POLYPHARMACY
Dr. Bill Dalziel
Chief
Ottawa Regional Geriatric Program
Question 1
Approximately how much was spent on
prescription drugs in Canada in 2003? (total
health care costs approximately $110B)
1. $ 5 B (4.5%)
2. $ 8 B (7.3%)
3. $11 B (10%)
4. $15 B (13.6%)
5. $22 B (20%)

10-15% of hospital admissions of the
elderly are due to ADRs: Adverse
Drug Reactions.
Consequences of ADR



30% of hospital admissions linked to ADR in
US ( Hanlon et al. JAGS 1997)
After discharge from TOH, 23% had at least
one ADR ( Forster et al. CMAJ 2004)
ADR in the older person linked to
depression, constipation, falls, immobility,
confusion, and hip fractures… (Bootman et
al. AIM 1997)
Question 2
What is the biggest reason why the elderly are at
such high risk for ADRs (Adverse Drug
Reactions)
1.
2.
3.
4.
Polysymptomatology breeding polypharmacy.
Homeostenosis.
Pharmacokinetics. Pharmacodynamics.
All those pharmacology lectures in medical
school (sic!).
5. Pharmaceutical companies: research and
marketing.
Drugs and The Older Person
Statistics




30% of prescription drug use
40% of non prescription drug use
Average use of 4.5 medications
(community)
Average use of 9.1 medications
(hospitalized)
Question 3
How much does the creatinine clearance
decrease as someone ages from 50 to 80?
(even though serum creatinine may not
change).
1.
2.
3.
4.
5.
5%
15%
25%
35%
45%
Calculation of Creatinine Clearance
Cockcroft / Gault Equation
Crcl= (140 - AGE) x wt (kgm) x 1.23 (x .085 for women)
Serum Creatinine
 Changing age from 50 to 80 decreases Crcl by 1/3!
The 10 Do’s and Don’ts
1.
Think of every drug prescribed as a
clinical trial with N=1.
The 10 Do’s and Don’ts
2.
Always think of drugs as the diagnosis of any new
symptom.
Drugs - Prescription
Drugs - OTC/OTF
Drugs - Alcohol
Drugs - Herbal
Question 4
The elderly (65+) are 12% of the Canadian
population; what % of OTC drugs do they
consume?
1.
2.
3.
4.
5.
10%
20%
30%
40%
50%
Over the Counter Medications in
the Elderly
• The elderly consume 40% of all OTC.
Top 5
Acetaminophen
Multivitamins
ASA
Aluminum Hydroxide
Cough and Cold
Seniors perceive as “safe”, usually don’t tell their doctor about
use.
• Toxicity and drug interaction problems.
The 10 Do’s and Don’ts
3.
The only rule you learned about the
elderly and drugs in medical school,
“START LOW GO SLOW” was only ½
correct.
The 10 Do’s and Don’ts
You need to push/titrate the dosage up until:
1. Therapeutic goals are met.
2. Side effects.
3. You have your maximum comfortable
dosage.
Question 5
? How many drugs do you need
(pharmacopia) to take care of 90% of
your elderly patient’s prescription needs?
1. 10
2. 25
3. 50
4. 75
5. 100
The Geriatric Pharmacopoiea
1.
2.
3.
4.
5.
6.
7.
8.
9.
Thyroid (2)
Tylenol (4)
Estrogen (12)
COX 2 NSAID
(10,16)
PPI (7, 16)
ECASA (5)
Statin (1)
SSRI (8, 9, 14)
CCB (19)
10. Antibiotic (broad
spectrum)
11. Coumadin
12. ACEI (3, 6)
13. HCTZ (15)
14. Lasix (11)
15. Cholinesterase
Inhibitors
16. Bisphosphonates
17. Atypical Neuroleptic
18. Benzodiazepine
(18, 20)
19. Sinemet
20. Oral Hypoglycemic
21. Insulin
22. Morphine
23. Prednisone
24. MOM/Lactulose
25. Respiratory
inhalers (13)
(x) = ranking in Canada 2003
Others: Nitates / NTG, Digoxin, Iron/Vitamin B12/Vitamin D/Calcium, Dilantin
The 10 Do’s and Don’ts
4.
You only need a small PHARMACOPOEIA.
(25)
The 10 Do’s and Don’ts
5.
Regularly review drug regimens and risk
reducing drugs regularly.
VA Study 74% of selected drugs d/cd
successful.
(? Why do we worry more about stopping drugs than
starting drugs?)
The 10 Do’s and Don’ts
6.
Avoid the bandwagon of new drugs unless
researched in the elderly or extensively
used elsewhere. Ask your drug reps about
trials and clinical experience involving
elderly subjects.
The 10 Do’s and Don’ts
7.
KNOWLEDGE is YOUR RESPONSIBILITY.
Trials in the elderly.
Absolute/Relative CI.
Major and minor adverse effects.
Drug/drug and drug/disease interactions.
Starting/usual/maximum dosages.
Cost.
The 10 Do’s and Don’ts
8.
IF YOU’RE GOING TO PRACTISE
POLYPHARMACY AT LEAST MAKE IT
EVIDENCE BASED POLYPHARMACY.
OR
“How do you extrapolate research trials
to 85 years old patients?
Question 6
In the EBM (evidence based medicine) world, usual
RCTs do not include patients over 75. How can you
extrapolate from these results to your 85 year old
patients in terms of RRR (relative risk reduction)
and ARR (absolute risk reduction). Generally with
increasing age above 65…
1.
2.
3.
4.
5.
RRR decreases, ARR decreases (NNT increases)
RRR decreases, ARR stays the same (NNT stays the same)
RRR stays the same, ARR increases (NNT decreases)
RRR stays the same, ARR stays the same (NNT stays the same)
RRR increases, ARR increases (NNT decreases)
In RCTs with Increasing age:

