Geriatric Polypharmacy, The Good The Bad And The Ugly John Kashani DO Staff Toxicologist, New Jersey Poison Center Attending, St. Joseph’s Regional Medical

Geriatric Polypharmacy, The Good The Bad And The Ugly

John Kashani DO

Staff Toxicologist, New Jersey Poison Center

Attending, St. Joseph’s Regional Medical Center

Objectives

• Discuss the epidemiology of the aging population

• Discuss polypharmacy and adverse drug reactions

• Outline pharmacokinetics as it relates to the aging population

Objectives

• Outline potentially inappropriate medications for the elderly population

• Discuss clinically significant drug interactions

• Provide a rational approach to elderly medication prescribing

• Illustrate polypharmacy cases

Introduction

• Over 30 new medications are introduced each year

• Recognizing drug interactions is a daily challenge and is becoming increasingly more difficult

• Multiple drug regimes carry the risk of adverse interactions

Introduction

• Precipitant drugs modify the object drugs absorption, distribution, metabolism, excretion or clinical effect

• Additionally, newly introduced medications, and medications with new indications may have multiple pharmacologic effects

Introduction

• The population is steadily aging:

– Greater than 65 years old

• 12% of the United States Population

• 43% of Emergency Department

• 48% of critical care admissions

Introduction

• 2003 Poison Center exposures

– Increases fatality ratio

– Greatest among those 80 years or older

• May be grossly underestimated

Introduction

• The elderly are prescribed more drugs

• 32% of prescriptions

– Cardiovascular disease

– Arthritis

– Gastrointestinal disorders

– Bladder dysfunction

Introduction

• Average use for persons 65 years or older:

– 2 to 6 prescription drugs and 1 to 3.4 over-the-counter medicines

• Average American senior spends $670/year for pharmaceuticals

Polypharmacy

• Polypharmacy means "many drugs“

• The use of more medication than is clinically indicated or warranted

• 5 or more drugs

Adverse Drug Reaction

• The most consistent risk factor for adverse drug reactions (ADRs) is the number of drugs being taken

– Risk rises exponentially as the number of drugs increases

Adverse Drug Reaction

ADRs occur as a result of

1. Drug-drug interactions

2. Drug-disease interactions

3. Drug-food interactions

4. Drug side effects

5. Drug toxicity

Polypharmacy

• Polypharmacy leads to:

– More adverse drug reactions

• Patient outcomes

– Poor quality of life

– High rate of symptomatology

– (Unnecessary) drug exposure/expense

Consequences: Quality of Life

• In ambulatory elderly: 35% experience ADRs and 29% require medical intervention

• In nursing facilities: 2/3 of residents experience ADRs

• Up to 30% of elderly hospital admissions involve ADRs

*Beers MH. Arch Internal Med. 2003

“If medication related problems were ranked as a disease, it

would be the fifth leading cause of death in the US!”

*Beers MH. Arch Internal Med. 2003

Pharmacokinetics and Aging

– Absorption

– Distribution

– Metabolism

– Excretion


• Absorption:

– Age-related gastrointestinal tract and skin changes seem to be of minor clinical significance for medication usage


• Distribution:

– Important Age-Related Changes:

• Decrease in Lean Body Mass and total body water

• Increased percentage Body Fat


• Increase in volume of distribution for lipophilic drugs

– Protein Binding changes are of modest significance for most drugs, especially at steady-state

• Volume of distribution (Vd)

– Apparent volume the drug is dissolved in

– Measured in Liters or Liters/Kg

• not a real volume


• Metabolism:

– Though liver function tests are unchanged with age, there is some overall decline in metabolic capacity

– Decreased liver mass and hepatic blood flow


• Hepatic conjugation

– Inactive metabolites

• Hepatic oxidation

– Active metabolites


• Renal Excretion:

– Age-related decreased renal blood flow and GFR is well-established

– Decreased lean body mass leads to decreased creatinine production


Cr clearance=(140-age)(IBW)/creatinine(72)(multiply by 0.85 for women)

Example: “70kg” 75 year old manCr Clearance= (140-75)(70)/1.0(72)=63

Pharmacodynamics and Aging

• Generally, lower drug doses are required to achieve the same effect with advancing age– Receptor numbers, affinity, or post-

receptor cellular effects may change– Changes in homeostatic mechanisms

can increase or decrease drug sensitivity

Avoiding Polypharmamcy

– Avoid automatic refills– Look for other sources of medications

ie. OTC– Caution with multiple providers– Don’t use medications to treat side

effects of other meds– What can you discontinue or

substitute for safer medication?

