What is the minimum toxic dose of Acetaminophen?
7.5 g/day in adults
Ingestion of ≥ 12 g in 24 hours is associated with a high risk of hepatotoxicity
Describe the pathophysiology of acetaminophen overdose.
Exhaustion of hepatic metabolic pathways causes increased formation of a toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine (NAPQI).
Glutathione initially inactivates NAPQI, but its reserves are eventually depleted, leading to NAPQI build-up.
NAPQI → irreversible oxidative hepatocyte injury → liver cell necrosis
List clinical features of acetaminophen overdose.
Nonspecific symptoms (nausea, vomiting, pallor lethargy) or asymptomatic in the first 24 hours after ingestion
Progressive liver impairment (RUQ pain, liver enlargement and tenderness, abnormal liver function tests)
If acute liver failure does not develop, patients typically begin to recover within 2 weeks after ingestion.
Acute kidney failure occurs in approx. 50% of patients with acute hepatic failure.
Describe the management of acetaminophen overdose.
Activated charcoal administered < 4 hours after ingestion (1 g/kg (maximum dose 50 g))
Measure acetaminophen (APAP) levels 4 hours after ingestion (or immediately, if ingestion occurred > 4 hours prior to presentation)
Antidote: PO or IV N-acetylcysteine (NAC)
Describe the antidote management of acetaminophen overdose.
Administered 4–24 hours after ingestion
NAC replenishes glutathione stores in the liver
Indications
Serum acetaminophen level above the treatment line when measured 4 hours after ingestion
Single ingestion of acetaminophen > 150 mg/kg (7.5 g irrespective of patient weight) if the acetaminophen level cannot be assessed within 8 hours of ingestion
History of acetaminophen ingestion with signs of liver injury
High serum acetaminophen level (> 10 mcg/mL) with an unknown time of ingestion
What are other options of management in acetaminophen overdose?
Treatment of liver failure
Liver transplant in severe cases
Describe the serotonin syndrome.
a life-threatening condition caused by serotonergic overactivity
List causes of the serotonin syndrome.
drugs that increase serotonin levels
Antidepressants (e.g., MAOIs, SSRIs, SNRIs, TCAs,vortioxetine, vilazodone, trazodone)
Anxiolytics (e.g., buspirone)
Opioids (e.g., tramadol, meperidine)
NMDA receptor antagonists (e.g., dextrometorphan)
Recreational stimulants (e.g., MDMA, cocaine)
Serotonin receptor antagonists (e.g., ondansetron)
Serotonin receptor agonists (e.g., triptane)
Antibiotics (e.g., linezolid)
Herbals (e.g., St. John's wort)
Risk-increasing factors
Concurrent use of two or more serotonergic drugs
Switching from one serotonergic drug to another without tapering
List clinical features of serotonin syndrome.
acute symptom onset (< 24 hours after intake of a drug that increases serotonin levels) [19]
Classic triad
Neuromuscular excitability
Autonomic dysfunction
Altered mental status
General: diaphoresis, hyperthermia
Cardiovascular: hypertension, tachycardia
Gastrointestinal: nausea, vomiting, diarrhea
Psychiatric: delirium, psychomotor agitation, anxiety
Neurological: hypertonia (especially in the lower extremities), hyperreflexia, myoclonus, tremor, clonus, horizontal ocular clonus, mydriasis, seizure, coma
Describe the diagnosis/DD of serotonin syndrome.
Diagnosis: is primarily based on patient history and clinical features.
Differential diagnoses
See differential diagnosis of drug-induced hyperthermia
Meningitis
Encephalitis
Describe the treatment of serotonin syndrome.
Immediate discontinuation of serotonergic drugs
Supportive care
Antihypertensives, fluid replacement
Benzodiazepines for sedation
Cyproheptadine
H1, 5-HT1A, and 5-HT2A receptor antagonists
Used for cases of serotonin syndrome that do not respond to supportive care
Cooling measures: ice packs and cold compresses
Prognosis: resolves within 24 hours with treatment
Describe the etiology of Anticholinergic syndrome.
Belladonna poisoning
Jimson weed/Angel's trumpet (Datura stramonium) poisoning: The plant contains alkaloids, such as atropine and scopolamine, which lead to anticholinergic intoxication and mydriasis (“gardener's pupil”).
Medications
Anticholinergic agents (e.g., atropine, benztropine, trihexyphenidyl)
Drugs with anticholinergic properties
Tricyclic antidepressives (predominantly doxepin, amitriptyline, imipramine, and trimipramine)
Antipsychotics (e.g., clozapine, quetiapine)
First-generation antihistamines (e.g., promethazine, dimenhydrinate)
List clinical features of anticholinergic syndrome.
Dry mouth, warm, flushed skin, thirst, tachycardia, arrhythmias, mydriasis, confusion, and agitation
Possibly anticholinergic delirium: Excessive use of tricyclic antidepressants (or other medications with significant anticholinergic effects) can cause life-threatening delirium, hallucinations, and psychomotor symptoms.
Describe the treatment of anticholinergic syndrome.
antidote for purely anticholinergic poisoning (e.g. atropine): physostigmine
Physostigmine is contraindicated in toxicity with tricyclic antidepressants, even in the case of severe anticholinergic symptoms, because it can cause cardiac arrest.
List early symptoms of salicylate toxicity.
tinnitus, nausea, vomiting, tachypnea, hyperpnea
List late symptoms of salicylate toxicity.
hyperthermia, agitation, delirium, seizures, noncardiogenic pulmonary edema
List diagnostics for ASS toxicity.
ABG: mixed respiratory alkalosis and increased anion gap metabolic acidosis [2]
Serum salicylate level: > 40 mg/dL [1]
BMP: hypokalemia, ↑ BUN, ↑ creatinine
Toxicology screen: evaluate for concurrent ingestions
Describe the treatment of ASS toxicity.
Stabilization of vitals
Oral/orogastric activated charcoal
IV sodium bicarbonate
Hemodialysis
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