Polypharmacy appropriate and inappropriate based on risk and benefit assessment case study, negative consequences of polypharmacy, deprescribing tools,

1. Polypharmacy in older adults: an integrated
approach
Hozaifa Hasan
M. Pharm, IRPh. POSCAR member
Consultant Pharmacist

2. WHAT IS THE MAIN OBJECTIVE OF POLYPHARMACY IN ELDERLY PEOPLE
UNIVERSALLY
• According to WHO Polypharmacy is the concurrent use of multiple medications. polypharmacy is often
defined as the routine use of five or more medications. This includes over-the-counter, prescription
and/or traditional and complementary medicines used by a patient.
• Health care interventions are intended to benefit patients, but they can also cause harm. Most of this
harm is preventable. Adverse events are now estimated to be the 14th leading cause of morbidity and
mortality in the world, putting patient harm in the same league as tuberculosis and malaria (1). Bates
DW, et.al. J Gen Intern Med.1995;10(4):199–205. The most important challenge in the field of patient
safety is how to prevent harm, particularly avoidable harm, to patients during their care. Early action
and effective management to protect patients from harm while maximizing the benefit from medication,

3. Polypharmacy in older adults : a global concern
World Health Organization has evaluated that in every nine people there is one elderly people, i.e. of age
60 years or older. This value is to be expected to increase to one in five people by 2050. Polypharmacy is
an area of concern for elderly because of several reasons. Elderly people are at a greater risk for adverse
drug reactions (ADRs) because of the metabolic changes on ageing and reduced drug clearance associated
with ageing; this risk is furthermore exacerbated by increasing the number of drugs used. Potential of
drug-drug interactions is further increased by use of multiple drugs. Various study has shown that more
the number of medication more the adverse drug reaction and increase the risk of morbidity and frailty
and hospitalisation and mortality rate (Lai et.al. Medicine 2010;89(5):295-9.)

4. Polypharmacy in older adults how prevalent in India
one study done by Kumar et al., 2015, revealed that the prevalence of polypharmacy was 73%;
among this, minor polypharmacy (2–4 drugs) accounted for 81.15% and major polypharmacy (≥5
drugs) for 18.85%. According to another study done in india in which they found prevalence of
polypharmacy was 33% among the elderly population. Joint disorders were highest, followed by
hypertension, diabetes mellitus, respiratory diseases and sleep disorders. The present study
concluded that polypharmacy is an emerging public health concern among elderly in India. Joint
disorders is highest, followed by hypertension, diabetes mellitus, respiratory diseases and sleep
disorders are the major risk factors of polypharmacy among elderly in India.

5. Appropriate polypharmacy is present, when
• All medicines are prescribed for the purpose of achieving specific therapeutic objectives that have
been agreed with the patient.
• Therapeutic objectives are actually being achieved or there is a reasonable chance they will be achieved
in the future.
• Medication therapy has been optimized to minimize the risk of adverse drug reactions (ADRs).
• The patient is motivated and able to take all medicines as intended .
There are many conditions in which the combined use of three or more drugs is beneficial and
appropriate. Diabetes mellitus. Tuberculosis and three or four in the HAART regimen used to treat AIDS.
A striking example of potentially beneficial polypharmacy is the ‘Polypill’, with six proposed ingredients —
clopidogrel, aspirin, a statin, beta blocker, ACE inhibitor/ ARB/CCB, Nitrates in case of CAD, ACS, and in
case of heart failure some times 10 drugs are used. (British Journal of General Practice, July 2006)

6. After discharge medication for HF
1. Beta blocker
2. Loop diuretcs
3. ACE
4. ARB
5. Nitrates
6. Aspirin
7. Statin
8. Clopidogrel
Appropriateness is based on risk and benefit assessment

