Community pharmacists'' views and beliefs about the treatment of symptoms suggestive of vaginal thrush in community pharmacies

Objective: To investigate the views and beliefs of community pharmacists about the benefits and disadvantages to the customer, pharmacy and pharmacist of treating women with symptoms suggestive of vaginal thrush. Design: Semistructured interviews.Setting: Community pharmacists from within Grampian Primary Care NHS Trust.Outcome Measures: Pharmacists' views and beliefs analysed using content analysis.Results: Of the 26 pharmacists contacted, 19 (73%) pharmacists from 16 pharmacies completed interviews. The pharmacists were generally positive towards the treatment of women with vaginal symptoms and perceived few disadvantages. Immediate access to treatment and rapid symptom relief were perceived to be the greatest advantages to the customer. The main problems were customer embarrassment, cost and the risk of masking a serious condition. Customer embarrassment was perceived to be influenced by lack of privacy and the gender of the member of staff involved in the consultation. Five pharmacists perceived vaginal thrush to be an infection that could be spread by sexual transmission. Discussion: There is a need to make pharmacists aware of the current evidence regarding the treatment of vaginal thrush, particularly that sexual partners of women with acute, uncomplicated thrush do not require treatment with an antifungal. The main difficulties that community pharmacists reported with the treatment of this condition were obtaining an accurate history and this was influenced by customer embarrassment. The gender of pharmacy staff and lack of private consultation facilities were suggested as factors that are associated with customer embarrassment and hence, the ability to obtain an accurate history.     

Clinical and economic impact of a pharmacist‐intervention to promote sequential intravenous to oral clindamycin conversion

A multicentre, prospective, controlled study compared the clinical efficacy, safety and economic impact of a pharmacist intervention to promote sequential intravenous to oral clindamycin conversion. A total of 473 patients receiving intravenous clindamycin for at least 72 hours were included in the study. Two groups were established: an intervention group (204 patients) in which an informative sheet recommending the sequential treatment was provided, and a control group (269 patients). Clindamycin was prescribed for respiratory infections in 38.9% and for prophylaxis in surgery in 25.4% of the patients (71% were contaminated surgery). No difference between groups regarding sex, infection severity, health status or clinical progress was observed. Both the stepdown treatments after 72 hours of intravenous clindamycin and the change to the oral route later on, were significantly increased with the intervention (p<0.001, p<0.001 respectively). No significant differences between both groups were found in the number of patients with adverse effects associated with the IV therapy, although the incidence tended to be lower in the intervention group (49/204 intervention versus 85/269 control, p=0.07). Compliance with the recommended clindamycin dosing regimen was significantly higher in the intervention group, in which 1.3 days reduction of intravenous therapy provided an average cost savings of PTA5246 (95%CI 25567935) per treatment. A higher reduction of 1.7 days was achieved in those patients candidates for switch therapy on the third day of intravenous clindamycin. A sequential program with clindamycin may provide a costeffective alternative to conventional therapy and the introduction of an information sheet is a costeffective strategy to promote it.     

Experience with a recently introduced drug information service in an Israeli hospital pharmacy

In July 1996, the Pharmacy Department of the Barzilai Medical Center in Ashkelon, Israel, initiated a prospective study aimed at justifying and evaluating the drug information service provided by the pharmacy team to the medical staff. The information is provided via telephone, with written consultations or bibliographies provided on request. All telephone queries and responses are computer recorded, so that the responses to requests can be evaluated. A standard form was prepared to evaluate this service. A total of 293 consultations took place during a oneyear period, yielding 528 different questions. The questions were received from different departments, including internal diseases (32.4%), surgery (31.2%), pediatrics (16.7%), obstetrics (10.9%), and psychiatry, oncology and hematology (together 6.8%). The pharmacy team provided this service to physicians and surgeons(51.2%), nurses (41.9%), and other medical professionals (6.9%). The types of drugs most frequently inquired about were antiinfectives, antihypertensives,TPN & infusion preparations and anticoagulant drugs. Requested data included information regarding administration/dosage (34.1%), indications (14.6%), and interactions (13.9%), with very few questions about the availability of products (4.7%), equivalency (2.1%) and cost (1.5%). The time devoted to this service justified an additional quartertime employee. This study proved to be a quality assurance tool in the assessment of the educational and functional requirements of the hospital's medical health team.     

