8.2 High-Risk Medications & Safe Deprescribing in Older Adults (Beers Criteria)

8.2 High-Risk Medications & Safe Deprescribing in Older Adults (Beers Criteria)

Quick Summary: Older adults (aged ≥ 65 years) undergo profound physiological transformations in pharmacokinetics (absorption, distribution, hepatic metabolism, renal clearance) and pharmacodynamics (upregulated receptor sensitivity). In mobile integrated healthcare, the Community Paramedic serves as a critical frontline barrier against medication-induced harm by applying the American Geriatrics Society (AGS) Beers Criteria. By identifying Potentially Inappropriate Medications (PIMs), conducting surveillance on high-alert drugs (anticoagulants, insulin, digoxin), and orchestrating structured deprescribing protocols, the clinician eliminates root causes of delirium, falls, and acute hospital admissions.

Geriatric patients represent the predominant demographic served by Community Paramedics. While comprising approximately 17% of the United States population, adults aged 65 and older consume over 40% of all prescription pharmaceuticals and account for more than 50% of all medication-related deaths and acute hospitalizations. In older individuals, the margin between a therapeutic dose and a toxic dose narrows dramatically. A pharmaceutical regimen that is well tolerated by a 40-year-old can precipitate catastrophic delirium, high-grade heart blocks, or fatal intracranial hemorrhage in an 80-year-old.

To standardize geriatric pharmacotherapy safety, the American Geriatrics Society publishes and periodically updates the AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. The Beers Criteria serve as an evidence-based clinical directive identifying medications that should generally be avoided, avoided in specific clinical syndromes, or used with extreme caution in older populations.

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Geriatric Pharmacokinetics & Pharmacodynamics

To effectively navigate the Beers Criteria, Community Paramedics must understand the underlying biological alterations that govern drug handling in the aging body:

┌─────────────────────────────────────────────────────────────────────────┐
│            AGE-RELATED PHARMACOKINETIC TRANSFORMATIONS                  │
├─────────────────┬──────────────────────────┬────────────────────────────┤
│ Parameter       │ Physiological Shift      │ Clinical Impact in Older   │
│                 │ with Aging               │ Adults                     │
├─────────────────┼──────────────────────────┼────────────────────────────┤
│ Total Body Water│ Decreased by 15% to 20%  │ Collapsed volume of        │
│                 │                          │ distribution for hydro-    │
│                 │                          │ philic drugs (Digoxin,     │
│                 │                          │ Lithium); higher peak      │
│                 │                          │ serum concentrations!      │
├─────────────────┼──────────────────────────┼────────────────────────────┤
│ Body Fat %      │ Increased relative fat   │ Expanded volume of distri- │
│                 │ mass                     │ bution for lipophilic drugs│
│                 │                          │ (Diazepam, Lorazepam);     │
│                 │                          │ prolonged half-life & sed- │
│                 │                          │ ation persisting for days. │
├─────────────────┼──────────────────────────┼────────────────────────────┤
│ Serum Albumin   │ Decreased hepatic        │ Reduced protein binding;   │
│                 │ synthesis                │ higher free (unbound,      │
│                 │                          │ active) fraction of acidic │
│                 │                          │ drugs (Warfarin, Phenytoin)│
│                 │                          │ causing unexpected toxicity│
├─────────────────┼──────────────────────────┼────────────────────────────┤
│ Hepatic Blood   │ Decreased hepatic blood  │ Slower Phase I cytochrome  │
│ Flow & CYP450   │ flow (20-40%) and mass   │ P450 oxidation; prolonged  │
│                 │                          │ clearance of sedatives,    │
│                 │                          │ beta-blockers, narcotics.  │
├─────────────────┼──────────────────────────┼────────────────────────────┤
│ Renal Clearance │ GFR declines ~1 mL/min/yr│ Reduced renal clearance of │
│ (GFR)           │ after age 40; sarcopenia │ active drugs & metabolites │
│                 │ masks rising Cr!         │ (DOACs, Digoxin, Gabapen-  │
│                 │                          │ tin); severe drug accum-   │
│                 │                          │ ulation despite 'normal' Cr│
└─────────────────┴──────────────────────────┴────────────────────────────┘

Pharmacodynamic Sensitivity Shifts

Beyond drug levels, the aging brain and cardiovascular system exhibit heightened target-organ sensitivity. Older adults have increased blood-brain barrier permeability, upregulated central nervous system GABAergic and dopaminergic sensitivity, and blunted autonomic baroreceptor reflexes. Consequently, therapeutic doses of central sedatives produce profound confusion, while standard antihypertensives easily induce orthostatic syncope.

