Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
POLYPHARMACY (POLYPRAGMASIA)IN THE ELDERLY
Gyula Bakó and Miklós SzékelyMolecular and Clinical Basics of Gerontology – Lecture 20
Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
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Specific therapeutic challenge of prescribing for the elderlyPrinciple factors:I Multiple and severe illnesses – Multiple drug
therapyDrug 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.
II Poor adherence to medication regimensIII Altered pharmacokinetics and
pharmacodynamics
TÁMOP-4.1.2-08/1/A-2009-0011The most common chronic diseases in which the elderly need more medicationsCardiovascular diseases: • angina pectoris• cardiac failure• hypertension• atrial fibrillationNeurological diseases: • cerebral hemorrhage• Parkinson’s diseasePsychiatric disorders: • dementia• depression• confusion
Urological disorders: • urinary incontinenceMusculoskeletal disorders: • arthritis• arthrosis• osteoporosis Endocrinological disorders: • thyroid diseasesGastrointestinal diseases: • constipation• GERD
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Prevalence of multimorbidityUsing 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.
On average there are 2.3 chronic conditions reported by people aged 65 and older.
Wolff JL, Starfield B, Anderson G. Arch Intern Med. 2002;162:2269-2276
0
10
20
30
40
50
60
70
80
90
1 or more 2 or more 3 or more 4 or more
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Polypharmacy for the elderlyVienna studyNumber of agents and their distribution depending on the
patients’ age
Age cohort
Perc
enta
ge o
f pa
tient
on a
ll in
sure
d pe
rson
05
10152025303540
61 to 70 years 71 to 80 years 81 to 90 years91 years or older
Active substances:1 – 4 5 – 8 9 – 12 13 or more
TÁMOP-4.1.2-08/1/A-2009-0011Polypharmacy for the elderly: a representative sample from HungaryThe distribution of the frequency (%) in fuction of the number of therapeutic agents.
Drug consumption0%1%
6%
11%
11% 14
%
11%
10%
11%
6%
19%
6% 4%
7%
10%
8%
15%
10%
10%
7%
5%
17%
0%
5%
10%
15%
20%
0 1 2 3 4 5 6 7 8 9 10<pill/person/day
Perc
enta
ge o
f the
pa
rticip
ants
health care social institution
TÁMOP-4.1.2-08/1/A-2009-0011Why are so many elderly patients using a lot of drugs inappropriately?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.
• Due to the uncertain origin of the drugs (from friends, relatives, and commercials), side effects and interactions can appear.
TÁMOP-4.1.2-08/1/A-2009-0011Why are so many elderly patients using a lot of drugs inappropriately?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.
TÁMOP-4.1.2-08/1/A-2009-0011Physiological and pathophysiological changes in the elderly influencing drug effects1 reduced body weight*2 decreased muscle mass3 reduced total body water4 increased (later decreased) mass of adipose
tissue 5 decreased mass of plasma proteins6 reduced stroke volume7 impaired kidney functions8 reduced weight and blood flow of liver9 reduced amount of certain hormones*The decrease in body weight is due to decreased bone mass and due to causes under #2-3.
TÁMOP-4.1.2-08/1/A-2009-0011Physiological and pathophysiological changes in the elderly influencing drug effectsThe 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.
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Age-dependent basic pharmacological alterations
of the elderly
Pharmacokinetics Pharmacodynamics
Altered pharmacokinetics and pharmacodynamics
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Pharmacokinetics in the elderly1 ABSORPTION2 TRANSPORT3 DISTRIBUTION4 METABOLISM5 ELIMINATION
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Pharmacokinetics in the elderly:absorptionAging-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 the absence of gastrointestinal pathology.
* The area under the curve depicting changes in concentration over time is proportionate with the overall amount of absorbed drug, irrespective of the speed of absorption.
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Pharmacokinetics in the elderly:transportAging-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: side effects, drug interactions. (e.g. coumarins, theophylline, salicylates)
• unexpected drug toxicity !
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Pharmacokinetics in the elderly:distributionAging-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 insufficient water intake may lead to enhanced (toxic) drug effects (e.g. aminoglycosides, antiarrhythmic drugs, digoxin, lidocain, theophylline)!
• Underdose of fat soluble drugs (e.g. benzodiazepines).
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Pharmacokinetics in the elderly:distribution in very old people• Very old individuals loose weight and become 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.
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Pharmacokinetics in the elderly:metabolismAging-associated changes: • The weight of the liver (by about 25-35%) 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 often
associated with decreased first pass effect.
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Pharmacokinetics in the elderly:eliminationAging-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, digoxin, enalapril, furosemide, gentamycin, hydrochlorothiazide, vancomycin)!
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Pharmacodynamic changes in the elderlyResponsiveness 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, • intensity, • peak,• duration of physiological actions.
TÁMOP-4.1.2-08/1/A-2009-0011Pharmacodynamic changes in the elderly: increased responsivenessResponsiveness 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. • Antihypertensive agents:
- due to baroreceptor sensitivity: orthostatic hypotension.
- due to thirst: exsiccosis.- due osmoreceptor dysfunction : hyponatremia.
TÁMOP-4.1.2-08/1/A-2009-0011Pharmacodynamic changes in the elderly: decreased responsiveness2 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.
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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
Medicine in the elderly, since they are not involved in clinical trials.
TÁMOP-4.1.2-08/1/A-2009-0011Main aspects of medication in the elderly: Drug side effects 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• gait disorders, falls
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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 is due to side effects of medication.number of drugs risk for side effects5 types of drug/day 4%6-10 types of drug/day 10%10-15 types of drug/day 28%more than 16 types of drug/day
54%• Simply decreasing the number of drugs may prevent
harmful side effects without affecting the quality of life or the life span.
TÁMOP-4.1.2-08/1/A-2009-0011Main aspects of medication in the elderly: Drug interactionsIn 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-2009-0011Illness-medication problemsto which the elderly are susceptible because of their medical problems
Illness
Medication
Druginteraction
Drugadverseeffect
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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.
