10.1 Geriatric Pharmacotherapy, Beers Criteria & Deprescribing

Geriatric Pharmacotherapy, Beers Criteria & Deprescribing

Executive Summary: Older adults represent the largest consumers of prescription medications, experiencing a disproportionate burden of adverse drug events (ADEs), drug-drug interactions, and medication-related hospital admissions. Age-related physiological decline alters drug absorption, volume of distribution, hepatic clearance, and renal elimination. The Board Certified Ambulatory Care Pharmacist (BCACP) must apply evidence-based screening tools—specifically the 2023 American Geriatrics Society (AGS) Beers Criteria® and STOPP/START criteria—to detect potentially inappropriate medications (PIMs), mitigate anticholinergic cognitive burden, and execute structured deprescribing protocols to optimize patient safety, functional independence, and quality of life.

1. Physiological Changes of Aging & Pharmacokinetics (ADME)

Aging is characterized by progressive, heterogeneous declines in organ function that fundamentally alter drug disposition and sensitivity.

┌────────────────────────────────────────────────────────────────────────┐
│            PHARMACOKINETIC ALTERATIONS IN OLDER ADULTS (ADME)          │
├──────────────┬─────────────────────────────┬───────────────────────────┤
│ PARAMETER    │ PHYSIOLOGICAL CHANGE        │ CLINICAL IMPLICATION      │
├──────────────┼─────────────────────────────┼───────────────────────────┤
│ Absorption   │ • ↑ Gastric pH (less acid)  │ • ↓ Absorption of iron,   │
│              │ • ↓ Splanchnic blood flow   │   calcium carbonate, and  │
│              │ • Delayed gastric emptying  │   ketoconazole/itraconazole│
├──────────────┼─────────────────────────────┼───────────────────────────┤
│ Distribution │ • ↓ Total body water (10-15%)│ • ↓ Vd for hydrophilic   │
│              │ • ↑ Body fat percentage     │   drugs (digoxin, ethanol,│
│              │ • ↓ Serum albumin           │   lithium, aminoglycosides)│
│              │ • ↑ Alpha-1-acid glycoprot. │   → ↑ peak concentrations │
│              │                             │ • ↑ Vd & prolonged t1/2  │
│              │                             │   for lipophilic drugs    │
│              │                             │   (diazepam, lidocaine)   │
│              │                             │ • ↑ Free fraction of acidic│
│              │                             │   drugs (phenytoin,       │
│              │                             │   warfarin, valproate)    │
├──────────────┼─────────────────────────────┼───────────────────────────┤
│ Metabolism   │ • ↓ Hepatic blood flow (20-40%)│ • ↓ Phase I metabolism  │
│              │ • ↓ Hepatic mass & volume   │   (oxidation, reduction)  │
│              │ • ↓ First-pass metabolism   │ • Phase II (conjugation)  │
│              │                             │   intact ('LOT' benzos:   │
│              │                             │   Lorazepam, Oxazepam,    │
│              │                             │   Temazepam preferred)    │
├──────────────┼─────────────────────────────┼───────────────────────────┤
│ Excretion    │ • ↓ Renal mass & glomeruli  │ • Marked ↓ renal clearance│
│              │ • ↓ GFR & tubular secretion │ • Falsely normal serum Cr │
│              │ • ↓ Skeletal muscle mass    │   due to low muscle mass  │
│              │   (decreased Cr production) │ • Must estimate CrCl via  │
│              │                             │   Cockcroft-Gault         │
└──────────────┴─────────────────────────────┴───────────────────────────┘

Detailed Pharmacokinetic Mechanisms

1. Absorption

While passive intestinal absorption remains largely intact with aging, decreased gastric hydrochloric acid secretion raises gastric pH. This impairs the dissolution and absorption of pH-dependent medications, such as calcium carbonate (calcium citrate is preferred in older adults because it does not require an acidic milieu), iron salts, and azole antifungals (itraconazole, ketoconazole). Delayed gastric emptying slows the rate of drug absorption ($C_{max}$ delayed, $T_{max}$ prolonged), though total bioavailability ($AUC$) is usually unaffected.

