Pharmacotherapy Considerations in Elderly Adults

James M. Wooten, PharmD

South Med J. 2012;105(8):437-445.

Abstract and Introduction

Abstract

Life expectancy for Americans has increased dramatically since 1900, as have the available pharmacotherapeutic options. Unfortunately, pharmacotherapy mishaps occur commonly in the older adult population. This problem greatly affects the morbidity and mortality of elderly patients and greatly increases healthcare costs. To improve patient care among elderly adults, healthcare practitioners must consider several issues when developing a pharmacotherapy plan. A thorough understanding of pharmacokinetics, pharmacodynamics, adverse drug reactions, drug interactions, and several other factors is necessary for practitioners to develop a safe and effective drug therapy plan for older adults. This review provides a general but comprehensive review of the issues pertaining to pharmacotherapy in elderly people and offers several suggestions for improving their pharmaceutical care.

Introduction

Elderly patients represent an extremely large and continuously growing population of healthcare consumers. The evidence-based guidelines developed for younger patients with specific disease states actually improve mortality such that the population of patients living to old age is increasing. Data from 2003 show that US life expectancy at birth for the total population was 77.5 years compared with 49.2 years at the turn of the 20th century.^[2] As a group, elderly adults are difficult to distinguish. Patients can be classified as "young-elderly" (70–85 years old) or "old-elderly" (85 years old and older). This distinction may be important when evaluating drug studies in different age groups. Gender also can be used to distinguish patients. Because most elderly patients have more than one disease state and are prescribed many more medications than are nonelderly people, establishing definitive treatment guidelines can be difficult.^[1–5]

Treatment guidelines must be tailored to fit each elderly individual's specific pharmacology for prescribed drugs and for each patient's unique comorbidity or comorbidities. A specific pharmacotherapy regimen should be considered based on the patient's specific condition, disease states, and pharmacotherapy history. Establishing specific pharmacokinetic and pharmacodynamic profiles for specific drugs in individual patients is imperative to developing a well-tolerated and effective pharmacotherapy plan. This can be difficult to accomplish. Most new drugs are not studied in elderly patients and even less in elderly sick patients with various comorbidities who are taking a large number of different medications.^[6–13]

The establishment of an individualized pharmacotherapeutic plan is possible only if careful consideration is undertaken regarding each drug's pharmacokinetic and pharmacodynamic profile in a specific patient. Because drugs may behave differently in different patients, a specific profile must be developed for each patient. Aspects of this profile can include the following:

A drug's pharmacokinetic and pharmacodynamic profile in a specific patient
The potential for drug interactions in a specific patient
The potential for adverse drug reactions in a specific patient
The issue of patient compliance with the pharmacotherapy plan

If each of these issues is considered, then a safe and effective pharmacotherapy plan can be established for each elderly patient.^[7–12]

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Next Section

Abstract and Introduction
Pharmacokinetics
Pharmacodynamics
ADRs/Drug Interactions
Polypharmacy
Compliance
Tools for Appropriate Medication Decisions
Conclusions
References
Sidebar

Table 1. Formulas available for estimating creatinine clearance ^{1,14,15,17,18}
Creatinine clearance estimate	Formula	Comments
Cockcroft-Gault formula	Estimated creatinine clearance (mL/min) = [140 - age (y) × weight (kg)]/(72 × SCr) Multiply by 0.85 if female Use ideal body weight: Men = 50 + (2.3 × number of inches over 5 ft) Women = 45.5 + (2.3 × number of inches over 5 ft)	Widely used; Cockroft-Gault equation is used to make dosage adjustments, because this is how drug manufacturers establish their dosing recommendations. This is mandated by the FDA. The process of rounding the SCr concentration up by 1.0 mg/dL is not supported by medical evidence.
Abbreviated MDRD equation	Estimated glomerular filtration rate (mL/min/1.73 m²) = 186 × serum creatinine (mg/dL) Y 1.154 × age (y) Y 0.203: • × (0.742 if female) • × (1.210 if African American)	May be most effective in patients with diabetic kidney disease, patients with chronic kidney disease in middle age (average age 51 y), black patients with hypertensive chronic kidney disease, and patients with preexisting kidney disease. The MDRD equation is often used to stage patients' degree of kidney dysfunction.
Actual 24-h creatinine collection	Time-consuming and increases work for nursing	Pregnant women, patients with extremes of age and weight, patients with malnutrition, patients with skeletal muscle diseases, patients with paraplegia or quadriplegia, patients consuming a vegetarian diet and with rapidly changing kidney function

