Pharmacotherapy in the Elderly

1
Pharmacotherapy in the Elderly

• Seki A. Balogun, MD
• Assistant Professor of Clinical Internal Medicine
• Division of General Medicine and Geriatrics

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Geriatric Assessment

• Physical Assessment
• Cognitive Assessment
• Psychologic Assessment
• Social Assessment
• PHARMACOTHERAPY key component!

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Why?

• Persons aged 65years and older are prescribed the
  highest proportion of medications
• constitute 13 of the population yet purchase 33
  of all prescriptions
• High risk for adverse drug effects

4
Predisposing factors to adverse drug effects in
the elderly

• Physiologic changes due to aging
• Drug - disease interactions
• Drug- Drug interactions (polypharmacy)
• Compliance
• -cognition
• - functional status
• - personal beliefs
• - financial issues

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Physiologic Changes with Aging

• ABSORPTION
• Rate may be slow, but extent of absorption
  remains unchanged
• Peak serum concentration of a drug may be lower
  in an older adult (time to reach it delayed)
• Overall aging does not affect drug absorption to
  any clinically significant degree

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Physiologic Changes with Aging

• DISTRIBUTION
• Older adults have less body water and lean body
  mass and greater fat stores
• Water soluble drugs have lower volume of
  distribution
• - reach peak concentrations quicker
• - digoxin, lithium, ethanol
• Fat soluble drugs have increased volume of
  distribution
• - longer to reach steady state and longer
  to be eliminated
• - CNS acting drugs

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Case 1.

• A 90 year old woman who has CHF, NIDDM,
  Depression, Insomnia and GERD comes to you for a
  clinic visit. She lives with her daughter who
  notes new mild forgetfulness. Her medications are
  Omeprazole 20mg qd, Rosiglitazone 4mg qd,
  Glipizide10mg qd, Furosemide 40mg qd, Digoxin
  0.5mg qd, Amitriptyline 25mg qd, Fluoxetine 20mg
  qd, Cyclobenzaprine 10mg tid, Valerian 1pill a day

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Case 2.

• 83 year old man with urge incontinence, frequent
  falls, anxiety, forgetfulness and fatigue comes
  to see you in clinic. Past medical history
  includes CAD, CHF. His medications are
• Oxybutynin 5mg bid (antispasmodic)
• Timolol eye drops
• Diazepam 5mg qhs
• Furosemide 40mg qd
• Ibuprofen 200mg bid

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Physiologic Changes with Aging

• Drugs bound to plasma proteins
• higher proportion unbound and pharmacologically
  active
• - Coumadin
• - Digoxin
• - phenytoin
• - valproic acid
• - ceftriaxone

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Case 3.

• An 81 year old man, a resident in the nursing
  home with a medical history of Hemorrhagic
  Stroke, Dementia, CAD, HTN, Seizure disorder
  (controlled), is admitted to the hospital with
  Urosepsis and treated with Levaquin. His
  condition improves. Other medications( unchanged
  for 5 years) are Phenytoin 200mg bid,

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Case 3. contd

• ASA 325mg qd, Atenolol 25mg qd, MVI, HCTZ. His
  labs reveal a low total phenytoin level,
  otherwise normal. His phenytoin dose is increased
  300 mg bid and is discharged to HealthSouth. A
  few days later, he develops altered mental status

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Physiologic Changes with Aging

• METABOLISM
• most common site liver
• Decreased liver mass and hepatic blood flow
• Reduced clearance of drugs

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Physiologic Changes with Aging

• ELIMINATION
• Usually involves the kidney
• Glomerular filtration declines
• - decreased renal blood flow
• - loss of nephrons
• decrease in kidney size
• Decline begins in mid-thirties
• Serum creatinine is NOT an accurate reflection of
  creatinine clearance in the elderly

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Physiologic Changes with Aging

• To calculate appropriate dose for renally
  eliminated medications- estimation of creatinine
  clearance required
• Cockroft and Gault equation
• CrCl(ml/min) (IBW in kg)(140-age in years) x
  (0.85 if female)
• (72)(serum creatinine
  in mg/dl)
• For men IBW in kg 50 (2.3) (each inch gt 5
  feet).
• For women IBW in kg 45 (2.3) (each inch gt5
  feet)

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Case 4.

