Marked increase in proton pump inhibitors use in Australia

Objectives: To examine the trends in the prescribing of subsidised proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), in the Australian population from 1995 to 2006 to encourage discussion regarding appropriate clinical use. PPIs and H2RAs are the second highest drug cost to the publicly subsidised Pharmaceutical Benefits Scheme (PBS). Design: Government data on numbers of subsidised scripts, quantity and doses for PPIs and H2RAs were analysed by gender and age, dose and indication. Main outcome measure: Drug utilisation as DDD [defined daily dose]/1000 population/day. Results: The use of combined PPIs increased by 1318%. Utilisation increased substantially after the relaxation of the subsidised indications for PPIs in 2001. Omeprazole had the largest market share but was substituted by its S-enantiomer esomeprazole after its introduction in 2002. There was considerable use in the elderly with the peak use being in those aged 80 years and over. The utilisation of H2RAs declined 72% over 12 years. Conclusions: PPI use has increased substantially, not only due to substitution of H2RAs but to expansion in the overall market. Utilisation does not appear to be commensurate with prevalence of gastro-oesophageal reflux disease (GORD) nor with prescribing guidelines for PPIs, with significant financial costs to patients and PBS. This study encourages clinical discussion regarding quality use of these medicines. © 2010 John Wiley & Sons, Ltd.

Helicobacter pylori: resistance and treatment results in Finland

Background: Helicobacter pylori infection is usually acquired in early childhood and is rarely resolved spontaneously. Eradication therapy is currently recommended virtually to all patients. While the first and second therapies are prescribed without knowing the antibiotic resistance of the bacteria, it is important to know the primary resistance in the population. Aim: This study evaluates the primary resistance of H. pylori among patients in primary health care throughout Finland, the efficacy of three eradication regimens, the symptomatic response to successful therapy, and the effect of smoking on gastric histology and humoral response in H. pylori-positive patients. Patients and methods: A total of 23 endoscopy referral centres located throughout Finland recruited 342 adult patients with positive rapid urease test results, who were referred to upper gastrointestinal endoscopy from primary health care. Gastric histology, H. pylori resistance and H. pylori serology were evaluated. The patients were randomized to receive a seven-day regimen, comprising 1) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d. (LAM), 2) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) or 3) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d. and tetracycline 500 mg q.d. (RMT). The eradication results were assessed, using the 13C-urea breath test 4 weeks after therapy. The patients completed a symptom questionnaire before and a year after the therapy. Results: Primary resistance of H. pylori to metronidazole was 48% among women and 25% among men. In women, metronidazole resistance correlated with previous use of antibiotics for gynaecologic infections and alcohol consumption. Resistance rate to clarithromycin was only 2%. Intention-to-treat cure rates of LAM, LAC, and RMT were 78%, 91% and 81%. While in metronidazole-sensitive cases the cure rates with LAM, LAC and RMT were similar, in metronidazole resistance LAM and RMT were inferior to LAC (53%, 67% and 84%). Previous antibiotic therapies reduced the efficacy of LAC, to the level of RMT. Dyspeptic symptoms in the Gastrointestinal Symptoms Rating Scale (GSRS) were decreased by 30.5%. In logistic regression analysis, duodenal ulcer, gastric antral neutrophilic inflammation and age from 50 to 59 years independently predicted greater decrease in dyspeptic symptoms. In the gastric body, smokers had milder inflammation and less atrophy and in the antrum denser H. pylori load. Smokers also had lower IgG antibody titres against H. pylori and a smaller proportional decrease in antibodies after successful eradication. Smoking tripled the risk of duodenal ulcers. Conclusions: in Finland H. pylori resistance to clarithromycin is low, but metronidazole resistance among women is high making metronidazole-based therapies unfavourable. Thus, LAC is the best choice for first-line eradication therapy. The effect of eradication on dyspeptic symptoms was only modest. Smoking slows the progression of atrophy in the gastric body.

