Toxicology Flashcards
History of poisoned patient
-The poison
=Type (drug/chemical/plant/animal)
=Duration (acute/chronic)
=Time
=Route
=Nature (deliberate/accidental)
-The patient
=Symptoms
=Signs
=Med and psych history
=Alcohol
Examination of poisoned patient
A to E
Opioid exam
-Pinpoint pupils not always that obvious), reduced respiration, reduced GCS, hypotension
=Codeine, morphine, heroin, methadone
Anticholinergic exam
-Dry mouth, mydriasis (blurred vision as dilated), urinary retention, reduced bowel sounds
SLOW DOWN
=Tricyclic antidepressants, antihistamines
Sympathomimetic/ stimulant
-Tachycardia, sweating, anxiety, seizures
=Amphetamines, cocaine, legal highs
-similar to MDMA, amphetamines and cocaine, resulting in increased levels of serotonin, dopamine and noradrenaline, resulting in a ‘high’ and feeling of euphoria
a common example is a stimulant NPS is mephedrone (‘bath salts’,’M-CAT’.’meow meow’). It is a cathinone and structurally similar to khat, a plant found in East Africa
another example is benzylpiperazine (‘Exodus’, ‘Legal X’, ‘Legal E’)
typically swallowed as a pill/powder (‘bombing’) or snorted
adverse effect profile similar to MDMA/cocaine, with the risk of serotonin syndrome
-Supportive, IV fluids active cooling ice, cooled fluids), diazepam for agitation/temperature, think about serotonin syndrome, early involvement of critical care
Sedative/ hypnotic
-Depressed conscious level, ataxia, dysarthria
-Alcohol, benzodiazepines, GHB/GBL
Cannabinoids
termed synthetic cannabinoid receptor agonists
commonly referred to as ‘spice’
typically sprayed on to herbal mixtures which are then smoked. Also available in liquid form which is then inhaled using e-cigarettes
similar adverse effects to cannabis
Hallucinogenic
can be either dissociatives and psychedelics
dissociatives produce a similar effect to ketamine, with a sense of not being connected to the physical body or time. A common dissociative NPS is methoxetamine (‘mexxy’)
psychedelics have a similar effect to LSD although NPS versions may also be a stimulant
Depressant
can be either opioid or benzodiazepine-based
usually taken as a pill or a powder
often structurally very similar to the original drug class, hence the adverse effects are similar
benzodiazepine NPS often have a significantly longer half-life
Investigations
-Obs
=Toxidrome, temp usually not sepsis and associated with poor prognosis (critical care)
-ECG
=QRS and QT intervals
-Bloods
=FBC, UE, LFT (INR, CK depending on drug)
=Assays: paracetamol, salicylate (aspirin), antiepileptic, lithium, digoxin
-Other clinical
=CXR
=Blood gases
General principles of management
-Decontamination (removal of chemical before absorbed)
=External (wash skin/ irrigation of eyes)
=GI (activated charcoal, whole bowel: large volume of polyethylene glycol administered orally/NG to flush, only used in life-threatening overdose of very toxic substance as metabolic shift and hemodynamically unstable)
Activated charcoal
-Reduced gut absorption of many drugs
-Consider inly if patient presents within 1 hour of ingestion
-Contraindicated
=Unprotected airway, intestinal obstruction
-Substance which activated charcoal does not absorb
=Iron, Lithium, ethanol/ ethanol, cyanide, acids/alkalis
Paracetamol overdose
-Clinical features
=Nausea, vomiting, abdominal pain
=Silent toxidrome: many are asymptomatic
=If untreated: liver failure 2-3 days, renal 3-5 days
-Investigations
=Paracetamol concentration ( 4 hours after ingestion, take immediately if already after 4 hours post ingestion)
=ALT (reflects liver structure if damaged)
=INR (synthetic function)
=Creatinine (renal function)
-Single acute overdose ingested in <1 hour
=Plot paracetamol against time, treat above line
=The minority of patients who present within 1 hour may benefit from activated charcoal to reduce absorption of the drug.
-Staggered overdose (therapeutic excess ingested in >1 hour
=Treat all patients
=NAC should be started, may be stopped depending on bloods
Risk factors for developing hepatotoxicity in paracetamol overdose
patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John’s Wort)
malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days
Interestingly, acute alcohol intake, as opposed to chronic alcohol excess, is not associated with an increased risk of developing hepatotoxicity and may actually be protective.
