13.1 The Geriatric 5Ms Framework, Multimorbidity & Polypharmacy Deprescribing

The Geriatric 5Ms Framework, Multimorbidity & Polypharmacy Deprescribing

Geriatric care in advanced practice nursing demands a paradigm shift from traditional organ-specific, disease-siloed management toward comprehensive, goal-concordant, whole-person care. Older adults frequently live with multimorbidity—the co-occurrence of two or more chronic medical conditions—which dramatically increases clinical complexity, therapeutic conflicts, and vulnerability to adverse drug events. For the Adult-Gerontology Primary Care Nurse Practitioner (AGPCNP), mastery of the Geriatric 5Ms framework, frailty assessment, aging pharmacology, and structured deprescribing is essential for optimizing function and preserving quality of life.

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1. The Geriatric 5Ms Framework

Originally developed by geriatricians Mary Tinetti, Frank Molnar, and colleagues, and adopted by the American Geriatrics Society (AGS) and Health Resources and Services Administration (HRSA), the Geriatric 5Ms provides a structured, memorable taxonomy for organizing the care of older adults.

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|                                 THE GERIATRIC 5Ms FRAMEWORK                                       |
|                                                                                                   |
|   1. MIND                                                                                         |
|   - Mentation, Memory, Dementia, Delirium, Depression, Cognitive Capacity                         |
|   - Focus: Early screening, delirium prevention, neurocognitive diagnostics, behavioral support   |
|                                                                                                   |
|   2. MOBILITY                                                                                     |
|   - Gait, Balance, Fall Risk, Physical Function, Assistive Devices, Muscle Sarcopenia            |
|   - Focus: Maintaining independence, environmental safety, physical therapy, Timed Up and Go (TUG)|
|                                                                                                   |
|   3. MEDICATIONS                                                                                  |
|   - Polypharmacy, Deprescribing, Adverse Drug Reactions (ADRs), High-Risk Prescribing, PK/PD      |
|   - Focus: Beers Criteria, STOPP/START rules, reducing anticholinergic burden, avoiding cascades   |
|                                                                                                   |
|   4. MULTI-COMPLEXITY                                                                             |
|   - Multimorbidity, Frailty, Biopsychosocial Vulnerability, Discordant Chronic Conditions         |
|   - Focus: Navigating clinical guideline conflicts, caregiver strain, social determinants of health|
|                                                                                                   |
|   5. MATTERS MOST                                                                                 |
|   - Individual Health Priorities, Patient-Defined Goals of Care, Quality of Life vs Longevity     |
|   - Focus: Advance care planning, living wills, surrogate decision-makers, goal-concordant care   |
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Integrating the 5Ms into Primary Care Clinical Encounters

1. Mind: Evaluate cognitive trajectory at every annual wellness visit using validated tools (e.g., Mini-Cog, MoCA). Screen for depressive symptoms with the Geriatric Depression Scale (GDS-15). Ensure high vigilance for acute fluctuating inattention (delirium) during acute illness.
2. Mobility: Inquire about near-falls, unsteadiness, and changes in walking speed. Measure functional mobility objectively via the Timed Up and Go (TUG) test or 30-Second Chair Stand test. Screen for sarcopenia (loss of muscle mass, strength, and physical performance).
3. Medications: Conduct exhaustive "brown bag" medication reconciliations, cross-referencing prescription drugs, over-the-counter (OTC) supplements, herbals, and PRN agents against the 2023 AGS Beers Criteria. Inquire about financial strain and pill-splitting.
4. Multi-complexity: Recognize how management of one condition destabilizes another (e.g., tight blood pressure control exacerbating orthostatic hypotension and fall risk; beta-blockers masking hypoglycemia or worsening peripheral artery disease).
5. Matters Most: Align all clinical decision-making with the patient's self-articulated core values. When multimorbidity and severe frailty limit life expectancy, prioritize functional independence, symptom freedom, and cognitive clarity over rigid surrogate biomarkers.

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2. Multimorbidity, Discordant Conditions & Frailty Syndromes

Clinical Guideline Discordance

Traditional single-disease clinical practice guidelines (CPGs) are designed based on randomized controlled trials that routinely exclude frail, multimorbid older adults. When applied cumulatively to a patient with 5 or 6 chronic illnesses, single-disease guidelines lead to extreme treatment burden, polypharmacy, and therapeutic contradiction:

• Concordant Conditions: Chronic illnesses that share common pathophysiological pathways and management strategies (e.g., Type 2 Diabetes Mellitus, Hypertension, Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease). Interventions for one condition generally benefit the others.
• Discordant Conditions: Chronic illnesses that are pathophysiologically unrelated and often have conflicting therapeutic requirements (e.g., Severe Osteoarthritis requiring NSAIDs in a patient with Stage 4 CKD and Heart Failure with reduced Ejection Fraction; or Severe COPD requiring beta-agonists in a patient with symptomatic Atrial Fibrillation with rapid ventricular response).

