Transcript Factors influencing drug effects in older adults

Charles University in Prague, Third Faculty of Medicine
GENERAL MEDICINE 6-YEAR MASTER‘S STUDY PROGRAMME
Cycle II, Modul NURG (nephrology,
urology, rheumatology a geriatry–
CVSE4P0023
GERIATRIC PHARMACOLOGY
Prof. M. Kršiak
Department of Pharmacology, Third Faculty of Medicine,
Charles University in Prague
Academic year 2013-2014
http://vyuka.lf3.cuni.cz
CVSE4P0023 TU 531
OLD AGE MAY HAVE A HIGH VALUE
1. Drugs can significantly increase life
excpectancy and quality of life in old age
2. However, they can also produce the opposite
How to realize the first possibility
and avoid the second one?
1. Factors affecting drug effects in older adults
2. Inappropriate pharmacotherapy in the elderly
(„Beers criteria“)
3. Analgesics in older adults
„older adults“ or the ‚elderly‘ = > 65 yers old
age of 65 years is accepted as a
definition of 'elderly' or older person
Factors influencing drug effects in older adults (>65y):
1.
2.
3.
4.
5.
Pharmacokinetic changes
Pharmacodynamic changes
Less robust homeostasis
Concomitant diseases
Polypharmacy (↑drug interactions)
Factors influencing drug effects in older adults (>65y):
1. Pharmacokinetic changes:
- reduced elimination (major factor)
kidney 
liver 
aminoglycosides, digoxin [Case study 1], atenolol, ranitidin
diazepam  halflife („tolik hodin, kolik je let“)
- distribution (water/fat, minor factor)
- absorption
(minor factor)
Case Study No. 1
1. An 85-year-old man complaining of chest pain
and shortness of breath was brought to the
emergency room
2. ECG revealed atrial fibrilation. The patient was
given a standard dose of digoxin
(a loading dose 1 mg over the 24 hours followed by a maintenance
oral dose of 0.25 mg/day)
By the third day the patient was ambulating
comfortably, with normal sinus rhytm. He was
discharged.
Melmon-Morrelli‘s Clinical Pharmacology 2000, p.1165
Do you agree with this dosage? YES / NO / DON‘T KNOW
Case Study No. 1 - contd:
3. Six days later, the man was brought back to the
hospital. There he complained of nausea and
vomiting . He was disoriented. The serum digoxin
concentration was 2.7 ng/ml
Melmon-Morrelli‘s Clinical Pharmacology 2000, str.1165
SPC and Beers criteria: do not give more than
0.125 mg/day in the old age (>65 years of age)
Factors influencing drug effects in older adults (>65y):
2. Pharmacodynamic changes –
due to ageing e.g. in targets for drug actions
consequences e.g.
confusion, cognitive impairment, delirium
CONFUSION
can be caused by various drugs in the old age,
particularly by:
benzodiazepines, drugs with anticholinergic effects
(e.g. some antidepressants, antipsychotics),
opioids, levodopa,
but also by:
metoprolol (or other betablockers), ranitidin (or
other H2 antagíonists), corticoids, digoxin, lithium,
anticonvulsants, and others
Factors influencing drug effects in older adults (>65y):
3. Less robust homeostasis
e.g.
antihypertensives –orthostatic hypotension more likely
and other changes in the old age e.g.
prostatic hypertrophy – anticholinergic drugs micturition problems (urinary retention or too frequent needs to
urinate during night, etc)
Factors influencing drug effects in older adults (>65y):
4. Concomitant diseases e.g.
- NSAIDs 10x  risk of hospitalization due to cardiac
insufficiency in patients with preceding/concomitant cardiac
disorders
- cardiac insufficiency lower blood flow in the liver 
 lower 1st-pass effect halflife of morphine
Factors influencing drug effects in older adults (>65y):
5. Polypharmacy (↑drug interactions)
e.g.
SSRI + NSAIDs 13x  risk of GIT bleeding
SSRI + warfarin  risk of bleeding
How to improve pharmacotherapy in
older adults?
1. Withdraw unnecessary drugs or reduce doses if appropriate
2. Determine whether „manifestations of the old age“ such as
confusion, urination problems, dizzines, insomnia, etc are not due
to drugs
3. In general, begin therapy with low doses
4. If possible avoid administration of drugs inappropriate (more risky)
in the old age („Beers criteria“) . Instead select more appropriate
alternative drugs.
