The half-lives of many benzodiazepines and barbiturates increase by 50–150% between ages 30 and 70. Much of this change occurs during the decade from 60 to 70. For some of the benzodiazepines, both the parent molecule and its metabolites (produced in the liver) are pharmacologically active (see Chapter 22). The age-related decline in renal function and liver disease, if present, both contribute to the reduction in elimination of these compounds. In addition, an increased volume of distribution has been reported for some of these drugs. Lorazepam and oxazepam may be less affected by these changes than the other benzodiazepines. In addition to these pharmacokinetic factors, it is generally believed that the elderly vary more in their sensitivity to the sedative-hypnotic drugs on a pharmacodynamic basis as well. Among the toxicities of these drugs, ataxia and other stability impairments lead to increased falls and fractures.
The opioid analgesics show variable changes in pharmacokinetics with age. However, the elderly are often markedly more sensitive to the respiratory effects of these agents because of age-related changes in respiratory function. Therefore, this group of drugs should be used with caution until the sensitivity of the particular patient has been evaluated, and the patient should then be dosed appropriately for full effect. Opioids are not as effective in chronic pain syndromes as they are for acute pain, eg, fracture pain (see Chapter 31). Unfortunately, studies show that opioids are consistently underutilized in patients who require strong analgesics for
CHAPTER 60 Special Aspects of Geriatric Pharmacology 1061 chronic painful conditions such as cancer. Good pain management plans are readily available (see Morrison, 2006; Rabow and Pantilat, 2011).
The traditional antipsychotic agents (phenothiazines and halo peridol) have been very heavily used (and often misused) in the management of a variety of psychiatric conditions in the elderly.
There is no doubt that they are useful in the management of schizophrenia in old age, and also in the treatment of some symptoms associated with delirium, dementia, agitation, combat iveness, and a paranoid syndrome that occurs in some geriatric patients (see Chapter 29). However, they are not fully satisfactory in these geriatric conditions, and dosage should not be increased on the assumption that full control is possible. There is no evi dementia, and on theoretical grounds the antimuscarinic effects of the phenothiazines might be expected to worsen memory impair ment and intellectual dysfunction (see below).
Much of the apparent improvement produced by these drugs in effects. When a sedative antipsychotic is desired, a phenothiazine such as thioridazine is appropriate. If sedation is to be avoided, haloperidol or a second generation (atypical) antipsychotic is more appropriate. Haloperidol has increased extrapyramidal toxicity, however, and should be avoided in patients with preexisting extra- pyramidal disease. The phenothiazines, especially older drugs such as chlorpromazine, often induce orthostatic hypotension because of their α-adrenoceptor-blocking effects. They are even more prone to do so in the elderly. Dosage of these drugs should usually be started at a fraction of that used in young adults. The second generation antipsychotic agents (clozapine, olanzapine, quetiapine, risperi done, aripiprazole) do not appear to be significantly superior to the effects. Evidence supporting the benefits of olanzapine is somewhat stronger than that for the other second generation agents.
Lithium is often used in the treatment of mania in the aged.
Because it is cleared by the kidneys, dosages must be adjusted appropriately and blood levels monitored. Concurrent use of thiazide diuretics reduces the clearance of lithium and should be measurement of lithium blood levels.