JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D II Year PHARMACOTHERAPEUTICS-I Previous Question Paper (October/November - 2019 - R08)

Pediatric pharmacotherapy requires careful consideration because children are not merely miniature adults; their physiological and developmental differences significantly alter drug disposition. Key factors affecting therapy include:

• Absorption: Gastric pH is higher in neonates, affecting the absorption of weak acids and bases. Gastric emptying is prolonged, and intramuscular absorption is erratic due to reduced muscle blood flow.
• Distribution: Neonates have a higher percentage of total body water and lower body fat compared to adults, affecting the volume of distribution for water-soluble and lipid-soluble drugs. Reduced plasma protein binding (lower albumin levels) increases the free fraction of highly protein-bound drugs.
• Metabolism: Hepatic enzyme systems, particularly the cytochrome P450 pathways and glucuronidation, are immature at birth and reach adult levels at different rates during childhood, necessitating age-adjusted dosing.
• Excretion: Glomerular filtration rate (GFR) and tubular secretion are significantly lower in neonates and infants, reaching adult efficiency by 6 to 12 months of age. This requires careful monitoring to prevent drug accumulation and toxicity.
• Developmental factors: Rapid growth and developmental changes mean that drug requirements must be frequently recalculated based on body weight or body surface area.

Aging is associated with progressive physiological changes that alter the pharmacokinetics and pharmacodynamics of drugs, increasing the risk of adverse drug reactions. Key changes include:

• Gastrointestinal changes: Increased gastric pH, decreased gastric emptying, and reduced intestinal blood flow can delay or decrease the absorption of certain medications.
• Body composition: Elderly patients typically have decreased total body water and lean muscle mass, but increased body fat. This increases the volume of distribution for lipid-soluble drugs (prolonging their half-life) and decreases it for water-soluble drugs (increasing plasma concentrations).
• Hepatic function: Liver mass and hepatic blood flow decrease with age, leading to reduced first-pass metabolism and slower clearance of drugs metabolized by the liver.
• Renal function: A progressive decline in GFR and renal blood flow is common. This is the most critical factor in geriatric therapy, as it significantly reduces the excretion of renally cleared drugs, necessitating dose reductions.
• Pharmacodynamic changes: Increased sensitivity to certain drugs (e.g., benzodiazepines, anticholinergics, and antihypertensives) occurs due to changes in receptor sensitivity or homeostatic mechanisms, such as impaired baroreceptor reflex leading to orthostatic hypotension.