Potenciais interações medicamentosas com dano grave e sua relação com o aprazamento estabelecido por enfermeiros

Trata-se de estudo multicêntrico, com revisão retrospectiva de prontuário, que teve como objeto a associação entre o aprazamento de medicações intravenosas realizadas por enfermeiros e as potenciais interações medicamentosas (PIM) graves, encontradas em prescrições de pacientes críticos adultos hospitalizados. Os objetivos foram: a) apresentar os grupos medicamentosos e medicamentos prevalentes em cada Unidade de Tratamento Intensivo (UTI) pesquisada; b) descrever o perfil do aprazamento dos medicamentos intravenosos em cada UTI pesquisada; e, c) analisar a frequência das potenciais interações medicamentosas graves favorecidas pelo aprazamento feito por enfermeiros. Para coleta de dados foi utilizado um instrumento que contemplou o nome do medicamento, a dose, a via, a frequência de administração e os horários aprazados pelo enfermeiro, dando origem a um imenso banco de dados. Os dados foram coletados em 3 UTIs conveniadas ao SUS e pertencentes à Rede Sentinela. O levantamento das PIM foi feito de prescrição a prescrição, pareando-se todos os medicamentos intravenosos conforme critérios de inclusão, obtendo-se assim uma lista com as interações encontradas. As PIM foram identificadas nas bases Micromedex Drugs-Reax System.12 e Drugs.com. Foi encontrada uma chance quase três vezes maior (OR: 2,96) de PIM em prescrições com mais de 5 medicamentos. Às 6h foi encontrada nas UTIs A e B a maior chance de PIM. Na UTI C não foi encontrada prevalência nem OR significativa, assim como o número de doses comprometidas com PIM foi o menor entre todas as UTIs. Houve predomínio de medicamentos que atuam no sistema digestivo (31,99%), com destaque para ranitidina (44,08%). As UTI A e B seguem um mesmo padrão no que diz respeito a acumular o aprazamento, preferencialmente em quatro horários: 14h, 18h, 22h e 6h. A UTI C distribui seu aprazamento por nove horários, inclusive no horário de visitas (16h) e no início de plantão (08h e 20h). Na UTI A e B predominaram aprazamentos noturnos; na UTI C foram tarde e noite, sugerindo uma rotina organizada de acordo com o processo de trabalho de médicos, enfermagem e farmácia. Foram encontrados 47 PIM graves nos horários prevalentes. A UTI A apresentou o maior número de PIM graves (n=32). Destacam-se cinco medicamentos que, repetidamente, foram aprazados associados em PIM grave: haloperidol, metoclopramida, tramadol, furosemida e prometazina. Conclui-se que a rotina de atividades na UTI favorece o aprazamento padronizado e concentrado em poucos horários, logo a ocorrência de PIM graves, desconsiderando assim os aspectos farmacocinéticos e farmacodinâmicos dos medicamentos em uso concomitante.

A psychophysical investigation of binary bitter-compound interactions

The aim of this study was to determine if taste interactions occur when bitter stimuli are mixed. Eight bitter stimuli were employed: denatonium benzoate (DB), quinine-HCl (QHCl), sucrose octaacetate (SOA), urea, L-tryptophan (L-trp), L-phenylalanine (L-phe), ranitidine-HCl, and Tetralone. The first experiment constructed individual psychophysical curves for each subject (n = 19) for each compound to account for individual differences in sensitivities when presenting bitter compounds in experiment 2. Correlation analysis revealed two groupings of bitter compounds at low intensity (1, L-trp, L-phe, and ranitidine; 2, SOA and QHCl), but the correlations within each group decreased as the perceived intensity increased. In experiment 2, intensity ratings and two-alternative forced-choice discrimination tasks showed that bitter compounds generally combine additively in mixture and do not show interactions with a few specific exceptions. The methods employed detected synergy among sweeteners, but could not detect synergy among these eight bitter compounds. In general, the perceived bitterness of these binary bitter-compound mixtures was an additive function of the total bitter-inducing stimuli in the mouth.

