The simplest definition of age is a chronological count of calendar years (Jyrkämä 1995). Subjectively, many elderly persons do not feel themselves old even when retired or at the advanced age of 75. The elderly population has been divided into the young elderly aged 60–74 years and the very elderly over 74 years old (Devroey et al. 2002). With the increasing life expectancy, the terms “the oldest old” and “very elderly people” are currently used to refer to people 80 or 85 years of age or over (Haavisto & Mattila 1981, Päivärinta et al. 1999, Simiand-Erdociain et al. 2001).
In the literature, aging is defined most simply as a biological, psychological, and social phenomenon. Biological aging is associated with changes in the human organism and biological aging processes. (Jyrkämä 1995). Biological age is an attribute of body tissue relevant to pathogenesis (Last 1995). Pharmacokinetic and pharmacodynamic changes of drug efficacy are associated with the biological aging of the elderly (Pollock 1998). These changes are discussed in more detail below in section 2.1.4. of this thesis. The major organs affected by aging are the kidneys, the liver, and the cardiovascular (Pollock 1998) and central nervous systems (Koponen 2001). Aging may cause changes in the neurotransmission systems, and these changes may increase sensitivity to sedation by drugs (Pollock 1998, Koponen 2001).
Psychological aging takes place in the person´s psychic activities. Social aging is connected with the person as a member of society, and the term “the elderly” generally refers to people who have reached the socio-political age of 65 years. Social aging is more complicated to define than either biological or psychological aging, and the definitions partly overlap. Social aging is associated with changes that take place in the indivual´s or social group´s relationship with their environment, and these changes may manifest at both individual and societal levels. (Koskinen 1994)
From the age of 75 years onward, chronic morbidity increases (Pitkälä & Strandberg 2003). It is important to differentiate changes associated with primary aging from those caused by illnesses, called secondary aging. Significant age-related changes take place in the body composition of the healthy elderly after the age of 59 years, as the body cell mass and the skeletal muscle mass decrease. (Kyle et al. 2001)
Physical disabilities are connected with advanced age, multiple diseases, particularly cardiovascular and musculosketelal diseases (Stewart et al. 1989, Pitkälä & Strandberg 2003), depressive symptoms, and cognitive capacity (Laukkanen et al. 1994). Self-rated health is a useful indicator of physical health, but it may be sensitive to the cultural environment (Jylhä et al. 1998). Decline in vision and hearing also typically occurs in the course of aging (Lupsakko 2001, Bergman & Rosenhall 2001, Aromaa & Koskinen 2002), which may diminish the individual’s capacity for normal physical functioning and medical self-care. Poor visual acuity is a risk factor for fracture-causing falls (Luukinen et al. 1997).
Good physical functioning and an optimistic attitude toward life increased and the need for assistance decreased in the older population over the 10 years from 1989 to 1999 (Pitkälä et al. 2001b). Physical functioning has also improved in the general Finnish population over the past 20 years, though chronic morbidity increases systematically from the young age groups toward the oldest elderly populations (Koskinen & Aromaa 2002). Based on the compression of morbidity hypothesis, healthy lifestyles may postpone and compress disability into a shorter period toward the end of life (Fries 1980). Thus, among the oldest persons, multiple chronic diseases may require long-term medical treatment and lead to the use of several medications. Most of the elderly suffer from chronic diseases. The prevalence of chronic morbidity grew among home-dwelling Finnish persons aged 75 years or over from 70% in 1964 to 79% in 1976 (Klaukka 1982) and to 90% in 1995–96 (Arinen et al. 1998). The prevalence was 86% in 75- to 84-year-olds and nearly 90% in over 84-year-olds in 2000–01 (Koskinen & Aromaa 2002).
In the general Finnish population, mental health has remained stable over the past 20 years (Aromaa & Koskinen 2002). The most prevalent mental disorders among the elderly are dementia, depression, and delirium (Johnson et al. 1994). Dementia with psychosis and depression with dementia or anxiety disorder are also common among them. Schizophrenia is not so common in the elderly.