Relative Risk Reduction (RRR) generally
remains the same

Absolute risk reduction (ARR) increases

 NNT decreases
Question 7
What is your chance of having a patient in which
an adverse drug significantly contributed to
mortality? Which is true?
Canada (Annual Deaths related
to ADR)
Physician Risk
1. 1,000
1 patient per 60 years
2. 5,000
1 patient per 12 years
3. 10,000
1 patient per 6 years
4. 30,000
1 patient per 2 years
5. 200,000
3.3 patients per year
The 10 Do’s and Don’ts
9.
The sword is DOUBLE EDGED!
Canadian Estimate: 200,000 serious ADRs/year
10,000 deaths/year
But also under-medication.
Question 8
What % of patients on antihypertensives
are significantly non-compliant within 1
year of initiating therapy?
1.
2.
3.
4.
5.
10%
20%
33%
50%
75%
The 10 Do’s and Don’ts
10.
Noncompliance is a HUGE ISSUE
(75% antihypertensives at 1 year).
KISS
Non-childproof containers.
Clear, large labels.
Patient explanation/education.
Pharmacists -- total pharmaceutical care.
The Top 10 Drugs to Use Less
1. Conventional NSAIDS.
 GI bleeds use without prodromal c/o
 Na/H2O retention
  CR.  K
  BP
The Top 10 Drugs to Use Less
2. Benzodiazepines.
 Falls, falls, falls
 First time anxiety in the elderly is not
a benzodiazepine deficiency
syndrome.
 Alternatives for insomnia.
 R/O causes
 Non pharmacologic
 Trazadone (25-50 mgm)
Question 9
What is the rate of tardive dyskinesia within 3
years of starting therapy with conventional
neuroleptics in elderly patients (65 +).
1.
2.
3.
4.
5.
5%
25%
40%
70%
100%
The Top 10 Drugs to Use Less
3. Conventional Neuroleptics.
 70% Tardive Dyskinesia (3 year)
 EPS
 Oversedation
 18% efficacy above placebo
 40 vs 58%
The Top 10 Drugs to Use Less
4. Beta Blockers.
 Less effective than HCTZ in  BP
 Useful post MI
 Very useful in CHF
(NY II – IV ( EF)
(Start lower, go slower).
The Top 10 Drugs to Use Less
5.
Glyburide
– More hypoglycemia.
– 16.6 / 1000 patient years
Question 10
How much $ is spent in Canada per year
on colace a drug with ABSOLUTELY NO
laxative properties?
1.
2.
3.
4.
5.
$1 million
$5 million
$25 million
$50 million
$150 million
The Top 10 Drugs to Use Less
6. Colace/Irritant Laxatives.
 Colace is not a laxative but we
spend in Canada $50M/yearly
 Sennosides ok short term but risk
of cathartic colon long term.
The Top 10 Drugs to Use Less
7. Elavil/Amitriptyline
 Very anticholinergic
 Other alternatives in chronic
pain – nortryptaline and
desipramine.
 SSRIs