Vitamin and Herbal Use in Older Adults

• Highly prevalent among older adults

• Generally not reported to the physician

• Some serious drug interactions are possible:

– Warfarin: gingko biloba, vitamin E

– SSRI’s: St. Johns Wort

(Potentially)Inappropriate Medications for Older Adults *

• Propoxephene

• Diphenhydramine

• Amitryptiline

• Alprazolam

• Diazepam

* Beers, MH et al. Arch Intern Med 151:1825,1991.

Polypharmacy in the Making…

• Drug reactions in the elderly often produce effects that simulate the conventional image of growing old:

unsteadiness drowsiness dizziness falls confusion depression nervousness incontinence fatigue malaise insomnia


• Avoid treating adverse reactions/side effects of drug with more drugs!

– Dizziness from anti-hypertensive treated with meclizine

– Edema from a calcium-channel blocker treated with furosemide and KCL


• Drugs most frequently associated with adverse reactions in the elderly:

– psychotropic drugs

– anti-hypertensive agents

– diuretics

– digoxin


– NSAIDS

– corticosteroids

– warfarin

– theophylline

Warfarin

• Drugs that inhibit warfarin's metabolism include ciprofloxacin (Cipro), clarithromycin (Biaxin), erythromycin, metronidazole (Flagyl) and trimethoprim-sulfamethoxazole (Bactrim, Septra)

• Acetaminophen

Warfarin

• Aspirin

• Nonsteroidal Anti-inflammatory Drugs

Fluoroquinolones

• Divalent cations (calcium and magnesium) and trivalent cations (aluminum and ferrous sulfate)

Antiepileptic Drugs

• Carbamazepine (Tegretol), phenobarbital and phenytoin (Dilantin)

– CYP450 interactions

2D6/3A4

• Fluoxetine (Prozac)Paroxetine (Paxil)Sertraline (Zoloft)

• Cimetidine (Tagamet)Clarithromycin (Biaxin)ErythromycinFluvoxamine (Luvox)Grapefruit juiceItraconazole (Sporanox)Ketoconazole (Nizoral)Lovastatin (Mevacor)Nefazodone (Serzone)Cisapride (Propulsid)

Lithium

• Diuretics

• Ace Inhibitors

• NSAIDS

Sildenafil

• Nitrates

3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors

• Concomitant use of statins and erythromycin, itraconazole, niacin or gemfibrozil (Lopid) can cause toxicity that manifests as elevated serum transaminase levels, myopathy, rhabdomyolysis and acute renal failure

Serotonergic Agents

• Inhibit 5-HT uptake

• Enhances 5-HT release

• Inhibits 5-HT breakdown

• Metabolized to 5-HT

• 5-HT1A agonist

• Enhances 5-HT receptor response to stimulation

Case 1

80 year old widow who now lives with her

daughter comes to Emergency Department

complaining of being a nervous wreck and

not being able to “turn off her mind

for the past 2 yrs”. She brings with her a bag

of all her meds

Case 1

PMHx: CHF, irritable bowel syndrome,

depression, HTN, recurrent UTIs, stress

incontinence, anemia, occipital

headaches, osteoarthritis, generalized

weakness

Case 1

Meds: sucralfate, Cimetidine, enteric

ASA, Atenolol, Digoxin, Alprazolam,

Naproxen, Oxybutynin, Dicyclomine TID,

Lasix, Tylenol #2, Verapramil

Medication Red Flags:

• High risk drugs: alprazolam, oxybutynin, tylenol #2, dicyclomine, NSAIDS

• Digoxin

P-Glycoproteins, Digoxin and polypharmacy

Small Intestine

Biliary Excretion

Renal Tubular Secretion

Lumen Enterocyte Plasma

Bile Hepatocyte Plasma

Urine Tubular Cell Plasma

**

*

P-Glycoproteins

• Inhibitors– Amiodarone– Clarithromycin– Cyclosporine– Diltiazem– Erythromycin– Ketocanazole– Quinidine– Verapramil– tacrolimus

• Inducers– Rifampin– St. John’s Wort– Dexamethasone– Indinavir– Ritonavir– Retonoic acid– Morphine– Phenothiazine– clotrimazole


• naproxen and aspirin carry the potential drug related adverse events of gastritis/GIB and sucralfate and cimetidine are being used to treat these side effects