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|                         NAVIGATING CLINICAL GUIDELINE DISCORDANCE                                 |
|                                                                                                   |
|   [ASSESS TOTAL DISEASE BURDEN & TRAJECTORY]                                                      |
|   - Identify all active diagnoses, organ failures, and baseline functional reserves               |
|                                     |                                                             |
|                                     v                                                             |
|   [ESTIMATE PROGNOSIS & REMAINING LIFE EXPECTANCY]                                                |
|   - Utilize validated prognostic calculators (e.g., ePrognosis, Lee/Schonberg Index)              |
|   - Determine Time-to-Benefit (TTB) for each preventive/therapeutic intervention                  |
|                                     |                                                             |
|                                     v                                                             |
|   [IDENTIFY THERAPEUTIC CONFLICTS & RISKS]                                                        |
|   - Cross-reference drug mechanisms against co-existing comorbidities                             |
|   - Weigh symptom relief vs future risk reduction                                                 |
|                                     |                                                             |
|                                     v                                                             |
|   [ESTABLISH GOAL-CONCORDANT PRIORITIZATION WITH PATIENT / SURROGATE]                             |
|   - De-escalate strict biomarker targets (e.g., relax HbA1c to 8.0-8.5% in advanced frailty)      |
|   - Deprescribe therapies whose Time-to-Benefit exceeds remaining life expectancy                 |
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Frailty: Pathophysiology and Clinical Models

Frailty is a biological syndrome of decreased physiological reserve and diminished resistance to stressors, resulting from cumulative declines across multiple physiological systems. In frail individuals, minor acute stressors (e.g., mild UTI, minor medication adjustment, change in living environment) trigger disproportionate, catastrophic functional decline, delirium, institutionalization, or death.

Models of Frailty

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3. Pharmacokinetic & Pharmacodynamic Remodeling in Aging

Aging causes profound alterations in drug disposition and target-tissue sensitivity. Understanding these alterations prevents toxicities and informs safe dosing strategies.

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|                         PHARMACOKINETIC & PHARMACODYNAMIC REMODELING                              |
|                                                                                                   |
|   [ABSORPTION]                                                                                    |
|   - Increased gastric pH (decreased gastric acid secretion) -> Reduced B12, iron, calcium absorp. |
|   - Delayed gastric emptying and decreased intestinal motility -> Slower rate of drug absorption  |
|                                                                                                   |
|   [DISTRIBUTION]                                                                                  |
|   - Decreased Total Body Water (~15-20% decrease) -> Decreased Vd of hydrophilic drugs            |
|     * Higher peak serum concentrations of Digoxin, Lithium, Aminoglycosides, Ethanol              |
|   - Increased Total Body Fat (~20-40% increase) -> Increased Vd of lipophilic drugs               |
|     * Prolonged half-life (t1/2) and prolonged CNS accumulation of Diazepam, Flurazepam           |
|   - Decreased Serum Albumin (especially in malnutrition/illness) -> Increased free active fraction|
|     * Elevated free fraction of Warfarin, Phenytoin, Valproic acid, Ceftriaxone                   |
|                                                                                                   |
|   [METABOLISM]                                                                                    |
|   - Decreased hepatic mass and hepatic blood flow (~20-40% reduction)                              |
|   - Impaired Phase I hepatic metabolism (Oxidation, Hydrolysis, Reduction via CYP450 enzymes)      |
|   - Phase II metabolism (Glucuronidation, Conjugation) generally PRESERVED                        |
|     * Benzodiazepine rule: Use "LOT" (Lorazepam, Oxazepam, Temazepam) due to pure Phase II metab. |
|                                                                                                   |
|   [ELIMINATION]                                                                                   |
|   - Decreased renal cortical mass, reduced renal plasma flow, sclerotic glomeruli                 |
|   - GFR declines by ~0.75 to 1.0 mL/min/year after age 40                                         |
|   - Serum creatinine remains deceptively NORMAL due to age-related sarcopenia (low muscle mass)   |
|     * ALWAYS calculate CrCl via Cockcroft-Gault equation; never rely on raw serum creatinine!    |
|                                                                                                   |
|   [PHARMACODYNAMICS]                                                                              |
|   - Increased CNS blood-brain barrier permeability and heightened receptor sensitivity:           |
|     * Exaggerated sedation and respiratory depression from Benzodiazepines and Opioids             |
|     * Pronounced confusion, memory loss, and urinary retention from Anticholinergics              |
|   - Decreased beta-adrenergic receptor sensitivity and blunted baroreceptor reflex:               |
|     * Impaired compensatory tachycardia -> Severe orthostatic hypotension and syncope             |
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Estimating Renal Function: The Cockcroft-Gault Equation