• An 80 year old woman with a history of DJD,
  presents with knee pain. Her baseline Creatinine
  is 1.1. She is prescribed Naproxen 500mg bid

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Potentially Inappropriate Medications (Beers
List)

• HIGH RISK
• Analgesics
• indomethacin
• pentazocine (talwin)
• trimethobenzamide (tigan)
• Muscle relaxants/
• antispasmodics
• metocarbamol (robaxin)
• Carisoprodol (Soma)
• Chlorzoxazone (paraflex)
• Benzodiazepines long acting
• Diazepam (valium)
• Chlodiazepoxide (librium)
• Flurazepam

• Antidepressants
• Tricyclic antidepressants, Doxepin
• Antiarrythmics
• Disopyramide (Norpace)
• Antihypertensives
• Methyldopa
• Reserpine
• GI antispasmodics
• Dicyclomine (bentyl)
• Hyoscyamine (levsin)
• Donnatal
• Antihistamines
• Diphenhydramine (benadryl)

Fick DM, Cooper JW et al. Arch Intern Med
20031632716-24
Fick DM, Cooper JW et al. Arch Intern Med
20031632716-24
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Potentially Inappropriate Medications (Beers
List)

• LOW RISK
• Digoxin dose gt 0.25mg /day
• Ferrous sulfate dose gt325mg/day
• Propoxyphene (darvon)
• Dipyridamole (persantine) orthostatic
  hypotension
• Clonidine
• Cimethidine (tagamet) CNS effects
• Diabinese (chlorpropamide) prolonged half life

Fick DM, Cooper JW et al. Arch Intern Med
20031632716-24
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Drug Disease Interactions

• Higher disease burden associated with increased
  risk of adverse drug reactions
• Inappropriate medication use (40) is highest in
  frail older adults with greater disease burden

Rigler SK - Am J Geriatr Pharmacother -
01-DEC-2004 2(4) 239-47
Rigler SK - Am J Geriatr Pharmacother -
01-DEC-2004 2(4) 239-47
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Case 5.

• 76 year old woman with a medical history of CHF
  and renal failure is seen in your clinic for the
  first time. Her medications are
• Lisinopril 10mg qd
• Spironolactone 25mg qd PO
• Dyazide (triamterene/HCTZ, 25/37.5) 2 tabs qd PO

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Case 6.

• 89 year old man is brought to the ER by his
  daughter, with agitation, confusion, abdominal
  discomfort and urinary incontinence. Symptoms had
  been getting worse over the last week. Had been
  hospitalized three weeks ago for an unknown
  condition and was discharged home on Nifedipine,
  Simvastatin, Terazosin, Cromolyn inhaler,
  Aspirin.
• Physical exam revealed a distended bladder.
  Catheterization is performed without difficulty,
  it yielded 385ml and relieved abdominal discomfort

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Case 7.

• 83 year old woman with a history of osteoporosis
  and renal insufficiency, comes to your clinic
  with severe low back pain of 2 weeks duration,
  has been taking Tylenol extra strength 2 tabs tid
  and Advil 400mg qid and saw another physician
  recently who added Percocet 10/325 2 tabs q4hrly

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Case 8.

• An 81year old man, who recently moved to an
  assisted living facility, comes to see you in the
  clinic with his wife. His medical history is
  significant for hypertension, CAD and mild
  Dementia. His wife is concerned about a change in
  their sexual relationship. He admits to loss of
  libido in the last few months. His medications
  are aspirin, Imdur, atenolol

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Drug- Drug Interactions (Polypharmacy)

• Studies have shown that patients over 65 years of
  age use an average of 2 to 6 prescribed
  medications and 1 to 3.4 non-prescribed
  medications in different settings
• Higher in home bound patients
• NH residence is associated with reduced use of
  potentially inappropriate drugs
• Study of NH in Charlottesville, mean no. of 11
  medications (range 0 -30) in newly admitted
  residence
• Increases the risks of adverse drug reactions and
  drug-drug interactions
• makes compliance with medication regimens more
  difficult

Stewart RB - Drugs Aging - 01-JUN-1994 4(6)
449-61 Balogun SA, Evans JE. In press
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Case 9.