7. Polypharmacy: Medications may be inappropriate if:

8. • Inappropriate polypharmacy is present, when one or more medicines are
prescribed that are:-
Not or no longer needed, either because:
• There is no evidence based indication, the indication has expired or the dose is unnecessarily high.
• One or more medicines fail to achieve the therapeutic objectives they are intended to achieve.
• One, or the combination of several medicines cause ADRs, or put the patient at a high risk of ADRs.
• The patient is not willing or able to take one or more medicines as intended.
• Overuse and misuse of medication in the older population are among the major concern in India. The
growing culture of irrational and unnecessary prescribing of medications in the older population may
increase the risk of adverse outcomes. Multiple studies demonstrated that poor prescribing practices,
inappropriate medication and frequent misuse of drugs to earn profit are some of the factors that result in
polypharmacy, hyperpolypharmacy, and PIM use in India. In particular, older people with multiple
comorbidities are exposed to polypharmacy, and suboptimal prescribing may increase their likelihood of
receiving PIMs (porter and grills, 2016).

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Atkin PA, Veitch PC, Veitch EM, Ogle SJ. The epidemiology of serious adverse
drug reactions among the elderly. Drugs Aging 1999;14:141-152
Adverse Drug reaction and Polypharmacy
Risk factor for ADR in older adults is Polypharmacy

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Age related change to organ system
Aging is typically accompanied by
physiological changes, including a
declined immune system, increased
susceptibility to infections, deteriorated
kidney function, and geriatric syndrome.
These conditions, added to the burden
of polypharmacy, may enhance the risk
of morbidity and mortality, especially in
cases of acute infections.
(Therapeutics and Clinical Risk
Management 2020:16 )

11. .
AGING POSE RISK
The elderly are at high risk for drug interactions due to polypharmacy, comorbidities,and decreased
nutritional status, which may affect the pharmacokinetic and pharmacodynamic properties of
medications ( Bhavik M. Shah, PharmD geriatric.theclinics.com).
Chronic diseases are prevalent among the older population; about 80% of older adults have at least one
chronic condition, and about half have at least two. These chronic conditions, which include heart disease,
hypertension, diabetes, arthritis, and cancer, often require multiple medications for optimal management
Drug treatment planning in old age is made more complex because comorbid diseases may affect the
absorption, volume of distribution, protein binding, and, especially, elimination of many drugs, leading to
fluctuation in therapeutic levels and increased risk of under- or overdosing. Drug excretion is affected by
renal and liver changes with aging that may not be detectable with usual clinical tests. Formulas for
estimating glomerular filtration rate in older patients are available, whereas estimating changes in hepatic
excretion is still a challenge.
(International Journal of Medical Science and Public Health | 2015 | Vol 4 | Issue 8 )

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HOW AGING AFFECT PHARMACOKINETIC AND PHARMACODYNAMIC
Ageing is associated with physiological changes that affect how medicines are handled, including
alterations in volumes of drug distribution, metabolism and clearance which can prolong half-life,
increase potential for drug toxicity and the likelihood of adverse drug reactions. In addition, elderly
patients may have altered drug responsiveness, due to reduced homeostatic reserve in different organ
systems e.g. the risk of orthostatic hypotension is greater in older people prescribed vasodilators,
because a progressive decline in baroreflex sensitivity (BRS ). First-pass metabolism (metabolism,
typically hepatic, that occurs before a drug reaches systemic circulation) is also affected by aging,
decreasing by about 1%/year after age 40. Thus, for a given oral dose, older adults may have higher
circulating drug concentrations. Important examples of drugs with a higher risk of toxic effects because
of age-related reductions in first-pass metabolism include nitrates, propranolol, phenobarbital,
and nifedipine.
One of the most important pharmacokinetic changes associated with aging is decreased renal
elimination of drugs. After age 40, glomerular filtration rate (GFR) decreases an average ; however, the
age-related decrease varies substantially from person to person. Serum creatinine levels often remain
within normal limits despite a decrease in glomerular filtration rate (GFR) because older adults generally
have less muscle mass and are generally less physically active than younger adults and thus produce less
creatinine. Maintenance of normal serum creatinine levels can mislead clinicians to assume those levels
reflect normal kidney function. Decreases in tubular function with age parallel those in glomerular