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The AGS Beers Criteria: Potentially Inappropriate Medications (PIMs)

Community Paramedics systematically screen medication profiles against the Beers Criteria, focusing on four primary high-risk drug classes:

1. Anticholinergic Medications

• Representative Agents: First-generation antihistamines (Diphenhydramine, Hydroxyzine, Chlorpheniramine), tricyclic antidepressants (Amitriptyline, Nortriptyline, Doxepin), and bladder antimuscarinics (Oxybutynin, Tolterodine).
• Mechanism & Beers Hazard: Anticholinergics block central and peripheral muscarinic acetylcholine receptors. In older adults who already experience baseline cholinergic deficits, anticholinergics trigger acute delirium, accelerated cognitive decline, sedation, and high fall risk.
• Peripheral Toxicity: Marked by the classic clinical triad of urinary retention (often precipitating overflow incontinence or acute urosepsis), severe constipation / fecal impaction, and blurred vision / pupillary dilation (which impairs balance and can trigger acute angle-closure glaucoma).
• The Anticholinergic Cognitive Burden (ACB): Anticholinergic risk is cumulative. A patient taking diphenhydramine for sleep, oxybutynin for bladder spasms, and amitriptyline for neuropathic pain carries an intolerable ACB score that guarantees cognitive impairment.

2. Benzodiazepines & Non-Benzodiazepine Sedative-Hypnotics ("Z-Drugs")

• Representative Agents: Long- and short-acting benzodiazepines (Diazepam, Clonazepam, Lorazepam, Alprazolam) and "Z-drugs" (Zolpidem, Eszopiclone, Zaleplon).
• Mechanism & Beers Hazard: Positive allosteric modulators of the $GABA_A$ receptor complex. Because older adults possess expanded adipose volume and reduced hepatic clearance, the elimination half-life of these agents is extended multi-fold (e.g., diazepam active metabolites persist for $>100\text{ hours}$). These drugs induce profound motor ataxia, uncoordinated gait, daytime somnolence, nocturnal confusion, motor vehicle collisions, and a 2- to 3-fold increase in fall-related hip fractures and subdural hematomas.
• Paradoxical Excitation: In patients with underlying neurocognitive disorders, benzodiazepines frequently trigger paradoxical agitation, disinhibition, and violent behavioral decompensation.

3. Antipsychotics in Dementia-Related Psychosis

• Representative Agents: First-generation (Haloperidol) and second-generation (Risperidone, Olanzapine, Quetiapine, Aripiprazole) antipsychotics.
• Mechanism & Beers Hazard: Frequently misprescribed as a chemical restraint to manage agitation, wandering, or sundowning in dementia. All antipsychotics carry an explicit FDA Black Box Warning for a statistically significant increase in cerebrovascular adverse events (ischemic stroke, TIA) and all-cause mortality in older adults with dementia.
• Additional Risks: Blockade of $D_2$ receptors induces severe extrapyramidal symptoms, drug-induced parkinsonism, tardive dyskinesia, profound orthostatic hypotension (via $\alpha_1$-adrenergic antagonism), and fatal ventricular arrhythmias secondary to QT prolongation.

