Differences in drug prescribing patterns in elderly parkinsonian patients identified at hospital admission.

In the period July 1984 to June 1993 a total of 4541 admissions to a Department of Medicine for the Elderly were investigated. Approximately 9% of the total were diagnosed to have parkinsonism. Full drug histories together with the available demographic and clinical data were investigated in order to identify differences in the prescribing patterns in this group compared to those of non-parkinsonian patients admitted during this time frame. There was a statistically significant lower incidence among the parkinsonian group for the prescribing of all cardiovascular drug groups, anticoagulants, hypoglycaemics, bronchodilators, and corticosteroids compared with non-parkinsonian patients. In contrast, the incidence of hypnotics, laxatives, antidepressants and antipsychotics were significantly higher.

Changes in prescribing patterns of oral hypoglycaemics in elderly patients, over a period of 10 years: matching with general practitioners' perceptions of their own prescribing.

A 10-year hospital admissions database had demonstrated a steep decline in the prescribing of chlorpropamide, and to a lesser degree, of glibenclamide, with tolbutamide, metformin and the most recently introduced oral hypoglycaemic, gliclazide, maintaining relatively uniform levels. Glipizide was the most popular emerging agent. Interviews with 20 general practitioners (GPs) revealed that 55% had a definite first choice agent with a priority order of gliclazide, tolbutamide and glibenclamide. For the remaining GPs without a sole preference, gliclazide (30%), glipizide (30%) and glibenclamide (20%) featured as their most commonly prescribed agents.

Development and use of a gastropathy index for ranking the safety of non-steroidal anti-inflammatory drugs in the elderly.

This study, conducted at the Royal Devon & Exeter Hospital, Department of Geriatric Medicine, was carried out using 2987 sets of admission data. The number of patients taking non-steroidal anti-inflammatory drugs was identified together with a suite of clinical factors used to indicate the presence of gastrointestinal pathology. From this a gastropathy index was developed to establish a rank order for the individual drugs. Ketoprofen, piroxicam and fenbufen were all significantly associated with factors suggestive of gastropathy, whereas indomethacin, diclofenac and ibuprofen appeared relatively free of such association. Naproxen, azapropazone and mefenamic acid ranked in an intermediate category. This noninvasive analysis of routinely acquired data provides a potentially useful discriminator between individual non-steroidal anti-inflammatory drugs for this age group.

An investigation of the association of benzodiazepines and other hypnotics with the incidence of falls in the elderly.

Clinical and medication data from 2,878 admissions to a Department for Care of the Elderly were examined retrospectively to determine the association between the administration of hypnotics/benzodiazepines and the incidence of falls. Only lorazepam prescribed to females and nitrazepam prescribed to males were associated with a significantly increased incidence of falls. Women fell significantly more frequently than men, and 7.5% of falls resulted in fractures. Stroke was the most common major diagnosis in fall-cases, followed by infection, Parkinsonism and confusion.

Is valproate monotherapy a practical possibility in chronically uncontrolled epilepsy?

In a prospective open study of 20 male epileptic residents of a mental handicap institution, polytherapy was gradually reduced to valproate monotherapy in 18 subjects. In terms of seizure frequency this was significantly disadvantageous but when carbamazepine was added or substituted, seizure control improved significantly. Drugs with documented adverse effects on cognitive function such as phenobarbitone and phenytoin were phased out. In the 18 subjects who achieved valproate monotherapy, no association between serum levels and seizure control could be demonstrated. Adverse effects of valproate were pancreatitis and thrombocytopenia; in one subject thrombocytopenia appeared to be associated with levels in the toxic range but in six other subjects 'toxic' levels of valproate did not give rise to any clinically detectable toxic signs. There was no instance of tremor or weight gain. It was concluded that, in the population studied (institutionalized patients with chronically uncontrolled seizures) valproate monotherapy was inappropriate but carbamazepine with or without valproate was a better option. Phasing out phenytoin and phenobarbitone was successful. Valproate serum levels did not contribute significantly to the conduct of the study; no general relationship between valproate serum levels and either seizure control or toxicity could be demonstrated.

Anti-rheumatic and analgesic drug usage and acute gastro-intestinal bleeding in elderly patients.

The records of 1878 general medical in-patients (aged 75 years and over) at Hereford have been examined for associations between the commonly used antirheumatic and analgesic drugs and acute gastro-intestinal bleeding. One third of 93 in-patients admitted because of acute bleeding had been taking ibuprofen, indomethacin or aspirin. The usage of these drugs was significantly greater than in the control population who comprised the remaining 1785 elderly medical in-patients. It is suggested that very elderly patients taking any of these three drugs form a vulnerable high risk group who are liable to develop acute gastro-intestinal bleeding.

Acetylation of some novel hemicholinium compounds by soluble choline acetyltransferase: structure-activity relationships.

