Selected Toxins

Acetaminophen

Mechanism of Toxicity

In overdose, depletion of glutathione leads to toxic effects

• NAPQi is formed during the metabolism of acetaminophen

• NAPQi is toxic but generally quickly converted to a benign compound after conjugated with glutathione when glutathione levels are adequate

Toxic Effects

There are four phases of toxicity

• Phase 1: 0-24 hours

Loss of appetite, nausea, and vomiting

• Phase 2: 24-72 hours

RUQ Abdominal pain, elevation of hepatic enzymes

• Phase 3: 72-96 hours

Continued abdominal pain/tenderness, vomiting

• Liver failure: Coagulopathy, jaundice, encephalopathy

• Death possible

• Phase 4: 96 hours-3 weeks

Recovery phase

Treatment

N-acetylcysteine

• Acts as a precursor to glutathione, which allows metabolism of NAPQi

Rumack-Matthew nomogram used to determine if treatment is necessary

Caution: there may be a window of time shortly beyond 24 hours when liver enzymes have not risen and levels of acetaminophen may seem non-toxic. Intermittently timed ingestions may also pose difficulty in diagnosis.  Always consult with a toxicologist or poison control center in acetaminophen overdose.

Methanol & Ethylene Glycol

Mechanism of Toxicity

Alcohol dehydrogenase converts methanol and ethylene glycol to toxic metabolites

Toxic Effects

Ethylene glycol

• Renal failure

• Heart failure

• Metabolic acidosis

• Hypocalcemia

Methanol

• Blindness

• Seizures

• Coma

• Metabolic acidosis

Treatment

Fomepizole

• Inhibits alcohol dehydrogenase allowing alcohols to be excreted by the kidney rather than converted to toxic metabolites

Ethanol

• Competes for alcohol dehydrogenase allowing alcohols to be excreted by the kidney rather than converted to toxic metabolites

Carbon Monoxide

Mechanism of Toxicity

Colorless, odorless gas produced during combustion (furnaces, cars, etc.)

Binds to hemoglobin and is converted to carboxyhemoglobin (binds preferably over oxygen)

• Other oxygen carrying sites also then bind to oxygen more tightly reducing the ability of oxygen to be released in tissue. This causes tissue level hypoxia.

Toxic Effects

• "Cherry red" skin appearance

• Lethargy

• Headaches

• Confusion

• Seizures 

• Coma 

• Death

Treatment

• Removal from CO containing environment

• 100% oxygen

• Hyperbaric oxygen

Cyanide

Mechanism of Toxicity

Can be in gas or salt form. Typical toxicity is from house fire. Other exposure sources are petroleum refining and photograph development. Apricot kernels have also been found to produce cyanide toxicity.

Inactivates metalloenzymes after binding. Cellular respiration is inhibited by inactivation of cytochrome oxidase leading to inadequate production of ATP.

Toxic Effects

• Cellular death

• Highly metabolic organs affected first (heart, brain)

• Death

Treatment

Hydroxocobalamin

Sodium nitrite

• Older treatment limited by induced methemoglobinemia

Iron

Mechanism of Toxicity

Traditionally a major cause of pediatric morbidity and mortality due to accidental ingestion

X-rays can confirm ingestion as iron pills are radiopaque

Toxic to GI tract, cardiovascular, and CNS systems

Toxic Effects

• Toxicity dependent on levels

As little as 20 mg/kg can be toxic

• GI disturbance (nausea, vomiting, abdominal pain)

• Hypotension

• Hypovolemia, metabolic acidosis

• Liver failure

• Multisystem organ failure

• Death

Treatment

Deferoxamine

• Chelator that binds iron and facilitates excretion by kidneys

Lead

Mechanism of Toxicity

Exposure occurs from environment

• Removal of lead from gasoline has decreased exposures

• Most exposure now comes from lead in paint applied prior to 1978.

• Lead exposure from plumbing and water supply can also occur such as in Flint, Michigan

Children absorb lead more readily than adults

Lead can be distributed into tissues such as bone and soft tissues

• Half-life of lead in bone and similar tissues is 20-30 years, which leads to long-term toxicity

Toxic Effects

CNS

• Depressed IQ

• Headaches

• Clumsiness

• Confusion

• Convulsions

• Coma

GI

• Intestinal spasms

• Constipation (sometimes diarrhea)

Blood

• Anemia (hypochromic, microcytic)

Treatment

Succimer

Dual therapy in setting of encephalopathy:

• Dimercaprol

Suspended in peanut oil, contraindicated with peanut allergy

• Calcium disodium edta

Organophosphates/Carbamates

Mechanism of Toxicity

Carbamates

• Reversibly bind to acetylcholinesterase leading to elevated acetylcholine levels

Organophosphates

• After a period of time, irreversibly bind to acetylcholinesterase leading to elevated acetylcholine levels

• Compounds used in insecticides

• Similar compounds used in nerve agents such as sarin and soman

Toxic Effects

Excess acetylcholine

• Miosis

• Diarrhea

• Lacrimation

• Salivation

• Vomiting

• Urination

• Weakness

• Hypertension

Treatment

Atropine 

Pralidoxime

• Reactivates acetylcholinesterase