Programme to improve the use of drugs in older people and involve general practitioners in community education.

As part of a multi-pronged approach to improving the quality of drug use in the elderly, a pharmacist was contracted by the Division of General Practice (Northern Tasmania) to develop educational material and implement two academic detailing sessions for general practitioners on the issues of adverse drug reactions and drug interactions in older people. The project aimed to involve general practitioners in community education after optimizing relevant therapeutic knowledge and standardizing prescribing practices. Sixteen general practitioners were involved in the project and 13 of these agreed to participate in academic detailing. The pharmacist developed prescribing guidelines for general practitioners and discussed these and illustrative case studies at the academic detailing sessions. General practitioner-conducted education sessions were completed by nine general practitioners to groups of carers, general practitioners, nurses and older people. Despite the relatively low numbers of general practitioners involved, the results of the project were encouraging. Academic detailing by the pharmacist was well received by the general practitioners, who indicated they would be willing to participate in further sessions. Pre- and post-project multiple-choice tests on therapeutic issues in the elderly indicated a strong trend for an increase in knowledge. Analysis of general practitioners' patient records found a statistically significant decline in the median number of medications prescribed per patient during the project. There was also a statistically significant decline in prescribing of 'indicator' medications, particularly psychoactive drugs and nonsteroidal anti-inflammatory drugs in patients resident in nursing homes. The project demonstrated that academic detailing by a pharmacist can be effective as part of a combined approach to improve the quality of drug use in older people.

Drug-related admissions to an Australian hospital.

This study was conducted to determine the prevalence of drug-related hospital admissions in southern Tasmania, Australia. The causes of consecutive admissions to medical wards of the Royal Hobart Hospital were reviewed. Comprehensive data were collected over a 10-week period on 691 admissions (median age: 67 years and range: 11-97 years; 50.8% males). Sixty-eight (9.8%) of the admissions were classified as being either probably or definitely drug-related. Most of these admissions were attributable to intentional overdose (38.2%) or an adverse drug reaction (30.9%). The overdoses often involved benzodiazepines or antipsychotics. Gastrointestinal bleeding related to the use of nonsteroidal anti-inflammatory drugs was the most common adverse drug reaction (38.1% of all reactions). Other drug-related admission categories were poor compliance (14.7%), dosage decrease or therapy cessation by a doctor producing an exacerbation of symptoms (7.4%), substance abuse (4.4%) and drug interaction (4.4%). Patients with a drug-related admission were, on average, younger than the other medical admissions, with no significant difference in gender. Patients admitted due to an overdose or substance abuse were younger than other drug-related admissions and non-drug related admissions. In conclusion, this study has determined that almost 10% of medical admissions to the hospital are drug-related and it is estimated that 40 to 50 elderly people are admitted each year suffering from gastrointestinal bleeding related to nonsteroidal anti-inflammatory drugs.

Longitudinal trends in prescribing for elderly patients: two surveys four years apart.

BACKGROUND: Elderly people are prescribed more drugs than younger people. The consequences of excessive or unwise prescribing, such as drug interactions, are well known. AIM: A longitudinal study was undertaken to examine levels and patterns of prescribed drug use among a group of elderly people. METHOD: Use of prescribed drugs by a sample of elderly people in Nottingham aged 65 years and over was assessed on two occasions four years apart, in 1985 and 1989. RESULTS: Complete drug data were available for 1003 respondents in 1985 and 662 respondents in 1989 (with attrition due mainly to mortality). Drug use increased significantly with age. Women took significantly more drugs than men. Approximately half of respondents were taking at least two drugs. The overall number of drugs per person being taken in 1989 was significantly greater than in 1985. This difference remained significant when age and mortality were controlled, suggesting that changes in drug use over time within this sample may reflect genuine changes in prescribing practice (rather than simply the effects of ageing). The most commonly prescribed drug classes on each occasion were drugs for the cardiovascular system, central nervous system, musculoskeletal system, gastrointestinal tract and respiratory system. The subgroups of drugs most commonly reported at each interview were diuretics, hypnotics and anxiolytics, analgesics and non-steroidal anti-inflammatory drugs. Drugs within the category 'hypnotics and anxiolytics' showed clear and differential trends over time, with the use of anxiolytics falling, while the use of hypnotics increased. Among those respondents admitted to residential care during the course of the study higher levels of psychotropic drug use, and an increase in antipsychotic medication, were observed. CONCLUSION: It is important that the drug regimens of elderly people are frequently reviewed to ensure that only the minimum number of effective drugs, in the simplest regimen, are prescribed.

Enantiospecific gas chromatographic-mass spectrometric procedure for the determination of ketoprofen and ibuprofen in synovial fluid and plasma: application to protein binding studies.

A method for the enantiospecific quantitation of two commonly prescribed non-steroidal anti-inflammatory drugs (ketoprofen and ibuprofen) is described. The method involves formation of a mixed anhydride of the drug with ethylchloroformate and subsequent conversion to an amide by reaction with optically active amphetamine. The subsequently formed diastereomers are separated by gas chromatography-mass spectrometry using selected-ion monitoring. The assay is capable of quantifying ketoprofen (2 ng/ml) and ibuprofen (3 ng/ml) enantiomers from a 200-microliters sample of synovial fluid or plasma and is particularly suitable for protein binding studies.

