NURS 232 Normal Aging Physiology and PK

NORMAL AGING PHYSIOLOGY & PHARMACOKINETICS

  • Presented by M. Webb, adapted from Dr. Ruth Staus, DNP, RN, ANP-BC, VBI.

PHARMACOKINETICS: THE DRUG’S JOURNEY THROUGH THE BODY

  • Definition: The process a drug undergoes from ingestion to elimination.

  • Key Concepts:

    • Pharmacokinetics: What the BODY does to the drug.

    • Pharmacodynamics: What the DRUG does to the body.

  • Four main processes:

    • Absorption

    • Distribution

    • Metabolism

    • Elimination

ABSORPTION

  • Refers to how drugs enter circulation from various administration routes (oral, IV, etc.).

RATE OF GI TRACT ABSORPTION

  • Factors affecting absorption:

    • Gastric blood flow

    • Gastric motility

    • Gastric pH

  • Cardiac output significantly influences all these factors.

EFFECT OF AGING ON GI TRACT ABSORPTION

  • Important changes:

    • Decreased gastric blood flow and motility leads to prolonged drug presence in the gut, potentially causing erratic absorption.

    • Example: Delayed effects of narcotics due to slower absorption.

    • Typically, individuals over age 60 have 25% less gastric acid production, raising gastric pH.

EXAMPLE: CALCIUM CARBONATE

  • Requires an acidic environment for proper absorption (dissociates into ionized calcium).

  • Aging affects gastric acid levels, complicating calcium absorption.

ABSORPTION RECAP

  • Key changes in absorption due to aging:

    • Decreased blood flow, motility, and gastric acid contribute to reduced medication absorption.

DISTRIBUTION

  • Process after absorption where drugs are distributed in the body:

    • Albumin: Binds acidic drugs.

    • Body fat: Distributes lipophilic drugs.

    • Body water: Involves hydrophilic drugs.

PROTEIN BINDING: ALBUMIN

  • Albumin: Produced by the liver, attracts and binds highly acidic medications.

  • Normal range: 3.4-5.4 gm/dl.

HIGH LEVELS OF PROTEIN BINDING

  • Medications with high protein binding include:

    • Phenytoin

    • Warfarin

    • Valproic Acid

    • Benzodiazepines etc.

CAUSES OF LOW ALBUMIN LEVELS

  • Factors leading to low albumin include:

    • Poor nutrition

    • Chronic kidney and liver diseases

    • Inflammatory states

    • Metabolic acidosis

DISTRIBUTION: PROTEIN BINDING

  • Only unbound (free) drugs actively affect the body.

IMPORTANCE OF PROTEIN BINDING

  • Example: Warfarin (99% bound); displacing even a fraction produces significant effects.

  • Compared to Amoxicillin (20% bound), where displacement has minimal effects.

SARCOPENIA AND VOLUME OF DISTRIBUTION

  • Sarcopenia: Age-related muscle loss affecting medication distribution.

  • Volume of Distribution (VD): Represents how a drug distributes in body tissue vs. plasma.

LIPOPHILIC DRUG AND SARCOPENIA: DIAZEPAM

  • Increased fat volume leads to prolonged drug presence and possible adverse effects due to slow fat release into blood.

CLINICAL EXAMPLE: DIAZEPAM

  • Higher body fat percentage in elderly increases Diazepam's volume of distribution.

  • Age affects metabolism rates (CYP P450 function decreases).

T ½ (HALF-LIFE) REVIEW

  • Time required for drug concentration to reduce by half.

  • 3-5 half-lives needed to reach steady state; similar for drug elimination.

ELIMINATION RECAP

  • Renal function decreases with age (10% decline per decade); key measures include GFR.

PHARMACOKINETICS & AGING RECAP

  • Absorption: Decreased overall.

  • Distribution: Low albumin & increased body fat affects lipophilic drug levels.

  • Metabolism: Decreased CYP function increases drug half-lives.

  • Elimination: Decreased renal filtration leads to prolonged drug presence.