2. Distribution

• Decreased Total Body Water: Hydrophilic drugs distribute into a smaller volume of distribution ($V_d$). Standard weight-based loading doses of drugs such as aminoglycosides, digoxin, and lithium result in substantially higher initial peak plasma concentrations ($C_{max}$), increasing toxicity risk.
• Increased Body Fat (Adiposity): Relative body fat increases by 20% to 40% in older individuals. Lipophilic medications (e.g., diazepam, chlordiazepoxide, amiodarone) distribute into an expanded lipid reservoir. This substantially increases their $V_d$ and prolongs their terminal elimination half-life ($t_{1/2} = 0.693 imes V_d / Cl$), resulting in prolonged sedation and hangover effects.
• Decreased Serum Albumin: Malnutrition, chronic inflammation, and frailty decrease hepatic albumin synthesis. Acidic drugs that are highly protein-bound (>90%), such as phenytoin, warfarin, and valproic acid, demonstrate a higher unbound (free) active fraction. Standard total serum assays may appear normal or low while free drug concentrations reach toxic levels. For phenytoin, clinicians must calculate the adjusted concentration: $\text{Phenytoin}_{\text{adjusted}} = \frac{\text{Phenytoin}_{\text{measured}}}{(0.2 \times \text{Albumin}) + 0.1}$

3. Hepatic Metabolism

Hepatic blood flow decreases by 20% to 40% and functional liver volume declines with age.

• Phase I Metabolism (CYP450 oxidation, reduction, hydrolysis): Substantially diminished in older adults. Drugs undergoing extensive Phase I clearance (e.g., diazepam, alprazolam, theophylline, propranolol) exhibit reduced hepatic clearance and prolonged half-lives.
• Phase II Metabolism (Glucuronidation, sulfation, acetylation): Relatively preserved in healthy older adults. When a benzodiazepine is clinically essential, the 'LOT' agents (Lorazepam, Oxazepam, Temazepam) are preferred because they undergo direct Phase II glucuronidation to inactive polar metabolites without producing long-acting active Phase I oxidative intermediates.

4. Renal Elimination

Renal function declines progressively after age 40 at an average GFR loss of 0.8 to 1.0 mL/min/1.73 m² per year due to glomerulosclerosis, loss of functional nephrons, and decreased renal cortical perfusion. Sarcopenia (loss of skeletal muscle mass) results in reduced baseline endogenous creatinine production. Consequently, an older adult may have a 'normal' serum creatinine (e.g., 0.7–0.9 mg/dL) despite a severely impaired true creatinine clearance (<30 mL/min). Dosing adjustments for renally eliminated drugs (DOACs, gabapentinoids, digoxin, ACE inhibitors, cephalosporins) must always be calculated using the Cockcroft-Gault equation.

2. The 2023 AGS Beers Criteria®: High-Risk Medications to Avoid

The American Geriatrics Society (AGS) Beers Criteria® identifies medications that are potentially inappropriate for older adults across five distinct categories: (1) medications generally to avoid, (2) medications to avoid in specific diseases/syndromes, (3) medications to use with caution, (4) potentially clinically important drug-drug interactions, and (5) medications to avoid or dose-adjust based on renal function.

Comprehensive Review of High-Risk Beers Categories

3. Anticholinergic Cognitive Burden & The ACB Scale

Many medications possess anticholinergic activity, and the cumulative anticholinergic load—termed Anticholinergic Cognitive Burden (ACB)—is a major determinant of physical and cognitive impairment in older adults.