13. Most common medication used by older adults
Kaufman and colleagues reported that the most common prescription medications among older patients
are -
1.conjugated estrogens, 2.levothyroxine, 3.diuretics , 4.atorvastatin, and 5. beta blocker, 6. aspirin
7.analgesics, 8. gastrointestinal agents like PPI . Central Nervous system agents (antidepressants,
antipsychotics/neuroleptics, cognition enhancer,
The most common non-prescription medications are analgesics ( acetaminophen, and ibuprofen),
cough and cold medications (diphenhydramine and pseudoephedrine), vitamins and minerals
(multivitamins, vitamins E and C, calcium), and herbal products (ginseng, Ginkgo biloba extract). antacids
and laxatives
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Causes of polypharmacy
1. An aging population with comorbidities requiring several different medications and an
increasing availability of newer medications
2. Patients self-medicating with over-the-counter medications and herbal preparations without
a clear understanding of the adverse reactions and interactive effects
3. A “prescribing cascade” which occurs when patients take a medication and exhibit side
effects that are misinterpreted by the health-care practitioner as symptoms of a disease and
requiring additional medication
4. The patient sees several physicians and fills prescriptions at different pharmacies, but there is
a failure to keep all parties informed about each other's actions
5. Ineffective communication and coordination between health-care practitioners which is not
necessary

15. Common Chronic Conditions and Polypharmacy
• Prevention and/or Symptom Management
• Cardiovascular risk:
– Hypertension: 2 meds (of Calcium channel blocker, ACE inhibitor, diuretic) and beta blocker
– Hypercholesterolemia: 1 med (Statin)
– Diabetes: 2 meds as disease progresses (Metformin + Sulfonylurea-Glicazide
– Atrial fibrillation: 1 med (Warfarin, NOACS)
• Coronary artery disease: 2 meds (Aspirin, Beta-blocker- if angina)
• Heart failure: 3 meds (Diuretic, ACE-I, Beta-blocker)
• Chronic obstructive pulmonary disease: 2 drugs (Inhalers- Sympathetic/cholinergic systems)
• Bone metabolism (mostly women): 2 meds (Ca, Vit D), Bisphosphonate if osteoporosis and high
risk of fracture
• Osteoarthritis: If pain (analgesic- Acetaminophen, NSAID, opioid)
• GI: Dyspepsia (Antacid), Gastroesophageal reflux disease (GERD)- H2B, PPI

17. Prescribing Cascade example

18. Negative consequences of polypharmacy
1. Fall
2. Frail
3. Hip fracture
4. Cognitive impairment
5. Urinary incontinence
6. Health care cost
7. Drug interaction
8. Functional status
9. Adverse drug event
10.Non adherence
11.Nutrition

19. Deprescribing Tools and Potentially Inappropriate Medication (PIM)
The American Geriatric Society (AGS) and the National Institute on Aging (NIA) developed tools to identify
medications that are potentially inappropriate for older adults, describe priorities and guiding principles for
safe medication use, while promoting research on deprescribing practices in older populations.
1. AGS Beers Criteria
2. STOPP/START
3. The Pharmacist's Letter
4. Anticholinergic Burden (ACB) scale
Aim of above tools are to provide some practical considerations on deprescribing, dose reduction,
and drug selection in the older adult population.

20. So What Strategies Could Make The Path To Deprescribing More
Acceptable?
• Understand the individual health status, including chronic diseases and frailty, and the related Goals of
Care… this sets the context for addressing medications
• Explaining as:
– Dosage reduction, tapering with monitoring and review- this is a valid clinical strategy as well
– Stating the objective as ‘Pause and Monitor’ rather than ‘deprescribing’ or ‘stopping medications’-
this is a valid clinical strategy as well