• Your clinic nurse calls you about Ms Smiths
  blood work. Her INR is 7. She is an 80 year old
  woman with HTN, atrial fibrillation on coumadin.
  Is being treated for a UTI with Bactrim DS 1 tab
  bid PO for 14 days.
• Other medications are Metoprolol 50mg bid,
  Digoxin 0.25mg qd and gingko biloba

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Compliance

• 43 Elderly patients were able to correctly
  identify all of their prescription medications
• 32 patients named all dosages correctly

Chung MK - Ann Emerg Med - 01-JUN-2002 39(6)
605-8
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Case 10.

• 68 yr old woman is taking ciprofloxacin 250mg q12
  hrs for an uncomplicated UTI due to E. Coli. She
  remains symptomatic after 5 days of therapy and
  urine sample reveals persistent bacteria
• Other meds are theophylline 300mg bid,
  venlafaxine 75mg bid, and multiple OTC drugs
  including MVI, Pepcid
• Which medication is the most likely cause of this
  treatment failure?

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Case 11.

• You are asked to consult on a 62 year woman, who
  is status post hip replacement with a history of
  uncontrolled hypertension. She was admitted to
  the rehab hosp. She currently complains of
  worsening stress urinary incontinence and
  non-productive cough. Her medications are
  lisinopril 10mg qd, doxazosin 2mg qd (recently
  added for better BP control), Percocet 5/500 1
  tab q4/PRN, Ferrous sulfate 325mg tid, Vit C

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Case 12.

• An 82 year old man with Dementia is hospitalized
  for pneumonia. In the evening, he becomes very
  agitated, tries to get out of bed. He is given
  Ativan 2mg P.O., the dose repeated 1hour later
  with no effect. He is then given Haldol 5mg
  IM. The following day, he is difficult to arouse
  and sleeps all day. At night, the nurse calls to
  report that the patient is agitated and trying to
  get out bed again

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Other Risk factors

• Female gender
• Low educational status
• Low socio-economic status

Lechevallier-Michel N - Eur J Clin Pharmacol -
01-JAN-2005 60(11) 813-9
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Utility and clinical significance

• positive correlation between potentially
  inappropriate drug prescribing, as defined by the
  Beers criteria, and adverse drug reactions
• Geriatric evaluation and management reduces
  serious adverse drug reactions by 35
• Reduces suboptimal prescribing, in frail elderly
  patients.

Schmader KE - Am J Med - 15-MAR-2004 116(6)
394-401 Chang CM - Pharmacotherapy -
01-JUN-2005 25(6) 831-8
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Clinical Significance

• Inappropriate medication use increased the
  likelihood of experiencing at least one adverse
  health outcome ( hospitalizations, emergency
  department visits, or deaths ) more than twofold.
  

Perri M 3rd - Ann Pharmacother - 01-MAR-2005
39(3) 405-11
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Good news!

• significant decline in the use of potentially
  inappropriate drugs by elderly patients,
  particularly those drugs linked to the most
  severe outcomes. (25 - 21)

Stuart B - Am J Geriatr Pharmacother -
01-DEC-2003 1(2) 61-74
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Bad news!

• Approximately 7 million elderly patients still
  received potentially inappropriate drugs in 1999
• Underscoring the continued need for effective
  interventions to improve prescribing for this
  vulnerable population.

Stuart B - Am J Geriatr Pharmacother -
01-DEC-2003 1(2) 61-74
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Rules of prescribing in older adults

• Start low , go slow
• Try to limit number of medications and avoid
  prescribing a pill for every ill
• Try not to start two drugs at the same time
• Make sure it is the right dose
• Avoid inappropriate medications- Beers criteria
• Watch out for potential drug-drug, drug-disease
  interactions
• Make sure patient and caregiver understand what
  the medication is for , how and when to take it,
  possible side effects
• Avoid expensive new medications that have not
  been shown to be superior to less expensive
  generic alternatives

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Rules of prescribing

• Ask patient about all medications (including OTC,
  herbal prep)
• Ask patient how each medication is being taken
• Look for medications with duplicate therapeutic
  or pharmacologic profiles
• Eliminate unnecessary medications
• Simply the medication regimen fewest possible
  number of medications and doses per day
• Always review any changes in writing with the
  patient and caregiver
• If possible, use technology to monitor parameters
  of efficacy and eliminate duplicative therapy,
  and also to detect potential drugdrug
  interactions and drug disease interactions