variety of abnormal involuntary fine or coarse oscillations of gaze in all directions (examples (external link))
-can be continuous or triggered by rapid eye movement
-includes “ping pong gaze” (short cycle, periodic, alternating lateral gaze)
-prominent in lower limbs
•repetitive rotation of the head with the neck held in moderate extension
•altered mental state
•sialorrhoea
•active bowel sounds
•diarrhoea
Late features
•tachycardia •mydriasis •sweating •hypertension •hyperthermia •myoclonic jerks •muscular rigidity -mainly in lower limbs -rhabdomyolysis or increase in CK not common
Serotonin Syndrome Treatment
•cyproheptadine
-8 mg initial oral dose then 4 mg 4 hourly
or Phenothiazines:
- olanzapine 5 mg orally / IM
- chlorpromazine 50-100 mg IM/IV then 50-100 mg 6 hourly
•severe hyperthermia
- barbiturates, neuromuscular paralysis for intubation and thermal control
- dantrolene and bromocriptine have been reported to increase CNS serotonin levels and may cause clinical deterioration
Corrosive Airway Injury
Alkalis
Acids
Glyphosate (herbicide)
Paraquat (herbacide)
Ventricular Tachycardia, Fast Sodium channel blockade causes
Chloroquine / Hydroxychloroquine cocaine Flecanide Local Anaesthetics Procainamide Propranolol Quinine TCAs
Prolonged QRS Duration - fast Na channel blockade
Chloroquine / Hydroxychloroquine cocaine Flecanide Local Anaesthetics Procainamide Propranolol Quinine TCAs
Contraindications to Activated Charcoal
Resuscitation not yet complete non toxic ingestion / dose uncooperative patient ALOC without airway protection likely to progress to ALOC / seizure Corrosive ingestion Agent does not bind AC
Dose is 50 g for adults, 1g/kg children
Useful Drug Levels
Carbamazepine Digoxin Ethanol Ethylene Glycol Iron Lithium Methanol Methotrexate Paracetamol Phenobarbitol Salicylate Theophylline Sodium Valproate
Whole Bowel Irrigation
Indications:
- Iron OD > 60 mg/kg
- Slow Release KCL > 2.5 mmol / kg
- Life threatening Slow Release Verapamil or Diltiazem
- Symptomatic arsenic
- Lead ingestion
- Body Packers
Contraindications:
- unable to place NGT
- ileus or bowel obstruction
- ALOC/not ventilated/seizures etc
Dose - PEG
2l/hr adult
25/ml/kg hr child
Common toxicological causes of seizures
Venlafaxine Tramadol amphetamines Bupropion ETOH and BZD withdrawal
Multi-Dose Activated Charcoal
Adults: 50g then 25g every 2 hours
Children: 1g/kg then 0.5g/kg every 2 hours
Causes interruption of enterohepatic circulation and Gastrointestinal Dialysis (increases the diffusion gradient for the drug from intravascular space to bowel lumen)
INDICATIONS:
- carbamazepine coma
- phenobarbitone coma
- Dapsone overdose with methaemaglobinaemia
- Quinine overdose
- Theophyline overdose
Multi-Dose Activated Charcoal
Adults: 50g then 25g every 2 hours
Children: 1g/kg then 0.5g/kg every 2 hours
Causes interruption of enterohepatic circulation and Gastrointestinal Dialysis (increases the diffusion gradient for the drug from intravascular space to bowel lumen)
INDICATIONS:
- carbamazepine coma
- phenobarbitone coma
- Dapsone overdose with methaemaglobinaemia
- Quinine overdose
- Theophylline overdose
Haemodialysis
Toxic Alcohols Theophylline Severe Salicylate OD Severe Chronic Lithium OD Phenobarbitone coma Metformin Lactic acidosis Massive Valproate OD Massive Carbamazepine OD KCL OD with life threatening Hyperkalaemia
***agents with small VD, slow endogenous clearance and small molecular weights
Urinary Alkalinisation
Use for:
- Salicylate OD in any symptomatic patient
- Phenobarbitone coma
Dose is:
1-2mmol/kg 8.4% sodium bicarbonate IV boluis then 150mmol sodium bicarb in 850ml 5% dextrose @ 250ml/hr
AIM urine pH > 7.5
ANTIDOTES
Atropine / anticholinergic- Physostigmine Benzodiazepines - Flumazenil Cyanide - Dicobalt edetate, hydroxycobalamin Digoxin - Digoxin specific fab fragments (digibind) Insulin - dextrose Iron - Desferoxamine Isoniazide - Pyridoxine Methaemoglobinaemia - methylene blue Toxic Alcohols - fomepizole / ethanol Organophosphates/carbamates - Atropine Opioids - naloxone Paracetamol - NAC Sulphonylureas - Dextrose, octretide TCAs - Sodium Bicab Warfarin - Vitamin K
N-Acetyl-Cystine
Dose
200mg/kg bag over 4hr
100mg/kg bag over 16hr
**NB massive ingestions (>30g or >500mg/kg) or double the treatment normogram line should get 200mg/kg for the second bag (double dose)
indications
- paracetamol level > treatment normogram
- > 8hrs since ingestion of potentially toxic dose
Side-effects: (anaphylactoid reaction) Hypotension Flushing Rash Angiooedema -if severe then. cease, otherwise give antihistamine and restart when symptoms are settling.