                               ANTICHOLINERGIC BURDEN SCALE (ACB)
                               
    [ Score 1: Definite In Vitro Anticholinergic Activity (Weak Clinical Effect) ]
    • Atenolol, Captopril, Digoxin, Furosemide, Nifedipine, Prednisone, Ranitidine, Metoprolol
                         │
                         ▼
    [ Score 2: Moderate Anticholinergic Burden (Clinical Anticholinergic Activity) ]
    • Carbamazepine, Cyclobenzaprine, Amantadine, Oxcarbazepine, Loxapine, Pimozide
                         │
                         ▼
    [ Score 3: Severe Anticholinergic Burden (Marked Central & Peripheral Anticholinergic Toxicity) ]
    • Amitriptyline, Clomipramine, Doxepin, Imipramine, Paroxetine, Chlorpheniramine, Hydroxyzine,
      Diphenhydramine, Meclizine, Promethazine, Oxybutynin, Tolterodine, Benztropine, Trihexyphenidyl

Clinical Implications of ACB Score:

• A cumulative ACB Score $\ge 3$ is strongly associated with an increased risk of incident dementia, acute delirium, recurrent falls, functional dependence, and all-cause mortality.
• When evaluating an older patient presenting with memory loss, constipation, dry mouth, or unsteady gait, calculate the total ACB score before assuming primary neurodegenerative decline. Discontinuing or switching ACB Score 2 and 3 agents to non-anticholinergic alternatives frequently reverses cognitive and functional impairment.

4. STOPP/START Criteria

The STOPP (Screening Tool of Older Persons' Prescriptions) and START (Screening Tool to Alert to Right Treatment) criteria are validated, physiology-based explicit screening tools designed to identify both Potentially Inappropriate Medications (PIMs) and Potential Prescribing Omissions (PPOs) in adults $\ge 65$ years.

Key Comparisons between Beers and STOPP/START

• AGS Beers Criteria: Formulated primarily by drug classes; focuses on medications to avoid independent of or within specific disease states.
• STOPP/START Criteria: Formulated by organ system (Cardiovascular, CNS, Gastrointestinal, Respiratory, Musculoskeletal, Endocrine, Urogenital). It uniquely incorporates the START component to alert clinicians to guideline-directed therapies that should be initiated for older adults with specific chronic conditions.

High-Yield STOPP Criteria (PIMs)

1. Cardiovascular: Loop diuretics as first-line monotherapy for hypertension (unnecessary; use thiazides); Digoxin >125 mcg/day in renal impairment; Beta-blocker in combination with verapamil/diltiazem (severe bradycardia / heart block).
2. Central Nervous System: SSRIs with concurrent hyponatremia (worsens SIADH); TCAs in dementia, glaucoma, cardiac conduction abnormalities, or chronic constipation; First-generation antihistamines for >1 week.
3. Gastrointestinal: PPI for uncomplicated peptic ulcer disease at full therapeutic dose for >8 weeks; Antispasmodics in chronic constipation or bowel obstruction.
4. Renal / Musculoskeletal: Long-term NSAIDs in GFR <50 mL/min or severe heart failure; Long-term systemic corticosteroids for osteoarthritis.

High-Yield START Criteria (Prescribing Omissions)

1. Cardiovascular:
   • SGLT2 inhibitors and/or GLP-1 receptor agonists in older adults with Type 2 Diabetes and established ASCVD, heart failure, or CKD.
   • Oral anticoagulation (DOAC preferred) in older adults with non-valvular Atrial Fibrillation and elevated $\text{CHA}_2\text{DS}_2\text{-VASc}$ score (age alone provides $\ge 1-2$ points; chronological age and fall risk are NOT contraindications to anticoagulation!).
   • Statin therapy in secondary prevention of documented ASCVD (unless palliative care/frail).
   • ACE inhibitor / ARB in patients with HFrEF or CKD with persistent albuminuria.
2. Endocrine / Bone Health:
   • Bisphosphonate / Denosumab + Calcium / Vitamin D in patients with documented osteoporosis, prior fragility fractures, or receiving chronic systemic corticosteroids (>3 months).

5. Deprescribing Frameworks & Stepwise Tapering Protocols

Deprescribing is the planned, supervised process of dose reduction or medication discontinuation when potential harms outweigh current or future benefits within the context of an individual's goals of care, life expectancy, and functional status.