Circumstances under which these equations are not effective for estimating renal function: extreme body weight: body mass index <19 or > 35 kg/m², significant muscle mass abnormality (amputations, loss of muscle mass, muscle disease, or paralysis), acute kidney failure, pregnancy, severe hepatopathy, generalized edema, or ascites.
FDA, Food and Drug Administration; MDRD = modification of diet in renal disease; SCr = serum creatinine.

Table 2. Summary of pharmacokinetic changes observed with aging ^{5,7,9,14,15,17,18}
Pharmacokinetic parameter	Altered physiology with aging	Comments
Absorption	↓Gastric secretion ↑Gastric pH ↓GI motility ↓GI blood flow	Many drugs may diminish in their absorptive ability Time of onset of action may be delayed Absorption is the pharmacokinetic parameter least affected by aging
Distribution	↓Total body water ↓Lean body weight ↓Albumin ↑Body fat	Increased Vd of lipid-soluble drugs Increased free fraction of drug
Metabolism	↓Enzyme induction ↓Hepatic mass ↓Hepatic blood flow ↓ Activity in mixed function oxydase system	Reduced hepatic clearance of drugs Increased potential for drug interactions For elderly patients, dosage should be reduced for hepatically cleared drugs
Elimination	↓ GFR ↓ Renal blood flow	For elderly patients, drug accumulation will occur for renally cleared drugs

GFR, glomerular filtration rate; GI, gastrointestinal; Vd, volume of distribution.

Table 3. Drug classes that have potential pharmacodynamic changes in elderly adults ^1–8
Drug class	Potential pharmacodynamic issues	Comments
Antihypertensives	Orthostatic hypotension	Additive effect at lowering blood pressure Use with caution Start with lower dose
Benzodiazepines	Increased sensitivity (eg, drowsiness, confusion)	Use with caution Avoid other central nervous systemYactive drugs Use lowest tolerable dose
β -Adrenergic blockers (eg, propranolol)	β -receptors less responsive	May require greater β -blocker doses to have same effect
Anticoagulants (eg, warfarin)	Greater sensitivity to drug action	Initiate with lower dose Follow international normalized ratio closely
Diuretics	Greater sensitivity to drug action	Monitor blood pressure and electrolytes

Table 4. Drugs that commonly cause problems in elderly adults ^{5,7,15,20,25,26}
Drug	Adverse effect
Nonsteroidal anti-inflammatory drugs (eg, ibuprofen, naproxen)	Gastrointestinal bleeding, renal dysfunction
Diuretics (eg, hydrochlorothiazide, furosemide)	Hypotension, dehydration, electrolyte disturbance
Warfarin	Bleeding, many drug interactions
Angiotensin-converting enzyme inhibitors (eg, lisinopril)	Hypotension, renal dysfunction
Antidepressants (eg, amitriptyline)	Confusion, hypotension, constipation
Opiates (eg, morphine)	Confusion, disorientation, constipation
Prednisone	Osteoporosis, gastrointestinal problems, hyperglycemia
Benzodiazepines (eg, lorazepam)	Drowsiness, confusion

