Diii: Outline the pharmacokinetic consequences of old age with examples

Absorption

  • No ∆ absorption (oral)
  • ↑gastric pH 2° atrophy & ↓GI BF
  • ↓first pass = ↑bioavailability
  • ↓motility = ↓abs & ↓peak
  • ↓abs from IM injections → erratic
  • ↓transdermal abs 2° ↓tissue BF

Distribution

  • Altered body composition
    • ↑body fat
    • ↓lean mass
    • ↓TBW
  • Alters VD of drugs
  • ↑lipophilic VD (amiodarone)
  • ↓hydrophilic VD (aspirin)
  • ↓protein synthesis → ↓PPB → not chemically relevant because ↑free drug clearance
  • May ↑drug interactions

Metabolism

  • ↓liver size
  • ↓liver BF
  • ↓1st pass metabolism
  • Drugs with high 1st pass (propranolol) = ↑free drug
  • pH II reactions unchanged
  • ↓pH I reactions (oxidation, reduction)
  • ↓activation of prodrugs i.e. perindopril
  • ↓plasma cholinesterase à ↑DoA SUX

Excretion

Kidney

  • ↓renal function with ↑age
  • ↓GFR
  • Affects clearance of H2O soluble drugs e. diuretics, lithium, digoxin
  • Depends on drug therapeutic index e. Dig TI v. narrow ∴accumulation dangerous

Liver

    • Depends on Hep BF + HER
    • HER depends on metabolising ability of liver
    • ↓Ph 1 clearance 2° ↓ liver size + BF
    • Mainly affects drugs with high ER i.e. propranolol

Dynamic

  • Responsiveness to drugs ↓with age
    • Altered rec no.
    • ∆ binding affinity
    • Diminished homeostatic mechanisms

Receptors

  • β receptor downregulation → ↓anti-HTN effects β-blocker
  • ↓Dopaminergic neurons → ↑risk extrapyramidal SE
  • ↓Cholinergic n’s & rec’s → altered memory, poor compliance

Homeostatic Mechanisms

    • CNS
      • ↓BF brain
      • Altered sensitivity to CNS drugs
      • BZD = ↑risk of delirium & falls
    • Reflex responses
      • ↓BaroR sensitivity & response
      • ↑postural HypoT with CVS drugs
    • RAAS
      • ↓plasma renin 2° ↓symp innervation juxtaglomerular
      • ∴elderly respond better to diuretics/CCB cf. β-blockers/ACEi