Para‐methylthioamphetamine, a new amphetamine designer drug of abuse

A case study is described of a patient who was intoxicated after the intake of socalled herbal stimulants. A visit to a physician after the intoxication prompted to this investigation and the case was examined for its direct cause. An interview with the patient revealed that the source of the herbal stimulants was a socalled 'S5 tablet'. Information provided on the packings of the tablet only indicated the presence of natural alkaloids and vitamines. Toxicological analysis however proved that the 'S5 tablet' contained paramethylthioamphetamine (MTA), mainly. MTA is a relative unknown amphetamine designer drug, which has only been studied as a model compound in some structureactivity relationship studies. The fact that MTA appeared in tablets was therefore completely unexpected. Not only the potential abuse of this new amphetamine designer drug is a serious matter of concern, but also the misleading information provided with the tablet.     

Failure of “antigastrin” (SC-15 396) to inhibit gastric acid and pepsin secretion in anaesthetized gastric fistula cats

Summary 1. The effect of antigastrin (SC-15 396) on gastric acid and pepsin secretion produced by the gastrin-analogue tetrapeptide amide Try. Met. Asp. Phe-NH₂ and by electrical stimulation of the vagus was investigated in anaesthetized gastric fistula cats.2. Antigastrin failed to inhibit both acid and pepsin response stimulated by either the tetrapeptide or vagus excitation.3. It was concluded that the ineffectiveness of antigastrin in cats is due to a species difference between rats and dogs on the one hand and cats on the other, and that antigastrin is not a specific gastrin antagonist.Supported by the Deutsche Forschungsgemeinschaft and by the Alfred Teufel-Stiftung.     

Validity of questions in the use of specific drug-groups in health surveys

Objective: The aim of this study was to investigate whether morbidity in the general population could be assessed by questions on drug use in the Norwegian Health Survey 1995. Material and method: A sample of 6,702 persons, aged 2079 years was interviewed in their homes using computerassisted personal interviewing (CAPI).Mean outcome measure: The validity of questions on use of analgesics and drugs against dyspepsia/peptic ulcer has been assessed according to categories of selfevaluated health. Results: There was a difference between sporadic and daily users of the drugs to what extent they rated their health as poor. The validity of the drug questions assessed by sensitivity and specificity, showed that only using a dichotomous outcome variable, is too low to give a sufficiently valid measure of the morbidity in the population. Conclusions: Using "yes" or "no" as the only outcome of drug questions has the unfortunate effect of putting together chronic users of drugs with infrequent users for all of the subsequent analyses, which results in a considerable measurement error. This implies a need for improved methods to determine the optimal recall period for different drugs and it is crucial to include more details in questions on drug use to increase the validity of this information.     

Vasopressin stimulates release of β-lipotropin and β-endorphin in conscious rats as measured by radioimmunoassay of unextracted plasma

Summary Using a newly developed radioimmunoassay to determine the -endorphin-like immunoreactivity (-EI) in unextracted plasma, the effect of vasopressin injections on plasma -EI was investigated in conscious rats. Arginine vasopressin caused a dose-dependent increase of plasma -EI from 34.5±7.8 fmol ml^–1 (n=6) in vehicle-treated animals to 205.0±36.1 fmol ml^–1 (n=7) after injection of the highest vasopressin dose employed (486 ng/100 g b.w.). In view of the appreciable cross-reactivity of -lipotropin (-LPH) in the radioimmunoassay used, plasma was extracted and subjected to gel chromatography on a Sephadex G-50 column. On average, about 70% of the -EI co-eluted with human -LPH and about 30% with human -endorphin in plasma extracts obtained from both control and vasopressin-treated rats. No peripheral conversion of human -LPH occurred under the experimental conditions, since after i.v. bolus injection of human -LPH 97% of the -EI comigrated with human -LPH during gel filtration. A similar blood pressure increase to that induced by the vasopressin injections, when elicited by noradrenaline or angiotensin II i.v., was not followed by an elevation of plasma -EI.These data indicate that vasopressin stimulates -lipotropin and -endorphin release into the systemic circulation in vivo.     