Modifying the bitterness of selected oral pharmaceuticals with cation and anion series of salts

Purpose. NaCl has proven to be an effective bitterness inhibitor, but the reason remains unclear. The purpose of this study was to examine the influence of a variety of cations and anions on the bitterness of selected oral pharmaceuticals and bitter taste stimuli: pseudoephedrine, ranitidine, acetaminophen, quinine, and urea.
Method. Human psychophysical taste evaluation using a whole mouth exposure procedure was used.
Results. The cations (all associated with the acetate anion) inhibited bitterness when mixed with pharmaceutical solutions to varying degrees. The sodium cation significantly (P < 0.003) inhibited bitterness of the pharmaceuticals more than the other cations. The anions (all associated with the sodium cation) also inhibited bitterness to varying degrees. With the exception of salicylate, the glutamate and adenosine monophosphate anions significantly (P < 0.001) inhibited bitterness of the pharmaceuticals more than the other anions. Also, there were several specific inhibitory interactions between ammonium, sodium and salicylate and certain pharmaceuticals.
Conclusions. We conclude that sodium was the most successful cation and glutamate and AMP were the most successful anions at inhibiting bitterness. Structure forming and breaking properties of ions, as predicted by the Hofmeister series, and other physical-chemical ion properties failed to significantly predict bitterness inhibition.

Efeitos da cimetidina na resposta cronotrópica ao teste cardiopulmonar

Introdução: A histamina exerce vários efeitos no desempenho cardíaco em humanos, os quais são mediados por receptores H1e H2. A ocorrência de bradicardia e distúrbio da condução atrioventricular tem sido descrita após a injeção intravenosa de cimetidina ou ranitidina, porém ainda não foi avaliado seu potencial efeito na resposta cronotrópica ao exercício com suas implicações sobre o valor prognóstico e diagnóstico do teste de esforço Objetivo: Testar a hipótese, através de ensaio clinico randomizado, de que a administração de cimetidina altera a resposta cronotrópica ao exercício. Material e Métodos: Foram submetidos a dois testes cardiopulmonares, 20 indivíduos, após uso de placebo e de cimetidina. Os testes foram realizados em esteira rolante, com protocolo de rampa com analises diretas dos gases expirados. Foi avaliada freqüência cardíaca máxima atingida, além da freqüência cardíaca de repouso e no limiar anaeróbio. Resultados: Os indivíduos estudados estavam igualmente distribuídos por sexo, com idade média (± desvio padrão) de 43 ±11 anos. Os exames com placebo e com cimetidina tiveram igual duração (578 ± 90 seg vs 603 ± 131 seg) e igual VO2 pico (35 ± 8 ml/Kg.min vs 35 ± 8 ml/Kg.min). A administração de cimetidina não apresentou efeito significativo na freqüência cardíaca de repouso (75 ± 10 vs 74 ± 8 bpm), no pico do esforço (176 ± 12 vs176±11 bpm) e, da mesma forma, também não houve diferença entre as freqüências cardíacas de pico e de repouso (101 ± 14 vs101 ± 13 bpm). Conclusão: A administração de cimetidina por sete dias não altera a resposta cronotrópica ao exercício.

Involvement of nitric oxide in the gastroprotective effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen, Amaranthaceae, in rats

The plants belonging to Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at 4 degreesC), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20 mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1)) p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able to protect the gastric mucosa against IND-induced ulcers. When injected into the duodenal lumen, the AEP reduced total acidity and both basal and histamine-stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion from AEP-treated animals exhibited increased concentrations of nitrite and nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both the reduction of total acidity and the increase in NO, levels promoted by AEP treatment. In conclusion, AEP effectively protected the gastric mucosa and inhibited gastric acid secretion in rats, probably by involving the histaminergic pathway and an enhanced production of nitric oxide in the stomach. (C) 2003 Elsevier B.V. All rights reserved.

