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
- CNS