Pharmacoeconomics and therapeutic drug monitoring.

The ever increasing rate of inflation and the reality that resources for medical care are limited has led to significant changes in the reimbursement for health care services. These influences have convinced health care policy makers to closely evaluate innovative health services in terms of the benefits and costs. New pharmaceutical services must be economically justified in order to exist in the future. This is crucial to the expansion and adoption of pharmaceutical services.Application of economic evaluations is not new to the health care sector. Until recently, there were no incentives to transfer this interest into widespread use. As health care expenditures have escalated over the past two decades, the number of applications of these techniques has increased. Especially significant are costbenefit and costeffectiveness evaluations of medical practice, pharmaceuticals, and other health care technologies.Pharmacoeconomic analysis is an important tool to assist in the evaluation of new pharmaceutical services and technologies. Essentially, economic analytical methods are used to weigh the positive and negative consequences of alternative courses of action. The usefulness of pharmacoeconomic analyses is in resource allocation, with the purpose of achieving the highest return on investment or accomplishing a given objective in the least costly manner. Unfortunately, very few pharmacy programs have been evaluated using pharmacoeconomic techniques. The purpose of this article is to present various methods to assess the economic value of therapeutic drug monitoring services in society and for specific patient populations. Additionally, this article will review the previous attempts and various issues surrounding the economic justification of therapeutic drug monitoring.     

Diminished effect of sympathetic nerve stimulation in cats pretreated with 5-hydroxydopa; formation and liberation of false adrenergic transmitters

Summary Pretreatment of cats with 5-hydroxydopa (3×200 mg/kg i.p., given over a period of 28 hours) resulted in a marked depletion of norepinephrine in sympathetically innervated organs (heart 5%, spleen 3%, iris 16% and nictitating membrane 12% of controls) and in a greatly diminished response of the spleen and nictitating membrane to sympathetic nerve stimulation. The decreased contractile response of the isolated perfused spleen was accompanied by a corresponding diminution of the norepinephrine output. The effect of intravenously injected norepinephrine on the blood pressure and nictitating membrane did not differ significantly from that of untreated controls.The chromatographic analysis of amines present in the spleen and heart after administration of 5-hydroxydopa and [³H]5-hydroxydopamine revealed the accumulation of 5-hydroxydopamine, of two not yet definitely identified -hydroxylated metabolites (most probably the -hydroxylated derivatives of 5-hydroxydopamine and of one of its O-methylated metabolites) and three O-methylated derivatives chromatographically identified as 4-methoxy-3,5-dihydroxyphenethylamine, 3-methoxy-4,5-dihydroxyphenethylamine and 3,4-dimethoxy-5-hydroxyphenethylamine. 5-Hydroxydopamine, its two -hydroxylated and its two monomethoxylated metabolites were liberated as sympathetic transmitters. Their direct sympathomimetic effect (the -hydroxylated derivatives were not available as references) on the nictitating membrane and spleen was 300–10000 times weaker than that of norepinephrine. It is concluded that the diminished contractile response of the nictitating membrane and spleen to sympathetic nerve stimulation results from a reduction of the physiological transmitter available for liberation and its replacement by less potent transmitter substances.Preliminary results of this report have been communicated to the German Pharmacological Society in Mainz at the Spring Meeting 1967.     

Nasal Absorption Enhancement of 17β-Estradiol by Dimethyl-β-Cyclodextrin in Rabbits and Rats

A new formulation for nasal administration containing 17-estradiol (E₂) with dimethyl--cyclodextrin (DMC) as a solubilizer and absorption enhancer is described. Nasal administration of this E₂-DMC formulation gave a significantly higher E₂ absorption than an E₂ suspension in both rabbits and rats. Relative to an intravenous injection of the E₂-DMC formulation, absolute bioavailabilities of 94.6 and 67.2% were calculated for the nasal E₂-DMC formulation in rabbits and rats, respectively. Differences in bioavailability may have resulted from differences in experimental animal conditions. The effects on human nasal ciliary activity of the E₂-DMC formulation were studied with an in vitro method. The formulation was found to exert only a minor effect on ciliary beat frequency. Thus, nasal delivery of E₂, using a cyclodextrin inclusion formulation, may have potential for clinical application, e.g., in the therapy of postmenopausal disorders.     