21. INTEGRATED APPROACH TO IMPROVING POLYPHARMACY
Drug Regimen Review
• Schamder et al, 2004 has done a study on inpatient and outpatient geriatric evaluation and
management consisting of geriatrician, nurse, and pharmacist. Finally they found that
geriatric evaluation and management reduced the number of unnecessary and inappropriate
drugs in inpatients.
• Fick et al, 2004 Physicians were mailed a listing of patients who were taking potentially
inappropriate medications, as defined by the Beer’s criteria, as well as alternative
recommendations provided by multiple independent pharmacists and geriatrician. 12.5%
of potentially inappropriate medications were discontinued. The most common
discontinued medications were antihistamines, analgesics, and muscle relaxants.
• Zarowitz et al, 2005 Clinical pharmacists reviewed drug regimens, educated physicians
and patients on polypharmacy, and worked with physicians to reduce polypharmacy.
The rate of polypharmacy reduced by 67.5% after first intervention, After the
second intervention, the polypharmacy rate was reduced by 39%,
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22. Principles for Optimizing Drug Use in the Elderly
• Extensive medication histories should be obtained at the initial visit and updated with each subsequent
encounter. Medication histories should include both prescription and nonprescription medications and
any other health-related food or drink the patient is consuming. Patients and/or their caregivers should
be encouraged to bring in all prescription and OTC products with them to each health care visit.
• Two techniques, often referred to as SAIL and TIDE, are helpful to remember ways to reduce
polypharmacy
Simple: Keep the regimen as simple as possible. Use medications that can be dosed once or twice a
day. Use a medication that can treat multiple indications.When drug therapy has been titrated to ideal
doses, try to combine medications into single pills to reduce pill burden.
Adverse effects: Know the potential adverse effects of medications. Choose medications that have
broad therapeutic indices when possible. Identify medication that are treating adverse effects of other
medications.
Discontinue the drug that is causing the adverse effect if possible.
Indication: Ensure each medication has an indication and a defined, realistic therapeutic goal.
List the name and dose of each medication in the chart and share it with the patient and/or caregiver.
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TIDE
Time Allow sufficient time to address and discuss medication issues during each encounter.
Individualize Apply pharmacokinetic and pharmacodynamic principles to individualize medication
regimens. Consider dose adjustments for renal and/or hepatic impairment. Start medications at lower
doses than usual and titrate slowly.
Drug interactions Consider potential drug-drug and drug-disease interactions. Avoid potentially
dangerous interactions, such as those that can increase the risk for torsades de pointes.
Educate Educate the patient and caregiver regarding pharmacologic and nonpharmacologic treatments.
Discuss expected medication effects, potential adverse effects, and monitoring parameters.

24. Case Study: 1
• 65 year old man with diabetes, high blood pressure, heart failure, moderately severe kidney disease,
high cholesterol, heart burn, severe knee arthritis, burning neuropathy in her feet, depression, and
insomnia. In addition to her primary doctor, seen by an endocrinologist, cardiologist, neurologist,
psychiatrist.
• Metformin 1000 2 X daily , Glipizide 5 mg daily , Metoprolol 50 mg 2 X daily , Lisinopril 40 mg
daily Furosemide 20 mg 2 X daily , Simvastatin 40 md 2 X daily , Amitriptyline 25 mg at bedtime l
Duloxetine 20 mg daily , Clonazepam 0.5 mg 2 X daily , Gabapentin 600 mg 3 X daily , Ranitidine
150 mg 2 X daily , Acetaminophen with hydrocodone 500mg/5mg 4 X daily as needed , Timolol
0.5% 1 drop to both eyes daily l (OTC) Diphenhydramine 25 mg at bedtime

25. Case study 2
Patient is a man, 70 years of age, who resides in a nursing facility. One year ago, he fell and fractured his left hip
and underwent surgical repair. He returned to the nursing facility, completed rehabilitation, and regained most of his
prior function. After the surgery, Patient was prescribed warfarin to prevent deep vein thrombosis (DVT) after
surgery.
During a routine survey, a state surveyor discovers that Patient is still being administered warfarin. After further
investigation, it is discovered that the warfarin was never discontinued after the appropriate duration after the hip
fracture repair. The surveyor considers warfarin an unnecessary drug, and a citation (F757) is issued. After
contacting the attending physician, the warfarin is promptly discontinued.
Comments and Discussion : This case is an example of using the right drug but not using it for the correct duration.
After orthopedic surgery, warfarin is usually indicated for approximately two to three months or until
activity/ambulation has increased to a point that the risk of DVT is reduced. There is a substantial burden of
treatment with warfarin, including weekly evaluations of prothrombin time/international normalized ratio (PT/INR),
adverse reactions, interactions, and increased risk of bleeding and brain hemorrhage, especially for patients with a
history of falls.
There is shared responsibility for this error between the prescriber/healthcare provider and the facility. The provider
did not follow through and discontinue the medication when it was no longer needed, and the facility nursing staff
should have realized that the drug was no longer necessary and approached the provider for an order to discontinue.
The nursing facility could have called the orthopedic physician for orders and duration of warfarin treatment after
surgery. When a medication is started, the stop date for that medication should be considered and established. The
consultant pharmacist could have intervened as well.