4. Systemic Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

• Representative Agents: Ibuprofen, Naproxen, Meloxicam, Ketorolac, Celecoxib.
• Mechanism & Beers Hazard: Systemic NSAIDs inhibit cyclooxygenase (COX-1 and COX-2) enzymes. In older adults, maintaining glomerular filtration and renal perfusion depends critically on vasodilatory prostaglandins ($PGE_2$ and $PGI_2$) acting at the afferent arteriole. NSAIDs block prostaglandin synthesis, causing afferent arteriolar vasoconstriction, collapsed GFR, acute tubular necrosis, and acute kidney injury (AKI).
• Cardiovascular & Fluid Crisis: NSAID-mediated renal vasoconstriction leads to massive sodium and water retention. This directly antagonizes loop diuretics, blunts ACE inhibitors, worsens hypertension, and precipitates acute decompensated heart failure.
• Gastrointestinal Hemorrhage: Unchecked suppression of protective gastric mucus and bicarbonate secretion produces silent peptic ulceration and catastrophic, life-threatening upper gastrointestinal hemorrhage.

┌────────────────────────────────────────────────────────────────────────┐
│                     AGS BEERS CRITERIA MASTER SUMMARY                  │
├────────────────────┬─────────────────────────────┬─────────────────────┤
│ Drug Class         │ Major Clinical Toxicities   │ Safer Evidence-Based│
│                    │ in Older Adults             │ Alternatives        │
├────────────────────┼─────────────────────────────┼─────────────────────┤
│ First-Generation   │ Acute delirium, dry mouth,  │ Saline nasal spray, │
│ Antihistamines     │ urinary retention, blurred  │ oral 2nd-gen (cetir-│
│ (Diphenhydramine)  │ vision, severe falls.       │ izine/loratadine).  │
├────────────────────┼─────────────────────────────┼─────────────────────┤
│ Bladder Antimuscar-│ Cognitive decline, memory   │ Behavioral bladder  │
│ inics (Oxybutynin) │ loss, fecal impaction, acute│ training, pelvic floor│
│                    │ urinary retention.          │ therapy, Mirabegron.│
├────────────────────┼─────────────────────────────┼─────────────────────┤
│ Benzodiazepines &  │ Severe motor ataxia, hip    │ Sleep hygiene, CBT-I│
│ 'Z-drugs'          │ fractures, nocturnal falls, │ (cognitive behavior-│
│ (Zolpidem, Loraz)  │ paradoxical agitation.      │ al therapy insomnia)│
├────────────────────┼─────────────────────────────┼─────────────────────┤
│ Antipsychotics     │ Black Box Warning: Stroke & │ Non-pharmacologic   │
│ (Haloperidol,      │ mortality in dementia;      │ de-escalation, sensory│
│ Risperidone)       │ parkinsonism, QT prolong.   │ calming, music.     │
├────────────────────┼─────────────────────────────┼─────────────────────┤
│ Systemic NSAIDs    │ Blunts diuretics/ACEi; renal│ Topical NSAIDs (di- │
│ (Ibuprofen, Naprox)│ vasoconstriction (AKI); CHF │ clofenac gel), acet-│
│                    │ flare; silent GI hemorrhage.│ aminophen, PT.      │
└────────────────────┴─────────────────────────────┴─────────────────────┘

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High-Alert Domiciliary Medications: Management & Surveillance

"High-Alert Medications" are defined by the Institute for Safe Medication Practices (ISMP) as pharmaceuticals that bear a heightened risk of causing significant patient harm when used in error. In community paramedicine, three classes dominate in-home toxicity surveillance:

1. Oral Anticoagulant Therapy

┌─────────────────────────────────────────────────────────────────────────┐
│                    ANTICOAGULANT SURVEILLANCE MATRIX                    │
├─────────────────────┬───────────────────────────┬───────────────────────┤
│ Parameter           │ Warfarin (Coumadin)       │ DOACs (Apixaban,      │
│                     │                           │ Rivaroxaban)          │
├─────────────────────┼───────────────────────────┼───────────────────────┤
│ Mechanism           │ Vitamin K Epoxide         │ Direct Factor Xa      │
│                     │ Reductase inhibitor       │ inhibition            │
│ Target Range        │ INR 2.0 - 3.0 (AFib/DVT); │ Fixed dosing; adjust  │
│                     │ INR 2.5 - 3.5 (Mech Mitral│ for CrCl, age, weight │
│ Monitoring          │ Frequent POC INR testing  │ Baseline renal panel; │
│                     │ & dietary Vitamin K audit │ no routine INR needed │
│ Signs of Bleeding   │ Epistaxis, purpura, melena│ Epistaxis, hematuria, │
│                     │ hematuria, occult blood   │ syncope, fall trauma  │
│ Specific Reversal   │ 4-Factor PCC (Kcentra) +  │ Andexanet alfa        │
│ Agents              │ IV Vitamin K (phytonadione│ (Andexxa)             │
└─────────────────────┴───────────────────────────┴───────────────────────┘