“A” esterases and their role in regulating the toxicity of organophosphates

Esterases which can hydrolyse organophosphates without being inhibited by them are termed A esterases. Using paraoxon and pirimiphos-methyl oxon as substrates, high A esterase activity is found in the liver and plasma or serum of a range of mammalian species. In a study of serum A esterases of sheep and humans, over 80% of the activity separated into the high density lipoprotein (HDL) fraction following ultracentrifugation. When HDL fractions from sheep serum were run on Sepharose gel columns, most of the paraoxonase activity separated as a single peak of estimated molecular weight 360000, which corresponds to that of HDL₂ of humans.During the course of purification of A esterases by three different column procedures, contrasting esterase elution profiles were obtained with organophosphate and pyrethroid substrates. This was strong evidence for the existence of multiple forms of HDL A esterases.Levels of A esterase activity in plasma and liver of birds were much lower than those of mammals. This appears to be the main reason why birds are much more susceptible than mammals to organophosphates such as pirimiphos-methyl and diazinon which form active oxons that are good substrates for mammalian A esterases.No A esterase was detected in strains of rust red flour beetle (Tribolium castaneum) which were resistant to organophosphates. Similar observations have been made with strains of other insects resistant to organophosphates, raising the question to what extent esterases of this type are present in insects.Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthday     

Differences between full and partial α-adrenoceptor agonists in eliciting phasic and tonic types of responses in the longitudinal smooth muscle of the rat portal vein

Summary The aim of the present investigation was to study, taking into account both quantitative and qualitative differences, the influence of full and partial -adrenoceptor agonists on spontaneous myogenic activity in the rat portal vein.We found that the -adrenoceptor agonists cirazoline, adrenaline, noradrenaline, phenylephrine, St 587, Sgd 101/75, B-HT 920 and UK-14,304 could increase the amplitude of the phasic myogenic contractions in the rat portal vein with apparent differences in EC₅₀ and E_max values. In addition to an increase in phasic myogenic activity, the -adrenoceptor agonists cirazoline, adrenaline, noradrenaline, and phenylephrine were also able (in higher concentrations) to increase the basal tone of the rat portal vein preparation, again with apparent differences in EC₅₀ and E_max values. Changing the extracellular Ca²⁺ concentration from 0.9 mmol/l to 2.5 mmol/1 had no influence on the phasic character and the concentration range in which St 587 and UK-14,304 increased spontaneous myogenic activity, although changes in amplitude and frequency of the spontaneous myogenic contractions were less pronounced at a higher extracellular Ca²⁺ concentration (2.5 mmol/1). By the use of Schild analysis with the competitive a-adrenoceptor antagonists prazosin (pA₂ = 8.74) and 5-methyl-urapidil (pA₂ = 8.37), it was established that the contractile responses to St 587 were mediated by the same ₁-adrenoceptor subtype as the phasic and tonic type of contraction elicited by phenylephrine as described in a previous study. The concentration-response curve of UK-14,304 was significantly shifted to the right by low concentrations of prazosin (3 nmol/1–30 nmol/1), indicating stimulation of ₁-adrenoceptors by UK-14,304 in the rat portal vein. The -adrenoceptor antagonists phenoxybenzamine and chloroethylclonidine irreversibly blocked the contractile responses to St 587. Based on the method of receptor alkylation with phenoxybenzamine an affinity constant was calculated for St 587 (pK_a = 5.91). Phenoxybenzamine was approximately 1000-fold more potent in inactivating ₁-adrenoceptors than chloroethylclonidine.In conclusion there appeared to be a divergence in the excitation-contraction coupling of ₁-adrenoceptors in the rat portal vein, which is reflected by two types of contraction (phasic versus tonic). The extent to which both the phasic and tonic types of contraction are stimulated by agonists depends on the affinity and intrinsic efficacy for each of the receptor-coupled effector pathways. Thus, partial and full agonism can only meaningfully be discussed if confined to one particular effector pathway. Send offprint requests to H. R. Schwietert at the above address     