Digibind
Dose
indications
Side-effects
Naloxone
Dose
Indications
Side-effects
Paracetamol Acute Supra-therapeutic ingestion
RISK: > 10g or >200mg/kg
***if staggered ingestion then use time of first ingestion and the total ingested dose.
CLINICAL
Phase 1: early GI upset
Phase 2: 1-3 days, RUQ tenderness, raised bilirubin, AST/ALT and INR peak 48-72hrs, possible AKI
Phase 3: 3-4 days fulminant hepatic failure: coagulopathy, jaundice, encephalopathy, MODS, metabolic acidosis
Phase 4: Recovery 4 days - 2 weeks
MANAGEMENT
1) AC if <2hr or <4hr if modified release
2) if > 8hrs since ingestion, start NAC, check paracetamol level + ALT, if both normal can stop
3) if <8hrs since ingestion, plot 4 hr paracetamol level - treat if over
DISPOSITION
if NAC commenced - check ALT 2 hrs before the end of the infusion
INDICATION FOR TRANSFER TO LIVER CENTRE:
- INR > 3 @ 48hrs or > 4.5 at any time
- oligouria or creat >200
- acidosis pH < 7.3
- SBP < 80
- hypoglycaemia
- severe thrombocytopenia
- encephalopathy
Sodium Channel Blockade - drug causes
Agents responsible
•drugs from multiple classes
•toxic effects are not usually evident in therapeutic doses
-only evident in toxic doses
- amantadine
- carbamazepine
- chloroquine
- class Ia antiarrhythmics
- class Ic antiarrhythmics
- cocaine
- tricyclic antidepressants
- diltiazem
- verapamil
- propranolol
- diphenhydramine
- hydroxychloroquine
•local anaesthetics
-bupivacaine especially
- loxapine
- orphenadrine
- phenothiazines
- thioridazine
- propoxyphene
- quinine
CCBs / BBs
RISK
Verpamil or Diltiazem 2-3x the normal dose is serious, >10 tabs is life-threatening
CLINICAL Bradycardia 1st/2nd/3rd degree Heart Blocks Hypotension Refractory shock, myocardial ischaemia, stroke, mesenteric ischaemia Hyperglycaemia, lactic acidosis
MANAGEMENT
AC <1hr for IR, <4hr for SR
Whole Bowel Irrigation - if cooperative <4hrs, SR preparations
IVF
High Dose Insulin Therapy: 50ml 50% glucose + 1u/kg insulin bolus then 0.5u/kg/hr with 50ml 50% glucose /hr
IV Calcium: 20ml CaCL (60ml Ca gluconate) over 5-10mins, every 20mins x3
Catecholamines rarely effective
Electrical pacing may not achieve capture
Cardiopulmonary Bypass
ECMO
Intra-aortic Balloon Pump
DISPOSITION
d/c if normal vital signs and ECG
-4hrs for IR, 16hrs for SR
all others refer to ICU
Carbon Monoxide
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Hydrofluric Acid
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Lithium
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Iron
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Insulin / Sulfonylureas
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Organophosphates
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Anticonvulsants
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Venlafaxine
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Warfarin
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Corrosive agents
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Colchicine
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Cyanide
RISK
CLINICAL
MANAGEMENT
DISPOSITION
Paracetamol Modified Release
RISK:
≥ 10 g or ≥ 200 mg/kg (whichever is less)
Mx:
All patients meeting risk criteria should get AC if < 4hrs and should all receive the full 20hrs of NAC regardless of normogram levels
If not meeting RISK criteria then a level at 4 hours then another level 4 hours later should be checked
Paracetamol Repeated Supra-therapeutic Ingestion
RISK: ≥ 10 g or ≥ 200 mg/kg (whichever is less) over a single 24-hour period Or ≥ 12 g or ≥ 300 mg/kg (whichever is less) over a single 48-hour period Or ≥ a daily therapeutic dose‡ per day for more than 48 hours in patients who also have abdominal pain or nausea or vomiting
MANAGEMENT:
If meeting risk criteria then check paracetamol level and ALT. Commence NAC if paracetamol >20mmol/L or ALT > 50
Risk factors for hepatic toxicity in paracetamol OD
Alcohol abuse/dependance Prolonged fasting CYP 450 inducers -isoniazid -rifampicin -carbamazepine Ingestion of greater than 500mg/kg
Long QT Causes - other than drugs
Hypokalaemia Hypocalcaemia Hypomagnemaemia Hypothermia Raised ICP Congenital Long QT Syndrome
Long QT - drug causes
Antipsychotics Chlorpromazine Haloperidol Droperidol Quetiapine Olanzapine Amisulpride
Type IA antiarrhythmics
Quinidine
Procainamide
Type IC antiarrhythmics
Flecainide
Class III antiarrhythmics
Sotalol
Amiodarone
Tricyclic antidepressants
Amitriptyline
Doxepin
Nortriptyline
Other antidepressants Citalopram Escitalopram Venlafaxine Bupropion Moclobemide
Antihistamines
Diphenhydramine
Loratidine
Anti-infectives
Chloroquine / Hydroxychloroquine
Quinine
Macrolides: Erythromycin; Clarithromycin
Sodium Channel Blockade ECG
ECG
- clinically significant cases of toxicity will usually be evident on ECG by widening of the QRS complex.
- tall R wave in aVR is usually present and highly specific
- peaking of the T waves (as in hyperkalaemia) is usually absent
Indications for HCO3 therapy in Sodium Channel Blockade toxicity
•indications for HCO3-
- QRS duration > 100 msec
- persistent hypotension despite adequate fluid challenge
- haemodynamically significant arrhythmias
- seizures
