Toxicology Flashcards
What would be your approach to toxicological emergencies?
Resuscitation Identify agent and quantify exposure Drug manipulation to limit absorption Specific antidotes General supportive care
What is the anion gap?
AG is elevated by presence of unmeasured anions in plasma:
Na + K) - (Cl + HCO3
Normal is 10-14mmol/l
What causes a raised anion gap caused by drugs?
Metformin & Methanol Isoniazid Cyanide Ethylene glycol & Ethanol Salicylate
What are the causes of a raised anion gap?
Cyanide
Alcohol ketoacidosis/ starvation ketoacidosis
Toluene
Metformin/ Methanol Uraemia DKA Paracetamol/ Paraldehyde/ Propylene glycol Isoniazid/ Iron Lactic acidosis Ethylene glycol Salicylates
What is the osmolar gap?
Measured - Calculated Osmolality
2Na + K + Urea + Glucose
What is a normal osmolar gap?
<10mosm/l
What causes a raised osmolar gap?
A raised osmolar gap is >=10mosml
Benzodiazepines
Sorbitol
Mannitol/ methanol
Phenytoin
IVIg
TURPS (Glycine)
Ethylene glycol/ ethanol
What causes a normal anion gap acidosis?
Normal anion gap 10-14
Addisons/ Acetazolamide
Bicarbonate loss (GI / renal)
Chloride excess
What causes a low anion gap?
Multiple myeloma (IgG) Electrolytes (raised - you only get a medal if you score highly! - Na/ Ca/ Mg) Dilutional Albumin loss/ Amphotericin Lithium
Where is ethylene glycol found?
Anti-freeze Coolant fluids Detergents Brake fluids Plastics/ polymer industry
What drugs does activated charcoal NOT bind?
Heavy metals
Alcohol
Strong acids/ alkalis
Cyanide
What is forced alkaline diuresis?
Used to eliminate acidic drugs with a low pKa such as aspirin, methotrexate and phenobarbital
Infusion of IV Bicarbonate + IV diuretic to target urinary pH 7.5
The acidic drug molecules are converted to the ionic form in the glomerulus and so not reabsorbed
What are the properties of drugs removed by RRT?
Small molecules
Water soluble
Low protein binding
Small Vd
What drugs are removed by RRT?
Beta blockers
Dabigatran
Sodium valproate/ sotalol
Metformin/ methotrexate
Anticonvulsants (Phenytoin, carbamazepine, barbiturates)
Lithium
What are the features of a cholinergic toxidrome:
Salivation Lacrimation Urination Diarrhoea Gastric cramping Emesis
Confusion, decreased GCS, bradycardia, sweating, hypotension
What are the causes of a cholinergic toxidrome?
Organophosphates Nerve agents (Novichok) Cholinesterase inhibitor overdose
What are the management principles of a cholinergic toxidrome?
Anti-cholinergics (atropine)
Anti-cholinesterase reactivator (pralidoxime)
Benzodiazepine
What are the features of an anti-cholinergic toxidrome?
Dilated pupils Delirium Flushing Fever Tachycardia Hypotension Urinary retention
What are the causes of an anti-cholinergic toxidrome?
Anti-histamines Anti-depressants Anti-Parkinsonian Anti-psychotics Atropine
What is the treatment of an anti-cholinergic toxidrome?
Supportive
- Cool
- Fluids
- Benzos for seizures
What are the features of serotonin syndrome?
Triad of:
- Altered mental status
- Autonomic dysfunction
- Neuromuscular hyperactivity (increased temp, seizures, rhabdomyolysis)
Hunters criteria (one of):
- Spontaneous clonus
- Inducible clonus and agitation
- Nystagmus and agitation
- Increased temperature and nystagmus or clonus
- Tremor and hyper-reflexia
What are the causes of serotonin syndrome?
SSRIs
Amphetamines
Ecstasy
What is the treatment of serotonin syndrome?
Benzodiazepines
Cyproheptidine (serotonin antagonist)
What are the features of a sympathomimetic toxidome?