Case 2

Mrs. Jones is a 72 yr living in an assisted

living facility where she has been recently

complaining of increasing confusion,

lightheadedness in the am and difficulty

sleeping at night

Case 2

PMHx: CHF, NIDDM, OA, glaucoma, depression, and stress incontinence

Meds: Digoxin, Furosemide, Timolol gtts,Metformin, Ibuprofen, Paroxetine,Oxybutynin,Propoxyphene/apapprn, andDiphenhydramine


• Diphenhydramine: sedative, anticholinergic properties

• Oxybutynin: anticholinergic Propoxyphene - narcotic

• Digoxin

Case 3

Mr. Wilson is a 81 yr who had an URI and subsequently was admitted for acute confusion and disorientation. He then began wandering and having hallucinations while spiking a fever.

Case 3

PMHx: CAD with MI, COPD, DJD,

Hypothyroidism, Depression/anxiety,

chronic anemia and diarrhea, aortic valve

replacement, gout, neuropathy, bilateral

total knee replacements

Case 3

• Meds: aggrenox, neurontin, theophylline, synthroid, allopurinol, prozac, combivent, colchicine, Imodium prn, metamucil, calcium, iron, multivitamin, codeine

Case 3

• Medical workup: significant for negative head CT, EKG with no acute changes, UA, CBC, LP, Chem10, CXR shows possible RLL infiltrate


• Theophylline: low therapeutic index • Iron deficiency anemia is more rare in

men, so check levels and maybe discontinue supplement

• Chronic diarrhea: iatrogenic? From colchicine? Also Imodium is anticholinergic

Prescribing Pearls

• Use single daily dose regimens

• Limit the use of PRN medications

• Consider all new medicines as a therapeutic trial

Prescribing Pearls

• Discontinue a drug if it is ineffective or intolerable adverse effects occur

• Provide legible written instructions

• Instruct caregivers as needed

Patient Education

• Use one pharmacist/pharmacy• Use your PCP as intended…avoid

seeing multiple physicians• Do not use medications from others• Report symptoms• All medicines, even over-the-counter,

have adverse effects• Report all products used

Ways to Decrease Drug Costs

• Generics ok

• Change dosing regimen

• Older drugs, e.g. beta blockers, diuretics, acetaminophen

• Double duty drugs, e.g. beta and alpha blockers, ACE-inhibitors

• Avoid non-regulated products

Geriatric Rx Principles

• First consider non-drug therapies

• Match drugs to specific diagnoses

• Reduce meds when ever possible

• Avoid using a drug to treat side effects of another

Geriatric Rx Principles

• Review meds regularly (at least q3 months)

• Avoid drugs with similar actions/same class

• Clearly communicate with pt and caregivers

• Consider cost of meds!

Avoiding Polypharmamcy

• Avoid automatic refills• Look for other sources of medications

ie. OTC• Caution with multiple providers• Don’t use medications to treat side

effects of other meds• What can you discontinue or substitute

for safer medication?

Summary

• Polypharmacy and ADRs have profound medical and economic consequences

• Elderly have unique pharmacokinetics predisposing them to drug toxicity

• High risk medications include cardiovascular, analgesic, psychotropics, and meds with a low therapeutic index

Summary

• Drug toxicity may be masquerading as an illness

• Be a patient advocate! It may be you one day…

References

1. Swanson’s Family Practice Review. Fourth Ed. A. Tallia, D. Cardone, D. Howarth, K Ibsen; Mosby 2001.

2. Geriatrics: 20 common problems. A. Adelman, M. Daly; McGraw Hill 2001.

3. Primary Care Geriatrics: A Case- Based Approach. Third Ed. R. Ham, P. Sloane; Mosby 1997.

4. Essentials of Clinical Geriatrics. Fourth Ed. RL Kane, JG Ouslander, IB Abrass; McGraw Hill 1999.

5. Polypharmacy. Didactic at SFM by Dr. Pat Borman6. Holland EG, Degruy FV. Drug- Induced Disorders. American

Family Physician Vol 56, Nov 1, 1997.7. Beers MH. Updating the Beers Crieria for 003Potentially

Inappropriate Medication Use in Older Adults. Arch Internal Med. 2003: 2716-2724.

8. Personal Medical Record developed by Dr. Eric Coleman, UCHSC, HCPR : http://caretransitions.org/document/phr.pdf

http://caretransitions.org/document/phr.pdf

Documents

Geriatric Polypharmacy, The Good The Bad And The Ugly John Kashani DO Staff Toxicologist, New Jersey Poison Center Attending, St. Joseph’s Regional Medical