Because serum creatinine alone severely underestimates renal impairment in sarcopenic older adults, the AGPCNP must calculate estimated Creatinine Clearance ($CrCl$) using the Cockcroft-Gault equation for medication dosing:

$CrCl\text{ (mL/min)} = \frac{(140 - \text{Age}) \times \text{Weight (kg)}}{72 \times \text{Serum Creatinine (mg/dL)}} \quad [\times\; 0.85 \text{ for females}]$

Clinical Warning: When serum creatinine is very low (e.g., $0.4\text{--}0.5\text{ mg/dL}$) due to severe cachexia, calculating CrCl without clinical judgment can falsely inflate estimated clearance, leading to dangerous over-dosing of nephrotoxic or renally cleared drugs (e.g., direct oral anticoagulants, gabapentin, enoxaparin, digoxin).

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4. Polypharmacy & Prescribing Cascades

Definitions and Epidemiology

• Polypharmacy: The concurrent use of $\ge 5$ routine medications (or the use of more medications than clinically indicated).
• Hyperpolypharmacy: The concurrent use of $\ge 10$ routine medications.
• Polypharmacy exponentially increases the risk of adverse drug events (ADEs), drug-drug interactions (DDIs), falls, cognitive impairment, functional dependency, emergency department visits, and all-cause mortality.

The Prescribing Cascade

A prescribing cascade represents a major failure of clinical diagnostic reasoning in geriatrics: it occurs when an adverse drug effect (ADE) produced by an initial medication is misinterpreted as a new, de novo medical condition, leading to the initiation of a second medication to treat the drug-induced symptom. The second medication introduces its own risk of adverse effects, precipitating further inappropriate prescribing.

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|                             THE CLASSIC PRESCRIBING CASCADE CYCLE                                 |
|                                                                                                   |
|         [Initial Drug Prescribed for Legitimate Condition]                                        |
|                                 |                                                                 |
|                                 v                                                                 |
|         [Adverse Drug Event (ADE) Occurs]                                                         |
|                                 |                                                                 |
|                                 v                                                                 |
|         [CLINICAL MISINTERPRETATION: ADE Labeled as "New Medical Condition"]                     |
|                                 |                                                                 |
|                                 v                                                                 |
|         [Second Drug Prescribed to Treat the Adverse Effect]                                      |
|                                 |                                                                 |
|                                 v                                                                 |
|         [Compounded Toxicity, Polypharmacy, & Functional Decline]                                 |
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Classic Prescribing Cascades in Adult-Gerontology Primary Care

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5. Stepwise Structured Deprescribing Protocols

Deprescribing is the systematic, patient-centered process of identifying and discontinuing, tapering, or dose-reducing medications in instances where existing or potential harms outweigh current or potential benefits within the context of an individual patient's goals of care, current functioning, life expectancy, and values.

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|                         STEPWISE CLINICAL DEPRESCRIBING PROTOCOL                                  |
|                                                                                                   |
|   [STEP 1: COMPREHENSIVE MEDICATION RECONCILIATION]                                               |
|   - Compile all Rx, OTC, herbal, and PRN drugs; indications; actual usage patterns               |
|                                     |                                                             |
|                                     v                                                             |
|   [STEP 2: IDENTIFY POTENTIALLY INAPPROPRIATE MEDICATIONS (PIMs)]                                 |
|   - Cross-reference with Beers Criteria, STOPP/START, and Anticholinergic Burden Scales           |
|   - Identify drugs without clear indication, duplicate therapies, or negative risk/benefit        |
|                                     |                                                             |
|                                     v                                                             |
|   [STEP 3: ASSESS ELIGIBILITY & TIME-TO-BENEFIT (TTB)]                                            |
|   - Compare TTB of preventive drugs against estimated patient life expectancy                     |
|   - Identify high-risk medications for immediate vs gradual discontinuation                       |
|                                     |                                                             |
|                                     v                                                             |
|   [STEP 4: PRIORITIZE & NEGOTIATE DEPRESCRIBING PLAN]                                             |
|   - Engage patient, family caregiver, and surrogate in shared decision-making                     |
|   - Target ONE medication at a time to prevent withdrawal confusion and maintain patient trust    |
|                                     |                                                             |
|                                     v                                                             |
|   [STEP 5: IMPLEMENT TAPERING SCHEDULE & MONITORING PLAN]                                         |
|   - Provide written step-down tapering schedules to mitigate rebound / withdrawal phenomena       |
|   - Schedule structured clinical follow-up; define explicit parameters for re-escalation if needed|
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Evidence-Based Deprescribing Strategies by Drug Class

