NSAIDs: time to re-evaluate gut toxicity.
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Aged↗
Biomedical subjects
D N Bateman
Publications and source records attributed to D N Bateman.
The use of nitrates, calcium channel blockers and ACE inhibitors in primary care in the Northern Region: a pharmacoepidemiological study.
1. Prescribing rates for cardiovascular drugs have substantial local variation. The objectives of this study were to determine the prescribing prevalence of nitrates, calcium channel blockers and angiotensin-converting enzyme inhibitors in general practice, to examine the indications recorded for these prescriptions, and to identify which therapeutic areas contribute to the variation in prescribing. 2. Anonymised patient-specific prescription data were taken from computerised records in 41 VAMP research practices in the Northern Region (total population 330,749). All patients who received any prescription for calcium channel blockers, nitrates or angiotensin-converting enzyme (ACE) inhibitors during a 12 month period were included. Prescribing rates were determined in terms of patients per 1,000 population within age, sex and diagnostic groups. 3. Overall, 4.3% of the study population were prescribed one or more of the drugs. There was virtually no prescribing for patients under the age of 35 years, but thereafter the prevalences rose steeply to peak at ages 65-74 years for calcium channel blockers (91 per 1,000 population) and ACE inhibitors (34 per 1,000), and at ages 75-84 years for nitrates (100 per 1,000). Prescribing prevalence amongst the over 85's was less than half the peak rate for each drug group. Rates for men and women were comparable, except for nitrates where men had higher rates. 4. Recorded indication rates for patients with ischaemic heart disease and treated with any of these drugs reached 112 per 1,000 population in the 75-84 age group, and were higher in men than women, at all ages. Hypertension indication rates were substantially higher in women over 65; across the genders the peak rate was 88 per 1,000 for those aged 65-74 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Which patients are prescribed inhaled anti-asthma drugs?
BACKGROUND: Prescribing rates for inhaled anti-asthmatic drugs in the UK vary considerably from area to area and between individual practices. The objectives of this study were to determine the prevalence of patients prescribed inhaled steroids and beta agonist bronchodilators, the indications for these prescriptions, and to relate prescribing to the recorded levels of morbidity for specific respiratory disease. METHODS: Anonymised patient-specific prescription and diagnostic data were extracted from computerised general practice records for the 41 practices in the Northern region (total population 330,749) whose data had been validated for inclusion in a research databank. Patients were included if they were either prescribed an inhaled steroid or bronchodilator during a 12 month period, or had a recorded diagnosis of asthma, bronchitis or chronic obstructive pulmonary disease. Prescribing of inhalers per 1000 population was determined within age, sex, and diagnostic groups. Respiratory diagnosis rates within different patient groups were used to measure the underlying level of morbidity in the population. RESULTS: Inhaled anti-asthma drugs were prescribed for 5% of the study population. Prescribing prevalences peaked at ages 5-14 (steroids 40 per 1000 population; bronchodilators 68 per 1000) and at ages 65-74 (steroids 53 per 1000; bronchodilators 79 per 1000). Prescribing frequency for both drugs increased from two or three items per patient annually at age 0-14 to about six in the over 65 age group. Of the 39,424 respiratory patients 38% received inhalers and 7% only non-inhaler medication. Inhaler therapy was used in only 6% of patients with bronchitis, but in 66% of those with asthma, though the proportions varied with patient age and gender. Study practices differed in their overall levels of both inhaler prescribing and respiratory diagnosis, and had lower prescribing patterns of these drugs than other practices in the Northern region. CONCLUSIONS: Inhaled steroid and bronchodilator prescribing have age-related and gender-related prevalences. Treatment for respiratory diagnoses varies with patient age and gender, and with the diagnosis. Prescribing differences between practices are attributable to variation in both diagnostic rates for respiratory disease and therapeutic intervention patterns. For asthma patients study practices show consensus in approach, perhaps illustrating the value of clear guidelines for asthma prescribing.
Administration, Inhalation↗
Redtide in the Philippines.