Paranoia/ delirium Hyper-reflex is Tachycardia Hypertension Diaphoresis Piloerection
What are the causes of sympathomimetic toxidrome?
Cocaine
Amphetamines
Salbutamol
How is paracetamol metabolised?
Metabolised in the liver to gluconuride metabolites
Small amount metabolised by the P450 enzyme system to NAPQI (toxic)
NAPQI is bound to glutathione and renally excreted
In paracetamol OD the usual metabolism is overwhelmed, NAPQI production exceeds glutathione stores and NAPQI levels rise which results in toxicity
What is the antidote for paracetamol and how does it work?
N-acetylcysteine works by binding NAPQI and stimulating glutothione production
How does salicylate poisoning present?
Fever Tinnitus Hypoglycaemia Vertigo Visual disturbance Coagulopathy Pulmonary oedema Vomiting (activates CTZ) Respiratory alkalosis
What is the treatment of salicylate poisoning?
Forced alkaline diuresis
HD
How does tricyclic antidepressant overdose present?
- Anti-cholinergic sydrome (SLUDGE)
- Na channel blockade
Seizures, coma Tachycardia, Arrythmia prolonged QRS, hypotension Respiratory depression Dry mouth, prolonged gastric transit Urinary retention
What is the management of TCA overdose?
- Activated charcoal
- Sodium bicarbonate/ hyperventilation (to increase pH and reduced ionised free drug; NaHCO also increases Na load to overcome Na blockade)
- Lipid emulsion
What are the features of neuroleptic malignant syndrome?
NMS is due to dopaminergic blockade Triad of: - Fever - Rigidity - Autonomic instability Also: - Increased CK
What causes neuroleptic malignant syndrome?
Anti-psychotics Dopamine antagonists (metoclopramide) Rapid withdrawal of dopamine agonists (levodopa)
What is the treatment of neuroleptic malignant syndrome?
Dantrolene Bromocroptine (dopamine agonist)
What are the toxic effects of alcohols? (Methanol and Ethylene glycol)?
Methanol:
- Metabolic acidosis
- Optic nerve toxicity (blindness)
Ethylene glycol:
- Cerebral oedema
- Metabolic acidosis
- Renal failure
What is the antidote for alcohol poisoning and how does it work?
Fomepizole
- Key enzyme of alcohol metabolism is alcohol dehydrogenase
- Fomepizole inhibits alcohol dehydrogenase so preventing the metabolism of alcohol to toxic products
What is the pathophysiology of cyanide poisoning?
Cyanide reversibly binds to and inhibits cytochrome oxidase within the mitochondria, disrupting the electron transport chain and blocking aerobic respiration —> cytotoxic hypoxia
What are the features of cyanide toxicity?
- Confusion, seizures, tachypnoea, coma
- Lactic acidosis and raised ScvO2
What is the management of cyanide toxicity?
CAUTION - can be absorbed through skin
Antidotes:
- Amyl nitrate: converts Hb to metHb for which cyanide has a higher affinity (can result in failure of oxygen delivery)
- Hydroxocobalamin: binds cyanide to form cyanocobalamin - excreted in urine
- Sodium thiosulfate: binds cyanide to form thiocyanite (slow)
- Dicobalt edetate: colabate binds cyanide (toxic - administer with glucose)
What are the features of CO poisoning and why do they occur?
Features include:
- Mild confusion to coma
- Cherry red skin or cyanosed
- COHb >40% = life threatening, >60% = fatal
CO binds to Hb with a higher affinity than O2, shifting the O2 dissociation curve to the left. It also binds cytochrome oxidase, uncoupling cellular respiration (Like cyanide)
What are the features of paraquat poisoning?
Abdominal pain Vomiting Local corrosive effects Dyspnoea (due to pulmonary oedema —> pulmonary fibrosis - accelerated by oxygen) Cardiac, renal and hepatic dysfunction
Paraquat is founds in pesticides and has a low fatal dose with rapid onset
What is the management of paraquat poisoning?
- Minimise oxygen
- Cyclophosphamide/ methylprednisolone
- Palliative care
What is the management of beta blocker/ calcium channel blocker overdose?
