308 Overdose and poisoning Flashcards
How does cocaine cause toxicity?
-Increased levels of noradrenaline and dopamine in synaptic cleft
-↑Sympathetic activity as well as neuropsychiatric effects
-Increased heart rate → Arrhythmias
-Increased blood pressure →Aortic or coronary artery dissection, intracerebral bleed, subarachnoid haemorrhage
-Vasoconstriction → Coronary vasoconstriction leading to MI, splanchnic vasoconstriction leading to gut ischaemia
Remember: There may also be toxicity from whatever the drug is cut with!
What drugs is cocaine often cut with?
Caffeine; Aspirin; Benzocaine and Lidocaine (pain relief medications); Amphetamine
What are the signs and symptoms of cocaine toxicity?
-Euphoria/agitation, aggression, hallucinations, delirium, seizures
-Sweating, dilated pupils, nausea, vomiting
-Tachycardia, tachypnoea, hypertension, pyrexia
What are the diagnostic tests for cocaine toxicity?
ECG: Tachyarrhythmia
VBG/ABG: Metabolic acidosis
↑ creatinine kinase (↑5x upper limit=rhabdomyolysis)
What is the management of cocaine toxicity?
Treat symptoms
-If prolonged QRS: IV sodium bicarbonate
-Benzos for agitation, haloperidol if no response to two or more benzo doses
-If BP not coming down after benzos, can use -IV antihypertensives
-IV nitrate and local ACS protocol if chest pain with no response to benzos/signs of ischaemia on ECG
What is the mechanism of toxicity for opioids?
-Opioid receptors sit throughout nervous system, with activation generally leading to neuroinhibition
-Potentiated by coadministration of other CNS depressants such as alcohol and benzos
What are the signs and symptoms of opioid toxicity?
-Pinpoint pupils
-Respiratory depression leading to type 2 respiratory failure
-Decreased GCS +/- loss of airway
-Decreased BP and HR
-Milder toxicity: Nausea, vomiting, agitation
What are the diagnostic tests for opioid toxicity?
No specific tests
What is the management for opioid toxicity?
-Protect airway
-Remove opioid patches if present
-NALOXONE!
What is the mechanism of toxicity for Benzodiazepines?
-Positive modulator of GABA-A receptors
-GABA is your main inhibitory neurotransmitter
-This makes benzos CNS depressants
-MUCH more dangerous when combined with alcohol, opioids or TCAs
What are the signs and symptoms of benzodiazepine toxicity?
-CNS depression: Drowsiness, ataxia, dysarthria, coma
-Respiratory depression – far more serious in patients with COPD
-Severe: Rhabdomyolysis, Hypotension,hypothermia, AVN block,prolonged QT interval
What are the diagnostic tests for Benzodiazepine toxicity?
No specific tests
ECG: Potentially heart block or QT prolongation
What is the management of Benzodiazepine toxicity?
Protect airway and maintain adequate ventilation
Flumazenil: GABA-A receptor antagonist, can be used to avoid mechanical ventilation BUT high risk of rebound seizures, so uncommonly used
What are the features of toxicity for LSD?
Neuropsychiatric symptoms, risk of serotonin syndrome
What are the features of MDMA toxicity?
Release of serotonin and noradrenaline cause four potential profiles of severe toxicity:
- Severe serotonin syndrome (hyperpyrexial toxicity)
- Hepatic toxicity (can progress rapidly to fulminant liver failure)
- Cerebral toxicity (Neuropsychiatric symptoms, increased thirst drive leading to hyponatraemia and cerebral oedema)
- Cardiovascular toxicity (hypertension, tachyarrhythmias, heart failure)
What are the features of toxicity of popper (alkyl nitrates)?
Vasodilators that lead to methaemoglobinaemia and reduced oxygen carrying capacity of RBCs. MetHb concentration can be found on a blood gas.
Raised MetHb treated with methylthioninium chloride (also called methylene blue)
What are the features of toxicity of ketamine?
NMDA-receptor antagonist as well as some mu-opioid receptor agonism
Dissociation is main feature, followed by neuropsychiatric features, features similar to NMS, autonomic dysregulation and vasospasm
How does chlorine gas cause toxicity?
Once inhaled, diffuses into respiratory epithelium andhydrolyses into hydrochloric acid, which in turn generates chloride ions and ROS
Most commonly caused these days when hypochlorite bleach is mixed with an acid-based product like vinegar
What are the signs and symptoms of chlorine gas toxicity?