1. Proton Pump Inhibitors (PPIs)

• Rationale: Long-term use (>8 weeks without compelling indication such as Barrett's esophagus, chronic NSAID requirement, or severe erosive esophagitis) increases risk of Clostridioides difficile colitis, osteoporotic fractures, hypomagnesemia, acute interstitial nephritis, and vitamin B12 malabsorption.
• Tapering Protocol: Reduce daily dose by 50% for 2–4 weeks, or transition to every-other-day dosing for 2–4 weeks, then discontinue. Provide PRN H2-receptor antagonists (e.g., Famotidine 10–20 mg) or antacids to manage transient rebound gastric acid hypersecretion.

2. Benzodiazepines & Sedative-Hypnotic "Z-Drugs" (Zolpidem, Eszopiclone)

• Rationale: Marked increase in cognitive impairment, delirium, motor vehicle collisions, falls, and hip fractures. Tolerance develops rapidly, with no demonstrated long-term sleep efficacy.
• Tapering Protocol: Never discontinue abruptly due to risk of life-threatening withdrawal seizures, delirium, and rebound anxiety. Taper dose by 10% to 25% every 2 to 4 weeks over a 3- to 6-month period. For short-acting agents, consider switching to an equivalent dose of a longer-acting agent with Phase II metabolism (e.g., Lorazepam, Oxazepam) before gradual reduction. Implement concurrent Cognitive Behavioral Therapy for Insomnia (CBT-I).

3. Antihyperglycemic De-intensification in Frail Older Adults

• Rationale: Strict glycemic control (HbA1c <7.0%) in older adults with multimorbidity, dementia, or limited life expectancy provides zero macrovascular or microvascular benefit (Time-to-Benefit is 8–10 years) while exponentially increasing fatal hypoglycemic episodes.
• De-intensification Targets (ADA / AGS Guidelines):
  • Healthy Older Adults (Few co-existing conditions, intact cognition/function): $\text{HbA1c} < 7.0\text{--}7.5%$.
  • Complex / Intermediate Frailty (Multiple chronic illnesses, mild-moderate cognitive impairment, $\ge 2$ IADL dependencies): $\text{HbA1c} < 8.0%$.
  • Very Complex / Severe Frailty / Poor Health (Long-term care residents, end-stage chronic illnesses, severe dementia, ADL dependencies): $\text{HbA1c} < 8.5%$ (rely primarily on avoiding symptomatic hyperglycemia and acute hypoglycemia; discontinue sliding scale regular insulin and high-risk sulfonylureas entirely).

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6. Board-Yield Summary & Clinical Pearls

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|                                 ANCC AGPCNP CLINICAL EXAM PEARLS                                  |
|                                                                                                   |
|   - Whenever a new symptom arises in an older adult, ALWAYS consider an adverse drug event (ADE)   |
|     FIRST before formulating an extensive medical workup or adding a new medication!             |
|                                                                                                   |
|   - Sarcopenic older adults generate very little creatinine. A serum creatinine of 0.8 mg/dL in a |
|     frail 86-year-old female weighing 42 kg may correspond to a dangerously low CrCl of <25 mL/min|
|     Always calculate Cockcroft-Gault CrCl for drug dosing.                                        |
|                                                                                                   |
|   - The Geriatric 5Ms 'Matters Most' dictates that in severe frailty or terminal illness,         |
|     preventive therapies with long Time-to-Benefit (e.g., statins for primary prevention, tight   |
|     HbA1c control, routine colonoscopies) should be deprescribed in favor of symptom palliation.  |
|                                                                                                   |
|   - For benzodiazepines in older adults requiring brief anxiolysis, remember LOT: Lorazepam,      |
|     Oxazepam, Temazepam. They undergo direct Phase II glucuronidation and do not accumulate active|
|     lipophilic Phase I oxidative metabolites. However, non-pharmacologic therapy is always first. |
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