Drug Response in Infants and Children

Drug Response in Infants and Children

• Infants and children have different drug responses compared to adults due to their unique physiological characteristics.
• Body Composition: Infants have higher total body water than adults, primarily extracellular. Their fat content is lower, and their skin is thinner, leading to increased percutaneous absorption.
• Gastrointestinal Function: Gastric acid output is lower in neonates than in adults.
• Plasma Protein Binding: Plasma protein binding is reduced in neonates due to lower albumin concentration.
• Blood Brain Barrier: The blood-brain barrier (BBB) is more permeable in neonates, allowing for faster drug entry into the brain.
• Hepatic Enzyme Activity: Hepatic enzyme activity is low in neonates, affecting drug metabolism.
• Renal Clearance: Renal clearance is less efficient in neonates, with adult glomerular filtration rate attained after 3-5 months and adult secretory and reabsorptive capacity achieved after 7 months.
• Drug Elimination: Drugs that rely on renal elimination, such as aminoglycosides, are cleared slowly during the first few weeks of life.

Drug Response in Geriatrics

• Pharmacokinetics:

  • Absorption: Aging affects drug absorption due to reduced blood flow, intestinal surface area, gastric secretions, and delayed gastric emptying. This can lead to slower absorption and onset of drug action.
  • Distribution: Reduced water content and increased fat content in the elderly affect drug distribution. Lipid-soluble drugs have slower elimination, longer half-lives, and longer durations of action.
  • Metabolism: The rate of drug metabolism decreases with age due to reduced liver enzyme production.
  • Excretion: Decreased renal elimination leads to increased half-lives and durations of drug action.

• Pharmacodynamics: Drug responses in the elderly differ from adults because of alterations in receptor function and impaired physiological adaptive mechanisms associated with aging.

Challenges with Elderly Compliance

• Complicated Dosing Regimens and Polypharmacy: Elderly individuals may have difficulty adhering to complex dosing regimens and managing multiple medications (polypharmacy).
• Confusion: Age-related memory loss, cognitive impairments like Alzheimer's disease, or living alone can contribute to confusion and reduce compliance.
• Unpleasant Side Effects: Unpleasant side effects can discourage the use of medication.
• Drug Form: Difficulties swallowing large capsules or other forms of medication can affect compliance.
• Drug Container: Containers that are difficult to open or understand can also present challenges.

Drug Response in Infants & Children

• Body Built Differences:

  • Infants and children have a higher percentage of total body water compared to adults, with a larger proportion being extracellular.
  • Fat content in children is lower than adults.
  • Due to thinner skin, infants and children have an increased rate of percutaneous absorption.

• Gastrointestinal Function:

  • Neonates have lower gastric acid output compared to adults.

• Plasma Protein Binding:

  • Plasma protein binding is reduced in newborns due to a lower concentration of albumin.

• Blood Brain Barrier (BBB):

  • The BBB is more permeable in neonates.

• Hepatic Enzyme Activity:

  • Hepatic enzyme activity is low in the neonatal stage.

• Renal Clearance:

  • Renal clearance is less efficient in infants and children compared to adults.
  • Adult glomerular filtration rate is achieved after 3-5 months.
  • Adult secretory and reabsorptive capacity is reached after 7 months.
  • Drugs reliant on renal elimination, like aminoglycosides, are cleared very slowly in the first weeks of life.

Drug Response in Geriatrics

• Aging Effects on Pharmacokinetics and Dynamics:
  • Both pharmacokinetics and dynamics of drugs are affected by aging.

Pharmacokinetics:

• Drug Absorption:

  • Reduced blood flow, absorptive surface area in the intestine, gastric secretions, and delayed gastric emptying occur with age.
  • This results in slower drug absorption and slower drug action.

• Drug Distribution:

  • Older individuals experience a decrease in muscle and water content, while fat content increases.
  • Lipid-soluble drugs exhibit slower elimination, a longer half-life, and a longer duration of action in older adults.

• Drug Metabolism:

  • The rate of drug metabolism declines with age due to decreased production of liver enzymes.

• Drug Excretion by Kidney:

  • Decreased elimination leads to increased half-life and duration of action.

Pharmacodynamics:

• Drug Responses in the Elderly:
  • Drug responses in older adults differ from those in younger adults due to alterations in receptors and age-related impairment of physiological adaptive mechanisms.

Challenges with Elderly Compliance:

• Complicated Dosing Regimens and Polypharmacy:

  • Complicated drug regimens and polypharmacy can make it challenging for elderly individuals to adhere to their medication schedules.

• Confusion:

  • Age-related memory loss, Alzheimer's disease, and living alone can contribute to medication confusion.
  • This confusion tends to be directly proportional to the number of medications taken.

• Unpleasant Side Effects:

  • Unpleasant side effects associated with medications may discourage use in older adults.

• Form of Medication:

  • Elderly patients may have difficulty swallowing large capsules or other specific medication forms.

• Container Difficulty:

  • Difficulty opening or reading and understanding medication containers can present a challenge.