Download in the elderly

Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Gyula Bakó and Miklós Székely
Molecular and Clinical Basics of Gerontology – Lecture
20
POLYPHARMACY
(POLYPRAGMASIA)
IN THE ELDERLY
Specific therapeutic
challenge of prescribing
for the elderly
TÁMOP-4.1.2-08/1/A-2009-0011
Principle factors:
I Multiple and severe illnesses –
Multiple drug therapy
Drug use in the elderly is
disproportionately high: patients
over 65 constitute 12% of the US
population and consume 31% of
prescribed drugs secondary to:
• increased severity of chronic
illnesses
• presence of multiple pathologies
• excessive prescribing.
The most common chronic
diseases in which the elderly
need more medications
TÁMOP-4.1.2-08/1/A-2009-0011
Cardiovascular
diseases:
• angina pectoris
• cardiac failure
• hypertension
• atrial fibrillation
• urinary incontinence
Musculoskeletal
disorders:
• arthritis
• arthrosis
• osteoporosis
Neurological diseases: Endocrinological
• cerebral hemorrhage
disorders:
• Parkinson’s disease • thyroid diseases
Psychiatric disorders: Gastrointestinal
• dementia
diseases:
• depression
• constipation
TÁMOP-4.1.2-08/1/A-2009-0011
Prevalence of
multimorbidity
Using 24 major
diagnostic categories…
• 82 percent of people
aged 65 and older
had one or more
chronic conditions
• 65 percent had two
or more
• 43 percent had three
or more
• 24 percent had four
or more.
Wolff
On average there are
90
80
70
60
50
40
30
20
10
0
1 or more2 or more3 or more4 or more
JL, Starfield B, Anderson G. Arch Intern Med.
Polypharmacy for the
elderly
Vienna study
TÁMOP-4.1.2-08/1/A-2009-0011
Number of agents and their distribution depending on
the 40
patients’ age
Percentage of
patient
on all insured
person
35
30
25
20
15
10
5
0
61 to 70 years
71 to 80 years
81 to 90 years
91 years or old
ctive substances:
Age cohort
1 – 4 5 – 8 9 – 12 13 or more
Polypharmacy for the
elderly: a representative
sample from Hungary
TÁMOP-4.1.2-08/1/A-2009-0011
The distribution of the frequency (%) in fuction of
the number of therapeutic agents.
19%
17%
Drug consumption
0%
0%
7%
6%
5%
6%
1%
5%
4%
6%
7%
10%
11%
10%
10%
10%
11%
14%
15%
15%
11%
10%
11%
8%
Percentage of the
participants
20%
0
1
2
3
4
5
6
health caresocial institution
7
8
9 10<
pill/person/day
Why are so many elderly
patients using a lot of
drugs inappropriately?
TÁMOP-4.1.2-08/1/A-2009-0011
Factors depending on the patient:
• Chronic diseases requiring long-term
treatment become more common.
• Atypical presentation of diseases.
• Expectations of both the family and the
patient (people keep going to see the doctor
until they get what they want).
• There is no satisfactory doctor-patient
relationship in time or in depth because of
the crowded outpatient services.
• The elderly often take OTCs (over-the-counter
drugs) about which the doctor is not
informed.
Why are so many elderly
patients using a lot of
drugs inappropriately?
TÁMOP-4.1.2-08/1/A-2009-0011
Factors depending on the physician:
• The treatment is frequently focused on the
symptoms: one additional symptom – one
additional drug.
• An additional drug is given to correct an
existing side-effect.
• Lack of personalized care: multiple parallel
drug prescriptions are subscribed by
different doctors.
• The control of drug efficacy is also missing.
Physiological and
pathophysiological changes in the
elderly influencing drug effects
TÁMOP-4.1.2-08/1/A-2009-0011
1
2
3
4
5
6
7
8
9
reduced body weight*
decreased muscle mass
reduced total body water
increased (later decreased) mass of
adipose tissue
decreased mass of plasma proteins
reduced stroke volume
impaired kidney functions
reduced weight and blood flow of
liver
reduced amount of certain hormones
Physiological and
pathophysiological changes in the
elderly influencing drug effects
TÁMOP-4.1.2-08/1/A-2009-0011
The listed changes generally develop
with aging, however, they differ
individually on a case by case basis.
The degree of these changes is
different and it is difficult to
determine to what extent the changes
can be considered physiological.
TÁMOP-4.1.2-08/1/A-2009-0011
Altered pharmacokinetics and
pharmacodynamics
Age-dependent
basic pharmacological alterations
of the elderly
Pharmacokinetics
Pharmacodynamics
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Pharmacokinetics in the
elderly
1
2
3
4
5
ABSORPTION
TRANSPORT
DISTRIBUTION
METABOLISM
ELIMINATION
Pharmacokinetics in the
elderly:
absorption
TÁMOP-4.1.2-08/1/A-2009-0011
Aging-associated changes:
• The pH in the stomach is closer to neutral.
• Longer transition time in the GI system.
• Decreased surface of the small intestine.
• Diminished blood perfusion (GI, transdermal etc.
absorption).
Consequences:
• Delayed absorption as indicated by a smaller and
delayed peak plasma level. The area under curve
(AUC*) hardly changes.
• Decreased first-pass effect after oral administration.
• Overall bioavailability remains maintained (slower
excretion!). Though numerous structural and
physiological age-related changes in the GI tract
exist, they are of minimal clinical significance in
Pharmacokinetics in the
elderly:
transport
TÁMOP-4.1.2-08/1/A-2009-0011
Aging-associated changes:
• Decrease in the albumin concentration
(by 10%).
