Adverse drug reactions in elderly patients.

Many studies from around the world show a correlation between increasing age and adverse drug reaction (ADR) rate, at least for some medical conditions. More than 80% of ADRs causing admission or occurring in hospital are type A (dose-related) in nature, and thus predictable from the known pharmacology of the drug and therefore potentially avoidable. Frail elderly patients appear to be particularly at risk of ADRs and this group is also likely to be receiving several medicines. The toxicity of some drug combinations may sometimes be synergistic and be greater than the sum of the risks of toxicity of either agent used alone. In order to recognize and to prevent ADRs (including drug interactions), good communication is crucial, and prescribers should develop an effective therapeutic partnership with the patient and with fellow health professionals. Undergraduate and postgraduate education in evidence-based therapeutics is also vitally important. The use of computer-based decision support systems (CDSS) and electronic prescribing should be encouraged, and when problems do occur, health professionals need to be aware of their professional responsibility to report suspected adverse drug events (ADEs) and ADRs. "Rational" or "obligatory" polypharmacy is becoming a legitimate practice as increasing numbers of individuals live longer and the range of available therapeutic options for many medical conditions increases. The clear risk of ADRs in this situation should be considered in the context that dose-related failure of existing therapy to manage the condition adequately may be one of the most important reasons for admission of the elderly to hospital. Thus, age itself should not be used as a reason for withholding adequate doses of effective therapies.

Older adults, diabetes mellitus and visual acuity: a community-based case-control study.

MAIN OBJECTIVES: to screen for impaired distance visual acuity in older adults living at home, both with and without diabetes mellitus to determine whether diabetes increases the likelihood of visual impairment and to identify associated factors. DESIGN: case-control study. SETTINGS: three districts of Wales: North Clwyd, Powys and South Glamorgan, with assessments in subjects' homes. SUBJECTS: 385 with diabetes mellitus and 385 age- and sex-matched controls. MAIN OUTCOME MEASURES: visual acuity measures, short form (SF)-36 quality of life scores RESULTS: we observed impairment of visual acuity in 40% of those with diabetes mellitus and 31% of controls. Diabetes was associated with an increased risk of visual impairment [odds ratio 1.50 (95% confidence interval 1.09-2.05), P = 0.013]. The pinhole test identified uncorrected refractive error in 11% of the 63 patients with diabetes and 12% of the 49 controls who wore glasses, and in 51% of the 91 patients and 84% of the 69 controls who did not wear glasses (P < 0.001). Increasing age (P < 0.001) and female sex (P = 0.014) were significantly associated with visual impairment in both groups, whilst history of foot ulceration (P = 0.001), duration of diabetes (P = 0.018) and treatment with insulin (P < 0.001) were significantly associated with visual impairment in subjects with diabetes. We observed a significant association between impaired visual acuity and five domains of the SF-36 (physical and social functioning, mental health, vitality, and health perceptions; P < 0.01 in each case). CONCLUSION: older adults living at home have a high prevalence of uncorrected visual impairment. Diabetes mellitus is associated with significantly increased risk of visual loss. This impairment is associated with detriments in health-related quality of life. We recommend earlier use of optometry services and assessment of visual acuity by clinicians.

Plasma esterases in cystic fibrosis: the impact of a respiratory exacerbation and its treatment.

OBJECTIVES: To determine the effect of an exacerbation of respiratory symptoms in cystic fibrosis (CF) on the activities of plasma benzoylcholinesterase and butyrylcholinesterase. METHODS: Twenty-nine patients with CF in a respiratory exacerbation and 27 healthy volunteers matched for age and sex were recruited. Blood was obtained from the patients when commencing antibiotic treatment and 14 days later on completion of treatment. One blood sample was taken from the healthy volunteers. The activities of benzoylcholinesterase and butyrylcholinesterase were determined by spectrophotometric assay. The circulating inflammatory markers, C-reactive protein and neutrophil elastase-alpha1antiproteinase complex were also measured. RESULTS: Benzoylcholinesterase activity was significantly (P = 0.001) lower in patients at the start of a respiratory exacerbation, compared with healthy controls [mean (SD): 917 (274) versus 1191(298) nmol x ml(-1) x min(-1)]. Benzoylcholinesterase activity increased significantly in patients to 1013 (237) nmol x ml(-1) x min(-1), following a course of antibiotic treatment (P = 0.006). Butyrylcholinesterase activity was also lower (P = 0.001) in patients at the start of a respiratory exacerbation, compared with healthy controls [5.54 (1.64) versus 7.01 (1.79) micromol x ml(-1) x min(-1)], and increased significantly in the patients to 6.31 (1.58) micromol x ml(-1) x min(-1) following treatment (P = 0.006). CONCLUSION: We demonstrated significant suppression of plasma esterase activities during an exacerbation of respiratory symptoms in CF, which was only partially reversed after antibiotic treatment. Further studies are needed to examine other pathways of drug metabolism in this group of chronically infected patients.

