geriatric polypharmacy the good the bad and the ugly
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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

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geriatric polypharmacy the good the bad and the ugly

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
Objectives
  • Discuss the epidemiology of the aging population
  • Discuss polypharmacy and adverse drug reactions
  • Outline pharmacokinetics as it relates to the aging population
objectives3
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
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
introduction5
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
introduction6
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
introduction7
Introduction
  • 2003 Poison Center exposures
    • Increases fatality ratio
    • Greatest among those 80 years or older
  • May be grossly underestimated
introduction8
Introduction
  • The elderly are prescribed more drugs
  • 32% of prescriptions
    • Cardiovascular disease
    • Arthritis
    • Gastrointestinal disorders
    • Bladder dysfunction
introduction9
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
  • Polypharmacy means "many drugs“
  • The use of more medication than is clinically indicated or warranted
  • 5 or more drugs
adverse drug reaction
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 reaction12
Adverse Drug Reaction

ADRs occur as a result of

  • Drug-drug interactions
  • Drug-disease interactions
  • Drug-food interactions
  • Drug side effects
  • Drug toxicity
polypharmacy13
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
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

slide15
“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
Pharmacokinetics and Aging
  • Absorption
  • Distribution
  • Metabolism
  • Excretion
pharmacokinetics and aging17
Pharmacokinetics and Aging
  • Absorption:
    • Age-related gastrointestinal tract and skin changes seem to be of minor clinical significance for medication usage
pharmacokinetics and aging18
Pharmacokinetics and Aging
  • Distribution:
    • Important Age-Related Changes:
      • Decrease in Lean Body Mass and total body water
      • Increased percentage Body Fat
pharmacokinetics and aging19
Pharmacokinetics and Aging
  • Increase in volume of distribution for lipophilic drugs
    • Protein Binding changes are of modest significance for most drugs, especially at steady-state
slide20
Volume of distribution (Vd)
    • Apparent volume the drug is dissolved in
    • Measured in Liters or Liters/Kg
      • not a real volume
pharmacokinetics and aging21
Pharmacokinetics and Aging
  • Metabolism:
    • Though liver function tests are unchanged with age, there is some overall decline in metabolic capacity
    • Decreased liver mass and hepatic blood flow
pharmacokinetics and aging22
Pharmacokinetics and Aging
  • Hepatic conjugation
    • Inactive metabolites
  • Hepatic oxidation
    • Active metabolites
pharmacokinetics and aging23
Pharmacokinetics and Aging
  • Renal Excretion:
    • Age-related decreased renal blood flow and GFR is well-established
    • Decreased lean body mass leads to decreased creatinine production
pharmacokinetics and aging24
Pharmacokinetics and Aging

Cr clearance=(140-age)(IBW)/creatinine(72)

(multiply by 0.85 for women)

Example: “70kg” 75 year old man

Cr Clearance= (140-75)(70)/1.0(72)=63

pharmacodynamics and aging
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
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
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
(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
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

polypharmacy in the making30
Polypharmacy in the Making…
  • 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
polypharmacy in the making31
Polypharmacy in the Making…
  • Drugs most frequently associated with adverse reactions in the elderly:
    • psychotropic drugs
    • anti-hypertensive agents
    • diuretics
    • digoxin
polypharmacy in the making32
Polypharmacy in the Making…
  • NSAIDS
  • corticosteroids
  • warfarin
  • theophylline
warfarin
Warfarin
  • Drugs that inhibit warfarin's metabolism include ciprofloxacin (Cipro), clarithromycin (Biaxin), erythromycin, metronidazole (Flagyl) and trimethoprim-sulfamethoxazole (Bactrim, Septra)
  • Acetaminophen
warfarin34
Warfarin
  • Aspirin
  • Nonsteroidal Anti-inflammatory Drugs
fluoroquinolones
Fluoroquinolones
  • Divalent cations (calcium and magnesium) and trivalent cations (aluminum and ferrous sulfate)
antiepileptic drugs
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)