• Warfarin Surveillance: Warfarin has a notoriously narrow therapeutic index. In the home, the Community Paramedic assesses dietary consistency (fluctuating intake of Vitamin K-rich broccoli, spinach, or kale destabilizes INR), evaluates alcohol consumption (acute binge inhibits metabolism, driving INR skyward; chronic alcohol induces enzymes, dropping INR), and inspects for occult bleeding. Point-of-care fingerstick INR testing enables immediate identification of supratherapeutic anticoagulation ($INR >4.5\text{--}5.0$), triggering urgent physician contact.
• Direct Oral Anticoagulants (DOACs): While DOACs (Apixaban, Rivaroxaban, Edoxaban) eliminate the need for routine INR testing, they depend heavily on renal elimination. If an older patient develops dehydration or acute kidney injury, DOAC elimination plummets, leading to drug accumulation and severe bleeding. Paramedics must verify that DOAC dosages are appropriately reduced according to age (≥ 80), body weight (≤ 60 kg), and serum creatinine (≥ 1.5 mg/dL).
• Reversal Protocols: In life-threatening hemorrhage or acute trauma:
  • Warfarin: 4-Factor Prothrombin Complex Concentrate (4F-PCC / Kcentra) containing non-activated Factors II, VII, IX, X, and Proteins C and S, administered alongside intravenous Vitamin K.
  • Factor Xa Inhibitors (Apixaban, Rivaroxaban): Andexanet alfa (Andexxa), a recombinant modified decoy Factor Xa protein.
  • Direct Thrombin Inhibitor (Dabigatran): Idarucizumab (Praxbind), a humanized monoclonal antibody fragment.

2. Insulin Regimens & Glycemic Disasters

• The Beers Ban on Sliding-Scale Insulin (SSI) Alone: The Beers Criteria explicitly condemn the use of sliding-scale regular or rapid-acting insulin as the sole treatment for diabetes in older adults. Reactive SSI treats hyperglycemia after it occurs rather than preventing it, producing extreme glycemic volatility ("roller-coaster effect") and dramatically increasing the incidence of severe, fatal hypoglycemia without improving overall glycemic control.
• Basal-Bolus Physiology: Safer geriatric regimens utilize steady, peakless long-acting basal insulins (Glargine, Detemir, Degludec) combined with planned, fixed mealtime boluses adjusted for oral intake.
• Hypoglycemia Thresholds: In older adults, hypoglycemia is defined as blood glucose $<70\text{ mg/dL}$ (Level 1), with severe neuroglycopenia occurring at $<54\text{ mg/dL}$ (Level 2). Geriatric patients often exhibit hypoglycemic unawareness due to blunted autonomic counter-regulatory epinephrine responses; they may not display classic diaphoresis or tremors, presenting instead with acute confusion, behavioral agitation, falls, focal stroke mimics, or seizures.

