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Toxicology Flashcards

1
Q

Ethylene Glycol

A

> 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
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2
Q

Methanol

A

> 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
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3
Q

Amisulpride

A

Atypical Antipsychotic

Risk > 4g

QT Prolongation, Torsades
Bradycardia - increases risk of torsades
Hypotension
CNS depression

16 hours observation, cardiac monitoring if abnormal ECG

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4
Q

Amphetamines / Sympathomimetics

A

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
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5
Q

Children, One Pill Kills

A 
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
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6
Q

Serotonin Syndrome - diagnostic criteria

A

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
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7
Q

Anticholinergic Syndrome

A 
•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
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8
Q

Neuroleptic Malignant Syndrome

A

•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)

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9
Q

Sympathomimetic Toxidrome

A 
•CNS excitation
-agitation
-tremor
-seizures
•hypertension
•tachycardia
•sweating
•mydriasis

Common sources

  • amphetamines
  • cocaine
  • LSD
  • caffeine
  • theophylline
  • phencyclidine
  • methylphenidate
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10
Q

Drugs with toxicity on withdrawal

A 
•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
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11
Q

Drug Withdrawal toxidrome

A 
•diarrhoea
•mydriasis
•piloerection
-“cold turkey”
•tachycardia
•lacrimation
•abdominal pain
•agitation
•hallucinations
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12
Q

Serotonin Syndrome Causes

A

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
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13
Q

Serotonin Syndrome Clinical Features

A

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
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14
Q

Serotonin Syndrome Treatment

A

•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
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15
Q

Corrosive Airway Injury

A

Alkalis
Acids
Glyphosate (herbicide)
Paraquat (herbacide)

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16
Q

Ventricular Tachycardia, Fast Sodium channel blockade causes

A 
Chloroquine / Hydroxychloroquine
cocaine
Flecanide
Local Anaesthetics
Procainamide
Propranolol
Quinine
TCAs
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17
Q

Prolonged QRS Duration - fast Na channel blockade

A 
Chloroquine / Hydroxychloroquine
cocaine
Flecanide
Local Anaesthetics
Procainamide
Propranolol
Quinine
TCAs
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18
Q

Contraindications to Activated Charcoal

A 
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

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19
Q

Useful Drug Levels

A 
Carbamazepine
Digoxin
Ethanol
Ethylene Glycol
Iron
Lithium
Methanol
Methotrexate
Paracetamol
Phenobarbitol
Salicylate
Theophylline
Sodium Valproate
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20
Q

Whole Bowel Irrigation

A

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

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21
Q

Common toxicological causes of seizures

A 
Venlafaxine
Tramadol
amphetamines
Bupropion
ETOH and BZD withdrawal
22
Q

Multi-Dose Activated Charcoal

A

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
23
Q

Multi-Dose Activated Charcoal

A

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
24
Q

Haemodialysis

A 
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

25
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
26
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 ```
27
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. ```
28
Digibind
Dose indications Side-effects
29
Naloxone
Dose Indications Side-effects
30
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
31
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
32
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
33
Carbon Monoxide
RISK CLINICAL MANAGEMENT DISPOSITION
34
Hydrofluric Acid
RISK CLINICAL MANAGEMENT DISPOSITION
35
Lithium
RISK CLINICAL MANAGEMENT DISPOSITION
36
Iron
RISK CLINICAL MANAGEMENT DISPOSITION
37
Insulin / Sulfonylureas
RISK CLINICAL MANAGEMENT DISPOSITION
38
Organophosphates
RISK CLINICAL MANAGEMENT DISPOSITION
39
Anticonvulsants
RISK CLINICAL MANAGEMENT DISPOSITION
40
Venlafaxine
RISK CLINICAL MANAGEMENT DISPOSITION
41
Warfarin
RISK CLINICAL MANAGEMENT DISPOSITION
42
Corrosive agents
RISK CLINICAL MANAGEMENT DISPOSITION
43
Colchicine
RISK CLINICAL MANAGEMENT DISPOSITION
44
Cyanide
RISK CLINICAL MANAGEMENT DISPOSITION
45
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
46
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
47
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 ```
48
Long QT Causes - other than drugs
``` Hypokalaemia Hypocalcaemia Hypomagnemaemia Hypothermia Raised ICP Congenital Long QT Syndrome ```
49
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
50
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
51
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

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