Toxicology Flashcards
How much ethylene glycol is potentially lethal?
> 1ml/kg or 1 mouthful in kids
What are the clinical features of ethylene glycol toxicity?
History - of drinking antifreeze, solvents, polish, brake fluid
30mins -> 12 hours: excitement, confusion, disorientation, ataxia, lethargy, stupor, coma N+V, myoclonus, seizures, CN deficits, nystagmus, ophthalmoplegia, facial palsy, dysarthria, dysphagia
12-24 hours: progressive cardio/resp failure
24-72 hours: renal failure from ATN
What will ix show in ethylene glycol toxicity?
- Raised ethylene glycol level
- Severe HAGMA -> this is artifactual due to high cross reactivity between lactate and glycolate
- High osmolar gap
- Low calcium - oxalate from ehtylene glycol metabolism celates ca and forms crystals
- Fluorescence of urine on exposure yo UV light
What is the goal of managing ethylene glycol toxicity?
Goal is to block alcohol dehydrogenase so ethylene glycol isn’t converted to glycolate (ethylene glycol is relatively non toxic, glycolate is extremely toxic)
How can you block ADH?
Alcohol
fomepizole (competitive inhibitor)
How is ethylene glycol toxicity managed?
RRT
Fomepizole
Thiamine (increased elimination)
B6 (increased elimination)
Don’t replace calcium unless low enough to cause clinical manifestations
What is serotonin syndrome?
Drug toxidrome precipitated by the use of serotonergic drugs leading to excessive activation of both central and peripheral serotonin post synaptic receptors
What are the peripheral actions of serotonin?
Vasoconstriction
Uterine contraction
Bronchoconstriction
GI motility
Plt aggregation
What does serotonin do in the CNS?
Modulates wakefulness, attention, mood, appetite, thermoregulation, motor tone and emesis
What drugs are serotonergic?
SSRIs e.g. fluoxetine
SNRIs e.g. venlafaxine
TCAs e.g. amitriptyline
MAOIs e.g. selegiline
Lithium
Antiepileptics lamotrigine, carbamazepine, valoprate
Antiemetics - ondansetron and metoclopramide
Anti-migraine - triptans
Opioids - fentanyl, methadone, tramadol
Illicit drugs - methamphetamine, apmphetamine, MDMA, psilocybin, LSD
Misc - linezolid, methylene blue, St John’s wort, fluconazole
What are the possible MOA of serotonergic drugs?
- Increased serotonin release
- Inhibit serotonin reuptakes
- Inhibit serotonin metabolism
- Activate serotonin receptors
- Inhibit cytochrome P450 (slows down metabolism of some serotinin drugs)
What are the clinical manifestations of serotonin syndrome?
Neuromuscular - clonus, tremor, hyperreflexia, hypertonicity
Autonomic - hyperthermis, tachycardia, hypertension, diarrhoea
Altered mental state - agitation, confusion, anxiety, coma
What is the differential diagnosis of serotonin syndrome?
Neuroleptic malignant syndrome
Anticholinergic toxicity
Serotonergic discontinuation syndrome
Malignant hyperthermia
Meningitis
Encephalitis
Describe anticholinergic syndrome
Occurs with the use of anticholinegrics and is characterised by hyperthermia, altered mental state but normal tone and reflexes along with dry erythematous skin
Describe NMS
Occurs secondary to drugs with dopaminergic effects e.g. antipsychotics
Progresses more slowly that serotonin syndrome and is a/w/ rigidity but not hyperreflexia or clonus. Resolves slowly.
How is serotonin syndrome managed?
- Discontinue serotonergic drugs
- Cyproheptadine can be used but evidence for its use is poor. It’s a serotonin antagonist
Usually resolves rapidly once trigger is stopped.