3. Digoxin Toxicity Surveillance

• Mechanism: Cardiac glycoside that inhibits the myocardial membrane sodium-potassium adenosine triphosphatase ($Na^+/K^+$-ATPase) pump, increasing intracellular sodium and calcium, producing a positive inotropic effect while slowing AV nodal conduction (negative dromotropy).
• Narrow Therapeutic Window: In modern clinical practice, the therapeutic serum digoxin concentration for heart failure is 0.5 to 0.9 ng/mL. Serum concentrations $\ge 1.0\text{ ng/mL}$ provide no additional hemodynamic benefit and are directly associated with increased all-cause mortality.
• The Critical Hypokalemia Connection: Extracellular potassium and digoxin compete directly for the identical phosphorylation binding site on the alpha subunit of the $Na^+/K^+$-ATPase enzyme. When an older patient becomes hypokalemic ($K^+ <3.5\text{ mEq/L}$)—most commonly induced by loop or thiazide diuretics—there is less potassium to compete with digoxin. Consequently, digoxin binds unchecked to myocardial enzymes, precipitating fatal digitalis toxicity even when the serum digoxin level is within the "normal" laboratory range!
• Clinical Manifestations of Digitalis Toxicity:
  • Gastrointestinal: Earliest signs include profound anorexia, nausea, vomiting, and abdominal pain.
  • Neurological & Visual: Confusion, lethargy, headache, and pathognomonic visual disturbances—specifically xanthopsia (yellow-green color halos around lights), scotomas, and blurred vision.
  • Cardiovascular Arrhythmias: Sinus bradycardia, high-grade AV block, junctional escape rhythms, premature ventricular complexes (frequently presenting as ventricular bigeminy), and pathognomonic bidirectional ventricular tachycardia.
• Antidote: Digoxin Immune Fab (DigiFab) fragments, which bind and neutralize free intravascular digoxin molecules.

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Principles of Safe Deprescribing

Deprescribing is the planned, structured process of identifying and discontinuing (or dose-reducing) drugs where existing or potential harms outweigh existing or potential benefits. Deprescribing is not a withdrawal of care; it is an active, therapeutic, patient-centered clinical intervention.

┌────────────────────────────────────────────────────────────────────────┐
│                     THE 5-STEP DEPRESCRIBING PROTOCOL                  │
├────────────────────────────────────────────────────────────────────────┤
│  1. Comprehensive Medication Inventory                                 │
│  Catalog all active prescriptions, OTCs, herbals, and indications.     │
├────────────────────────────────────────────────────────────────────────┤
│  2. Identify Inappropriate, High-Risk, or Low-Benefit Agents           │
│  Screen against Beers Criteria; locate prescribing cascades; identify   │
│  drugs without valid clinical indications or preventive drugs in frail │
│  patients with limited life expectancy (e.g., statins in dementia).   │
├────────────────────────────────────────────────────────────────────────┤
│  3. Assess Feasibility & Prioritize Discontinuation Targets            │
│  Evaluate which drug poses the most immediate life threat (e.g., sedat-│
│  ives causing falls vs. PPIs causing hypomagnesemia).                  │
├────────────────────────────────────────────────────────────────────────┤
│  4. Formulate a Structured, Gradual Tapering Schedule                  │
│  NEVER stop central sedatives, beta-blockers, or SSRIs abruptly!       │
│  Establish percentage-based dose decrements (e.g., 10-25% every 2-4 wk)│
│  to avoid severe withdrawal or physiological rebound phenomena.        │
├────────────────────────────────────────────────────────────────────────┤
│  5. Monitor for Rebound Symptoms & Provide Support                     │
│  Schedule serial in-home follow-ups; monitor vitals, mood, and sleep;  │
│  collaborate closely with primary care providers and family caregivers.│
└────────────────────────────────────────────────────────────────────────┘

[!CAUTION] Avoid Abrupt Discontinuation: Sudden cessation of chronic benzodiazepines can trigger life-threatening autonomic storms, delirium tremens, and status epilepticus. Abrupt withdrawal of beta-blockers precipitates rebound tachycardia, severe hypertension, and myocardial ischemia. Safe deprescribing mandates a slow, incremental, step-wise taper overseen by the interprofessional medical team.

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Step-by-Step Worked Clinical Scenario: Unraveling Geriatric Toxicity

Clinical Presentation

A Community Paramedic is dispatched for a safety evaluation of Mrs. Eleanor Vance, an 81-year-old female with moderate Alzheimer's disease, chronic low back pain, and hypertension. Her daughter called 911 because her mother has become progressively confused, unsteady, somnolent during the day, and suffered an unwitnessed nocturnal fall resulting in an extensive ecchymosis across her right hip.

