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Geriatric PharmacologyKwi Bulow, M.D.Clinical Professor of MedicineDirector, Academic Geriatric Resource Center
Silver Tsunami
•
2010: 40 million (13%)
•
2030: 72 million (20%)
•
Baby Boomers (1946-1964)•
started turning 65 in 2011
Drug Use in Patients >
65
•
13% of the U.S. Population
•
Purchase 33% of all prescription drugs
Pharmacokinetics•
Relationship between drug administration and concentration in the body•
Absorption•
Distribution•
Metabolism•
Elimination
Pharmacodynamics•
Cellular response to a drug
•
Drug-Receptor interaction
•
Intensity of pharmacological effect
Pharmacotherapy
Absorption
•
Minimally affected by aging•
Achlorhydria
•
Tube feeding•
Concurrent medications
•
Drug-drug and drug-food interactions are more likely to alter absorption
•
Reuben DB et al, 2012 Geriatrics At Your Fingertips, 14th Edition
Distribution
•
Increase in fat:water
ratio•
Decrease in plasma protein (albumin)
•
Heart failure and ascites
increase body water•
Fat-soluble drugs have a larger volume of distribution
•
Highly protein bound drugs have a greater active (free) concentration
•
Reuben DB et al, 2012 Geriatrics At Your Fingertips, 14th Edition
Metabolism
•
Decrease in liver mass and liver blood flow decrease drug clearance
•
Age related changes in CYP2C19; CYP3A4 and 2D6 are not affected
•
Smoking, genotype, concurrent drug therapy, alcohol and caffeine may have more effect than aging
•
Lower dosage may be therapeutic
•
Reuben DB et al, 2012 Geriatrics At Your Fingertips, 14th
Edition
Elimination
•
Age-related decrease in GFR
•
Renal impairment with acute •
and chronic diseases
•
Decreased muscle mass; •
serum Cr is not a reliable
•
measure of kidney function
Cockcroft-Gault
•
CrCl
=•
(140-age) x weight
•
72x serum creatinine
•
Basis for FDA –labeled dosing recommendations
•
Not the same as eGFR
Limitations•
Variability in age-related decline in renal function
•
People with reduced muscle mass
Renal Clearance
Pharmacodynamic
Changes
•
Opioids: prolonged pain relief at lower dosages (e.g. fentanyl
and EEG frequency spectra)
•
Benzodiazepines: increased sedation, respiratory depression and postural instability
•
Βeta-blockers: less sensitive to hypotensive
effect of beta- adrenoreceptor
antagonists
Beers Criteria
•
1991: List of potentially inappropriate medications (PIMs) was developed by Beers and colleagues for nursing home residents.
•
1997, 2003: expanded to include all settings of geriatric care•
2000: Medical Expenditure Panel Survey: $7.2 billion related to use of PIMs
•
Adverse drug events are preventable:•
27% of events in primary care •
42% of events in nursing homes
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
Potentially Inappropriate Medications (PIMs)
•
Demonstrated success in improving outcomes by reducing PIMs
•
Centers for Medicare and Medicaid Services (CMS) regulations
•
Medicare Part D•
Quality measure in National Committee for Quality Assurance (NCQA)
•
Healthcare Effectiveness Data and Information Set (HEDIS)
•
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
Benzodiazepines
•
Highly protein-bound, lipid soluble•
Widely distributed throughout the body
•
Crosses the Blood Brain Barrier•
Increase risk of •
Cognitive impairment
•
Delirium•
Falls
•
Fractures•
MVAs
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
Short and Intermediate Acting Benzodiazepines
•
Alprazolam
(Xanax)•
Half life 11 hours
•
Lorazepam
(Ativan)•
Half life 9-16 hours
•
Temazepam
(Restoril)•
Half life 8-20 hours
•
Triazolam
(Halcion)•
Half life 1.5-5.5 hours
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
Long Acting Benzodiazepines
•
Clonazepam
(Klonopin)•
Half life 18-50 hours
•
Diazepam (Valium)•
Half life 20-100 hours; 36-200 hours for active metabolite
•
Flurazepam
(Dalmane)•
Half-life 40-250 hours
Zolpidem
(Ambien, Intermezzo)
•
Benzodiazepine receptor agonist •
Adverse effects similar to benzodiazepines
•
Delirium•
Falls
•
Fractures•
MVA
•