1. Redtide is a marine phenomenon that poses great risk to the health and economic livelihood of people in coastal areas. Paralytic shellfish poisoning develops when a person consumes molluscs containing toxic dinoflagellates and suffers neurological and/or gastrointestinal manifestations. 2. Four redtide incidents in the Philippines are presented. The manner in which the problems were managed are described. 3. The clinical features of redtide poisoning in the Philippines included gastro-intestinal and neurological features with deaths secondary to ventilatory failure. Mortality ranged from 0% to 12% in the different redtide episodes. 4. There are many lessons to be learned in handling this kind of natural disaster. For an effective toxicovigilance programme, there must be a central co-ordinating responsible organization, a clear definition of roles and functions and good inter-agency co-operation. Appropriate surveillance procedures, resources to intensify surveillance at times of risks, prompt warning system, and the ability to impose bans on consumption are also necessary. 5. Poisons centres can play an important role during times of redtide. This may include toxicovigilant activities, such as early warning and educational campaigns to consumers, and seminars in the recognition and management of paralytic shellfish poisoning. 6. The contribution of the epidemiologists in investigating and monitoring the extent of public health damage and patterns of poisoning in a coastal community is emphasized.
Animals↗
A survey of intravenous drug administration by preregistration house officers.
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Clinical Competence↗
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.
Administration, Oral↗
Sexual function in women. Do antihypertensive drugs have an impact?
Drug-induced sexual dysfunction is well known to occur with antihypertensive drugs in men. There are much less data on the effects of drugs on female sexual function. The physiology of the female sexual response has similarities to that of the male sexual response and there are therefore good reasons for suspecting that antihypertensive drugs are likely to adversely affect sexual function in women. Present evidence suggests that clonidine, methyldopa, guanethidine and reserpine are associated with adverse effects on sexual function. In healthy volunteers, labetalol appears to reduce vaginal lubrication, but there are no studies in patients receiving the drug therapeutically. Thiazide diuretics may be associated with the worsening of sexual problems, which interestingly appear to be ameliorated by weight reduction. Present evidence on the effects of vasodilators is limited but the evidence suggests that sexual function in women receiving calcium antagonists is not altered by changing to an angiotensin converting enzyme (ACE) inhibitor. Although present evidence suggests that effects on female sexual function may not be very great, it should be recognised that there are very few data in this area. Further work is clearly necessary.
Antihypertensive Agents↗
Amplification of quinine cardiac effects by the resistance-reversing agent prochlorperazine in falciparum malaria.
The use of reversing agents to overcome drug resistance is a potential new treatment strategy for both malaria and cancer. Laboratory studies have raised questions about the safety of this therapeutic approach, but data in humans are lacking. We therefore assessed the toxic potential of reversing agent therapy in Thai patients receiving quinine (17 mg/kg given over 4.5 hr) for falciparum malaria by serial measurements of the QTc interval, an electrocardiographic (ECG) marker of the effect of quinine. Six patients were randomly assigned to receive intravenous quinine alone while another six received one intramuscular injection of 12.5 mg of the reversing agent prochlorperazine (PC; compazine, stemetil) 2.5 hr after the quinine infusion had begun. Compared with baseline values at 2.5 hr, there was prolongation of the QTc interval 30, 60, 90, and 120 min after PC was injected (P < 0.05) but no further lengthening with quinine alone (P > 0.2). Prochlorperazine alone did not lengthen the QTc interval in six healthy volunteers. Neither total nor free quinine plasma levels increased after PC was injected, suggesting that ECG changes may have been due to PC-induced intracellular accumulation of quinine. Although only minor quinine ECG effects were amplified by the reversing agent PC in this study, resistance-reversing therapy could potentiate more serious drug effects. The possibility that more serious toxic effects could be produced by this therapeutic approach should be investigated further.
Electrocardiography↗
More therapeutic conservatism.
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Decision Making↗
Mutant debrisoquine hydroxylation genes in Parkinson's disease.
The frequency of fifteen genotypes of CYP2D6 (debrisoquine 4-hydroxylase) in 53 patients with Parkinson's disease was determined by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses and compared with the findings in 72 healthy controls. The commonest mutant allele, CYP2D6B, was twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.70 (95% confidence interval 1.14-6.41; p = 0.0063) for subjects homozygous or heterozygous for this allele.