Consequences:
• Free plasma drug level increases by
about 10% (medication with narrow
therapeutic range, e.g. digoxin);
• In case of simultaneous
administration of multiple drugs, the
rate of binding to transporter
molecules becomes unpredictable: 
Pharmacokinetics in the
elderly:
distribution
TÁMOP-4.1.2-08/1/A-2009-0011
Aging-associated changes:
• Both the total body water and the distribution
volume of water soluble drugs decrease (by about
10-15%).
• The amount of the adipose tissue and the
distribution volume of lipid soluble drugs
increase (by about 20%).
• Although the fat content is higher in women than
in men, the relative change in the volume of
distribution for lipophilic drugs is more marked
in men than in women (18 to 36% in men, 33 to
45% in women).
Consequences:
• Concentration of water soluble drugs increases
(e.g. lithium, vancomycin). Diuretics and
Pharmacokinetics in the
elderly:
distribution in very old
people
• Very old individuals loose weight and become
TÁMOP-4.1.2-08/1/A-2009-0011
frail, the proportion of fat decreases so
that the volume of distribution for
lipophilic drugs again decreases and the
serum concentrations increase.
• The frailty of very old individuals tends to
be overlooked, low weight patients on average
receive higher doses per unit body weight
than heavier patients. Hence, low body
weight, in addition to advanced age,
constitutes a risk factor for overmedication.
Pharmacokinetics in the
elderly:
metabolism
TÁMOP-4.1.2-08/1/A-2009-0011
Aging-associated changes:
• The weight of the liver (by about 2535%) and the hepatic blood flow (by
about 30-40 %) decrease.
• The rate of hepatic drug clearance is
impaired.
Consequences:
• Increased risk for impaired liver
function is seen in exsiccosis and
chronic heart failure!
• Decrease in hepatic blood flow is
Pharmacokinetics in the
elderly:
elimination
TÁMOP-4.1.2-08/1/A-2009-0011
Aging-associated changes:
• Elimination (excretion) through the
liver is usually minimally reduced.
• Kidney functions are impaired due to
- decrease in glomerular filtration
rate
- reduced tubular functions (fibrosis,
atrophy).
Consequences:
• Toxic effects of drugs eliminated via
the kidney may increase (e.g.
amikacin, amiloride, ciprofloxacin,
TÁMOP-4.1.2-08/1/A-2009-0011
Pharmacodynamic changes in
the elderly
Responsiveness of the body changes with age:
• Changes in the blood-brain barrier
• Alteration in receptor properties
- affinity
- number
- post-receptor response
(enhanced/diminished)
• Homeostatic changes: decreased capacity to
respond to physiological challenges and to
the adverse side effects of drug therapy
(e.g. baroreceptors).
Cell-tissue response to a drug may be changed
concerning the
• mechanism,
Pharmacodynamic changes in
the elderly: increased
responsiveness
TÁMOP-4.1.2-08/1/A-2009-0011
Responsiveness of the body changes with age:
1 Increased responsiveness while taking
• ACE-inhibitor, CCB (Ca channel blocker),
coumarins.
• Digoxin and antiarrhythmics: alterations in
Na/K-ATPase and Ca2+ channels lead to
enhanced toxicity
• Opiates: may suppress respiration.
• Benzodiazepines: the probability of falls
increases.
• Antidiabetic agents: impaired glucose
counter-regulation predisposes the elderly
to hypoglycemia.
Pharmacodynamic changes in
the elderly: decreased
responsiveness
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2 Decreased responsiveness while taking
• Diuretics.
• Beta-blockers: the effect is slower due to
an increased level of epinephrine.
• Beta-adrenoceptor agonists: lower
sensitivity of the myocardium to
catecholamines.
TÁMOP-4.1.2-08/1/A-2009-0011
Main aspects of medication
in the elderly
• Multimorbidity increases with
age.
• The changes mentioned previously
have influence on the drug
effects in the body.
• Polypragmasy increases the number
of side-effects and drug
interactions.
• Compliance decreases with age.
• There is no real Evidence Based
Main aspects of medication
in the elderly: Drug side
effects
TÁMOP-4.1.2-08/1/A-2009-0011
Medical care of the elderly involves a
2-3 times higher risk for side effects.
Their number is endless. Typical side
effects:
• lack of appetite
• disturbance of gustatory sensation
• dryness in the mouth
• malabsorption (minerals, vitamins)
• iatrogenic incontinence (incontinentia
urinae seu alvi)
• impaired cognitive functions
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Drug side effects in numbers
• Regarding patients above the age of 65,
iatrogenic medication-associated disorders
are responsible for 5-10% of
hospitalizations in Western-Europe .
• Above the age of 85 every 5th
hospitalization
of
number of drugs is due to side
riskeffects
for side
medication.
effects
5 types of drug/day
6-10 types of drug/day
4%
10%
10-15 types of drug/day
28%
more than 16 types of
54%
• Simply decreasing the number of drugs may
drug/day
prevent harmful side effects without
Main aspects of medication
in the elderly: Drug
interactions
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In the long run the most dangerous drug
combinations are the following:
• warfarin + NSAID, or sulphonamides ,
or macrolides, or quinolones, or
phenytoin
• ACE inhibitors + K-sparing diuretics,
(spironolactone)
• digoxin + amiodaron or verapamil
• theophyllines + quinolones.
TÁMOP-4.1.2-08/1/A-2009-0011
Illness-medication problems
to which the elderly are susceptible
because of their medical problems
Illness
Drug
adverse
effect
Medicatio
n
Drug
interacti
on
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“Start low, go slow!”
• Start with a small dose, increase
the dose carefully.
• In case of unexplained
deterioration of the patient’s
condition, think about drug
interaction.
• In the elderly, quality of life
is at least as important as the
therapeutic success.