-Irritation of eyes and nose
-Sore throat, chest tightness, wheeze,SOB, stridor due to laryngeal oedema, pulmonary oedema
-Hypoxia and cyanosis can take up to 36 hours to develop
What is the management of chlorine gas toxicity?
-Supportive management, no antidote
-Nebulised bronchodilators if bronchospasm present
-CPAP for pulmonary oedema
-Intubation if at risk of airway compromise
What is the mechanism of toxicity for paracetamol?
-Hepatotoxicity due to accumulation of hepatotoxic metabolite, NAPQI (NAPQI detoxification needs glutathione)
Takes about 3-5 days to cause death
What are the signs and symptoms of paracetamol toxicity?
-Early: Usually asymptomatic, occasionally N&V, pallor, sweating
-24-72h: RUQ pain,deranged LFTs,raised INR
-72-120h: Signs of fulminant hepatic failure
What are the diagnostic tests for paracetamol overdose?
Paracetamol level
INR, albumin,ALT, AST
What is the management for paracetamol toxicity?
-N-Acetylcysteine replenishes glutathione and allows NAPQI to be detoxified
-Current guidance is to treat all patients with a staggered OD (paracetamol taken over more than one hour) and with biochemical abnormalities (e.g.: high ALT)
-For ODs taken over a time period of less than an hour, use paracetamol nomogram to determine need for treatment
King’s College Criteria for liver transplant in paracetamol OD
What things will prompt a referral/transfer to a liver transplantation centre?
Acidosis
Hepatic encephalopathy
Hyperlactatemia
Hyperphosphatemia
What is the mechanism of toxicity of NSAID’s?
-Accumulation of acidic metabolites leads to a metabolic acidosis
-Reduced prostaglandin synthesis leading to GI effects and AKI
What are the signs and symptoms of NSAID toxicity?
-N&V with epigastric pain in most patients
-AKI in large ODs
-Toxic encephalopathy in large ODs
-Metabolic acidosis
-Arrhythmias
What is the management of NSAID toxicity?
Supportive management
What is the mechanism of toxicity of aspirin?
-Uncouples oxidative phosphorylation, disrupts Krebs’ cycle, lactate rises, metabolic acidosis
-Salicylate stimulates respiratory centre leading to initial resp alkalosis
What are the signs and symptoms of aspirin toxicity?
-Mild: N&V, tinnitus, dizziness, hearing loss
-Moderate: Dehydration,restlessness, sweating, bounding pulse,hyperventilation
-Severe: Arrhythmias,ARDS, cerebral oedema (confusion, convulsions, coma), hyperpyrexia, heart failure, renal failure
What are the diagnostic tests for aspirin toxicity?
Salicylate levels
Blood gas
What is the management of aspirin toxicity?
-Raise pH of blood and urine to reduce penetration to CNS and increase excretion respectively
-Haemodialysis in severe poisoning
-Treat hyperthermia, convulsions and pulmonary oedema if present
What are organophosphates?
Insecticides
What is the mechanism of toxicity of organophosphates?
-Acetylcholinesterase inhibitors – work by binding to and inactivating acetylcholinesterase
-Acetylcholine stays bound to receptor, muscles do not have a chance to relax, go into spastic paralysis
Death due to not being able to breathe; either that or a ventricular arrhythmia
What is the management of organophosphate toxicity?
IV atropine
Pralidoxime if available (reactivatesacetylcholinesterase)
What is ethylene glycol found in?
Antifreeze, hydraulic brake fluids, some stamp pad inks, ballpoint pens, solvents, paints, plastics, films, and cosmetics
How does ethylene glycol cause toxicity?
It is an alcohol, so will cause intoxication
However, the issue is that it (eventually) is metabolised into oxalic acid
-Oxalic acid causes a metabolic acidosis and binds with calcium to make calcium oxalate crystals, which deposit in the brain (cerebral oedema), lungs (pulmonary oedema), heart (cardiac failure) and kidneys (acute renal failure)
What are the signs and symptoms of ethylene glycol toxicity?
Initially: Drunk
-Followed by: Metabolic acidosis,increased RR, HR and BP, pulmonary oedema, congestive cardiac failure
-And then, If still alive: Flank and renal angle pain,acute tubular necrosis
At some point: Seizures, multiple organ failure, death
What are the diagnostic tests for ethylene glycol toxicity?
Ethylene glycol level
Blood gas for pH
What is the management of ethylene glycol toxicity?
FOMEPIZOLE (competitive inhibitor of alcohol dehydrogenase, also used in methanol poisoning)
No fomepizole? Give them actual alcohol! (competitive inhibitor for alcohol dehydrogenase)
Give dialysis for severe poisoning
What is the mechanism of toxicity for local anaesthetics?