The prevalence of dementia ranges globally from 6% to 14% among elderly persons (Juva et al. 1993, Koivisto 1995) or from 8% to 13% among the home-dwelling elderly (declined cognition, mostly dementia) (Lim et al. 2003). Moderate to severe dementia ranges from 9% to 12% in the Finnish elderly (Juva et al. 1993, Viramo 1994), increasing with advancing age (Juva et al. 1993, Viramo 1994, Koivisto 1995). Almost 27% of persons aged 85 years old had dementia (Juva et al. 1993), and every fourth to every third (85+ years) had moderate to severe dementia according to some Finnish studies (Juva et al. 1993, Viramo 1994). Almost every third person aged 85 years or over had moderate to severe dementia in the elderly population (2000 concecutive patients) admitted to a medical department of a large university hospital (Erkinjuntti et al. 1986). It may be difficult to differentiate between a normal memory disorder and mild cognitive impairment (MCI) in an elderly person, because MCI is found in neurologically healthy individuals and may be a risk factor for dementia (Ylikoski et al. 1999).
Across Europe, the overall prevalence of depression in the elderly population is 12%, with women predominating (Copeland et al. 1999). Previous studies have shown 15–20% prevalences of depressive symptoms or depression in the elderly in community (Johnson et al. 1994, Pahkala et al. 1995, Manela et al. 1996), but as in the general population, 6% of the elderly suffer from major depression demanding drug treatment (Valvanne et al. 1996). Depression is associated with chronic morbidity, lowered physical functional capacity (Pahkala & Kivelä 1991, Penninx et al. 1996, Valvanne et al. 1996, Linjakumpu et al. 2001), and the use of cardiovascular, psychotropic, and analgesic drugs in the elderly (Pahkala & Kivelä 1991, Linjakumpu et al. 2001). Feelings of loneliness are typically experienced by the elderly, and they are associated with depression (Lindgren et al. 1994, Routasalo & Pitkälä 2003). Spousal bereavement is associated with increased morbidity and mortality (Charlton et al. 2001, Prigerson & Jacobs 2001).
Of the demented elderly admitted into a general hospital, 41% were delirious, and 25% of the delirious patients were demented (Erkinjuntti et al. 1986). Multiple acute illnesses, such as cardiovascular, neurological, endocrinological, metabolic, or infectious diseases, anticholinergic psychotropics, sedatives or cardiovascular drugs, intoxication, alcohol or sedative withdrawal, dementia, and psychosocial stress may precipitate delirium (Johnson et al. 1994).
Fifteen per cent of the home-dwelling elderly may suffer from anxiety (Manela et al. 1996), even though the prevalence of this disorder is lower among them than in younger adults (Aromaa et al. 1989, Flint 1994). Over one third of the home-dwelling elderly report sleeping disorders (Manela et al. 1996, Arinen et al. 1998). The incidence of psychoses increases with age (van Os et al. 1995, Targum & Abbott 1999), due to physical comorbidities, dementia, sensory deficits, social isolation, and polypharmacy (Targum & Abbott 1999). Panic symptoms are not so common in old age (Manela et al. 1996).
It has been concluded that the strong association between physical and mental health should be rigorously investigated (Berkman et al. 1986), and that the two aspects of health should not be considered separately. The social situation of the elderly should also be clarified. Mental disorders together with somatic diseases are common in the elderly. They therefore need drugs for the treatment of their diseases, and they use psychotropics more frequently than the general population (Blazer et al. 2000).
The pharmacokinetic and pharmacodynamic changes secondary to advanced age or various illnesses require careful attention, because these changes make the elderly particularly sensitive to adverse effects, toxic reactions, and interactions of many drugs. Pharmacokinetic alterations may be caused by changes in absorption, distribution, or elimination via metabolism in the liver and/or in excretion by the kidneys. (Hughes 1998, Pollock 1998, Paasonen & Tuomisto 2001). Renal function weakens clearly in advancing age because of decreased glomerular filtration rate in kidneys, whereas hepatic function is not reduced so much, provided there are no spesific diseases in liver. E.g., digitalis which is excreted via kidneys mostly as unchanged drug may accumulate in patients with advanced age leading to intoxication. (Neuvonen 2001). Cardiac output and pulmonary action deteriorate and influence the pharmacokinetics of drugs.
