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 response. Key factors include:

• Absorption: Gastric pH is higher in neonates, affecting the absorption of weak acids and bases. Gastric emptying time is prolonged, and intestinal motility is irregular, which can lead to unpredictable drug absorption.
• Distribution: Neonates have a higher percentage of total body water and lower body fat compared to adults. This leads to a larger volume of distribution for water-soluble drugs and a smaller volume for lipid-soluble drugs. Additionally, lower plasma protein concentrations (specifically albumin) result in higher free fractions of highly protein-bound drugs.
• Metabolism: Hepatic enzyme systems, such as the cytochrome P450 pathway, are immature at birth and reach adult levels at varying rates. This necessitates dosage adjustments to avoid toxicity from drugs cleared via hepatic metabolism.
• Excretion: Renal blood flow, glomerular filtration rate, and tubular secretion are significantly lower in neonates and infants. Renal function reaches adult maturity only by 6 to 12 months of age, making renally excreted drugs prone to accumulation.
• Developmental Factors: Rapid growth and developmental changes mean that drug requirements must be frequently reassessed based on weight, body surface area, and maturation of organ systems.

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

• Absorption: Aging leads to decreased gastric acid secretion, reduced gastric emptying, and decreased intestinal blood flow, which can slow the rate of drug absorption.
• Distribution: Elderly patients typically exhibit decreased total body water and lean body mass, but increased body fat. This increases the half-life of lipid-soluble drugs (e.g., diazepam) and decreases the volume of distribution for water-soluble drugs (e.g., digoxin). Serum albumin levels often decrease, leading to higher free concentrations of protein-bound drugs.
• Metabolism: Hepatic blood flow and liver mass decline with age, and the activity of phase I oxidative metabolic pathways (CYP450) is often reduced. This decreases the clearance of drugs that undergo extensive first-pass metabolism.
• Excretion: Renal function declines progressively due to a reduction in the number of functioning nephrons, decreased renal blood flow, and a decrease in glomerular filtration rate (GFR). This is the most critical factor in geriatric therapy, requiring dose reductions for drugs cleared renally.
• Pharmacodynamics: The elderly often show increased sensitivity to drugs affecting the central nervous system (e.g., benzodiazepines, opioids) and altered homeostatic responses, such as a diminished baroreceptor reflex, which increases the risk of orthostatic hypotension.