Instructor: Lynne Kallenbach, MD
Module Developed by: Lynne Kallenbach, MD
Reviewed by: Doug Woolley, MD, MPH
A drug is any substance that affects the physical or mental functioning of a living organism. Polypharmacy is defined as the use of several drugs or medicines together in the treatment of disease, suggesting indiscriminate, unscientific, or excessive prescription.
A. Introduction:
Before reviewing the learning objectives and content, please take the Pre-Test. The answers are given in the Post-Test that complete the module.
Please review the Objectives, Content material, and Cases before our class session. We will apply the tasks in the Skills Objectives to these cases, and you should think about them ahead of time.
B. Attitudes - Medical students will:
C. Knowledge - Medical students should be able to:
D. Skills - Medical students should be able to:
E. Readings
Required Readings:
- Chutka DS, Evans JM. Drug Prescribing for Elderly Patients. Mayo Clinic Proc, 1995; 70:685-693.
- Williams C. Using Medications Appropriately in Older Adults. American Family Physician. 2002;66(10):1917-1924.
This article describes the pharmacokinetic and pharmacodynamic changes that occur with aging and to discuss common problems noted with the use of medications often prescribed for elderly patients.
Recommended Readings:
- Beers M. Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Archives of Internal Medicine Dec 2003; 163:2716-2829.
- International Review Syllabus in Geriatrics - Aging and Drug Action by Healthandage.com, Novartis Foundation for Gerontology and the American Geriatrics Society.
- Avorn J, Gurwitz JH. Diagnosis and Treatment: Drug Use in the Nursing Home. Annals of Internal Medicine 1995;123:195-204.
- Zhan C, et.al. Potentially Inappropriate Medication Use in the Community-Dwelling Elderly. Journal of the American Medical Association. 2001;286122: 2823-2829.
F. Module Content
G. Cases
Digoxin
- Symptoms include nausea/vomiting, anorexia (even at therapeutic serum levels), visual changes, cardiac arrhythmias, and conduction disturbances
- Vd is reduced because of decreased muscle mass
- Clearance is delayed with decreased creatinine clearance
- Low K+, Mg+ and high Ca+ all may potentiate digitalis toxicity
- Use ECG to help identify severity of toxicity, serum levels are only a guide
- Digitalis available over 200 years
- Therapeutic use has come and gone over the years
- It has been observed that if it were submitted new to the FDA it would never be approved, because the Therapeutic Index is so small. The therapeutic dose is barely less than the amount that will do harm
- Digoxin is a very dangerous drug, but, used with proper monitoring can be remarkably useful in congestive heart failure and with atrial fibrillation
- Amazingly, it has only been known for about a decade that giving quinidine to a patient on digoxin will quickly increase the serum digoxin level and the dose of digoxin will have to be diminished accordingly
- Since it is possible to get blood levels for each of these drugs it is easily possible to compensate for the changes in concentrations with use of both
Thiazides
- May cause low K+ and Na+ resulting in:
- Delirium
- Arrhythmias
- In combination with K+ sparing diuretics or ACE inhibitors, it may lead to hyperkalemia
- May decrease carbohydrate tolerance and increase Uric Acid levels = Gout and Diabetes
Beta Blockers
- Decreased effect secondary to decrease receptor response (a pharmacodynamic change)
- Patients with diabetes may experience hypoglycemia because of blocking the gluconeogenesis and may impair the tachycardia response in hypoglycemia leading to a delay in the recognition of an insulin reaction
- By and large, however, the above problems are infrequent
Calcium Channel Blockers
- Negative Ionotropic effect and delay AV conduction - especially Verapamil and Diltiazem
- Use cautiously in patients with CHF
- Minor effects = flushing, headache, and peripheral edema
- Usually well tolerated but are costly
- Use if can treat more than one problem with one drug, i.e., high blood pressure and angina
Neuroleptics
- Block neurotransmitters and receptors
- Epinephrine, Dopamine, Alpha and Beta Receptors
- May result in effects of:
- Hypotension, dry mouth, sedation, constipation urinary retention, etc.