Continuing medical education in Wales: a survey of geriatricians.

OBJECTIVE: to determine what practising geriatricians in Wales do to continue their education; what they would prefer to do; and what their views are on study leave, resources and funding. DESIGN: questionnaire survey. SETTING: the principality of Wales. PARTICIPANTS: hospital-based, career-grade geriatricians. RESULTS: the overall response rate from a total of 56 questionnaires was 87%. More than half [26 (53%)] of the respondents stated they were able to take only half of their study leave entitlement of 10 days a year. Twenty-five (51%) considered this to be due to service commitment. Geriatricians regarded attendance at routine hospital meetings [47 (96%)] and specialist society meetings [45 (92%)], reading books and journals [49 (100%)] and discussion with colleagues [44 (90%)] as their preferred methods of keeping up to date. Most respondents [44 (90%)] said that the resources and funding required to underpin the system of continuing medical education (CME) should be provided by the employing authority. CONCLUSIONS: the many barriers to the continuing education of geriatricians in Wales include service commitments and funding constraints. Geriatricians placed great emphasis on the traditional CME methods such as reading books and journals, attending meetings and conferences and discussion with colleagues and were reluctant to use technology-based educational methods. The results of this study have implications for the way in which geriatricians fulfil CME obligations in the future and provide directions for the planners of CME.

Reliability of parathyroid hormone measurements in the period immediately following hip fracture.

AIM: As it is unclear whether parathyroid hormone (PTH) measurements performed immediately after hip fracture are reliable indicators of pre-fracture metabolic status, we set out to define how PTH levels are affected by hip fracture and its surgical repair. METHOD: In two longitudinal projects, we studied 12 patients presenting with hip fracture and eight patients undergoing elective hip replacement. PTH, calcium and 25-hydroxyvitamin D (25OHD) levels were measured on admission, 2 days and 1 week later and after recovery at least 2 months after initial admission. FINDINGS: In the subjects presenting with hip fracture, PTH levels during inpatient care were no different from those subsequently measured during the recovery period. In subjects undergoing elective hip surgery, PTH levels did not change following surgery and again remained unchanged into the recovery period. CONCLUSIONS: Measurements of PTH performed during inpatient care of those with hip fracture appear sufficiently reliable for use in assessment of metabolic status.

Fracture incidence in England and Wales: a study based on the population of Cardiff.

Despite the importance of fractures as an economic and health problem, and consequent interest in osteoporosis, few workers have previously attempted to define the overall incidence of fracture. This population based study was based in the Accident and Emergency Department of Cardiff Royal Infirmary and identified all patients presenting with fractures of any type. Over a single year a total of 6467 fractures were identified among the 306,600 people who live in the city of Cardiff. This gives an overall fracture incidence of 21.1/1000/year, (23.5/1000/year in males and 18.8/1000/year in females); a result very similar to those from similar work in the USA, Australia and Norway. This result is over twice the previous estimate of fracture incidence in the UK; the figure of 9/1000/year from the only equivalent study performed since the 1960s. In part, this discrepancy appears to reflect our more rigorous definition of the study population, and our improved ascertainment of minor fractures. We believe our result to offer the most accurate estimate of fracture incidence currently available for a UK population.

Age, environmental factors and drug metabolism.

Both ageing and the environment have a significant impact on xenobiotic metabolism. Furthermore, there is some evidence from in vivo studies that the elderly respond to environmental changes to a lesser degree than younger individuals. This article reviews the available evidence and concentrates on possible underlying mechanisms.

Drug formularies--good or evil? The clinical perspective.

Drug formularies, designed to encourage more clinically effective and cost effective prescribing, are now in widespread use in the secondary care system in the UK. Amongst their disadvantages, formularies are expensive to produce and require regular updating and policing. In addition, formularies do not consider alternate non-prescribing cost containment measures, and over-rigid application of formulary systems may alienate senior medical staff. In order to maximize the acceptability of formularies to all doctors, it is essential that the local Drugs and Therapeutics Committee has wide representation and focuses on clinical efficacy rather than simply on cost. Realistically, it is important that formulary committees are sufficiently flexible to allow the introduction of innovative, albeit expensive, new compounds. Enforcement of formularies into general practice is not presently achievable, but many primary care teams, realizing the benefits, have successfully introduced their own formularies to improve clinical drug usage and cost containment. If a reduction in costs is the primary aim, the global introduction of formulary systems may not be the best solution, and specific targeting of drug therapy may prove a more effective alternative. Indeed, in the South Glamorgan Health Authority, the introduction of a targeting system for the ten therapeutic areas with the highest expenditure allowed substantial savings to be made.