26. Case study 3
• Patient is 65 years of age with a history of congestive heart failure, glaucoma, hypertension, and osteoarthritis. Her current
medications are furosemide, potassium, lisinopril, metoprolol, aspirin, timolol maleate opthamic solution, Acacetaminophen (as
needed), multivitamin, and a calcium/vitamin D supplement (800 IU daily). She has an appointment with a new orthopedic
physician. During the appointment, the patient complains of persistent arthritic pain in her knee. The physician prescribes the
nonsteroidal anti-inflammatory drug (NSAID) meloxicam (7.5 mg per day) for pain and inflammation.
• Comments and Discussion : From the orthopedic standpoint, prescription of meloxicam is good practice, as it should help to
ameliorate patient symptoms. However, from a cardiac standpoint, this is a risky approach due to the potential side effect of fluid
retention and its effect on the heart. In general, NSAIDs can be dangerous for an individual of Patient age. NSAIDs (including
meloxicam, but also over-the-counter options like ibuprofen) have been issued "black box" warnings by the U.S. Food and Drug
Administration (FDA) for the increased risk of :-
• Serious and potentially fatal cardiovascular and thrombotic events, including myocardial infarction and stroke
• Serious adverse gastrointestinal events such as bleeding, ulcer, and intestinal perforation (higher in elderly patients)
Patient has a good working relationship with her primary care provider, who has instructed her to contact him regarding any
changes in her medication regimen. She calls her physician prior to taking the medication, and he advises her not to take the NSAID.
Instead, he devises a pain management plan that minimizes the potential risks. Previously, Patient was taking acetaminophen as
needed, averaging up to one dose daily. This is increased to twice daily extended-release acetaminophen (650 mg). For breakthrough
pain, tramadol 25 mg every four hours (as needed) is prescribed. Another option considered was the topical anti-inflammatory
diclofenac sodium 1% topical gel, which would have fewer side effects than systemic agents. Aside from pharmacotherapy, the
patient is scheduled with a physical therapist to create a safe exercise plan, including strengthening and range-of-motion exercises.

27. CASE STUDY 4
Patient is a man, 72 years of age, who resides in a long-term care facility. He has been diagnosed with
congestive heart failure, hypertension, arthritis, and hyperlipidemia and He requires minimal assistance
with his activities of daily living and remains ambulatory. His usual medications are:
Metoprolol ER: 50 mg daily
Aspirin: 325 mg daily
Omeprazole: 20 mg daily
Lisinopril: 10 mg daily
Furosemide: 40 mg every day
Potassium chloride: 20 mEq twice daily
Atorvastatin: 20 mg daily
Acetaminophen: 650 mg twice daily
Tramadol: 50 mg, as needed
Multivitamin
At baseline, he takes 10 medications/supplements.
Patient is transferred to the emergency department for increased shortness of breath. He is diagnosed
with bronchitis.

28. Levofloxacin: 500 mg daily
Prednisone: 20 mg daily
Levosalbutamol, inhalation solution for nebulizer: As needed for shortness of breath
Promethazine: 25 mg every six hours as needed
Haloperidol: 1 mg every four hours as needed
Bisacodyl: 10 mg every day as needed
Including the as-needed medications, Patient is currently prescribed 16 drugs. Physical assessment
reveals an elderly debilitated man who is in no acute distress (He is alert and oriented and answers
questions appropriately. His intake of food and fluids has been poor since his return from the hospital,
and he is using oxygen per nasal cannula at 2 L/minute.

29. Patient
Physician
Nurse
Pharmacist
Come together and Work together for medication safety and patient safety
Thank you

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