Describe NAC
-Replenishes glutathione (mops up paracetamol metabolites)
-Most effective if administered within 8 hours
Safe to stop NAC when ALT, INR, Paracetamol, creatinine normal
-Continue if ALT raised, INR >1.3, Paracetamol still present
-Adverse reactions to NAC very common
=Anaphylactoid (pseudo-allergic) reaction as histamine mediated (non-IgE mediated mast cell release)
=Clinically identical to anaphylaxis (histamine mediated)
=Not IgE mediated; do not need prior exposure to NAC, may not have a reaction ever again
=Not a contraindicated
=Temporarily stop NAC, antihistamines (chlorphenamine), bronchodilators (nebulised salbutamol), adrenaline, steroids prevent second phase response), restart after reaction settles at slower rate)
=Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects
When should NAC be given?
-the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity
-there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or
-patients who present 8-24 hours after ingestion of an acute overdose of more than 150 mg/kg of paracetamol even if the plasma-paracetamol concentration is not yet available
-who present > 24 hours if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal
=acetylcysteine should be continued if the paracetamol concentration or ALT remains elevated whilst seeking specialist advice
Criteria for liver transplantation after paracetamol liver failure
Arterial pH < 7.3, 24 hours after ingestion
or all of the following:
-prothrombin time > 100 seconds
-creatinine > 300 µmol/l
-grade III or IV encephalopathy
Antidepressant poisoning (TCA)
-Sodium channel blockade (heart and brain)
-Anticholinergic
-Alpha-1 adrenergic blockade
=QRS prolongation, tachycardia
=Reduced GCS, convulsions
=Temperature, delirium, urinary retention (anticholinergic)
-8.4% sodium bicarbonate to reverse sodium channel blockade if QRS
-Diazepam first line for convulsions, phenytoin contraindicated, if ongoing sedation intubation, ventilation
SSRI overdose
-QT prolongation, tachycardia, hyper/hypotension (blocked potassium channels): torsades
-Agitation, convulsions, reduced GCS
-Serotonin syndrome (neuromuscular excitation/ clonus, autonomic dysfunction, altered mental status, hyperpyrexia: DIC, Rhabdo, multi-organ failure)
-Long QT: give magnesium, risk of torsades
-Early referral to critical care, remove precipitating drugs, cooling, benzodiazepines, supportive care
Features of opioid misuse
rhinorrhoea
needle track marks
pinpoint pupils
drowsiness
watering eyes
yawning
Complications of opioid misuse
viral infection secondary to sharing needles: HIV, hepatitis B & C
bacterial infection secondary to injection: infective endocarditis, septic arthritis, septicaemia, necrotising fasciitis
venous thromboembolism
overdose may lead to respiratory depression and death
psychological problems: craving
social problems: crime, prostitution, homelessness
Management of opioid dependence
Harm reduction interventions may include
needle exchange
offering testing for HIV, hepatitis B & C
Management of opioid dependence
patients are usually managed by specialist drug dependence clinics although some GPs with a specialist interest offer similar services
patients may be offered maintenance therapy or detoxification
NICE recommend methadone or buprenorphine as the first-line treatment in opioid detoxification
methadone is a full agonist of the mu-opioid receptor - binds to these receptors in the brain and fully activates them. This action can relieve withdrawal symptoms and cravings. Has a long half-life
buprenorphine is a partial agonist of the mu-opioid receptor and an antagonist of the kappa-opioid. It binds to the mu-opioid receptors in the brain but only partially activates them. This partial activation is enough to alleviate cravings and withdrawal symptoms in individuals with opioid dependence. Furthermore, the binding of buprenorphine to the mu-opioid receptor is very strong, or ‘high affinity,’ meaning it can displace other opioids from these receptors and prevent them from exerting their effects. As a kappa-opioid receptor antagonist, buprenorphine may contribute to its ability to reduce symptoms of opioid withdrawal and potentially reduce depressive and dysphoric states.
compliance is monitored using urinalysis
detoxification should normally last up to 4 weeks in an inpatient/residential setting and up to 12 weeks in the community
Management of opioid
-Supportive
-IV fluids
-Active cooling (ice, cooled fluids)
-Diazepam for agitation/ temperature
-Emergency management of opioid overdose
IV or IM naloxone: has a rapid onset and relatively short duration of action. 200-400 micrograms IV/IM. Repeated doses or an infusion often required
Cannabis
Features of synthetic cannabinoid toxicity include:
CNS: agitation, tremor, anxiety, confusion, somnolence, syncope, hallucinations, changes in perception, acute psychosis, nystagmus, convulsions and coma.
Cardiac: tachycardia, hypertension, chest pain, palpitations, ECG changes.
Renal: acute kidney injury.
Muscular: hypertonia, myoclonus, muscle jerking and myalgia.