Reduced renal hemodynamic response to atrial natriuretic peptide in elderly volunteers.

Aging is associated with decreased ability to excrete salt and water, thus increasing the susceptibility to volume overload in older individuals. Meanwhile, plasma levels of atrial natriuretic peptide (ANP) increase progressively with age for unknown reasons. We compared the natriuretic and renal hemodynamic responses to low-dose ANP infusion in an elderly group of volunteers (mean age, 74 years) with those of a group of younger subjects (mean age, 29 years). A significant reduction below baseline values in effective renal plasma flow occurred in the young group after the 2-hour peptide infusion (657 +/- 125 v 476 +/- 92 mL/min [mean +/- 1 SD]) when compared with the elderly group (two-way analysis of variance; P < 0.02). A concomitant increase in renal vascular resistance was noted in the young group only during the same period (6,631 +/- 1,384 v 9,136 +/- 2,126 dyn s cm2 x 10(6)). This increase was also significantly higher than that in the elderly group (analysis of variance; P < 0.02). Both groups demonstrated similar natriuretic responses. Absolute sodium excretion had increased significantly above baseline values in both young and elderly subjects at the end of the 2-hour peptide infusion (111 +/- 25 mumol/min to 183 +/- 33 mumol/min v 107 +/- 23 mumol/min to 198 +/- 56 mumol/min) and remained elevated until 1 hour postinfusion. We conclude that the elderly subjects in our study demonstrated a diminished renal hemodynamic response to infusion of ANP while preserving a natriuretic response similar to that found in the younger subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

The association of age and frailty with the pharmacokinetics and pharmacodynamics of metoclopramide.

We have investigated the association of age and frailty with the pharmacokinetics and pharmacodynamics of the conjugated drug, metoclopramide. Six healthy young, six healthy elderly (> 65 years), and six frail elderly (> 65 years) subjects were studied on two occasions, receiving 10 mg metoclopramide by intravenous bolus and orally, in random order. Blood and urine were collected for measurement of pharmacokinetic parameters. Liver volume was measured by ultrasound. Sedation and contentment were self-recorded on visual analogue scales. Liver volume was not significantly different in the three groups, nor was bio-availability of metoclopramide. Clearance was similar in the young and fit elderly but reduced in the frail elderly subjects when compared with the young (p < 0.05), both when expressed in absolute terms and per unit liver volume. There were no differences in percentages cleared as the free drug or as the sulphate or glucuronide metabolite within or between groups, suggesting that frailty can produce a general impairment of conjugation pathways. The frail elderly subjects reported more sedation after intravenous dosage than the other subjects, whilst only young subjects reported akathisia. This did not relate to pharmacokinetic differences and seemed therefore to reflect associated pharmacodynamic changes in specific receptor or target sites.

A single-dose study of the pharmacodynamic effects of chlormethiazole, temazepam and placebo in elderly parkinsonian patients.

Nine elderly parkinsonian volunteers took single doses of 384 mg of chlormethiazole, 10 mg of temazepam and placebo capsules in a double-blind three-way cross-over study on separate visits at least one week apart. In the 6 hours following the dose, the level of drowsiness, performance on a series of psychomotor tests, effects on parkinsonian symptoms and signs, and standing and lying blood pressure were recorded. Chlormethiazole produced drowsiness on all tests and impaired psychomotor performance, as compared with placebo, without affecting parkinsonian symptoms and signs, or postural blood pressure. Temazepam was consistently less potent than chlormethiazole on tests of drowsiness and psychomotor performance. Both treatments were well tolerated. It is suggested that chlormethiazole is safe to use as a hypnotic at this dosage in this group of patients with Parkinson's disease, while temazepam did not appear to be effective as a hypnotic at this dosage.

The association of age with aspirin esterase activity in human liver.

The activity of the phase 1 enzyme aspirin esterase was studied in liver tissue from 16 patients, aged 45-88 years. No correlation between age and enzyme activity was found in post-mitochondrial, cytosolic and microsomal fractions. These results provide further evidence that age is not a major determinant of the activity of hepatic drug-metabolizing enzymes in man.

The association of age with the induction of drug-metabolizing enzymes in human monocytes.

In vivo studies in man suggest that the enzyme-inducing effect of environmental influences such as drugs or smoking may be reduced in elderly people. We have investigated the basal activity and response to induction of the oxidative enzyme, aryl hydrocarbon hydroxylase (AHH) in human monocytes. Three groups were studied: ten fit young, ten fit elderly and eight frail elderly subjects. Significant induction of AHH activity in response to the hydrocarbon benz(a)anthracene was achieved in all three groups. No impairment of basal AHH activity or in the synthesis of new enzyme protein was noted with age or frailty. There is still no direct evidence of an age-associated fall in drug metabolizing enzyme activities in man.