                               THE 5-STEP DEPRESCRIBING PROTOCOL
                               
    [ Step 1: Comprehensive Medication Reconciliation ]
    Ascertain all prescribed, OTC, herbal, and PRN medications taken by the patient.
                         │
                         ▼
    [ Step 2: Identify Potentially Inappropriate Medications ]
    Apply Beers and STOPP criteria; calculate ACB score; identify drug-disease interactions.
                         │
                         ▼
    [ Step 3: Prioritize Medications for Discontinuation ]
    Rank based on highest harm risk, lack of current indication, and patient-aligned goals.
                         │
                         ▼
    [ Step 4: Formulate a Structured Taper & Non-Pharmacologic Plan ]
    Establish gradual dose reductions (e.g., 10-25% weekly/monthly) to prevent withdrawal.
                         │
                         ▼
    [ Step 5: Monitor, Support & Reassess ]
    Follow up frequently (q1-4 weeks); assess for rebound symptoms, withdrawal, or symptom relapse.

Practical Deprescribing Protocols for High-Yield Ambulatory Classes

1. Proton Pump Inhibitors (PPIs)

• Eligibility for Deprescribing: Completed 4–8 weeks of therapy for acute GERD, uncomplicated peptic ulcer, or empirical heartburn without endoscopic findings of severe erosive esophagitis (Los Angeles Grade C/D), Barrett esophagus, or chronic high-risk NSAID/antithrombotic use.
• Tapering Regimen:
  • Reduce daily PPI dose by 50% for 2 to 4 weeks (e.g., Pantoprazole 40 mg daily $\rightarrow$ 20 mg daily OR Omeprazole 40 mg daily $\rightarrow$ 20 mg daily $\rightarrow$ alternate-day dosing).
  • Step-Down Option: Transition to a histamine-2 receptor antagonist (H2RA, e.g., Famotidine 10–20 mg daily to BID) or PRN calcium carbonate/magnesium hydroxide antacids.
• Patient Counseling: Warn patients about rebound acid hypersecretion (due to elevated gastrin levels), which can cause temporary heartburn exacerbation lasting 1 to 2 weeks. Advise dietary modifications (avoid eating within 3 hours of bedtime, elevate head of bed, avoid trigger foods).

2. Benzodiazepines & 'Z-Drugs'

• Tapering Protocol: Abrupt cessation precipitates severe withdrawal (rebound insomnia, panic attacks, tremors, seizures, delirium). Tapers must be slow and hyperbolic:
  • Reduce total daily dose by 10% to 25% every 1 to 2 weeks over a period of 6 to 12 weeks (or longer for chronic users of >1 year).
  • If using a short-acting agent with high potency (e.g., alprazolam), consider converting to an equivalent dose of a longer-acting agent (clonazepam or diazepam) before initiating the taper.
  • Mandatory Behavioral Adjunct: Concurrent initiation of Cognitive Behavioral Therapy for Insomnia (CBT-I) (stimulus control, sleep restriction, sleep hygiene) yields superior long-term cessation rates compared to medication taper alone.

3. Antihypertensive De-Intensification

• Clinical Indications for Deprescribing:
  • Standing systolic BP $< 110-120\text{ mmHg}$ or standing diastolic BP $< 60\text{ mmHg}$.
  • Symptomatic orthostatic hypotension (defined as a drop in SBP $\ge 20\text{ mmHg}$ or DBP $\ge 10\text{ mmHg}$ within 3 minutes of standing).
  • Severe frailty, high fall risk, or advanced cognitive impairment where tight blood pressure control increases syncope, falls, and acute renal injury without conferring cardiovascular protection.
• De-escalation Hierarchy: First discontinue centrally acting alpha-agonists (clonidine; taper slowly to avoid rebound hypertension) and peripheral alpha-blockers (terazosin, doxazosin, prazosin). Next, reduce or eliminate loop diuretics (if not in heart failure) or calcium channel blockers (if peripheral edema is present).

4. Statins in Palliative Care & Advanced Dementia

• In patients with advanced life-limiting illness (life expectancy $< 1-2$ years), severe dementia, or functional debility in hospice/palliative care, statin therapy provides no measurable cardiovascular survival benefit.
• Discontinuation is safe: Large randomized clinical trials demonstrate that stopping statins in palliative care patients significantly improves quality of life, reduces polypharmacy pill burden, and lowers medication costs without increasing cardiovascular events or 60-day mortality.