Other: cold extremities, dry mouth, dyspnoea, mydriasis, vomiting and hypokalaemia
Cocaine
Mechanism of action
cocaine blocks the uptake of dopamine, noradrenaline and serotonin
Adverse effects
-Cardiovascular
=coronary artery spasm → myocardial ischaemia/infarction
=both tachycardia and bradycardia may occur
=hypertension
=QRS widening and QT prolongation
=aortic dissection
-neurological
=seizures
=mydriasis
=hypertonia
=hyperreflexia
-psychiatric effects
=agitation
=psychosis
=hallucinations
-others
=ischaemic colitis is recognised in patients following cocaine ingestion. This should be considered if patients complain of abdominal pain or rectal bleeding
=hyperthermia
=metabolic acidosis
=rhabdomyolysis
Management of cocaine toxicity
-In general, benzodiazepines are generally first-line for most cocaine-related problems
-chest pain:
=benzodiazepines + glyceryl trinitrate
=if myocardial infarction develops then primary percutaneous coronary intervention
-Hypertension: benzodiazepines + sodium nitroprusside
-The use of beta-blockers in cocaine-induced cardiovascular problems is a controversial issue
=the American Heart Association issued a statement in 2008 warning against the use of beta-blockers (due to the risk of unopposed alpha-mediated coronary vasospasm) but many cardiologists since have questioned whether this is valid
=if a reasonable alternative is given in an exam it is probably wise to choose it
Ecstasy poisoning
Clinical features
neurological: agitation, anxiety, confusion, ataxia
cardiovascular: tachycardia, hypertension
hyponatraemia
this may result from either syndrome of inappropriate ADH secretion or excessive water consumption whilst taking MDMA
hyperthermia
rhabdomyolysis
Management
supportive
dantrolene may be used for hyperthermia if simple measures fail
Signs and symptoms of LSD intoxication
Patients with LSD toxicity typically present following acute panic reactions (known as bad trips), massive ingestions or unintentional ingestions.
Psychoactive symptoms
Variable subjective experiences
Impaired judgements which can lead to injury
Amplification of current mood which leads to euphoria or dysphoria
Agitation, appearing withdrawn - especially in inexperienced users
Drug-induced psychosis
Somatic symptoms
Nausea
Headache
Palpitations
Dry mouth
Drowsiness
Tremors
Signs
Tachycardia
Hypertension
Mydriasis
Paresthesia
Hyperreflexia
Pyrexia
Manifestations such as tachycardia, hypertension, pupillary dilation, tremor, and hyperpyrexia can occur within minutes following oral administration of 0.5-2 µg/kg.
LSD overdose complications
Respiratory arrest
Coma
Hyperthermia
Autonomic dysfunction
Bleeding disorders
The diagnosis of LSD toxicity is mainly based on history and examination.
Most urine drug screens do not pick up LSD.
Management of LSD overdose
Management of the intoxicated patient is dependent on the specific behavioural manifestation elicited by the drug.
Agitation, e.g. from a ‘bad trip’, should be first managed with supportive reassurance in a calm, stress-free environment. If ineffective, benzodiazepines are the medication of choice.
LSD-induced psychosis may require antipsychotics.
Massive ingestions of LSD should be treated with supportive care, including respiratory support and endotracheal intubation if needed. Hypertension, tachycardia, and hyperthermia should be treated symptomatically. Hypotension should be treated initially with fluids and subsequently with vasopressors if required.
Because LSD is rapidly absorbed through the gastrointestinal tract, activated charcoal administration and gastric emptying are of little clinical value by the time a patient presents to the emergency department.
Presentation of nitrous oxide misuse
Mechanism of action:
when inhaled, nitrous oxide acts as a dissociative anaesthetic, blocking the NMDA receptors, thus impairing the perception of pain and inducing a state of euphoria and relaxation
it also causes the release of endogenous opioids and dopamine, contributing to its addictive potential.
Clinical presentation:
psychological symptoms:
euphoria
altered perception of reality
hallucinations
anxiety
paranoia
neurological symptoms:
dizziness
headache
incoordination
numbness
tremors
physiological effects:
hypoxia
hypothermia
elevated heart rate and blood pressure
Long term effects of nitrous oxide abuse
vitamin B12 deficiency
chronic exposure to nitrous oxide can oxidise and inactivate vitamin B12, leading to deficiency
persistent misuse can lead to subacute combined degeneration of the spinal cord, resulting in irreversible neurological impairments.
psychological Issues: Chronic users may develop psychological dependencies, leading to mood disorders, anxiety, and other psychiatric conditions.
physical harm: The act of inhaling gas from containers or balloons poses a risk of lung damage, barotrauma, and frostbite.