5. Simplify use of drugs and encourage of compliance
- try to avoid intermittent schedules; once daily dosage is ideal
- give clear instructions, best in a written form
“Manifestations of the old age”
that might be caused (or increased) by drugs
• desorientation, confusion
[e.g. benzodiazepines and many other drugs (see above)],
• dizziness
[many drugs, e.g. tramadol]
• orthostatic hypotension [antihypertensives, antipsychotics]
• problems with prostatic hypertrophy [Case Study No 2]
Case Study No. 2
(„manifestations of the old age“ induced or
increased by drugs)
1. A 72-year-old man visited his physician with
concerns about difficulty sleeping
2. The physician prescribed diphenhydramine
3. The patient‘s sleep was better, but he had to
arise several times a night to urinate. He was
referred to a urologist.
4. The urologist revealed a benign prostatic
hypertorophy with post void residual. The patient
was scheduled for the prostatectomy.
Melmon-Morrelli‘s Clinical Pharmacology 2000, str.1172
Inappropriate pharmacotherapy
in the elderly
(„Beers criteria“)
Beers criteria:Potentially Inappropriate Medication Use
in Older Adults - Beers List
Fick D.M. et al.: Archives of Internal Medicine 163: 2716-2724, 2003*
examples:
Benzodiazepines
Drugs with anticholinergic effects
Nonsteroid Antiinflammatory Drugs
(NSAIDs)
Some cardiovascular drugs
methyldopa, amiodaron, digoxin > 0,125 mg/d,
Some opioids
pethidin, pentazocin
Miscellanea
cimetidine, androgens, estrogens
*Several upgrades of the list have been published since that time in several
countries. Recently by Topinková et al. Praktický lékař 92 (1): 11-22, 2012
indicating also alternative more appropriate drugs.
Beers criteria:Potentially Inappropriate Medication Use in
Older Adults
Medications to be avoided in older adults with these conditions
Fick D.M. et al.: Archives of Internal Medicine 163: 2716-2724, 2003
examples:
Urination problems
Drugs with anticholinergic effects
Hypertension
Sympatomimetics
Arrhytmia
Tricyclic antidepressants
Parkinson‘s disease
Metoclopramide, 1st generation
antipsychotics
Constipation
Drugs with anticholinergic effects
Calcium channel blockers
Obesity
Olanzapin
Insomnia
Cognition disorders
Sympatomimetics
Drugs with anticholinergic effects
Benzodiazepines
ANALGESICS IN OLDER ADULTS
The risks of nonsteroidal antiinflammatory drugs (NSAIDs) are
increased in older adults:
• ↑GI toxicity of NSAIDs in older adults
• ↑ Cardiotoxicity of NSAIDs in older adults
• ↑ Nephrotoxicity of NSAIDs in older adults
Hospitalisations for severe GI adverse reactions
caused by NSAIDs
J M Seager, C J Hawkey, BMJ, 2001;323:1236-1239
without NSAIDs: 2-3 GI bleeding / 1000 pacients >65y/year, ca 5 GI bleeding / 1000 pacients
>85y/year
Relative risk of severe gastrointestinal averse effects
Langman et
Menniti-Ippolito et al.,
al., 1994
1998
Lancet
Eur.J.Clin.Pharmacol.
piroxikam
13,7
7,0
indomethacin
11,3
diclofenac
4,2
3,8
nimesulide
2,1
ibuprofen
2,0
2,0
without NSAIDS
1,0
1,0
NSAIDs moderately increase a risk of
myocardial infarction :
risk of myocardial infarction:
rofecoxib
1.32 (1.09-1.61)
ibuprofen
1.24 (1.11-1.39)
diclofenac 1.55 (1.39-1.72)
Hippisley-Cox, Coupland BMJ 11 June 2005 Vol.330;pp1366-
Analgesics more appropriate in
older adults (then NSAIDs):
• paracetamol
• opioids
both belong among safest analgesics
(at therapeutic doses and non-invasive administration)
[dipyrone?, propyfenazone?]
Most frequently used analgesics in the elderly:
ibuprofen
diclofenac
thiaprofenic acid
tramadol
indometacin
Alnagon
propoxyfen
paracetamol
ČR*
38,7 %
19,4 %
13,7 %
8,1 %
4,0 %
3,2 %
2,4 %
*541 persons > 75 y
Kubešová et al. 2001
USA**
6,2%
2,3%
5,7%
0,4%
18,1%
37,4%
**18 394 pers. > 65y
Won et al. 2003
SUMMARY I:
1. In older patients we shoud take into account:
•
lower elimination of drugs,
•
higher probability of some adverse effects,
•
concomitant diseases,
•
polypharmacy
2. In older patients we shoud apply
„Beers criteria“, i.e. we should try to avoid
inapproriate drugs and select more appropriate
alternatives if possible
SUMMARY II:
3. Analgesics in older patients
paracetamol alone or in combination with
opioids
is more appropriate than NSAIDs in older
patients
4. If NSAIDs are necessary, it is advisable to coadminister proton pump inhibitors
or to administer NSAIDs locally, if appropriate