Absorption is usually minimally changed in advancing age. The distribution of drugs is altered because of the increasing fat/muscle ratio, while the total body water decreases. Many drugs, including many psychotropics, are highly lipophilic, which means that their half-lives usually prolong and the drugs accumulate in the elderly. (Pollock 1998). In the elderly, the half-life of diazepam is up to 4- to 5-fold compared to younger persons, being 35 to 100 hours (Klotz et al. 1975, Sorock & Shimkin 1988). Individual differences in the half-lives of benzodiazepines increase upon aging, and even short-acting drugs have a prolonged effect in the body (Herings et al. 1995).
Psychotropics taken daily tend to accumulate in the central nervous system (CNS), even though the substance is adequately eliminated from the circulation (Tuomisto et al. 1984, Herings et al. 1995). For these reasons, the psychotropic doses of the elderly should be half or even one fourth of the doses prescribed for middle-aged patients (Koponen 2002).
In the elderly, hepatic metabolism is reduced because the liver mass and blood flow decrease (Pollock 1998). Drugs tend to accumulate if many drugs are used concomitantly resulting in an overload of the metabolic pathways (Casey 1997). If several drugs use the same cytochrome P450 enzyme pathways in hepatic metabolism, inhibition or induction of the enzyme may lead to remarkable adverse effects and drug-drug interactions. For example, fluoxetin inhibits the metoprolol-metaboling enzyme, and the metoprolol concentration may consequently increase and cause bradycardia. (Pelkonen et al. 1998, Pollock 1998)
The pharmacodynamic changes induced by aging are less well characterized than the pharmacokinetic changes. Pharmacodynamics reflects an organ-specific response and a homeostatic counter-relation (e.g. postural hypotension), which changes along with aging. The sites of drug action include cell surface and intracellular receptors, enzymes, and membrane ion channels. (Cusack et al. 1997). Receptors control the quality of the drug’s influence and its biological activity. Drugs may block receptors (antagonists) or activate them (agonists). Neurodegeneration upon aging or in diseases and many drugs, such as psychotropics, cause disorders in neurotransmission in the cholinergic (muscarinic and nicotinic receptors), dopaminergic, serotonergic, and noradrenergic systems, which are responsible for memory and learning. (Koponen 2001, Scheinin 2001, Ylinen et al. 2001)
Specific receptor and neurotransmitter changes associated with senescence include reductions in central cholinergic and dopaminergic activities and leading to greater sensitivity to medications acting on these systems (Pollock 1998). The cholinergic muscarinic receptor block decreases extrapyramidal symptoms, but causes anticholinergic adverse effects (e.g., reduced cognition, confusion, orthostatism, urinary retention, constipation, etc.). The dopaminergic receptor block decreases the positive symptoms of schizophrenia, but causes extrapyramidal adverse effects (parkinsonism – rigidity, tremor, bradykinesia, weakness, autonomic dysfunction, dementia, and tardive dyskinesia). (Pickar 1995, Koponen 1997)
Drugs that inhibit structural brain disorders or protect nervous cells from neurodegenerative disorders and apoptosis are being investigated actively. Cholinergic drugs are used in Alzheimer´s disease and levodopa and dopaminergic receptor agonists in parkinsonism. (Cástren et al. 1998). Neurological adverse effects are less common in atypical antipsychotics than conventional ones (Pickar 1995, Casey 1997). New antidepressants (selective serotonin reuptake inhibitors = SSRIs) have fewer and less severe CNS and anticholinergic adverse effects than tricyclic antidepressants (Keller 2000).