Four bisquaternary nitrogen analogues of 2,2'-[1,1'-biphenyl]-4, 4'- diylbis [2-hydroxy-4,4- dimethylmorpholinium ] bromide (hemicholinium 3, HC-3) have been synthesized. These analogues differ from HC-3 in that they have a number of methylene groups inserted between the two phenyl rings. This study examines the significance of the internitrogen distance in these compounds with regard to their acetylation by soluble choline acetyltransferase (ChAc) in vitro. The hemicholinium compounds were incubated with [14C] acetylcoenzyme A and any acetylated products were isolated by liquid ion exchange. Only HC-3 and the analogue with three methylene groups between the two phenyl rings, that is, 2,2'-(1,3- propanediyldi -1,4-phenylene)bis[2-hydroxy-4, 4- dimethylmorpholinium ] ( 3CHC ), were found to be significantly acetylated. The acetylation rate of both these two compounds was 28% that of choline. It is concluded that an internitrogen distance of 14 A in bisquaternary nitrogen choline analogues provides the optimum distance for acetylation by ChAc in vitro.

3-Hydroxy-N,N-dimethylpiperidinium: a precursor of a false cholinergic transmitter.

A cyclic choline analogue, 3-hydroxy-N,N-dimethylpiperidinium, has been shown to be transported into a crude preparation of synaptosomes by high and low affinity transport mechanisms. Under conditions favouring the high affinity system the synaptosomes metabolized approximately 50% of the accumulated analogue to 3-acetoxy-N,N-dimethylpiperidinium, which was detected by paper electrophoresis. The phrenic nerve endplate region of a mouse hemidiaphragm accumulated 3-hydroxy-N,N-dimethylpiperidinium on nervous stimulation. This tissue metabolized approximately 60% of the accumulated analogue to the acetylated derivative which was released on nervous stimulation into the bathing medium. Compared to acetylcholine, 3-acetoxy-N,N-dimethylpiperidinium was shown to be 57 times less potent an agonist at the nicotinic receptors of the frog rectus abdominis muscle and 162 times less potent an agonist at the muscarinic receptors of the guinea-pig ileum. It is concluded that 3-hydroxy-N,N-dimethylpiperidinium is a precursor of a false cholinergic transmitter.

Pharmacological actions of some cyclic analogues of choline.

Two cyclic choline analogues (3-hydroxy-N,N- dimethylpiperidinium and 2-hydroxymethyl-N,N- dimethylpiperidinium ) and two cyclic homocholine analogues (4-hydroxy-N,N- dimethylpiperidinium and 3-hydroxymethyl-N,N- dimethylpiperidinium ) have been studied with regard to their actions at the cholinergic synapse. All the analogues had some direct depolarizing activity on the frog rectus abdominis muscle but they were less potent in this respect than acetylcholine. Compared to physostigmine, the analogues were weak inhibitors of cholinesterase enzymes. All the analogues were found to have a presynaptic blocking action on the rat phrenic nerve-hemidiaphragm preparation, which was reversed by choline. In addition, they all inhibited the high affinity transport of choline into synaptosomes but only the cyclic choline analogues were found to be acetylated by soluble choline acetyltransferase in vitro. We conclude that the hydroxypiperidinium analogues caused the presynaptic block seen at the neuromuscular junction by inhibiting acetylcholine synthesis.

The labelling of dispensed medicines for the elderly patient: a pilot survey.

The problems that elderly patients encounter when managing their own drugs were approached from the point of view of the understanding that these patients have of the labels on dispensed medicines. Thirty medically qualified volunteers at Burton District Hospital Centre were used to evaluate the adequacy of the present handwritten, labelling system for elderly out-patients by the use of a questionnaire. Further, by means of structured interviews with thirty elderly out-patients and a discriminating test procedure, the proposed, new, typed, labelling system was compared with two other labelling systems, the ability of the patients to understand the labels determined and the efficiency of the proposed, new system tested. The trends indicated by this pilot survey are that the present system of handwritten labels is inadequate and inefficient. Medical staff may repeatedly go over instructions and patients identify their drugs by means other than the label. Regardless of the quality of the label the regimen for a particular patient often determines the necessity for repeat instructions. Further, the proposed, typed, labelling system was ranked last by staff and patients when compared with two other systems (Ladywell and Thomas). The ability of patients to understand typed labels was very low. A new labelling system based on these trends is proposed.

The Hereford Hospital Prescribing Study. The function of a clinical pharmacist on the medical wards of a district general hospital.

The role of a clinical pharmacist is outlined as interviewing patients on admission, monitoring of 'at risk' patients and drugs, and counselling on discharge. These functions were assessed on a 118 bed medical unit to try to quantify the potential workload and staff requirements needed to achieve it. It is suggested that the establishment of pharmacists for ward pharmacy services may need to be increased two-fold to accomplish the outlined role, and that a 24-hour service would be needed to cover some duties. However, before such a level of staffing can be achieved, the positive benefits of clinical pharmacy must be demonstrated.

The Hereford Hospital Prescribing Study. Investigation of methods to identify patients with adverse drug reactions.

Four investigatory procedures are described for the detection of patients with possible adverse drug reactions. These were evaluated using computer data from the Hereford Hospital Prescribing Study. 120 patients receiving Indomethacin were studied from the total data base of 2,852 admissions during 1977. From this study, two of the methods involving the identification of the discontinuation of drug therapies and the prescribing of 'antidotes' seemed to be the most useful. These methods were also applicable to the routine monitoring of prescription sheets by ward pharmacists.