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
NSAIDs
•
Upper GI ulcers, GI bleed•
1% of patients treated for 3-6 months
•
2-4% of patients treated for 1 year
Indomethacin
has the most adverse effects
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
Dabigatran
(Pradaxa)
•
Beers criteria for medications to be used with caution
•
Lack of evidence that benefit outweighs risk in individuals >
80
•
Greater risk of bleeding than with warfarin
in adults >
75
•
Lack of evidence for efficacy and safety in adults with CrCl < 30 mL/min
•
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
Anticholinergic
Side Effects
•
Dry mouth•
Constipation
•
Orthostatic hypotension•
Sedation
•
Confusion•
Urinary retention
Drugs with Strong Anticholinergic
Properties
•
Antihistamines•
Diphenhydramine
(Benadryl)-Tylenol PM, Advil PM
•
Hydroxyzine
(Atarax)•
Antidepressants•
Amitriptyline
(Elavil)
•
Nortriptyline
(Pamelor)•
Anti-muscarinics•
Oxybutynin
(Ditropan)
•
Tolterodine
(Detrol)
•
AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr
Soc 2012
Hospitalizations for Adverse Drug Events
•
National Electronic Injury Surveillance System•
Frequency of hospitalization after ED visits for adverse drug events in older adults
•
100,000 admissions per year•
2/3 of admissions involved 4 medications/class•
Warfarin
(33%)
•
Insulin (14%)•
Anti-platelet agents (13%)
•
Oral hypoglycemic agents (11%)
Budnitz
DS et al, N Engl
J Med 365;21
CHADS Score-Stroke Risk per 100 Person Years
•
Points
On Warfarin
No Warfarin•
0
0.25
0.49
•
1
0.72
1.52•
2
1.27
2.50
•
3
2.20
5.27•
4
2.35
6.02
•
5-6
4.60
6.88
•
Gage BF et al, JAMA 2001 Jun 13;285(22)
Hospitalizations for Adverse Drug Events II
•
1.2% -HEDIS high-risk medications•
6.6% -Beers-criteria medications•
More than half involved Digoxin
Digoxin
•
Narrow therapeutic index•
Toxicity seen at <2 ng/mL
•
Renal clearance•
Drug-drug interactions
•
Measuring levels•
<
0.125 mg daily
Less Is More•
40% take 5-9 medications
•
18% take 10 or more
•
http://www.bu.edu/slone/Slone
Survey/AnnualRpt/SloneSurveyWebReport2006.pdf
•
Acyclovir 800 mg 2x daily•
Amitriptyline
10 mg nightly•
Bupropion
XL 150 mg daily•
Phenytoin
100 mg 3x daily•
Levetiracetam
(Keppra) 500 mg 2x daily
•
Gabapentin
300 mg 3x daily•
Topiramate
50 mg 2x daily•
Folic acid 400 mcg 2x daily•
Fentanyl
patch 25 mcg q48 h
•
Lutein
40 mg daily•
Amlodipine
5 mg daily•
Pantaprazole
40 mg daily•
Vitamin C 1000 mg daily•
Hydromorphone
2 mg q4hrs PRN•
Docusate
100 mg daily as needed•
Diphenoxylate-atropine (Lomotil) 2 tablets q6h PRN
•
Acetaminophen 650 mg q6h PRN•
Aspirin 81 mg daily
Mrs. Poly (3 MDs)
Avoid Polypharmacy
•
What are you treating? •
What are your therapeutic end points?
•
Is pharmacological treatment the best option?•
Is there proven efficacy?
•
Review for interactions with current medications•
Review for duplication: same class or actions
•
Avoid starting a medication to treat the side effects caused by another one
•
Are there medications that you can stop?•
Communicate with other prescribers
•
Re-evaluate!
N=1
•
Each patient is unique•
Increase in variability
•
Assess carefully
•
Apply data judiciously
•
Re-evaluate constantly
What are they taking?
•
Current prescriptions•
Old prescriptions
•
Prescriptions from specialists•
Spouse’s prescriptions
•
Over the counter medications•
Compound pharmacy
•
Vitamins, supplements•
Naturopathic medications
•
Medications purchased locally•
Mail order medications
Alcohol = Drug
•
Drug-alcohol interactions•
3-9%: 12-2 drinks/week
•
2-4%: alcoholism
Prescribing for the Older Patient
•
Include the medication’s purpose•
Include generic and brand names
•
Educate the patient/caregiver •
Start low; go slow
•
Keep it simple•
Encourage the use of a pillbox
•
Discuss cost/affordability
Medicare Part D Coverage Gap
-pay 100% of drug costs after $2250-pay 5% of drug costs after $5100-decreased prescriptions for
-blood pressure-lipid-pain-depression-acid suppression
Li P et al, Ann Intern Med 2012;156
Thank you!