Toxicology Management Principles Quiz

Toxicology

• Toxicology is the study of poisons and their effects on living organisms.
• Management of toxicity focuses on enhancing elimination of toxins from the circulatory system

Principles of Management of Toxicity

• Methods to enhance toxin elimination are employed when:
  • The toxin is highly concentrated in the plasma compared to the organs.
  • The toxin and its metabolites are readily excreted in urine.
  • The toxin quickly detaches from plasma proteins.
  • The toxin has a small molecular weight.

Forced Diuresis

• Enhances excretion of drugs/metabolites through the kidneys.
• Ineffective for chemicals reabsorbed by renal tubules (low concentration in urine)
• Diuretics are used to increase urine output.
  • Examples of diuretics include mannitol and furosemide.

Alkalinization of Urine

• Promotes excretion of weak acids.
• Increases ionization of weak acids, leading to "ion trapping" in renal tubules.
• Examples of chemicals alkalinized by urine include: Na bicarbonate, acetazolamide, and weak acidic drugs such as salicylates, phenobarbitone, and methotrexate.

Acidification of Urine

• Promotes excretion of weak bases.
• Increases the ionization of weak bases, leading to "ion trapping" in renal tubules.
• Examples of chemicals acidified by urine include ammonium chloride and ascorbic acid, and weak basic drugs such as amphetamine, quinine, and phencyclidine

Extracorporeal Techniques

• Dialysis is an adjunct treatment for severely intoxicated patients.
• Not necessary for toxins with specific antidotes (e.g., opioid toxicity with naloxone).
• Ineffective for rapidly acting toxins (e.g., cyanide).

Dialysis Techniques

• Chemicals diffuse through a semipermeable membrane from a higher concentration area (blood and interstitial fluids) to a lower concentration area (dialysis solution).

• Peritoneal dialysis uses the patient's peritoneum as a semipermeable membrane for fluid and chemical exchange.

  • Adequate peritoneal blood flow is crucial for its effectiveness.
  • Dialysis solution typically contains sodium chloride, lactate, bicarbonate, and high glucose to make the fluid hypertonic.
  • Albumin is added for protein-bound toxins.
  • Complications of peritoneal dialysis include abdominal pain, protein loss, intraperitoneal bleeding, water and electrolyte imbalances, and intestinal, bladder, liver, and spleen perforation.

• Hemodialysis uses an artificial semipermeable membrane (artificial kidney) to filter chemicals from the blood. The method is less effective for highly protein-bound chemicals that do not pass through the semipermeable membrane

• Complications include infection, hypotension, and bleeding/clotting.

• Hemoperfusion involves passing blood through a column containing activated charcoal or ion exchange resins to adsorb toxic chemicals.

• It is more effective than peritoneal and hemodialysis due to a larger surface area.

Advantages of Hemoperfusion

• Suitable for detoxifying lipid-soluble and high protein-bound chemicals.

Complications of Hemoperfusion

• Trapping of WBCs and platelets.
• Activation of the clotting system.

Plasmapheresis

• A method to separate red blood cells from plasma.
• Fresh frozen or treated plasma is mixed with red blood cells and returned to the body.
  • Disadvantage: can cause patient's plasma proteins to be lost.

Chemical Antidotes

• Chemical antidotes react chemically with the poison to produce less toxic compounds.
• Example 1: Calcium salts react with oxalic acid to form a less soluble compound, which prevents absorption.
• Example 2: Chelating agents (dimercaprol, deferoxamine, EDTA, penicillamine) bind to heavy metals, creating water-soluble complexes that are excreted in urine.

Receptor Antidotes

• Receptor antidotes antagonize the receptor targeted by the poison.
• Example 1: Naloxone (µ-receptor antagonist) is an antidote for opioid-induced respiratory depression.
• Example 2: Atropine (M-receptor antagonist) is used to antidote organophosphate-induced cholinergic syndrome.
• Example 3: Physostigmine (cholinesterase inhibitor) is an antidote for atropine toxicity.

Functional Antidotes

• Functional antidotes oppose the physiological effects of the poison.
• Example 1: Epinephrine is used to treat anaphylactic reactions to combat effects such as bronchial constriction.
• Example 2: Vitamin K is used to reverse the effects of coumarin-induced hemorrhage, enhancing blood clotting factors.

Enzymatic Antidotes

• Enzymatic antidotes work with endogenous enzymes to detoxify.
• Example 1: N-acetylcysteine activates the endogenous glutathione (GSH) enzyme to detoxify acetaminophen.
• Example 2: Pralidoxime reactivates acetylcholinesterase, which is inhibited in organophosphate poisoning.
• Example 3: Ethanol is used to detoxify methanol by inhibiting alcohol dehydrogenase and reducing the formation of formic acid.

Supportive Treatments

• Hypertension: Sodium nitroprusside and other vasodilators (e.g., nitroglycerin, calcium channel blockers) are used to treat hypertensive crises.
• Anaphylaxis: Epinephrine, intravenous fluids, antihistamines, corticosteroids, and bronchodilators manage severe allergic reactions.
• Seizures: Benzodiazepines (e.g., diazepam, midazolam) and phenytoin are treatments for seizures caused by toxins.
• Electrolyte disturbances: IV calcium gluconate, sodium bicarbonate, diuretics, and polystyrene sulfonate are employed to correct abnormal electrolyte levels.
• Hyperthermia: In cases of malignant hyperthermia, dantrolene is used to reduce Ca2+ release from the sarcoplasmic reticulum, thus relaxing muscles.
• Exertional heat stroke: Treatment includes anticonvulsants, neuromuscular blockers, and evaporative cooling.
• Anticholinergic syndrome: Evaporative cooling and physostigmine (a cholinesterase inhibitor) are used to stimulate cholinergic mechanisms and counteract hyperthermia.