Pharmacotherapy in the extreme longevity

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Abstract

The increased longevity brings to the appearance of more polypathologies, being frequently of chronic-degenerative type, and also an increased use of pharmaca. The present study evaluated the usual drug consumption in the ultralongevous people in comparison with their clinical conditions. A total of 602 centenarians were involved: clinical anamnesis, objective examinations and clinico-functional evaluations were performed. In 555 of them an acceptable pharmacological anamnesis was obtained. The results showed that 28 centenarians (5%) did not take any drug, 527 (95%) of them used regularly some pharmacological therapy. Their distribution was: 1 drug/day 68 (13%), 2 drugs/day 86 (16.3%), 3 drugs/day 344 (65.2%), more than 3 drugs/day 29 (5.5%). The mean daily drug consumption was 2.7 ± 1.4. Good clinical conditions could be established in 115 (20.7%) of the centenarians, of them 28 subjects (24.3%) had used no drugs, 87 (75.7%) of them used 1–3 drugs/day. It was an important observation that adverse drug events (ADE) occurred in 15.2%. The ADE occurs frequently also in polypharmacological treatments, with various pharmacodynamic and pharmaco-kinetic modifications of the drugs. The mean daily drug consumption of the ultralongevous subjects was lower than that of the common elderly. This may be due to the past life of our centenarians, characterized by satisfactory health conditions, and also to a higher attention of the general practitioners in the drug prescriptions, as well as of the family members who administer the pharmaca.

Introduction

The most relevant demographic phenomenon of the last century was a tendency for aging of the population (Boulding, 2003). The improvements of the environmental factors influenced positively the clinical conditions, compared to the past in the same age groups. In spite of this fact, the increase of the mean life span and aging of the population resulted in a global increase in the occurrence of the age-dependent chronic-degenerative complications (Golini, 1997).

As a matter of fact, with advancing age, the mortality curves are considerably separated from those of morbidity and disability, and those differences tend to increase today (Vaupel, 1997, Vaupel and Canudas, 2000). The longer survival brings about an increased incidence of polypathologies, being often of chronic-degenerative type, with a consequent increase of the drug consumption. As a matter of fact, the elderly subjects have become the major drug users since long time, in correlation not only with the real necessity, but also with the individual wishes for being cured and to achieve a well being.

These statements are confirmed by numerous studies (Rathore et al., 1998, Valderrama Gama et al., 1998). Both the European and USA data, based on wide statistical analyses demonstrate that the elderly people consume up to 7 and more pharmaca per day, with wide oscillations) (in average 3.8 ± 2.5 pharmaca/day) (Nobili et al., 1997, Kidder and Bae, 1999). For example, Salles Montaudon et al. (2000) described that in a population of 3777 subjects of 75 years of age, 89% was taking pharmaca regularly, and 49% of them consumed 1–4 medicines per day, 41% took 1–5 pharmaca/day. It is interesting to note that after a follow-up of 8 years, the 85–95-year-old subjects have consumed already fewer medicines.

The drug consumption of the elderly subjects is frequently inappropriate. Often the elderly patients take medicines without following the medical prescriptions, they use doses or applications different from the recommendations of the sanitary specialists, while a minority takes even pharmaca which are not identical to those of the prescribed ones (Barat et al., 2001).

This situation results in a higher occurrence of ADE in the elderly population, compared to the younger adults (14.6% vs. 3%) (Gray et al., 1998, Onder et al., 2002). The elderly patients often present adverse reactions due to the contemporary presence of comorbidities and polypharmacological treatments (Froom and Trilling, 2000). The increased risk for developing ADE, in addition to the contemporary use of more pharmaca, is due also to the reduced compensatory capacity of the subjects, which would be necessary to compensate the pharmacological “insults” (Bressler and Katz, 1993, Hanlon et al., 2002). As a matter of fact, the elderly subjects have a reduced water content in the body, have a lower muscular mass, serum proteins, and frequently an increased fat content of their body. All this may have a consequence of a reduced distribution volume of the pharmaca, and an increased concentration of the water-soluble compounds. It should also be underlined that liver and kidney functions are often reduced, resulting in difficulties in the distribution and metabolization of the pharmaca, causing a delay in the elimination of the pharmaca and/or their metabolites (Gurwitz and Avorn, 1991, Bowen and Larson, 1993). All this leads to an altered pharmacokinetics or pharmacodynamics with advancing age. Other possible factors rendering the elderly subjects particularly susceptible for ADE are the reduced visus and the disturbed cognitive abilities, which may cause an inappropriate usage of pharmaca, or even erroneous dosages in case of orally taken medicines (Hodinka, 1991, Beard, 1992).

While there exists numerous and well-documented studies on the consumption of pharmaca by the elderly subjects (Williams et al., 1999, Crucitti et al., 2000, Laurier et al., 2002, Vila et al., 2003), the research on the ultralongevous or centenarian subjects has been scarce, performed on small and non-selected pools (Gergely, 1990, Samuelsson et al., 1997, Andersen-Ranberg et al., 2001). One can establish in global sense that the consumption of pharmaca is reduced in the centenarians, even in cases of superimposed comorbidities, compared to the general elderly population (Fradà et al., 1991, Mazzoleni et al., 1996).

This situation motivated us to study the habitual drug consumption of centenarians, in a study pool which was numerically adequate, and which had been studied also in clinical terms adequately. Here we present our results.

Section snippets

Subjects and methods

The studies have been performed on a pool of 602 centenarians (127 males and 475 females), of the age from 100 completed years to 109 years (in average: 101.1 ± 1.4). A clinical record of all subjects was prepared, containing the anagraphic data, the socio-economic situation, the family anamnesis, the physiological anamnesis, the past and present pathological anamnesis, the general and organic objective examinations, and the cognitive-functional scores, such as the mini-mental state examination

Results

The very first observation was that 28 of 555 centenarians (5%) did not take regularly any pharmaca, 527 of them (95%) were taking regularly pharmaca for therapy. Of the latter, 68 subjects (13%) was taking 1 drug/day, 86 subjects (16.3%) was taking 2 drugs/day, 344 subjects (65.2%) consumed 3 drugs/day, and 29 of them (5.5%) was taking more than 3 drugs/day.

From these data the mean daily consumption amounted to 2.7 ± 1.4 pharmaca. The most frequently used pharmaca were the myocardiokinetics

Discussion

Our study pool derives from a national epidemiological investigation, i.e., it represents the universal Italian centenarian population, which is extremely variable. In this pool the Group A (20.7%) consists of subjects in good clinical conditions, which although display the common signs of aging, are free of chronic-degenerative complications, and also of fragility with polypathologies. The 43.6% of centenarians belonged to the Group B, and many of them could be considered as disabled.

Our

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