- Extrapyramidal symptoms are common
- Decreasing dose or discontinuation should always be considered in a patient taking neuroleptic meds
Benzodiazepines
- 40% of prescriptions of benzodiazepines are for patients over 65 years old
- Used primarily for anxiety, insomnia, or agitation
- Often work well for sleep at first but with chronic use, they lose their efficacy
- Some have active metabolites
- Diazepam, Flurazepam
- Long term treatment and long-acting formulations should be avoided
- It is always prudent to give careful and reasoned thought before making the decision to use a long-acting drug of any type to an older adult
- Daily doses of benzodiazepines are cumulative and, therefore, potentially dangerous
NSAIDS
- Variable effects within this class
- Gastritis and occult bleeding are most common
- In persons who develop serious UGI bleeding, first symptom often the hemorrhage
- Also can have acute tubular necrosis (uncommon) and acute renal failure (common and reversible)
- May increase the serum concentration of Digoxin
- May decrease effectiveness of B-Blockers, Thiazide
H2-Blocker
- Competes for the P-450 enzymes
- reduces metabolism of Warfarin, Phenytoin, Tegretol
- Adverse effects:
- Headache, nausea/vomiting, dermatologic reactions, dizziness
- Rare anemias and leukopenias
- Cimetidine occasionally has reversible CNS disturbances
- Gynecomastia
- Usually safe if prescribed as indicated
Clonidine
- alpha-2 adrenergic agonist
- Rebound hypertension can occur with abrupt discontinuation
- Side effects may be limiting in older adults; as this medication is centrally acting, may cause CNS depression and sedation. Orthostasis and dry mouth can be problematic as well.
Polypharmacy... Drug Use Case Study #1:
From the Sublime to the Ridiculous
Max Levin is an 83 year old retired tailor. Born in Kiev he came to the United States with his parents and older sisters shortly after the revolution in Russia. After living 10 years in New York City the family moved to Kansas City. For nearly 60 years he had his own tailor shop, retiring finally at age 81. Most of his customers were gone and business declined over the years so his sons closed the shop and Mr. Levin moved to a retirement home. Mr. Levin is a proud and patriotic man, being especially proud of his World War II military service with the U.S. Navy in the South Pacific, where he was awarded a Purple Heart. Widowed since age 76 he has two sons and two daughters who monitor his health and welfare closely, too closely Mr. Levin complains.
Since age 50 he has been treated for hypertension with a variety of drugs by a variety of physicians. After angina pectoris of increasing frequency over a two week period he had a four vessel CABG at age 73. He has occasional angina for which he wears a 0.2 mg per hour transdermal nitroglycerin patch and for which he takes nitroglycerin tablets when physical exertion or anger brings on chest pain. He has been on digoxin 0.25 mg daily for many years. Because of frequent ventricular premature beats he was started on Quinidex Extentabs 300 mg every eight hours about a year ago. His other medications include metoprolol 100 mg twice daily and furosemide 80 mg daily for his elevated blood pressure. He uses fexofenadine for seasonal allergies. His major complaint is of a hiatal hernia which he says gives him belching and dyspepsia. For this he takes cimetidine 400 mg four times daily and metoclopramide 10 mg with meals.
During the winter he takes clarithromycin intermittently to prevent bronchitis.
He smokes about six cigars daily, having cut down in recent years. He enjoys beer when watching television, particularly sporting events, and mixed drinks at social events.
At your initial examination you find the patient to have a regular pulse with a rate of 52 per minute. His blood pressure is 180/90 in the left arm seated and 140/70 standing. His pulse increases only to 56 when he stands but he does not have symptoms of postural hypotension. He has bruits in both carotid arteries. There is a loud ejection murmur over the aortic area and a prominent fourth heart sound. His lungs are clear and his abdominal examination is normal. His prostate gland is large and soft. Stool is hemoccult negative. His neurological examination is normal and his Folstein shows a score of 28/30. His screening laboratory results show a normal CBC and normal chemistries except for a creatinine of 1.5 and a BUN of 28. His serum potassium is 3.3 meq/L. His cholesterol is 270, TSH is 5.8, and PSA is 6.1. Chest x-ray is unremarkable and EKG shows only mild left ventricular hypertrophy.
Besides his chronic dyspepsia and belching he complains of diminished appetite and ten pounds weight loss during the past several months. He tells you that his younger daughter, a dietitian, constantly badgers him about following his low cholesterol diet. His other daughter is particularly concerned that he has recently started seeing a 75 year old widow. Though Mr. Levin has much to say about his health and his family, he seems to enjoy life and is comfortably and securely situated in the retirement home. Within two days of his seeing you for the first time both of his daughters have called you.
Questions:
Polypharmacy... Drug Use Case Study #2:
Polypharmacy... Drug Therapy
As a consultant in Geriatric Medicine you are asked to see a 92 year old retired school teacher in your clinic. Hortense Connolly is brought to you by her niece, her only living family member. The patient has always lived alone and retired as a primary school teacher 30 years previously. Her niece is concerned because the patient has fallen three times during the past two months, once being seen in a local Emergency Department when she was diagnosed as having a crush fracture of her T-12 vertebra. She still has considerable back pain from this healing fracture. The niece is also concerned that her aunt is not as mentally sharp as she was just six months ago. A high school English teacher she has long been able to complete the New York Times Crossword Puzzle most days of the week. In the past month she has not even attempted it. She has been reasonably healthy during her life. She had a hysterectomy for menorrhagia at age 40 and a cholecystectomy at age 56. A lean woman she is 5'4" tall and weighs 110 lbs. She thinks she was 5'6" when in her 20s. Her physical examination reveals her vital signs to be remarkable only in that her blood pressure is 155/90 sitting and 120/85 standing. Her pulse rate is 76 and regular both sitting and standing. She has a fourth heart sound and no murmurs. There are soft systolic bruits in both carotid arteries and a bruit in her upper abdomen. Her neurological examination is normal except for a Babinski on the left and slight left arm and left leg spasticity with clonus in the left ankle. Her medicines include: hydrochlorothiazide 25 mg. every other day for pedal edema, a clonidine patch for hypertension, an NSAID for arthritis, about four Tylenol #3 each day for back pain, diazepam 5 mg. tid for anxiety, and Ambien 5 mg. prn hs for sleep. Her laboratory profile is normal except for a hemoglobin of 10.3 gm/dl with an MCV of 74, a serum creatinine of 1.6 mg/dl, and a fasting blood sugar of 134 mg/dl.