Efeitos colaterais da ranitidina aplicada em dose terapêutica em cães saudáveis

O objetivo deste trabalho foi verificar se a dose de ranitidina 2mg kg-1, aplicada via intravenosa, causa êmese ou hipotensão em cães saudáveis. Foram selecionados 10 cães da raça Retriever do Labrador, 10 da raça Beagle e 10 cães sem raça definida, sendo cinco animais de cada sexo. Os animais foram submetidos ao exame clínico e à avaliação da pressão sanguínea antes da aplicação do fármaco e também 10 minutos e quatro horas após a administração deste. Após a aplicação, observou-se que 13,3% dos animais apresentaram-se normais; 6,7% dos cães apresentaram apatia; 50% dos animais apresentaram salivação e 30% apresentaram apatia, salivação, mímica de vômito ou êmese. Não houve diminuição significativa da pressão arterial após a administração do fármaco. Conclui-se que o uso de ranitidina na dose terapêutica, aplicada via intravenosa, pode provocar apatia, salivação, mímica de vômito e êmese.

Takayasu's arteritis: What should the dentist know?

Takayasu's arteritis is a chronic inflammatory disease that affects large blood vessels, especially the aorta and/or its major branches. The condition presents with segmental lesions adjacent to normal, apparently unaffected, areas. The lesions include stenosis, occlusion, dilatations or aneurysm formations along the path of the affected artery. Because of the severity of the disease and the possibility of cardiovascular complications, patients with Takayasu's arteritis require medical treatment based on immunosuppressive and antihypertensive drugs, as well as regular follow up and surgical intervention in many instances. The aim of this paper was to describe the characteristics of Takayasu's arteritis, to report dental treatment carried out on an affected patient, and to discuss the main implications and care required during routine treatment for children in the dental office. © 2005 BSPD and IAPD.

Toxicidade de fármacos nitrofurânicos

During the structural designing of new drugs, it is possible predict the influence of specific chemical groups on pharmacological activity. Among these, the nitro group has potential antiparasitic activity, being present in many antimicrobial drugs, such as metronidazole, nitrofurazone, furazolidone, oxamniquine and chloramphenicol. Also, the introduction of the nitro group into a molecule can modify the physicochemical and electronic properties of the substance. Besides antimicrobial drugs, this group is also found in other drug classes, such as antiulcer, anti-inflamatory and anxiolytic. However, the use of the nitro group in drug design has encountered restrictions, due to the associated toxicity. This article is a review of the toxicity of nitrofuran compounds, as well the possible mechanisms involved and the strategy of latentiation by molecular modification to decrease their toxicity.

Anestesia para colecistectomía videolaparoscópica en paciente portador de enfermedad de Steinert. Relato de caso y revisiõn de la literatura

BACKGROUND AND OBJECTIVES: Myotonic dystrophies are autosomal dominant neuromuscular diseases. Among them, myotonic dystrophy type 1 (MD1), or Steinert disease, is the most common in adults, and besides muscular involvement it also has important systemic manifestations. Myotonic dystrophy type 1 poses a challenge to the anesthesiologist. Those patients are more sensitive to anesthetics and prone to cardiac and pulmonary complications. Besides, the possibility of developing malignant hyperthermia and myotonic episodes is also present. CASE REPORT: This is a 39-year old patient with DM1 who underwent general anesthesia for videolaparoscopic cholecystectomy. Total intravenous anesthesia with propofol, remifentanil, and rocuronium was the technique chosen. Intercurrences were not observed in the 90-minute surgical procedure, but after extubation, the patient developed respiratory failure and myotonia, which made tracheal intubation impossible. A laryngeal mask was used, allowing adequate oxygenation, and mechanical ventilation was maintained until full recovery of the respiratory function. The patient did not develop further complications. CONCLUSIONS: Myotonic dystrophy type 1 presents several particularities to the anesthesiologist. Detailed knowledge of its systemic involvement along with the differentiated action of anesthetic drugs in those patients will provide safer anesthetic-surgical procedure.

