Toxicology Flashcards
Describe the metabolic pathway/biochemistry of toxicity in tylenol overdose?
Cytochrome P450 converts acetaminophen into the toxic metabolite (NAPQI).
Glutathione metabolizes the toxic metabolic into non-toxic conjugates.
Hyperactive P450 or inadequate glutathione leads to toxicity.
How much acetaminophen is generally ingested to lead to toxicity?
Acute: more than 150 mg/kg, ~10 grams in an adult. More than 200mg/kg in kids.
Chronic: varies, but generally more than 3 grams per day leads to most deaths
What are the primary parts of the body and organs that are damaged by acetaminophen toxicity? What time frame?
Liver: centrilobular liver necrosis within 3-4days
Kidneys and pancreas also injured
Acetaminophen leads to what pH derangement?
Metabolic acidosis
Sometimes dialyzed
What patients are at a higher risk for acetaminophen toxicity and why?
Chronic ETOH abuse: increased ability to make the toxic metabolite
Anticonvulsants: induce P450 increasing production of toxic metabolite, phenobarbitol, carbamazepine, phenytoin
Starvation: decreases glutathione levels
How quickly do symptoms of toxicity develop in acetaminophen toxicity? What is the time frame of injury?
12-24 hours: Clinically silent, LFT’s often normal (in massive ingestions may present with early coma, metabolic acidosis, elevated lactate from mitochondrial toxicity)
24-72 hours: Onset of liver injury, AST is the most sensitive test, vomiting, RUQ pain
72-96 hours: Liver necrosis occurs, fulminant liver failure, encephalopathy, renal failure, coagulopathy, metabolic acidosis, cerebral edema, death
How is acetaminophen toxicity diagnosed?
Measure acetaminophen levels at 4 hours or more. Levels above 150mcg/mL at 4 hours indicates possible tox. Use Rumack-Matthew Nomogram.
Less than 4 hours is not useful unless zero
Labs: PT/INR is the first to increase, but note that NAC can increase INR up to 1.3. AST/ALT can get extremely high. AST is most sensitive. Bilirubin elevation indicates liver failure. Lipase. Lactate in massive ingestion. NH3 in altered mental status. BMP.
How is acetaminophen toxicity treated?
N-acetylcysteine (NAC):
Regenerates glutathione
Encourages sulfation pathway of acetaminophen metabolism
Antioxidant
Increases oxygenation of damaged hepatocytes
How is N-acetylcysteine administered and what special considerations are given to pregnant patients?
Given PO or IV
Both are equally efficacious, but IV is preferred with hepatic failure and intractable vomiting
Pregnant patients should be given IV because the baby is affected and higher concentrations are needed to cross the placenta.
Patient presents for acetaminophen overdose with unknown time of ingestion. What are the next steps to determine if treatment is indicated?
Measure acetaminophen levels and AST/ALT
If level is above 10mcg/mL or AST/ALT are elevated, then consider treatment.
If level is below 10 and AST/ALT are normal no treatment is required.
Also take into account symptoms. Coma, nausea, vomiting, RUQ pain, encephalopathy, renal failure, coagulopathy, acidosis.
Patient presents for acetaminophen overdose with a known time of ingestion. What is the next step in determining treatment?
Check acetaminophen levels and use Rumack-Matthew nomogram.
For acetaminophen tox. when can NAC be discontinued?
Acetaminophen levels less than 10mcg/mL, AST/ALT and PT are within normal limits or declining, and clinical improvement of patient.
What adjunctive therapy can be used in acetaminophen toxicity and when is it used?
Hemodialysis
For massive ingestions leading to metabolic acidosis
What toxidrome is seen with antihistamines such as diphenhydramine, chlorpheniramine, and with cyclic antidepressants?
Anticholinergic
What are the classic symptoms of anticholinergic toxicity?
Dry, hot, flushed, mydriasis, delirium, urinary retention
Tachycardic, hypertensive, mild hyperthermia
What toxodrome is seen with Jimson weed?
Anticholinergic
What are the agents that lead to anticholinergic toxodrome?
Jimson weed
Atropine, Benztropine
Antihistamines
Cyclic antidepressants
What is the treatment for anticholinergic tox?
Benzodiazepines
Cooling if needed
Foley for urinary retention
Physostigmine is mostly diagnostic and only given with consultation with toxicologist due to high risks to patient when giving
What are considerations to keep in mind when considering physostigmine in anticholinergic tox?
High risk to patients with history of seizures and reactive airway disease
Do not use with sodium channel blockers or prolonged QRS and or QTc
Use only with consult with toxicologist
TCA’s can cause what toxidrome?
Anticholinergic
Explain Botulism
C. botulinum has spores that create botulinum toxin
Prevents Ach from releasing at NM junction leading to weakness: dysphagia, ptosis, blurred vision, respiratory failure, floppy baby, descending paralysis
Infection through: home canning, raw honey, inhale spores from construction site, black tar heroin use, open wound infection, Botox
Therapy is supportive, ventilator support, antitoxins, contact CDC
Describe beta blocker toxicity: presentation, therapy
Which two beta blockers have unique effects?
Presentation: bradycardia, hypotension, heart block, hypoglycemia in kids, bronchospasm
Therapy: atropine, glucagon, epinephrine, norepinephrine, massive doses of insulin, intralipid, GI decontamination, charcoal in large doses that may be life threatening, IVF crystalloid, heart pacing, ECMO
Propranolol also blocks Na channels to stabilize the bembrane, but too much prolongs QRS duration and also can cause seizures
Sotalol blocks potassium efflux leading to prolonged QTc predisposing to torsades
Which beta blocker can prolong QRS duration and why?
Propranolol
Blocks sodium channels leading to prolonged QRS and can also cause seizures
Which beta blocker can affect the QTc and why?
Sotalol
Inhibits release of K+ from cells leading to prolonged QTc and predisposing to torsades
How can Calcium channel blocker and beta blocker toxicities be differentiated?
Beta blockers can cause hypoglycemia, though this is more common in peds.
Ca channel blockers cause hyperglycemia and tend to be sicker
What do you give in beta blocker toxicity when QRS duration is prolonged and hypotension is present?
Sodium bicarbonate
Common symptoms with CO poisoning
Headache, dizziness, nausea, vomiting, myalgias, loss of consciousness, confusion, seizures
What is the pathophysiology of CO poisoning?
Binds hemoglobin and shifts O2 dissociation curve to the left. Also inhibits phosphorylation in mitochondria both leading to chemical asphyxia. Inhibits myoglobin.
What are the delayed effects of CO poisoning? What are predictive factors of this?
Delayed neurological sequelae up to 40 days after exposure. Older age and loss of consciousness predict onset of delayed neuro findings. Can be focal neurologic findings or psych findings like apathy and memory deficits.
Patients extricated from fires should be empirically treated for what toxicities? What are the treatments?
Carbon Monoxide: O2 therapy, hyperbarics
Cyanide: hydroxocobalamin