In-Home Medication Audit

• Prescription 1: Donepezil 10 mg daily (for Alzheimer's disease).
• Prescription 2: Oxybutynin 10 mg ER daily (prescribed 2 months ago for new urinary urgency).
• Prescription 3: Zolpidem (Ambien) 10 mg at bedtime (prescribed for insomnia).
• Prescription 4: OTC Diphenhydramine 50 mg nightly (daughter added this "to help mom sleep better").
• Prescription 5: Naproxen 500 mg BID (for lumbar back pain).
• Prescription 6: Lisinopril 20 mg daily.

Objective Clinical Findings

• Vitals: BP 96/58 mmHg, HR 56 bpm, SpO2 96%, Temp 98.4°F (36.9°C).
• Exam: Moderate psychomotor lethargy; dry, cracked tongue; lower abdominal distension with palpable suprapubic fullness; severe gait ataxia on Timed Up and Go (TUG = 28 seconds).
• Point-of-Care Testing: Point-of-care bladder ultrasound reveals 650 mL of retained urine (acute urinary retention). Point-of-care blood testing: BUN $38\text{ mg/dL}$, Creatinine $1.9\text{ mg/dL}$ (baseline $0.9\text{ mg/dL}$, indicating acute kidney injury).

Systematic Identification of Beers Criteria Violations

1. Severe Anticholinergic Toxicity & Pharmacologic Antagonism: Oxybutynin (antimuscarinic) and Diphenhydramine (antihistamine) exert massive anticholinergic burden. Centrally, they directly block the action of Donepezil (an acetylcholinesterase inhibitor), rendering Mrs. Vance's dementia medication utterly useless while triggering acute delirium. Peripherally, they have induced severe urinary retention (650 mL) and xerostomia.
2. Dangerous Sedative-Hypnotic Synergy: Zolpidem (Z-drug) combined with Diphenhydramine produced profound motor ataxia, confusion, and the nocturnal fall that bruised her hip.
3. NSAID-Induced Nephrotoxicity & Hypotension: Naproxen has constricted her renal afferent arterioles, causing an acute drop in GFR (Cr 1.9) and blunting renal autoregulation.

Paramedic Deprescribing & Escalation Plan

1. Acute Bladder Decompression: Paramedic contacts online medical direction; receives orders to place a temporary in-and-out urinary catheter, immediately draining 650 mL of clear amber urine and relieving severe bladder distension.
2. Collaborative Provider Deprescribing Plan: Paramedic contacts the primary geriatrician via SBAR:
   • Recommend immediate discontinuation of OTC Diphenhydramine.
   • Recommend structured taper and discontinuation of Zolpidem and Oxybutynin.
   • Transition back pain management from systemic Naproxen to topical Diclofenac gel and non-pharmacologic physical therapy.
   • Initiate non-pharmacologic sleep hygiene and scheduled toileting protocols.
3. Monitoring Plan: Paramedic schedules 48-hour follow-up visit to re-evaluate renal function, post-void residuals, and mobility.

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Common Exam Traps & Board Pearls

• Trap: Believing normal serum creatinine guarantees normal renal function in older adults. Due to age-related sarcopenia (loss of skeletal muscle mass), older adults generate very little daily creatinine. A frail 80-year-old female with a "normal" serum creatinine of $0.9\text{ mg/dL}$ may actually have a severely compromised CrCl of $<30\text{ mL/min}$! Always calculate estimated GFR or CrCl.
• Trap: Assuming sliding-scale insulin is appropriate if blood sugar is high. The Beers Criteria explicitly state that sliding-scale insulin alone without basal coverage must be avoided in older adults due to extreme hypoglycemia risk.
• Trap: Overlooking the electrolyte trigger in digitalis toxicity. Digitalis toxicity can manifest with completely normal serum digoxin levels if the patient is hypokalemic. Exam questions frequently present a patient with a digoxin level of $0.8\text{ ng/mL}$ who is toxic because their serum potassium is $2.8\text{ mEq/L}$ from furosemide.
• Trap: Missing the Black Box Warning on dementia agitation. Antipsychotics are not approved for behavioral management of dementia-related psychosis and carry a Black Box Warning for increased stroke and mortality.