Geriatric Polypharmacy, The Good The Bad And The Ugly

1
Geriatric Polypharmacy, The Good The Bad And The
Ugly

• John Kashani DO
• Staff Toxicologist, New Jersey Poison Center
• Attending, St. Josephs Regional Medical Center

2
Objectives

• Discuss the epidemiology of the aging population
• Discuss polypharmacy and adverse drug reactions
• Outline pharmacokinetics as it relates to the
  aging population

3
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

4
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

5
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

6
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

7
Introduction

• 2003 Poison Center exposures
• Increases fatality ratio
• Greatest among those 80 years or older
• May be grossly underestimated

8
Introduction

• The elderly are prescribed more drugs
• 32 of prescriptions
• Cardiovascular disease
• Arthritis
• Gastrointestinal disorders
• Bladder dysfunction

9
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

10
Polypharmacy

• Polypharmacy means "many drugs
• The use of more medication than is clinically
  indicated or warranted
• 5 or more drugs

11
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

12
Adverse Drug Reaction

• ADRs occur as a result of
• Drug-drug interactions
• Drug-disease interactions
• Drug-food interactions
• Drug side effects
• Drug toxicity

13
Polypharmacy

• Polypharmacy leads to
• More adverse drug reactions
• Patient outcomes
• Poor quality of life
• High rate of symptomatology
• (Unnecessary) drug exposure/expense

14
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

15

• 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

16
Pharmacokinetics and Aging

• Absorption
• Distribution
• Metabolism
• Excretion

17
Pharmacokinetics and Aging

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

18
Pharmacokinetics and Aging

• Distribution
• Important Age-Related Changes
• Decrease in Lean Body Mass and total body water
• Increased percentage Body Fat

19
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

20

• Volume of distribution (Vd)
• Apparent volume the drug is dissolved in
• Measured in Liters or Liters/Kg
• not a real volume

21
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

22
Pharmacokinetics and Aging

• Hepatic conjugation
• Inactive metabolites
• Hepatic oxidation
• Active metabolites

23
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

24
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

25
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

26
Avoiding Polypharmamcy

• Avoid automatic refills
• Look for other sources of medications ie. OTC
• Caution with multiple providers
• Dont use medications to treat side effects of
  other meds
• What can you discontinue or substitute for safer
  medication?

27
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
• SSRIs St. Johns Wort

28
(Potentially)Inappropriate Medications for Older
Adults

• Propoxephene
• Diphenhydramine
• Amitryptiline
• Alprazolam
• Diazepam
• Beers, MH et al. Arch Intern Med
  1511825,1991.

29
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

30
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

31
Polypharmacy in the Making

• Drugs most frequently associated with adverse
  reactions in the elderly
• psychotropic drugs
• anti-hypertensive agents
• diuretics
• digoxin
  

32
Polypharmacy in the Making

• NSAIDS
• corticosteroids
  
• warfarin
• theophylline

33
Warfarin

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

34
Warfarin

• Aspirin
• Nonsteroidal Anti-inflammatory Drugs

35
Fluoroquinolones

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

36
Antiepileptic Drugs

• Carbamazepine (Tegretol), phenobarbital and
  phenytoin (Dilantin)
• CYP450 interactions

37
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)

38
Lithium

• Diuretics
• Ace Inhibitors
• NSAIDS

39
Sildenafil

• Nitrates

40
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

41
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

42
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

43
Case 1

• PMHx CHF, irritable bowel syndrome,
• depression, HTN, recurrent UTIs, stress
• incontinence, anemia, occipital
• headaches, osteoarthritis, generalized
• weakness

44
Case 1

• Meds sucralfate, Cimetidine, enteric
• ASA, Atenolol, Digoxin, Alprazolam,
• Naproxen, Oxybutynin, Dicyclomine TID,
• Lasix, Tylenol 2, Verapramil

45
Medication Red Flags

• High risk drugs alprazolam, oxybutynin, tylenol
  2, dicyclomine, NSAIDS
• Digoxin

46
P-Glycoproteins, Digoxin and polypharmacy
Small Intestine
Biliary Excretion


Bile
Hepatocyte
Plasma
Lumen
Enterocyte
Plasma
Renal Tubular Secretion

Urine
Tubular Cell
Plasma
47
P-Glycoproteins

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

• Inducers
• Rifampin
• St. Johns Wort
• Dexamethasone
• Indinavir
• Ritonavir
• Retonoic acid
• Morphine
• Phenothiazine
• clotrimazole

48
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

49
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

50
Case 2

• PMHx CHF, NIDDM, OA, glaucoma,
• depression, and stress incontinence
• Meds Digoxin, Furosemide, Timolol gtts,
• Metformin, Ibuprofen, Paroxetine,
• Oxybutynin,Propoxyphene/apapprn, and
• Diphenhydramine

51
Medication Red Flags

• Diphenhydramine sedative, anticholinergic
  properties
• Oxybutynin anticholinergic Propoxyphene -
  narcotic
• Digoxin

52
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.

53
Case 3

• PMHx CAD with MI, COPD, DJD,
• Hypothyroidism, Depression/anxiety,
• chronic anemia and diarrhea, aortic valve
• replacement, gout, neuropathy, bilateral
• total knee replacements

54
Case 3

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

55
Case 3

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

56
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

57
Prescribing Pearls

• Use single daily dose regimens
• Limit the use of PRN medications
• Consider all new medicines as a therapeutic trial

58
Prescribing Pearls

• Discontinue a drug if it is ineffective or
  intolerable adverse effects occur
• Provide legible written instructions
• Instruct caregivers as needed

59
Patient Education

• Use one pharmacist/pharmacy
• Use your PCP as intendedavoid seeing multiple
  physicians
• Do not use medications from others
• Report symptoms
• All medicines, even over-the-counter, have
  adverse effects
• Report all products used

60
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

61
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

62
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!

63
Avoiding Polypharmamcy

• Avoid automatic refills
• Look for other sources of medications ie. OTC
• Caution with multiple providers
• Dont use medications to treat side effects of
  other meds
• What can you discontinue or substitute for safer
  medication?

64
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

65
Summary

• Drug toxicity may be masquerading as an illness
• Be a patient advocate! It may be you one day

66
References

• Swansons 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