Toxicology

Question 1

Describe the metabolic pathway/biochemistry of toxicity in tylenol overdose?

Answer 1

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.

Question 2

How much acetaminophen is generally ingested to lead to toxicity?

Answer 2

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

Question 3

What are the primary parts of the body and organs that are damaged by acetaminophen toxicity? What time frame?

Answer 3

Liver: centrilobular liver necrosis within 3-4days

Kidneys and pancreas also injured

Question 4

Acetaminophen leads to what pH derangement?

Answer 4

Metabolic acidosis

Sometimes dialyzed

Question 5

What patients are at a higher risk for acetaminophen toxicity and why?

Answer 5

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

Question 6

How quickly do symptoms of toxicity develop in acetaminophen toxicity? What is the time frame of injury?

Answer 6

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

Question 7

How is acetaminophen toxicity diagnosed?

Answer 7

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.

Question 8

How is acetaminophen toxicity treated?

Answer 8

N-acetylcysteine (NAC):
Regenerates glutathione
Encourages sulfation pathway of acetaminophen metabolism
Antioxidant
Increases oxygenation of damaged hepatocytes

Question 9

How is N-acetylcysteine administered and what special considerations are given to pregnant patients?

Answer 9

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.

Question 10

Patient presents for acetaminophen overdose with unknown time of ingestion. What are the next steps to determine if treatment is indicated?

Answer 10

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.

Question 11

Patient presents for acetaminophen overdose with a known time of ingestion. What is the next step in determining treatment?

Answer 11

Check acetaminophen levels and use Rumack-Matthew nomogram.

Question 12

For acetaminophen tox. when can NAC be discontinued?

Answer 12

Acetaminophen levels less than 10mcg/mL, AST/ALT and PT are within normal limits or declining, and clinical improvement of patient.

Question 13

What adjunctive therapy can be used in acetaminophen toxicity and when is it used?

Answer 13

Hemodialysis

For massive ingestions leading to metabolic acidosis

Question 14

What toxidrome is seen with antihistamines such as diphenhydramine, chlorpheniramine, and with cyclic antidepressants?

Answer 14

Anticholinergic

Question 15

What are the classic symptoms of anticholinergic toxicity?

Answer 15

Dry, hot, flushed, mydriasis, delirium, urinary retention

Tachycardic, hypertensive, mild hyperthermia

Question 16

What toxodrome is seen with Jimson weed?

Answer 16

Anticholinergic

Question 17

What are the agents that lead to anticholinergic toxodrome?

Answer 17

Jimson weed
Atropine, Benztropine
Antihistamines
Cyclic antidepressants

Question 18

What is the treatment for anticholinergic tox?

Answer 18

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

Question 19

What are considerations to keep in mind when considering physostigmine in anticholinergic tox?

Answer 19

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

Question 20

TCA’s can cause what toxidrome?

Answer 20

Anticholinergic

Question 21

Explain Botulism

Answer 21

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

Question 22

Describe beta blocker toxicity: presentation, therapy

Which two beta blockers have unique effects?

Answer 22

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

Question 23

Which beta blocker can prolong QRS duration and why?

Answer 23

Propranolol

Blocks sodium channels leading to prolonged QRS and can also cause seizures

Question 24

Which beta blocker can affect the QTc and why?

Answer 24

Sotalol

Inhibits release of K+ from cells leading to prolonged QTc and predisposing to torsades

Question 25

How can Calcium channel blocker and beta blocker toxicities be differentiated?

Answer 25

Beta blockers can cause hypoglycemia, though this is more common in peds.
Ca channel blockers cause hyperglycemia and tend to be sicker

Question 26

What do you give in beta blocker toxicity when QRS duration is prolonged and hypotension is present?

Answer 26

Sodium bicarbonate

Question 27

Common symptoms with CO poisoning

Answer 27

Headache, dizziness, nausea, vomiting, myalgias, loss of consciousness, confusion, seizures

Question 28

What is the pathophysiology of CO poisoning?

Answer 28

Binds hemoglobin and shifts O2 dissociation curve to the left. Also inhibits phosphorylation in mitochondria both leading to chemical asphyxia. Inhibits myoglobin.

Question 29

What are the delayed effects of CO poisoning? What are predictive factors of this?

Answer 29

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.

Question 30

Patients extricated from fires should be empirically treated for what toxicities? What are the treatments?

Answer 30

Carbon Monoxide: O2 therapy, hyperbarics

Cyanide: hydroxocobalamin