Elevated plasma levels of clozapine after concomitant use of fluvoxamine

Selective serotonin reuptake inhibitors can be added to clozapine therapy in order to treat remaining negative symptoms and obsessive compulsive symptoms. The present case report describes a 44yearold man exhibiting extremely elevated plasma levels of clozapine after the addition of fluvoxamine, up to 4160 mcg/l. The elevated plasma levels of clozapine, which were discovered 6 months after the SSRI was added, is likely to be caused by a drugdrug interaction. Clozapine is a substrate of CYP 1A2 and is predominantly metabolised in the liver. Of the SSRIs, fluvoxamine is one of the most potent inhibitors of the isoenzyme CYP 1A2. This case serves to emphasise the need for continuous attention to drugdrug interactions, especially when they might be easily overlooked due to the lack of clear symptoms.     

A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Theoretical implications for potency differences among neuroleptics

In a double-blind, cross-over study, the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics — haloperidol and chlorpromazine — and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics. Periodic measurements were made for 32 dimensions of psychopathology, social participation, span of attention, sleeplessness, pulse rate and neurological side effects. The results showed that haloperidol was generally a more effective drug over the period studied. This was particularly apparent in terms of social and emotional responsiveness, communicativeness and cognitive processes. The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol. Haloperidol also proved to be more rapid in its action. The data failed to support the clinical validity of the distinction often made between sedative and activating neuroleptics. Consistent with previous reports, benztropine had the effect of diminishing therapeutic response to both neuroleptics. However, haloperidol again proved less susceptible to this effect. The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anticholinergic properties acting in opposition to its antipsychotic activity. The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics. It was suggested that one of the factors determining potency differences among neuroleptics may be the degree of built-in anticholinergic activity.     

The quality of Dutch hospital drug formularies: Evaluation of technical features and organisational information

Introduction: Hospital drug formularies (HDFs) are widely used tools to help influence clinicians' prescribing behaviour. Besides the therapeutic quality of HDFs, the available information and the way in which this is presented are key factors in HDFs' success or failure to influence prescribing behaviour and enhance prescribing quality. This research evaluates the technical features and organisational information of Dutch HDFs. Methods: Seventytwo (75%) of all Dutch HDFs were evaluated based on criteria retrieved from international literature and additional criteria drafted by occupational groups working with HDFs. Aspects that were studied were physical appearance and layout, practicability with respect to the available information and how easily this could be retrieved from the HDFs, information regarding drug choice policies such as seamless care, and the available type of therapeutic and pharmaceutical information. Results: Thirtythree (46%) of the HDFs were less than 3 years old. Physical appearance of all HDFs was very well looked after. Two (3%) HDFs were diseaseoriented rather than drugoriented. Changes from preadmission therapy were addressed in 30 (42%) of the HDFs, but other seamless care policies were addressed in less than 20% of the HDFs. Finally, less than 50% provided therapeutic information that clinicians indicated as important. Discussion: Although Dutch HDFs are technically practicable with respect to userconvenience, practiceoriented features are capable of improvements. Furthermore, Dutch HDFs lack important clinical information for daily practice. To enhance seamless care across healthcare, generic prescribing and prescribing on admission from and discharge to any other sectors should be addressed more specifically.     

Continuous infusion of chemotherapy: focus on 5‐fluorouracil and fluorodeoxyuridine.

Continuous infusion of chemotherapy is one of the developments to try to improve the treatment of metastic cancer. There is a sound theoretical rationale to deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of reliable venous access devices and portable infusion pumps enables patients to be treated in an ambulatory setting. This review focuses on the continuous infusion of the most frequently used drugs: 5fluorouracil (5FU) and fluorodeoxyuridine (FUDR). An overview is given of both preclinical studies and studies in humans. Continuous infusion of 5FU and FUDR has proven to be feasible in all studies. However, the results (response rate and especially survival) are rather disappointing. So far, continuous infusion of cytostatic drugs can stil be considered as an experimental procedure. Whether protracted, intermittent or circadian modulated continuous infusion is the optimal treatment schedule has still to be proven in future studies. Furthermore, studies are needed to demonstrate whether dose intensity for most tumours is important for treatment outcome. Also, studies are needed to investigate quality of life and economic issues.