JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D IV Year CLINICAL TOXICOLOGY Previous Question Paper (November/December - 2021 - R08)

Dialysis is an extracorporeal technique used to remove toxic substances from the blood. Its efficacy depends on the molecular weight, protein binding, water solubility, and volume of distribution of the toxin. It is highly effective for small, water-soluble molecules with low protein binding and low volume of distribution, such as methanol, ethylene glycol, lithium, and salicylates.

Indications for dialysis include severe clinical intoxication refractory to supportive care, ingestion of lethal doses of dialyzable toxins, presence of severe metabolic acidosis, or renal failure induced by the toxin.

Contraindications are relative but include severe hemodynamic instability, inability to achieve vascular access, or cases where the toxin is highly protein-bound or has a large volume of distribution, making the procedure ineffective.

Complications include hypotension due to rapid fluid shifts, electrolyte imbalances (e.g., hypokalemia, hypocalcemia), bleeding risks due to systemic anticoagulation, air embolism, infection at the access site, and rebound phenomena where toxin levels rise again after dialysis is terminated.

Genetic polymorphism refers to the occurrence of two or more genetically determined phenotypes in a population. In toxicokinetics, these variations in drug-metabolizing enzymes, transporters, and receptors significantly influence the absorption, distribution, metabolism, and excretion (ADME) of toxins.

• Metabolic Variation: Polymorphisms in cytochrome P450 enzymes (e.g., CYP2D6, CYP2C19) categorize individuals as poor, intermediate, extensive, or ultra-rapid metabolizers. This dictates the rate at which a pro-toxin is bioactivated or a toxin is detoxified.
• Toxicity Thresholds: Individuals with deficient enzyme activity may accumulate toxic metabolites, leading to enhanced toxicity at standard exposure levels, whereas ultra-rapid metabolizers may experience toxicity due to the rapid production of reactive intermediates.
• Transporter Polymorphisms: Variations in efflux transporters like P-glycoprotein affect the distribution of toxins into sensitive tissues such as the brain, altering the toxicodynamic profile.
• Clinical Significance: Understanding these genetic differences allows for the prediction of inter-individual variability in susceptibility to environmental toxins and chemicals, facilitating personalized risk assessment and the development of targeted therapeutic interventions in poisoning cases.