Pharmacotherapy Considerations in the Elderly

PK/PD Shifts - Old Doses, New Rules

• Pharmacokinetics (PK):
  • Absorption: Rate ↓, extent often similar.
  • Distribution: ↑ Body fat (↑ Vd lipophilic drugs, e.g., diazepam); ↓ body water (↓ Vd hydrophilic, e.g., lithium); ↓ albumin (↑ free drug).
  • Metabolism: ↓ Phase I (CYP450); Phase II preserved. 📌 LOGS (Lorazepam, Oxazepam, Temazepam) safer.
  • Excretion: ↓ Renal clearance (↓ GFR). Use $eGFR$ for dosing.
• Pharmacodynamics (PD):
  • ↑ Sensitivity to CNS drugs (benzos, antipsychotics).
  • Altered receptor response.
  • Impaired homeostasis. ⭐ > Elderly often require 50% of adult dose for many psychotropics due to PK/PD changes.

Psychotropics Parade - Mind Meds & Mishaps

General: 📌 "Start Low, Go Slow, But Go" (SLGSBG). ↑Sensitivity, ↓clearance.

• Antidepressants:
  • SSRIs (Sertraline, Escitalopram): 1st line. Risks: SIADH, hyponatremia, GI upset, QTc prolongation (Citalopram).
  • SNRIs (Venlafaxine, Duloxetine): Risks: ↑BP, falls. Duloxetine for neuropathic pain.
  • Mirtazapine: Sedating, appetite stimulant. Good for insomnia/poor appetite.
  • TCAs: Avoid (anticholinergic, cardiotoxic). 📌 "Can't see, can't pee, can't spit, can't shit".
• Antipsychotics:
  • Use: Psychosis, agitation in dementia (last resort). Lowest effective dose, shortest duration.
  • Risks: EPS, metabolic syndrome, falls, QTc prolongation.

  ⭐ Antipsychotics carry a Black Box Warning for increased mortality in elderly patients with dementia-related psychosis.

• Anxiolytics (Benzodiazepines - BZDs):
  • Avoid long-term. Risks: Sedation, falls, cognitive impairment, paradoxical disinhibition.
  • Prefer short-acting (e.g., Lorazepam, Oxazepam) if essential. 📌 "LOT" (Lorazepam, Oxazepam, Temazepam) BZDs.
• Mood Stabilizers:
  • Lithium: Narrow therapeutic index, ↓renal clearance. Target level: 0.4-0.8 mEq/L. Monitor renal function.
  • Valproate: Risks: Hepatotoxicity, thrombocytopenia. Monitor LFTs, platelets.
  • Lamotrigine: Risk: Stevens-Johnson Syndrome (SJS). Slow titration essential.

Prescribing Pearls - Wise Dosing & De-Escalation

• Dosing Strategy:
  • "Start Low, Go Slow": Initiate at 25-50% of standard adult dose; titrate slowly.
  • Factor in altered PK (Pharmacokinetics: ↓clearance, ↑Volume of distribution for lipophilic drugs) & PD (Pharmacodynamics: ↑sensitivity).
  • Choose drugs with better safety profiles; avoid high anticholinergic burden.
• Polypharmacy & Deprescribing:
  • Polypharmacy = ≥ 5 drugs. ⚠️ High Adverse Drug Event (ADE) risk.
  • Review meds regularly: Use Beers Criteria, STOPP/START to identify Potentially Inappropriate Medications (PIMs).
  • Taper PIMs gradually; monitor for withdrawal symptoms or condition relapse.

> ⭐ Polypharmacy (concurrent use of ≥ **5** medications) is a major independent risk factor for adverse drug events (ADEs), falls, cognitive impairment, and increased mortality in older adults. 

ADR Alert - Spotting Side Effect Specters

• ↑ ADR risk: Polypharmacy, ↓ renal/hepatic clearance, altered receptor sensitivity.
• Watch for common culprits & effects:
  • Anticholinergics: Confusion, dry mouth, constipation, urinary retention.
  • Benzodiazepines/Z-drugs: Sedation, cognitive impairment, ↑ fall risk.
  • Antipsychotics: EPS, tardive dyskinesia, metabolic syndrome, QTc prolongation.
  • TCAs: Cardiotoxicity, orthostasis.
  • NSAIDs: GI bleeds, renal toxicity.
• Mantra: "Start low, go slow." Review meds regularly.

⭐ Polypharmacy (use of ≥5 medications) is a major risk factor for ADRs, falls, and cognitive impairment in older adults.

High‑Yield Points - ⚡ Biggest Takeaways

• "Start low, go slow" is the guiding principle in geriatric prescribing.
• Altered pharmacokinetics (↓ clearance) & pharmacodynamics (↑ sensitivity) heighten ADR risk.
• Beware polypharmacy; simplify regimens and regularly review medications.
• Benzodiazepines: Use short-acting (e.g., LOT) sparingly due to fall/confusion risk.
• Antipsychotics: ↑ CVA/mortality risk in dementia; use lowest dose, shortest duration.
• Antidepressants: SSRIs (Sertraline, Escitalopram) preferred; avoid TCAs due to side effects.
• Minimize total anticholinergic burden to prevent delirium and cognitive decline.