L4. Management of Specific Poisoning

Management of Specific Poisoning

• Objectives: Management of specific poisoning conditions
  • Ionizing radiation
  • Benzene
  • Carbon monoxide
  • Cyanide
  • Alcohols
  • Acetaminophen
  • Salicylates/Aspirin

Ionizing Radiation (IR)

• Clinical effects: Acute radiation syndrome (N/V, fall in blood count, fever, infection). Chronic radiation syndrome (radiation sickness, cancer)
• Mechanism of toxicity: Production of free radicals (ROS). ROS damage DNA through electron scavenging causing DNA strand breaks (irreversible). ROS can induce mutation of the p53 gene leading to increased cancer risk.
• Treatment: Primarily supportive, blood transfusions, antibiotics for infection

Aromatic Hydrocarbons- Benzene

• Routes of Exposure: Swallowing, inhalation, cigarette smoke
• Clinical effects: Irritating to skin, eyes, GI and respiratory tract. Can cause chronic exposure toxicity resulting in anemia, leukopenia, thrombocytopenia and bone marrow depression.
• Mechanism of toxicity: Benzene metabolites bind covalently to proteins, DNA, and RNA affecting cells by mutation or apoptosis (human carcinogen). Oxidative stress contributes to benzene toxicity.
• Treatment: Supportive care (aspiration caution), no specific antidote

Carbon Monoxide (CO)

• Sources: Combustion of fuel, indoor heating, smoke, automobile exhaust
• Mechanism of toxicity: CO combines with Hb (220X more affinity that O2) forming carboxyhemoglobin (COHb) blocking O2 transport to tissues, leading to cellular hypoxia(potentially reversible), and damages endothelial cells leading to oxidative injury, impaired myocardial contractility, and lipid peroxidation. Heart and brain most affected
• Clinical Effects: Headache, confusion, loss of visual acuity, tachycardia, respiratory difficulty, convulsions, shock, metabolic acidosis, respiratory failure, and death
• Treatment: Stop exposure, remove patient (decontamination), maintain respiration, assist ventilation, O2 therapy, possibly hyperbaric O₂ therapy

Cyanide (CN)

• Sources: Fumigants, industrial chemicals, nail polish remover, burning plastics, fire
• Mechanism of toxicity: Inhibits cellular cytochrome oxidase, blocks aerobic O₂ utilization and forces a shift to anaerobic metabolism, leading to lactic acidosis.
• Clinical presentation: Headache, dyspnea, metabolic acidosis, nausea, vomiting, ataxia, coma, seizures, collapse and death
• Treatment: Supportive care, 100% oxygen (immediately to all patients), Hydroxocobalamin to bind and detoxify free cyanide forming less-toxic cyanocobalamin (vitamin B12).Sodium nitrite produces cyanide-scavenging methemoglobinemia, and sodium thiosulfate is used to treat cyanide converting it to a less toxic form (thiocyanate)

Alcohol Poisoning

• Methanol and Ethylene Glycol: Toxic alcohols often ingested accidentally or as ethanol substitutes
• Ethylene glycol: Used as antifreeze found in coolants.
• Toxicokinetics (EG): Metabolized by Alcohol Dehydrogenase (ADH) to glycoaldehyde, then to glycolic acid and glyoxylic acid. The final toxic metabolite is oxalic acid, causing kidney damage.
• Clinical presentation: CNS depression, nausea/vomiting, ataxia, nystagmus, hallucinations, coma, seizures; followed by cardiorespiratory toxicity(hypotension, tachypnea, congestive heart failure, myositis, pulmonary edema). Renal toxicity (flank pain, oxalate crystalluria, oliguric renal failure).
• Lab findings: Severe metabolic acidosis (increased anion gap), hypocalcemia, calcium oxalate crystals in the urine
• Treatment: Support, Decontamination, Ethanol (inhibit ADH), correction of acidosis (bicarbonate), and cofactors(like thiamine, pyridoxine). Hemodialysis might be needed for removal of the toxins

Methanol (Wood alcohol)

• Sources: Component of perfumes, solvents, brake fluid, windshield washer fluid
• Toxicokinetics: Converted to formaldehyde and then formic acid. Formic acid is highly toxic and causes metabolic acidosis
• Clinical presentation: Acute presentation with gastrointestinal symptoms, followed by visual disturbances, metabolic acidosis, difficulty breathing, coma or death.
• Treatment: Similar to ethylene glycol—supportive care, decontamination, ADH inhibition (ethanol or fomepizole), and bicarbonate for acidosis

Acetaminophen (Paracetamol) Poisoning

• High-risk groups: Malnourished, anorexic patients. Liver disease, HIV, chronic alcoholics,
• Mechanism of toxicity: Initially metabolized by glucuronidation and sulfation (non-toxic) pathways. However, at high doses CYP2E1 produces NAPQI, a highly reactive metabolite that damages liver tissues through depletion of glutathione.
• Toxicokinetics: Well-absorbed in the GI tract and metabolized rapidly in the liver. Less than 5% is excreted unchanged in urine.
• Clinical presentation: Initially asymptomatic, then nausea, vomiting, abdominal pain, followed by jaundice, liver failure.
• Treatment: Gastric decontamination, supportive care. N-acetylcysteine (NAC) within 8 hours for best outcome.

Salicylates

• Sources: Many over-the-counter products (e.g., aspirin).
• Mechanism of toxicity: Stimulates respiratory center in the brain causing hyperventilation initially, leading to respiratory alkalosis. Later, causes metabolic acidosis, hypoglycemia, and hypokalemia. Also can affect platelets and cause GI bleeding.
• Clinical presentation: Nausea, vomiting, dizziness, tinnitus (mild toxicity); hyperventilation, ataxia and malaise (moderate toxicity); lethargy, seizures, coma, metabolic acidosis, GI bleeding, increased prothrombin time, renal failure, hepatic toxicity, lung injury.
• Treatment: Supportive care, decontamination, alkalinization of urine and plasma to increase excretion. Hemodialysis for severe toxicity.