Aged↗
The pharmacokinetics and effects of prochlorperazine in elderly female volunteers.
The pharmacokinetics and effects of prochlorperazine (PCZ) have been studied in six healthy elderly female volunteers in a double-blind placebo-controlled study of 3.125 mg intravenous (IV) and 25 mg oral PCZ. The pharmacokinetics of IV PCZ in elderly subjects appear similar to those previously obtained in young subjects, with a terminal half-life of 7.5 +/- 1.8 h after intravenous dosing. Oral bioavailability was low (14.7 +/- 1.5%). The pharmacological actions of prochlorperazine in elderly people appear to include antidopaminergic (prolactin rise) and anticholinergic (reduced salivary flow) effects. At the dose of PCZ used in this study, no significant haemodynamic or psychomotor changes were observed though there was a trend to prolongation of the movement component of the reaction time.
Administration, Oral↗
Pharmacokinetic optimisation of antiemetic therapy.
Antiemetic drugs are used to treat nausea and vomiting due to a variety of causes and have a wide range of pharmacological properties. The choice of drug will, therefore, depend in part on the condition being treated. The drugs can be classified as dopamine antagonists (including phenothiazines and nonphenothiazines), corticosteroids, cannabinoids, benzodiazepines, serotonin antagonists, antihistamines and anticholinergics. There is very little evidence of a relationship between plasma drug concentrations and either their efficacy or the incidence of adverse effects with most antiemetic drugs. With drugs for which concentration-effect studies have been performed, e.g. the benzodiazepines and antihistamines, the effects monitored have not been directly relevant to their use as antiemetics. Antiemetics are used widely, for example, in cancer chemotherapy. Nonetheless, apart from metoclopramide, little work has been done on the influence of indicators of systemic disease on the pharmacokinetics of antiemetic drugs.
Adrenal Cortex Hormones↗
Clinical pharmacology--the European challenge.
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Europe↗
Attitudes to adverse drug reaction reporting in the Northern Region.
1. The attitudes and knowledge of doctors in the Northern Region to reporting of adverse drug reactions were assessed using a postal questionnaire to all doctors in two, previously identified, high reporting and two low reporting health districts. Comparisons were made of the attitudes and knowledge within professional groups (GPs, Consultants and Junior Hospital Doctors), and between the amalgamated doctor groups. 2. 1181 of 1600 doctors (74%) responded. Despite being selected on the basis of previous adverse drug reaction reporting patterns, GPs and consultants from high and low reporting districts perceived they had sent a similar number of ADR reports, and there were few differences in opinion and attitude within these two groups. 3. Most differences within doctor groups were found for junior doctors, with those from low reporting districts indicating they had sent significantly less yellow cards than those in high reporting districts. There were also significant differences in the estimates junior doctors made with a frequency of adverse drug reactions, the existing documentation on adverse drug reactions, and the purposes of the adverse reaction scheme. 4. General Practitioners in low reporting areas stated they wrote more prescriptions (P < 0.02), consultants spent more time in clinical contact (P < 0.01) and junior doctors did both (P < 0.01), all of which suggest different workloads may effect reporting of adverse drug reactions. 5. When given clinical examples, or asked about the CSMs black triangle scheme, all doctor groups performed poorly. 6. The number of reports stated as being sent increased with time from qualification for 10 years, then seemed to plateau.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
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.
Aged↗
Geographical differences in adverse drug reaction reporting rates in the Northern Region.
The reporting rates of adverse drug reactions in the Northern Region have been examined with respect to source (hospital or general practice) and district of origin for the 3 years 1986-88. Mean annual reporting rates, corrected for population, or clinical activity, varied approximately 4-fold in general practice (0.066 to 0.257 reports per 1000 resident population) and more than 12-fold in hospitals (0.14 to 1.77 reports per 1000 deaths and discharges). There was no correlation between hospital and general practice reporting rates in the same health district. Overall more reports were received from general practice (1606) than hospitals (1000), although proportionally more reports of serious adverse reactions originated from hospitals. The reasons for these differences are unclear.
Drug-Related Side Effects and Adverse Reactions↗