A. Factors Influencing Drug Metabolism in Elderly [1,3]

1. Reduced creatinine clearance
2. Reduced hepatic metabolism
3. Increased proportion of fat to muscle
4. Comorbid conditions
5. Polypharmacy
6. Non-drug induced gastric achlorhydria is uncommon in elderly [4]
7. Undertreatment of many conditions, particularly pain, is common in elderly [5]

B. Frequently Used Agents in Elderly

1. Antipsychotics [6,7]
   1. Often used inappropriately for sedation
   2. High incidence of side effects with classical antipsychotics including hypotension, extrapyramidal symptoms, arrhythmias
   3. Use of classical, particularly anticholinergic, antipsychotics should be minimized
   4. Very low doses of sedating type antipsychotics (anticholinergic) may be tried
   5. Consider atypical antipsychotics (newer) agents with reduced side effect risks
   6. Behavioral issues surrounding elderly, particularly with dementia, are important
   7. Atypical antipsychotics associated with potentially increased risk of death in elderly [6]
   8. Typical (classical) antipsychotics associated with at least, and possibly ~35% higher, risk of death compared with atypical agents in elderly patients [7,8]
   9. Key issue is that behavior needs to be stabilized
   10. Atypical antipsychotics especially olanzapine are useful adjuncts for depression (particularly apathy) in elderly persons
2. Sleeping Aides (Hypnotics)
   1. Caution with use of sedative-hypnotics in elderly persons with insomnia [11,12]
   2. Cognitive behavioral therapy superior to zopiclone (non-benzodiazepine GABA agonist) in chronic primary insomnia in older adults [11]
   3. Adverse effects of sedative-hypnotics outway improvements in sleep quality in elderly [12]
   4. If non-benzodiazepine sleeping aids required, sugest zelepelon (Sonata®) or zolpidem
   5. Benzodiazepines were previously used extensively
   6. Benzodiazepines should be avoided, especially long acting agents
   7. Note that metabolism of these agents increases with increasing age
   8. Specifically avoid chlordiazepoxide, diazepam, flurazepam
   9. Coffee and other caffeinated beverages should be avoided after 1:00 PM
   10. Many elderly patients required only 4-7 hours of sleep
   11. Chloral hydrate (250mg po qhs) or melatonin receptor agonist can be tried if needed
3. Anticholinergic Agents
   1. Usually given as antihistamines, often for sedation
   2. Also used as antispasmodis and muscle relaxants
   3. Cognitive dysfunction is common and may last >24 hours
   4. Also causes bowel and bladder dysfunction, tachycardias
4. Nonsteroidal Anti-Inflammatory drugs (NSAIDs)
   1. High incidence of gastrointestinal side effects
   2. Increased incidence of azotemia and hypertension in elderly
   3. Can often be replaced with acetaminophen for pain control
   4. Specifically avoid ketorolac as it has high ulcerogenic potential
   5. May be combined with misoprostal (Cytotec®) for prevention of ulcers
   6. Major side effect of Misoprostal is diarrhea
5. Stool Softeners and Laxatives
   1. Colace, a stool softener, is frequently used to reduce pain on defacation
   2. Dose is 100mg po qd-tid
   3. Chronic laxative use can lead to myenteric plexus damage
   4. Sorbitol or lactulose may be safer chronically than irritant agents (such as Dulcolax®)
   5. Chronic enemas should be avoided if possible
   6. High fiber diets and adequate hydration, with physical activity are critical
   7. For patients on opioids, addition of Senekot® may prevent constipation
6. Digoxin [9]
   1. Frequently prescribed for any sign of heart failure or for atrial fibrillation
   2. Many elderly patients with heart failure have diastolic dysfunction
   3. Digoxin will worsen diastolic dysfunction
   4. In addition, digoxin can exacerbate arrhythmias, cause nausea, mental status changes
   5. Small therapeutic window; requires frequent blood monitoring
   6. Calcium blockers or ß-adrenergic blockers are preferred therapy for atrial fibrillation
   7. Digoxin should usually withdrawn slowly to reduce side effects
7. H2-Histamine Blockers
   1. Cimetidine (Tagamet®) may cause cognitive impairment in elderly
   2. Other agents rarely cause problems
   3. However, indication(s) for use should be reviewed carefully
   4. Sucralfate (non-absorbed) may be used in some patients instead of H2-blockers
   5. However, sucralfate has aluminum in it, and chronic use may lead to bone weakness
8. Opioids [3]
   1. Increase risk of cognitive impairment (see below)
   2. Specifically avoid meperidine, propoxyphene
   3. Morphine is best overall opiate in elderly