- Fluids
- Atropine
- Inotropes/ vasopressors
- Electrical pacing
- Calcium chloride infusion
- Glucagon: increases intracellular cAMP (positive inotrope)
- HDIT
- VA-ECMO
What are the risk factors for digoxin toxicity?
- Drug interactions: amoxicillin, clarithromycin, amiodarone,quinine
- Reduced excretion: AKI
- Electrolyte abnormalities: hypoMg, hypoK, hyperNa, hyperCa
How does digoxin toxicity present?
- Bradycardia, hypotension
- ECG change: AV block, paroxysmal tachycardia with AV block, sinus Brady, ventricular tachycardia
What is the management of digoxin toxicity?
- AC
- Electrolyte correction
- Atropine
- Digibind (antibody fragments which bind digoxin)
What are the features of lithium toxicity?
Neurological: ataxia, dysarthria, tremor, seizures, coma
GI: N+V, diarrhoea
Renal: Polyuria, AKI
What is the management of lithium toxicity?
- HD
- Keep Na raised as impedes renal clearance
What is the pathophysiology of propofol infusion syndrome?
Prolonged infusion of high dose propofol (>4mg/kg/h)
Impaired mitochondrial function
How does propofol infusion syndrome present?
Metabolic acidosis
Rhabdomyolysis
Bradyarrythmias
Myocardial dysfunction
What is DRESS syndrome?
Drug Related Eosinophilia and Systemic Symptoms
A severe drug reaction with ~10% mortality
What are the causes of DRESS syndrome?
Anticonvulsants: Phenytoin, carbamazepine, sodium valproate
Antibiotics: Cefotaxime, Linezolid, Metronidazole, Vancomycin
Antidepressants: Fluoxetine
Antihypertensives: Amlodipine, Captopril
Allopurinol
Antiinflammatories: NSAIDs
How does DRESS syndrome present?
A delayed response - 2-6 weeks after exposure
- Fever
- Rash
- Lymphadenopathy
- Haematological and hepatic are most common systemic complications
**Eosinophilia only present in 30% of cases, however leukocytosis is common
What are the differentials for DRESS syndrome?
Steven-Johnson Syndrome/ Toxic Epidermal Necrolysis: Commonly with bullae and epidermal necrosis; faster onset of 1-3 weeks
Also consider: chemical/ toxins, GVHD, toxic shock syndrome (staph scalded skin)
What is the management of DRESS syndrome?
Withdraw the offending agent
Steroids
Supportive care
Consider referral to a burns centre
What is Steven Johnson Syndrome and TENs
Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare, acute and potentially lethal reactions that result in epidermal detachment and mucosal loss
SJS has <10% TBSA involvement
TEN has >30% TBSA involvement
They are immune mediated hypersensitivity reactions that are usually caused by drugs (75%) but also infection (25%)
What are the risk factors for SJS/ TEN?
Antibiotics: Co-trimoxazole (thus increased risk in HIV patients treated prophylactically)
Anticonvulsants: Carbamazepine, Phenytoin, Sodium Valproate
Bacterial infections: Mycoplasma pneumonia
Viral infections: Herpes, EBV, CMV
Other drugs: Paracetamol, NSAIDs, steroids (thus increased risk in patients with conditions such as SLE)
Radiotherapy
Genetic predisposition
What are the clinical features of SJS/ TEN?
Prodromal flu like illness Skin rash Mucosal ulceration Macular skin rash progressing to blistering Desquamation Epidermal detachment with pressure
What is the management of SJS/ TEN?
Withdraw any offending agent
Refer to dermatology and plastic surgeons
If >10% should be transferred to burns centre
Fluid resuscitation
Heat preservation
Treat as a burns patient
Strict barrier nursing
Eye care
Oral hygiene/ nutrition support
Analgesia (avoid NSAIDs, consider procedural sedation)
Why does Albumin effect the anion gap?
It is a negatively charged protein, a fall in albumin will result in an overestimation in anion gap
For every 1g, subtract .25