Psychoactive drug prescribing in the Tasmanian community.

OBJECTIVE: To gather data on the prescribing of psychoactive drugs (benzodiazepines, antidepressants and antipsychotics) using a network of Tasmanian community pharmacies. DESIGN SETTING AND PARTICIPANTS: The prescribing of psychoactive drugs in the community was studied during 1989 using data retrospectively obtained from computerised dispensing systems in 11 community pharmacies in Tasmania. The data collection procedure included all prescriptions dispensed in the pharmacies, irrespective of supply under the Pharmaceutical Benefits Scheme, the Repatriation Pharmaceutical Benefits Scheme or as a private prescription. MAIN OUTCOME MEASURES: Results of the pooled data were quantified by both the number of prescriptions and the defined daily doses (DDDs) dispensed for the psychoactive drugs. RESULTS: When extrapolated to the population of Tasmania, the estimated annual prescribing rates for the benzodiazepines, antidepressants and antipsychotics (including lithium) were 853.3, 316.2 and 54.8 prescriptions per 1000 persons, respectively. Prescriptions for the psychoactive drugs accounted for 13.2% of all prescriptions dispensed. In terms of DDDs, the estimated prescribing rates for the total Tasmanian population for the benzodiazepines, antidepressants and antipsychotics were 47.8, 12.5 and 2.1 DDDs per 1000 persons per day, respectively. The rate of benzodiazepine prescribing appeared to be high in comparison with the limited Australian data available. The relative prescribing rates of the long acting benzodiazepine hypnotics, flunitrazepam and nitrazepam, were also disturbingly high. CONCLUSIONS: This study has demonstrated the potential value of comprehensive pharmacoepidemiological data obtained from a network of community pharmacists and will form the basis for future studies using an expanded collection procedure.

Effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) and its metabolites.

The effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) 500 mg and its metabolites were studied in 8 healthy men. The mean residence times for paracetamol or its metabolites were significantly altered by change in posture or by sleep, whereas other pharmacokinetic parameters were unchanged. The change in mean residence time is consistent with a faster absorption of paracetamol during ambulation. The present data suggest that the proposed posture-related changes in volume of distribution do not exist, and that there is no pharmacokinetic basis for a headache being relieved by taking paracetamol and lying down.

The effects of posture on the pharmacokinetics of intramuscular benzylpenicillin.

Previous reports have produced conflicting results as to whether changes in posture affected the pharmacokinetics of the penicillins. We have studied the pharmacokinetics of intramuscularly administered benzylpenicillin in normal subjects during bedrest and ambulation and compared it with data obtained following intravenous administration of the same dose to the same subjects under the same conditions. The values of area under the curve, total clearance, mean residence time and renal clearance found during ambulation were 1175 (min.min.l-1), 488 (ml.min-1), 101 (min), and 264 (ml.min-1) (means). The corresponding values for bedrest were 1032 (min.mg.l-1), 544 (ml.min-1), 96.7 (min), and 315 (ml.min-1). There was a significant difference between the areas under the curve with change of posture but not between any of the other pharmacokinetic variables. The differences observed in this study are unlikely to be of clinical relevance. We suggest that the differences between the results of this study and those of previous studies may be related to the level of exercise undertaken by the subjects in the various studies.

The effect of posture on the pharmacokinetics of intravenous benzylpenicillin.

We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4 +/- 100.5 ml/min, 36.23 +/- 13.45 min, and 309.4 +/- 93.4 ml/min (means +/- SD). The corresponding values for bedrest were 543.6 +/- 122.6 ml/min, 35.27 +/- 10.21 min, and 324.1 +/- 145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.

Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease.

Plasma aspirin, salicylate and salicyluric acid concentrations were monitored in young, elderly and alcoholic subjects after ingestion of a single 1.2 g dose of soluble aspirin. The plasma aspirin, salicylate and unbound salicylate concentration-time profiles varied considerably between individual subjects. Most of the pharmacokinetic parameters derived from these profiles were not significantly different between young subjects, elderly subjects and subjects with alcoholic liver disease. Individual plasma albumin concentrations provided a better index of the unbound plasma salicylate clearances and salicylate plasma protein binding than the age of the subject or the presence of alcoholic liver disease. Highest unbound plasma salicylate concentrations were found in subjects with the lowest plasma albumin concentrations.

Metabolism of salicylate during chronic aspirin therapy.

1. The effects of chronic administration of aspirin in therapeutic doses (3.9 g/day) on plasma and salivary salicylate levels were studied in eight subjects. 2. The urinary excretion profile for free salicylic acid and metabolites of salicylate were examined. 3. Plasma and salivary salicylate levels declined significantly after peak levels were achieved between days 3 and 10. 4. The decline in plasma and salivary salicylate levels may be due to an induction of a metabolic pathway such as salicylurate formation (Furst, Gupta & Paulus, 1977). Only the mean fraction of salicylate excreted as salicylurate appears to increase with time during the present study, although the change was not significant statistically. 5. The decline in plasma and salivary salicylate levels during chronic therapy may lead to an apparent 'tolerance' of some rheumatoid patients to aspirin.