2D6/3A4
lithium
Lithium
  • Diuretics
  • Ace Inhibitors
  • NSAIDS
sildenafil
Sildenafil
  • Nitrates
3 hydroxy 3 methylglutaryl coenzyme a reductase inhibitors
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
Serotonergic Agents
  • Inhibit 5-HT uptake
  • Enhances 5-HT release
  • Inhibits 5-HT breakdown
  • Metabolized to 5-HT
  • 5-HT1A agonist
  • Enhances 5-HTreceptor response to stimulation
case 1
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 143
Case 1

PMHx: CHF, irritable bowel syndrome,

depression, HTN, recurrent UTIs, stress

incontinence, anemia, occipital

headaches, osteoarthritis, generalized

weakness

case 144
Case 1

Meds: sucralfate, Cimetidine, enteric

ASA, Atenolol, Digoxin, Alprazolam,

Naproxen, Oxybutynin, Dicyclomine TID,

Lasix, Tylenol #2, Verapramil

medication red flags
Medication Red Flags:
  • High risk drugs: alprazolam, oxybutynin, tylenol #2, dicyclomine, NSAIDS
  • Digoxin
p glycoproteins digoxin and polypharmacy
P-Glycoproteins, Digoxin and polypharmacy

Small Intestine

Biliary Excretion

*

*

Bile

Hepatocyte

Plasma

Lumen

Enterocyte

Plasma

Renal Tubular Secretion

*

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

P-Glycoproteins
medication red flags48
Medication Red Flags:
  • 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
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 250
Case 2

PMHx: CHF, NIDDM, OA, glaucoma,

depression, and stress incontinence

Meds: Digoxin, Furosemide, Timolol gtts,

Metformin, Ibuprofen, Paroxetine,

Oxybutynin,Propoxyphene/apapprn, and

Diphenhydramine

medication red flags51
Medication Red Flags:
  • Diphenhydramine: sedative, anticholinergic properties
  • Oxybutynin: anticholinergic Propoxyphene - narcotic
  • Digoxin
case 3
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 353
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 354
Case 3
  • Meds: aggrenox, neurontin, theophylline, synthroid, allopurinol, prozac, combivent, colchicine, Imodium prn, metamucil, calcium, iron, multivitamin, codeine
case 355
Case 3
  • Medical workup: significant for negative head CT, EKG with no acute changes, UA, CBC, LP, Chem10, CXR shows possible RLL infiltrate
medication red flags56
Medication Red Flags:
  • 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
Prescribing Pearls
  • Use single daily dose regimens
  • Limit the use of PRN medications
  • Consider all new medicines as a therapeutic trial
prescribing pearls58
Prescribing Pearls
  • Discontinue a drug if it is ineffective or intolerable adverse effects occur
  • Provide legible written instructions
  • Instruct caregivers as needed
patient education
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
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
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 principles62
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 polypharmamcy63
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
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
summary65
Summary
  • Drug toxicity may be masquerading as an illness
  • Be a patient advocate! It may be you one day…
references
References
  • Swanson’s Family Practice Review. Fourth Ed. A. Tallia, D. Cardone, D. Howarth, K Ibsen; Mosby 2001.
  • Geriatrics: 20 common problems. A. Adelman, M. Daly; McGraw Hill 2001.
  • Primary Care Geriatrics: A Case- Based Approach. Third Ed. R. Ham, P. Sloane; Mosby 1997.
  • Essentials of Clinical Geriatrics. Fourth Ed. RL Kane, JG Ouslander, IB Abrass; McGraw Hill 1999.
  • Polypharmacy. Didactic at SFM by Dr. Pat Borman
  • Holland EG, Degruy FV. Drug- Induced Disorders. American Family Physician Vol 56, Nov 1, 1997.
  • Beers MH. Updating the Beers Crieria for 003Potentially Inappropriate Medication Use in Older Adults. Arch Internal Med. 2003: 2716-2724.
  • Personal Medical Record developed by Dr. Eric Coleman, UCHSC, HCPR : http://caretransitions.org/document/phr.pdf
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