Acesso a medicamentos essenciais em farmácias e drogarias do Município de Araraquara

A survey to determine the availability of 20 essential medicines for the diseases with highest prevalence in primary health care was conducted in the city of Araraquara. The presence and the price of these medicines in private sector pharmacies and drugstores of the city were recorded. Two forms, recommended by the WHO, were used in the survey, one for availability and the other for prices. The drugs most commonly available in pharmacies and drugstores were: propranolol (90.5%), captopril (96%) and ranitidine (96%), while the least available were ferrous sulfate (27%), beclomethasone (33.8%) and ibuprofen (41.9%). The drugs that showed the greatest variation among the prices charged were: propranolol (97.1%), hydrochlorothiazide (96.4%) and glibenclamide (95.0%), while the least variable were salbutamol (30.8%) and trimethoprim-sulfamethoxazole (30.2%). Generic drugs, which were half (10) of those assessed, had the lowest prices. The indicators of access, referring to the ability of patients to acquire drugs for the treatment of major diseases at the primary health care level, showed that no establishment stocked all 20 essential drugs and that wide variations existed in their prices, undermining their availability to drug users, whose only sources are pharmacies and drugstores. These data demonstrate the importance of the popular pharmacy to improve the access to medicines, by lowering the cost and increasing the availability of the items selected for the National List of Essential Drugs (RENAME).

Development and application of a highly selective biomimetic sensor for detection of captopril, an important ally in hypertension control

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Thermal behavior of some antihistamines

Thermogravimetry (TG), differential scanning calorimetry (DSC), polarized light thermal microscopy (PLTM), as well as X-ray powder diffraction (XRD) and Fourier transformed infrared spectroscopy (FTIR) were used to study the thermal behavior and the chemical structure of cimetidine, famotidine, ranitidine-HCl, and nizatidine. The TG-DSC curves show that the famotidine and ranitidine-HCl suffer decomposition during melting and they are thermally less stable in comparison with cimetidine and nizatidine, the latter being the most stable of all the drugs studied in this study. The DSC curves of famotidine and ranitidine-HCl show exothermic peaks immediately after the melting, confirming the occurrence of thermal decomposition. The DSC curves also show that the cimetidine and nizatidine have some thermal stability after melting. The thermal events shown in the PLTM images are consistent with the results shown in the TG-DSC and DSC curves. The XRD patterns show that the cimetidine and famotidine are less crystalline compared with ranitidine-HCl and nizatidine. The theoretical FTIR bands are in agreement with those obtained experimentally, and in some cases, no difference is observed between the theoretical and experimental values, even being identical in one of the cases. © 2012 Akadémiai Kiadó, Budapest, Hungary.

A role for histamine in cardiovascular regulation in late stage embryos of the red-footed tortoise, Chelonoidis carbonaria Spix, 1824

A chorioallantoic membrane artery in embryos of the red-footed tortoise, Chelonoidis carbonaria was occlusively cannulated for measurement of blood pressure and injection of drugs. Two age groups of embryos in the final 10 % of incubation were categorized by the ratio of embryonic body to yolk mass. All embryos first received cholinergic and β-adrenergic blockade. This revealed that β-adrenergic control was established in both groups whereas cholinergic control was only established in the older group immediately prior to hatching. The study then progressed as two series. Series one was conducted in a subset of embryos treated with histamine before or after injection of ranitidine, the antagonist of H2 receptors. Injection of histamine caused an initial phasic hypertension which recovered, followed by a longer lasting hypertensive response accompanied by a tachycardia. Injection of the H2 receptor antagonist ranitidine itself caused a hypotensive tachycardia with subsequent recovery of heart rate. Ranitidine also abolished the cardiac effects of histamine injection while leaving the initial hypertensive response intact. In series, two embryos were injected with histamine after injection of diphenhydramine, the antagonist to H1 receptors. This abolished the whole of the pressor response to histamine injection but left the tachycardic response intact. These data indicate that histamine acts as a non-adrenergic, non-cholinergic factor, regulating the cardiovascular system of developing reptilian embryos and that its overall effects are mediated via both H1 and H2 receptor types. © 2013 Springer-Verlag Berlin Heidelberg.