The Top 10 Drugs to Use Less
8. Anticholinergic Drugs.
 Central = delirium/dementia
 Peripheral = retention,
constipation.
The Top 10 Drugs to Use Less
9. Talwin, Demerol, p.o.
 Ineffective, toxic.
The Top 10 Drugs to Use Less
10.
Serc/gravol.
 Ineffective, toxic.
The Top 10 Drugs to Use More
1. COX 2 NSAIDS.
 Only better than conventional
NSAIDs in major GI events.
 Cardiovascular toxicity concern.
The Top 10 Drugs to Use More
2.
Drugs to treat depression:
• SSRI (Celexa), Effexor XR and TCA with low
anticholinergic properties
(desipramine,’nortryptaline).
• > 2 year maintenance
 SSRIs have side effects:
 GI
 Parkinson’s
 Anxiety
 SIADH
 Seizures
 Discontinuation syndrome.
The Top 10 Drugs to Use More
3.
Drugs to treat dementia: ACHEI
(Aricept, Exelon, Reminyl).
 Standard of care = trial.
 ¼ super responder.
 ½ mild responder.
 ¼ non responder (switch).
(9 weeks of holidays for caregiver)
NNT < 10
Question 11
With respect to Coumadin for atrial fibrillation
and the concerns about falls in the elderly, how
many falls per year do you need to = the risk of
not anticoagulating?
1.
2.
3.
4.
5.
2
5
10
100
300
The Top 10 Drugs to Use More
4. Coumadin (for atrial fibrillation).
 68% RRR vs 21% ASA.
 INR must be over 2.0 (2.5).
 295 falls/year.
The Top 10 Drugs to Use More
5.
Drugs to treat hypertension, especially
systolic:
(diuretics, CCB/ACEI)/ARB.
 CVA, CVS, dementia
Systolic 165 = diastolic 105
 Goal = 140/90 (add ASA)
 Small doses triple Rx
The Top 10 Drugs to Use More
6.
Drugs to treat osteoporosis:
(calcium, vitamin D, bisphosphonates),
raloxifene.
 2002 CPG CMAJ Nov. 12/02
 All 65  DXA screening
 Vit D 800 IU/Ca 1500 mgm/exercise
 Fosamax/Actonel/didrocal
 hPTH (to come)
The Top 10 Drugs to Use More
7. Drugs to treat diabetes.




Metformin
2nd generation sulfonylurea
Glucosidase inhibitors
Thiazolidinediones (glitazones)
Question 12
What % of patients cannot metabolize
codeine (prodrug with no analgesic effect)
into the active metabolite morphine?
1. 0.7%
2. 1%
3. 2.5%
4. 5%
5. 10%
The Top 10 Drugs to Use More
8. Anaglesics (regular dosing, not PRN).



10% can’t metabolize codeine
New acetaminophen limit 3gm/d
SR strong opioids/duragesic
(AGS Guidelines, JAGS June 1 2002, Supplement)


Nocioceptive: TCA (yes) SSRI (no)
Neuropathic: TCA (better than SSRI)
The Top 10 Drugs to Use More
9.



Statins.
A huge lost opportunity!
CVS m & m reduction: 1o/2o
Dementia
(www.cvtoolbox.com)