C. Drugs that May Cause Cognitive Impairment in Elderly [1]

1. Anticholinergics
2. Antiepileptics
3. Antiparkinson drugs
4. Antipsychotics
5. Barbiturates
6. Benzodiazepines
7. ß-Adrenergic Blockers
8. Calcium channel blockers
9. Chlolinesterase (anti-Alzheimer's agents)
10. Fluoroquinolones
11. Glucocorticoids
12. Histamine H1- and H2- receptor antagonists
13. NSAIDs
14. Opioids
15. Selective serotonine reuptake inhibitors (SSRIs)
16. Tricyclic Antidepressants

D. Other Drugs To Avoid [3]

1. Chlorpropamide (Diabinese®, others) - long half life predisposes to hypoglycemia
2. Cimetidine (Tagamet®, others) - confusion, many drug interactions; recommend famotidine
3. Nitrofurantoin (Macrobid®, others) - limited efficacy in renal impairment
4. Trimethobenzamide (Tigan®, others) - extrpyramidal effects, limited effectiveness

E. Underused Agents in Elderly

1. Acetaminophen
   1. Minimal side effects except with concommitant alcohol ingestion
   2. No gastric toxicity or predisposition to hypertension
   3. Dose is 650-1000mg po or pr q6-8 hours; maximum ~3gm per day
2. Antidepressants
   1. Depression is quite common in the elderly
   2. May be mistaken for sleep disorder and/or pschosis
   3. Elderly persons are frequently given benzodiazepines or antipsychotics inappropriately
   4. Selective Serotonin Reuptake Inhibitors (eg. sertraline, paroxetine) are first choice
   5. Secondary amine tricyclic antidepressants (eg. nortriptyline, desipramine) may be used
   6. Tertiary tricyclics (amitriptyline, imiprimine) are not recommended
3. Vaccinations
   1. All persons >65 years should receive yearly influenza vaccines unless contraindicated
   2. All persons >65 years should receive a pneumococcal vaccine
   3. Tetanus boosters should be given every 10 years
   4. We recommend aggressive vaccination plan, all persons >50-55 years
   5. Persons with undlerlying chronic disease / immunosuppression receive vaccines earlier
4. Hormone replacement therapy shows similar beneficial effects on lipids in women >75 compared with <75 years of age [10]
5. Chronic pain is poorly treated in the elderly [5]

References

1. Drugs and Cognitive Disorders in the Elderly. 2000. Med Let. 42(1093):111
2. Avorn J and Gurwitz JH. 1995. Ann Intern Med. 123(3):195
3. Drugs in the Elderly. 2006. Med Let. 48(1226):6
4. Hurwitz A, Brady DA, Schaal E, et al. 1997. JAMA. 278(8):659
5. Bernabei R, Gambassi G, Lapane K, et al. 1998. JAMA. 279(23):1877
6. Kuehn BM. 2005. JAMA. 293(20):2462
7. Wang PS, Schneeweiss S, Avorn J, et al. 2005. NEJM. 353(22):2335
8. Gill SS, Bronskill SE, Normand ST, et al. 2007. Ann Intern Med. 146(11):775
9. Senni M and Redfield MM. 1997. Mayo Clin Proc. 72(5):453
10. Binder EF, Williams DB, Schechtman KB, et al. 2001. Ann Intern Med. 134(9):754
11. Sivertsen B, Omvik S, Pallesen S, et al. 2006. JAMA. 295(24):2851
12. Glass J, Lancrot KL, Herrmann N, et al. 2005. Brit Med J. 331(7526):1169