Pharmacokinetics and Pharmacodynamics in Aging

Special Populations

• Topics include obstetrics, pediatrics, and geriatrics.

Requirements

• Review the "Special Populations" presentation on Brightspace.
• Read these articles: Medication and the elderly, Drug-related illness in the elderly, Drug categories of concern in the elderly, Changes in Drug Response in Pregnancy, Changes in Drug Response in Neonates and Infants.
• Watch these videos: Elderly and their medication (3:03)

Objectives

• Describe how pregnancy affects pharmacokinetics and pharmacodynamics.
• Discuss the placenta's role in drug transfer to the fetus.
• Discuss medication risk labeling in pregnancy, lactation, and reproduction.
• Explain how neonates and pediatrics affect pharmacokinetics and pharmacodynamics.
• Note special considerations for pediatric drug administration.
• Explain how aging affects pharmacokinetics and pharmacodynamics.
• Discuss special considerations in drug administration for the elderly.

Pregnancy

• No further details

Pharmacokinetic Changes (Pregnancy)

• Absorption: Decreased gastric emptying, increased blood flow, increased pH. Cardiac output increases blood flow to organs and tissues. IV/IM/SC absorption increases.
• Distribution: Plasma volume increases 30-50%, decreasing circulating levels of some drugs. Body fat increases, which is a larger reservoir for lipophilic drug distribution. Protein dilution decreases protein binding.
• Metabolism: Pregnancy hormones influence metabolic enzymes, creating a variable drug effect.
• Elimination: Increased blood flow to the kidneys results in faster drug elimination. Tubular reabsorption increases, but hepatobiliary drug clearance decreases. Renal clearance can be difficult to predict.

Pharmacodynamic Changes (Pregnancy)

• Increased sensitivity to anesthetics
• Drug therapeutic indices may change
• Fetal considerations

Transfer to the Fetus

• The placenta is a semipermeable membrane that can metabolize some drugs.
• Approximately 40-60% of umbilical venous blood flow enters the fetal liver and undergoes first-pass metabolism.
• Drugs that increase placental transfer include lipophilic drugs, small molecular size drugs, drugs using placental transporters and drugs with a low degree of protein binding.

Pregnancy Risk Categorization

• The FDA removed the A, B, C, D, and X categories from drug labeling.
• Instead, labels now include a risk summary, clinical considerations and available drug data for Pregnancy, Lactation, and Females/Males of reproductive potential.

Nearpod Question 1

• Discuss factors affecting drug and dose choices for a man or woman trying to conceive, a woman in her first trimester and a woman in labor.

Pediatrics

• No further details

Pharmacokinetic Changes (Pediatrics)

• The primary difference in pharmacokinetics in pediatrics is the change in body composition with age.
• Lower muscle mass, lower body fat, lower plasma protein content, and higher total body water affect drug distribution and storage.
• The blood-brain barrier is more permeable.

Pharmacokinetic Changes (Pediatrics) -- Absorption

• Delayed gastric emptying (neonates), increased pH, delayed intestinal absorption (infants).
• Thin stratum corneum (skin) increases absorption.
• Variable IM absorption rates due to poor muscle mass, decreased movement, and increased capillary network.
• Respiratory: High minute ventilation but low tidal volumes and flow rates leads to increased absorption of gases but decreased absorption of some drugs

Pharmacokinetic Changes (Pediatrics) -- Distribution

• Greater for water-soluble drugs, lower for lipid-soluble drugs, decreased protein binding.
• Immature blood brain barrier increases CNS distribution.

Pharmacokinetic Changes (Pediatrics) -- Metabolism

• Phase I metabolism activity reduced in neonates.
• Increases progressively during the first 6 months, exceeds adult rates by the first few years for some drugs, slows during adolescence, and attains adult rates by late puberty.
• Drug metabolites eliminated primarily through bile or the kidneys.

Pharmacokinetic Changes (Pediatrics) -- Elimination

• Decreased glomerular filtration rate (GFR) in infants results in reduced elimination
• Decreased in tubular secretion leading to decreased elimination.

Pharmacodynamic Changes (Pediatrics)

• Respiratory immaturity
• Limited cardiovascular compensation
• Hypoglycemia risk
• Vulnerable to CNS depression

Nearpod Question 2

• How does the age of an infant, toddler, and teenager affect drug, dose, and frequency choices?
• Factors to consider for each age group.

Pediatric Drug Administration

• Intramuscular injections: use smaller gauge needle, site varies, volumes depend on age.
• Subcutaneous injections: Use 27 or 23 gauge needle in the upper arm.
• Intravenous injections: Appropriate size for the vein.
• Oral administration: Absorption variable, vomiting, use needle-less syringe.
• Other routes: Rectal, topical (vasoconstriction common in young children).

Nearpod Question 3

• A patient with generalized malaise provides a blister pack of medications without labels. How to identify the medications?

Nearpod Question 4

• Discuss common social complications regarding medication adherence in the elderly. (e.g., issues like confusion, memory loss, difficulties accessing medications, understanding directions).

Geriatrics

• No further details

Pharmacotherapy in the Elderly

• Prevalence of prescription drug use increases substantially with age. (Most older adults frequently take multiple medications)
• Despite decrease in gastric pH and gastric emptying, drug absorption is not drastically disturbed.
• Elderly are more likely to have chronic disorders that may worsen due to drug effects
• Mobility and fixed incomes can affect affordability / availability

Table of Changes in Aging

• Data presented in a table format. (e.g. Body water, lean body mass, body fat, serum albumen, kidney weight, and hepatic blood flow)

Pharmacokinetic Changes (Geriatrics) - Absorption

• Delayed gastric emptying, consumption of numerous medications and non-prescription drugs, altered nutritional habits.

Pharmacokinetic Changes (Geriatrics) - Distribution

• Reduced lean body mass, total body water, and increased fat percentage.

Pharmacokinetic Changes (Geriatrics) - Metabolism

• Reduction in Phase I metabolism
• First-pass metabolism impacted by aging (decreases by about 1 percent per year after age 40)
• Co-morbidities affect cardiac output.

Pharmacokinetic Changes (Geriatrics) - Elimination

• Reduced renal clearance: maintenance doses may need adjustments in ill or dehydrated patients.

Pharmacodynamic Changes (Geriatrics)

• No further details

Problematic Drugs in Elderly

• List of problematic medications and conditions to consider.

Preventable Causes of Drug-Related Events

• Categorizes causes of preventable drug-related events.

This quiz explores the changes in pharmacokinetics and pharmacodynamics that occur in older adults, particularly after the age of 40. It covers topics such as first-pass metabolism, medication dosage adjustments, and the impact of gastrointestinal physiology during pregnancy on drug absorption. Test your knowledge on how these factors affect drug efficacy and safety in elderly patients.