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.     

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.     

Patient sources of drug information and attitudes to their provision: a corticosteroid model

Aim: To determine patients' preferred sources of drug information and their attitudes to how this is provided.Design: A quantitative evaluation via personal interviews using a formal questionnaire.Subject and settings: A group of 101 inpatients in a chest ward at the Royal Devon & Exeter Healthcare NHS Trust.Outcome measures: Preferred sources for medication advice; personal involvement in own treatment; adequacy of consultation period; medication compliance; post discharge sources of drug information; recalled benefits and side effects of corticosteroids.Results: Preferred source of drug information was: doctor (35%), pharmacist (11%) and nurse 4%. Sixty percent of patients wanted to be involved in the choice of their medication, thirtynine percent leaving it totally to the doctor and one patient who wanted the final word in what was prescribed. Sufficient discussion time with GPs was reported by 66% of patients (12%, insufficient) and 53% with hospital doctors (19%, insufficient). Noncompliance with medication was reported by 66% and compliance by 24%. Medication advice sources used when at home were; community pharmacists (22%), GPs/books & magazines/specialist societies (all 18%), nurses (10%) and others less than 8%. Benefits of corticosteroids recalled by patients were: 'improving breathing' (14), 'general improvement' (9) and 'improved mobility'/'greater appetite' (both 5) 'with little change' reported by 13. Knowledge of side effects was much more comprehensive with; oedema/weight gain (50), skin/hair problems (33), osteoporosis (33), bruising (12) and mood changes (10) most commonly featured in responses. Almost all patients confirmed they liked to be given printed information about their medication.Conclusion: Patients sought their medication advice from a variety of sources and armed with this almost two thirds of patients wished to exercise their rights to be involved with their treatment planning. Sufficient discussion time appeared to be available to about half of the interviewees though only a few understood the intended benefits of prescribed corticosteroids used as an example in this work. A much better knowledge of drug side effects might have partly explained the high level of declared noncompliance. Although pharmacists featured as the preferred source of drug information for some patients, a much more detailed investigation is needed of patients' attitudes to the profession and to individuals' consultation and communication skills.     

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.     

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.     

Prevention of heterotopic ossification after total hip replacement with NSAIDs

Introduction: non steroidal antiinflammatory drugs ((NSAIDs) and prophylactic radiotherapy can prevent ectopic bone formation around the hip after total hip arthroplasty. Methods: We retrieved from Medline, Embase and the Cochrane Register (clinical)) trials and other relevant literature on the prevention of heterotopic ossification (HO) from 19902002 for further review.Results: Review of these clinical trials shows that HO is effectively prevented by a postoperative NSAID treatment with indomethacin for at least seven days. The best evidence is available for indomethacin, although naproxen, diclofenac and ibuprofen are also well documented. Short term use of ibuprofen is not effective. If NSAIDs are contraindicated, preoperative or postoperative radiotherapy is a very effective therapeutic option to prevent HO. Discussion and conclusion: Because of the potential of serious gastrointestinal side effects of NSAIDs and their interaction with anticoagulant drugs, rofecoxib and other COX2 specific NSAIDs may be a safer option for the treatment of HO. However, randomised controlled studies are needed to confirm the results of the rofecoxib study.     

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.     

The reduction of excitability of the γ-loop by 1,3-dimethyl-5-aminoadamantane (DMAA)

Summary The -loop of pretibial flexor muscles was investigated before and after i.v. injection of 10 mg/kg DMAA in precollicular and prenigral decerebrate cats. DMMA reduces significantly the reflex discharge rate of Ia muscle spindle afferents, a result which might be important in regard of a hyperactive -motor system.Supported by the Deutsche Forschungsgemeinschaft, SFB 33.     

The functional pool of brain catecholamines: Its size and turnover rate

Behavioral data are reviewed that give evidence for an indiscriminate involvement of brain catecholamines (CA), especially dopamine (DA), in nervefunction, regardless of the time elapsed from their synthesis. Critical analysis of biochemical and pharmacological studies shows that a clear-cut distribution of brain catecholamines in two compartments [newly synthesized (NS) and main storage] is not at all established, and moreover that there is no adequate proof that the difference in turnover rates attributed to these two supposed pools is due to a preferential extraneuronal release of NS-CA during nerve function rather than to a preferential (nonfunctional) intraneuronal deamination of NS-CA, or at least of NS-DA.     

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.     

Cotransport of Estradiol and Ethanol Through Human Skin in Vitro: Understanding the Permeant/Enhancer Flux Relationship

The thermodynamic and kinetic limits of ethanol-enhanced estradiol skin transport have been investigated by studying the relationship between estradiol and ethanol steady-state flux in the cotransport of permeant and enhancer in situations in which there exists an enhancer solvent gradient across the skin (asymmetric configuration). For aqueous ethanol solution saturated with estradiol, the flux of estradiol across the human epidermal membrane is empirically observed to be linear with the ethanol flux. A physical model approach has been used to determine the basis of this empirical linearity and to predict permeant/enhancer transport across the skin for the asymmetric configuration. Enhancement factors, determined with a balanced ethanol concentration across the skin (symmetric configurations), are used to predict fluxes in the asymmetric configurations. The model demonstrates that ethanol enhances the stratum corneum transport of estradiol and of itself by increasing the respective diffusion coefficients at lower concentrations (<50%) and by both increasing the diffusion coefficients and decreasing the membrane activity coefficients at moderate concentrations (50 to 75%). The model also demonstrates that the permeant flux, in general, is not linear with the cotransported enhancer flux.     

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     

Rational pharmacotherapy and clinical practice guidelines Theories and perspectives on implementing pharmacotherapeutic treatment guidelines

Several theories behind implementing clinical guidelines have been described within the literature. At first sight, these may seem different. However, there are similarities and eventually they are rather complementary than mutually exclusive. This article integrates several theoretical views on implementation of pharmacotherapeutic treatment guidelines and subsequently addresses some empirical considerations. Furthermore, specific limitations and potential harms of implementating guidelines are addressed. Several checklists are provided in order to make pharmacists, pharmacologists and clinicians aware of perspectives on dissemination, implementation, and subsequent application of pharmacotherapeutic treatment guidelines.