Blockade of voltage gated sodium and potassium channels
Most common cause of poisoning is accidental IV administration
What are the signs and symptoms of local anaesthetic toxicity/.
CNS: Agitation, paraesthesia, drowsiness, confusion, paralysis, convulsions, respiratory depression
Cardiac: High BP and HR followed by practically any arrhythmia
N&V, metabolic acidosis,hypokalaemia
What is the management for local anaesthetic toxicity?
-Atropine for bradycardia
-Sodium bicarbonate for metabolic acidosis
-IV lipid emulsification (Intralipid) therapy if life threatening cardiotoxicity
-Crucial to monitor heart
What is the mechanism of toxicity of carbon monoxide?
Binds to Hb, displaces oxygen, reduces oxygen carrying capacity
What are the signs and symptoms of carbon monoxide toxicity?
-Headache (90%), irritability, confusion, N&V, vertigo (50%), alteration in consciousness (30%)
-Ataxia, syncope, coma, death
-Cherry red skin colour is rarely seen
What are the diagnostic tests for carbon monoxide toxicity?
-Carboxyhaemoglobin (COHb) concentration on blood gas
-Sats probe will show high sats, as cannot differentiate between different forms of Hb
What is the management for carbon monoxide toxicity?
-High flow oxygen until COHb back within normal range
What is the mechanism of toxicity of tricyclic antidepressant?
-HIGHLY TOXIC due to combination of antimuscarinic blockade and cardiac sodium channel blockade
-Main cause of death is an arrhythmia leading to cardiovascular collapse
What are the signs and symptoms of tricyclic antidepressant toxicity?
-Anticholinergic signs and symptoms
-Drowsiness, convulsions, coma, clonus
-No real distinguishing features that will immediately make it obvious that the patient has taken a TCA OD
-Serotonin syndrome
What are the diagnostic tests for tricyclic antidepressant toxicity?
-No specific diagnostic test
-ECG is of upmost importance, with features includingprolongation of the PR, QRS and QT intervals, non-specific ST segment and T wave changes, and atrioventricular block. Prolonged QRS is a predictor ofconvulsions and ventricular arrhythmias
What is the management of tricyclic antidepressant toxicity?
-IV sodium bicarbonate if QRS is prolonged or refractory metabolic acidosis
-Otherwise supportive management, e.g.: treatinghypotension and convulsions whilst waiting for drug to leave circulation
What is the mechanism toxicity of SSRI’s?
Fatality is uncommon when taken alone which makes them safe
Main concern is SEROTONIN SYNDROME, if taken with other serotonergic agents
Serotonin syndrome tends to come on over minutes to hours post-exposure and death is usually due to hyperpyrexia induced multi-organ failure
Serotonin has an important role in thermoregulation, as well as promoting platelet aggregation and smooth muscle contraction (think blood vessels, bronchi, GI tract, etc)
What are the signs and symptoms of serotonin syndrome?
Triad of:
1. Altered mental state (occurs in 40% of patients with serotonin syndrome): Agitation, confusion, hallucination, drowsiness, coma
2. Neuromuscular hyperactivity (50%): Shivering, tremor, myoclonus, hyperreflexia, rhabdomyolysis
3. Autonomic instability (50%): Tachycardia, fever, high or low BP, flushing, diarrhoea, vomiting
What are the diagnostic tests for serotonin syndrome?
No specific tests
What is the management of serotonin syndrome?
-Mild cases resolve spontaneously within 24 hours
-Benzodiazepines are standard treatment
In severe cases, 5HT-2A antagonists such as cyproheptadine can be used (no RCT evidence however)
Treat hyperthermia, convulsions and rhabdomyolysis if present
What are some drugs that precipitate serotonin syndrome?
SSRI
SNRI
MAOI’s
Tricyclic antidepressants
Tramadol
Triptans
St John’s Wort
Linezolid
MDMA
Amphetamines
Cocaine
What is the mechanism of toxicity of SNRI’s?
More dangerous than SSRIs, because now we have lots of noradrenaline, so cardiovascular toxicity becomes a danger
What are the signs and symptoms of SNRI toxicity?
-Features of serotonin syndrome
AND
-Cardiovascular features: Sinus tachycardia, hypotension or hypertension and prolongation of the QT and QRS intervals
Torsade de pointes and cardiac arrest have been reported
What is the management of SNRI toxicity?
-Treat serotonin syndrome if present
-Treat hypotension if present
-Sodium bicarbonate for fluid-resistant metabolic acidosis and/or prolonged QRS
What is the mechanism of toxicity of antipsychotics?