Questions:
Polypharmacy... Drug Use Case Study #3:
What am I supposed to do with this list?!
A 92 year old male comes to your office to establish a primary care relationship after having just been discharged from another hospital. He was admitted for a GI bleed but his stay was complicated by delirium, acute vision loss in his left eye, a large occipital lobe stroke, and the discovery of severe aortic stenosis and coronary artery disease. Since his discharge, he has required an in-home caregiver and reports much functional loss, as well as concerns about his balance and cognitive abilities. As requested, he brings all of his medications with him for evaluation. The bag contains the following:
1. Omega 3 fatty acid capsules
2. Vitamin E
3. Stelazine 2 mg @ hs
4. Percocet q4 hr
5. Propanolol 10 mg qd
6. Aspirin 81 mg qd
7. Vitamin B complex
8. Lipitor 10 mg qd
9. Metoprolol 50 mg bid
10. Prilosec 20 mg qd
11. Imipramine 25 mg qhs
12. Fish oil capsules
13. Propoxyphene/ acetaminophen q6 hr prn
14. Dalmane 15 mg qhs
15. Ranitidine 150 mg bid
16. Tylenol PM, over the counter prn
17. Digoxin 0.25 mg qd
Questions:
Polypharmacy... Drug Use Case Study #4:
Use of Sedative Medications in Demented Patients
Igor Sinkovich is a 79 year old retired laborer who has had gradually progressive symptoms of memory compromise and combative behavior for about two years. He is brought to your clinic by his wife of nearly 60 years, and his oldest son. A short muscular man he has an iron-grey crew cut and looks ten years younger than his real age. He is cordial with you during the interview but most of the history is given by his wife. His speech is heavily accented and he has little concept of dates and time. He remembers Franklin Roosevelt as the president and expresses considerable affection for him. He has enjoyed good health during his life. He drank to excess during his younger years and would drink more now then the limited amount of wine and beer his family lets him have. He and his wife have lived in the same house for nearly 50 years. His physical examination and laboratory screen are essentially normal. On the Folstein examination he scores 15/30. He completed only grade school, and that in the old country. The son takes you aside and tells you that his father's behavior is becoming a real problem. He becomes angry easily and has threatened to hit his wife, though the son thinks he has not done so. In any event, his mother has denied this when asked directly by the son. He roams the house at night and is obsessed that intruders may break in. He has been seen by two doctors in the past year who have attempted to alter his obstreperous behavior with drugs. Amitriptyline did help him to sleep at night but caused him difficulties with urination and he was seen twice in Emergency Service for acute urinary retention. Alprazolam made him more tractable but it was hard to get him to take it, he thought he was being poisoned by the little white tablets. Diazepam made him quite unsteady and he fell twice, once needing stitches on his head. His family, particularly his wife, wants him to be in his home but they are at their wits end.
Questions:
Polypharmacy... Drug Use Case Study #5:
Anticoagulation in the Aged Patient
Grace Hall is an active 68 year old executive secretary who is under your care in the hospital for her second episode of right leg deep vein thrombosis in six months. With this episode there was clot into her femoral vein, at least, and she had a small pulmonary embolus. Her past medical history is also significant for a DVT years ago with the second of her two pregnancies. She had a vaginal hysterectomy for menorrhagia at the age of 50 and has been on Premarin 1.25 mg daily since that time. Otherwise, she takes antacids and over the counter pepcid for heartburn. In the past year, she has taken metronidazole suppositories for trichomoniasis, trimethoprim / sulfamethoxazole for a presumed urinary tract infection, and fluconazole for a vaginal yeast infection. She smokes a pack of cigarettes a day and does not use alcohol
Her blood pressure is often elevated, in the range of 150-170 / 90-100, but she does not take antihypertensive medications on a regular basis. She was anticoagulated with warfarin after the first recent DVT episode, but it was discontinued when it proved too difficult to control her prothrombin time; she also had hematuria on two occasions.
Questions:
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