Table 5. Common ADRs in elderly adults associated with various symptomatology and drug classes ^21,25,26
Adverse effect	Manifestation of effect	Possible drugs or drug classes involved	Comments
Anticholinergic effects	Dry mouth, blurred near vision, hypotension, exacerbated narrow-angle glaucoma, excessive sedation, confusion or disorientation, constipation, dizziness, impaired gait and balance, impaired sweating, urinary hesitancy, urinary retention	First-generation antihistamines (diphenhydramine), antipsychotics, antidepressants, gastrointestinal tract motility agents, certain analgesics (tramadol), over-the-counter cough and cold preparations, etc	Common adverse effects from commonly used drugs Adverse effects are many times additive (eg, constipation from anticholinergics + narcotics) Central nervous system adverse effects can be insidious and develop over several years
Mental status changes	Confusion (acute or chronic), excessive sedation (drowsiness to soporific states), delirium, trouble concentrating, cognitive impairment, memory loss, dementia, impaired gait and balance, deficits in judgment or orientation to time, place, or person	All drug classes listed above plus muscle relaxants; drugs that may affect electrolytes (diuretics); central nervous system effects from other drug classes (eg, digoxin, amiodarone)	Adverse effects are additive and insidious, difficult to distinguish from metabolic problems, practitioner must take careful drug history to discern
Orthostatic hypotension	Sudden drop in blood pressure, dizziness, falling down	All blood pressure medicines (eg, β-blockers, calcium channel blockers), narcotics, phenothiazines, antidepressants, others	Fall risk is a major problem If this effect results in a fall causing broken hip or other bones, it can be devastating for patient Many effects are additive
Gastrointestinal tract disturbance; urinary incontinence	Constipation, diarrhea, nausea, vomiting, bladder problems	Diuretics, anticholinergics, antibiotics, almost all drugs can cause some form of GI problem	Results in less interaction for patient Can cause noncompliance Can cause nutritional disturbances Can contribute to bed sores, etc
Cardiac changes	Prolonged QTc leading to heart rhythm abnormality	Anticholinergics, antipsychotics, atypical antipsychotics, erythromycin	Effect can be fatal May be more common in patients with electrolyte abnormalities or previous cardiac history

Table 6. Selected disease states that may be aggravated by medications ⁹
Disease state	Aggravating drug	Potential adverse effect
Diabetes	Corticosteroids (eg, prednisone)	Drug-induced hyperglycemia
Osteoporosis	Corticosteroids (eg, prednisone)	Increased fracture risk
Constipation	Anticholinergics/antihistamines/narcotics	All slow gastrointestinal tract motility
Parkinson	Antipsychotics	Aggravate movement disorder
Hypertension	Nonsteroidal anti-inflammatory drugs	Fluid retention increases blood pressure
Benign prostatic hypertrophy	Anticholinergics/antihistamines	Urinary problems

Table 7. Methods to improve drug-related problems in elderly adults ^1–7
Medication issues	Comments
Improve compliance	Use as few drugs as possible Written instructions Council patient and family/caregiver Improve communication skills (eg, language) Make medications affordable Memory techniques (eg, calendars) Recognize potential health literacy issues that may cause compliance issues (eg, language issues, dementia)
Reduce polypharmacy	Use only 1 primary care provider who communicates with specialists Use only 1 pharmacy Reduce the number of drugs necessary because of adverse effects of another agent (eg, laxatives for drugs that cause constipation) Review all medications on each visit to doctor (brown bag) Maximize doses when possible instead of adding a new drug
Always consider pharmacokinetics/pharmacodynamics	Assess patient's renal function using specific formula on each visit (or obtain measured creatinine clearance) Establish any new or previous hepatic problems Ensure that patient can swallow and take oral medications Check for any weight loss or nutritional issues that can affect pharmacokinetics Assess for drug-induced changes in renal or hepatic function on each visit
Interactions	Assess for drugYdrug interactions Assess for drugYdisease interactions
Monitoring	Implement monitoring plan for every drug the patient is receiving and put this plan in writing Monitoring plan must include ways to monitor for beneficial effect as well as adverse effects Always make patient and/or caregiver part of the monitoring process Ensure that this plan is shared with all of the patient's healthcare providers, including other physicians, nurses, pharmacists, nursing facility, hospice Always make sure patient and/or caregiver understands why medications are being used and instructions for use
Communication	Patients must be able to communicate with their healthcare providers easily and must be encouraged to do so Healthcare providers must work together and must be able to communicate with one another to ensure that the best possible care is provided to the patient Physicians must be able to use the latest technology so that medical information is readily available for them to make proper pharmacotherapy plans Recognize potential health literacy issues that may cause communication problems

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Pharmacotherapy Considerations in Elderly Adults

Abstract and Introduction

Abstract

Introduction

Tables

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References

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