All antipsychotics share dopamine-2 receptor blockade as a feature
-Typicalstend to bind to D2 receptors more strongly, so are more likely to cause extrapyramidal side effects, and also block to mAChRs, alpha-1 adrenoreceptors andhistamine-1 receptors
-Atypicals also bind to these receptors, but with a lower affinity
There is also some blockade of cardiac potassium channels
What are the signs and symptoms of antipsychotic toxicity?
-Acute dystonic reactions (D2 receptor blockade)
-Hypotension (alpha-1 adrenoceptor blockade) and tachycardia (mAChR blockade)
CNS depression (histamine-1 receptor blockade)
-Arrhythmias associated with prolonged QRS or QT (cardiac potassium channel blockade)
-Neuroleptic malignant syndrome (NMS) - rare in acute overdose
What is the management of antipsychotics toxicity?
-Procyclidine for dystonia
-IV magnesium if TDS or high-risk QT (note: this does not shorten the QT interval)
-Manage NMS if present
What is neuroleptic malignant syndrome?
A life-threatening, neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs
What is the cause of neuroleptic malignant syndrome?
It’s a multifactorial mechanism of action secondary to decreased dopamine activity
Most commonly occurring within3-9 days ofinitiation
Most common in patients being treated with an antipsychotic for the first time, rapid increasing of dose or when high doses are being used
Can be caused by withdrawal of dopaminergic agents like levodopa
What are the signs and symptoms of Neuroleptic malignant syndrome?
Neuromuscular: RIGIDITY (not present in serotonin syndrome), muscle cramps and tremors (usually first symptoms)
-Fever, excessive sweating
-Altered mental state: Agitation, drowsiness,delirium, coma
-ANS dysfunction
-Rhabdomyolysis
-High HR and RR
What is the management of Neuroleptic malignant syndrome?
Mainly supportive therapy. As death is usually a result of hyperthermia and rhabdomyolysis, treating these is a priority
Dantrolene can be used in severe cases (treats spasticity)
What are the signs and symptoms of lithium toxicity?
Mild: Tremor (lithium normally causes a fine tremor, which becomes coarse when toxic), blurred vision, polyuria, drowsiness, GI upset
Moderate: Increasing confusion,myoclonic jerks,choreoathetoid movements, incontinence,restlessness
Severe: Ataxia, convulsions, cerebellar signs,coma,arrhythmias, RENAL FAILURE
How is lithium toxicity diagnosed?
By testing the blood lithium level
What are the signs and symptoms of beta blocker toxicity?
Low HR
Low BP
AV block, asystole,QRS or QT prolongation
Bronchospasm
How is beta blocker toxicity treated?
-Atropine for bradycardia; can give inotropes if bradycardia associated with hypotension
-Severe hypotension, heart failure or cardiogenic shock: Can use IV glucagon
-Temporary pacing if bradycardia with AVN or SAN block
-Correct metabolic acidosis if present
-Nebulised bronchodilators for bronchospasm
How do Ca 2+channel blockers cause toxicity?
Dihydropyridine CCBs:
-Profound peripheral vasodilation
Non-dihydropyridine CCBs (cardioselective): -Bradycardia
-Effects more severe when taken with other cardiac drugs
What are the signs and symptoms of Ca2+ channel blockers
Hyperglycaemia is a marker of severe poisoning
What is the managements of Ca2+ channel blockers toxicity?
Treat symptoms
-Bradycardia alone: Atropine
-Mild to moderate hypotension: IV calcium
-Severe hypotension, heart failure or cardiogenic shock: IV glucagon. Vasopressors and inotropes can also be used
What is the mechanism of toxicity of digoxin?
It competes with potassium for N/K ATPase, so toxicity more likely when patient is hypokalaemia
What are the signs and symptoms of digoxin toxicity?
-Bradycardia with prolonged PR and QRS; sinus arrest, AVN block, ventricular ectopics, bigeminy, VF and VT can also occur.
-Hyperkalaemia in severe poisoning – marker of poor prognosis
-Xanthopsia (yellow bias in vision), N&V, blurry vision usually within 1-2h of acute OD
What is the diagnostic test for digoxin toxicity?
Blood digoxin concentration
What is the management of digoxin toxicity?
Digoxin specific antibodies (DigiFab) are the treatment of choice for severe
bradyarrhythmias and life-threatening ventricular arrhythmias, as well as severe hyperkalaemia not responding to conventional measures
Treat hyper/hypokalaemia conventionally
What is the antidote for Heparin poisoning?
Protamine
