Download Internal Medicine Morning Report

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
Pharmacokinetics and Aging
• Absorption:
– Age-related gastrointestinal tract and
skin changes seem to be of minor
clinical significance for medication
usage
Pharmacokinetics and Aging
• Distribution:
– Important Age-Related Changes:
• Decrease in Lean Body Mass and
total body water
• Increased percentage Body Fat
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
• Volume of distribution (Vd)
– Apparent volume the drug is dissolved in
– Measured in Liters or Liters/Kg
• not a real volume
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 Aging
• Hepatic conjugation
– Inactive metabolites
• Hepatic oxidation
– Active metabolites
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 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
• Generally, lower drug doses are
required to achieve the same effect with
advancing age
– Receptor numbers, affinity, or postreceptor 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
dizziness
confusion
nervousness
fatigue
insomnia
drowsiness
falls
depression
incontinence
malaise
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 Making…
• Drugs most frequently associated with
adverse reactions in the elderly:
– psychotropic drugs
– anti-hypertensive agents
– diuretics
– digoxin
Polypharmacy in the Making…
– 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)
Erythromycin
Fluvoxamine (Luvox)
Grapefruit juice
Itraconazole (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
*
*
Lumen
Enterocyte
Bile
Hepatocyte
Plasma
Renal Tubular Secretion
*
Urine
Tubular Cell
Plasma
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
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
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, and
Diphenhydramine
Medication Red Flags:
• 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
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
• 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.
2.
3.
4.
5.
6.
7.
8.
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