Phytochemical Estimation and Therapeutic Amelioration of Aesculus hippocastanum L. Seeds Ethanolic Extract in Gastric Ulcer in Rats Possibly by Inhibiting Prostaglandin Synthesis / 中国结合医学杂志

OBJECTIVE@#To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats.@*METHODS@#Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE2), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings.@*RESULTS@#The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE2 and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups.@*CONCLUSIONS@#LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE2 biosynthesis.

Profilaxis para sangrado gastrointestinal en pacientes del servicio de medicina interna de un hospital universitario / Gastrointestinal bleeding prophylaxis in internal medicine patients of a univeristy hospital

Introducción: Los medicamentos antiulcerosos son utilizados frecuentemente en pacientes hospitalizados, sin embargo, a menudo este uso no está indicado. Objetivo: Describir la frecuencia de prescripción e indicación de medicamentos para prevenir el sangrado gastrointestinal en pacientes hospitalizados. Materiales y métodos: Estudio de corte trasversal, descriptivo, prospectivo del servicio de Medicina Interna de la Sociedad de Cirugía de Bogotá- Hospital de San José de Bogotá, Colombia. Se excluyeron pacientes con diagnóstico de sangrado gastrointestinal o antecedente de alergia a los medicamentos antiulcerosos. Se recolectaron datos demográficos, así como fármacos prescritos. Se determinó si la indicación del fármaco era adecuada y se identificó el tipo de error de prescripción. Resultados: Se incluyeron 179 pacientes, 102 (57%) mujeres. Promedio de edad de 61,3 años (±20,2). El principal diagnóstico de ingreso fue enfermedad infecciosa 76 (42,4%). Del total de pacientes, 165 (92,17%) recibieron medicamento para prevención del sangrado gastrointestinal. La indicación fue adecuada en 75 pacientes (41,89%). El error más frecuente fue el uso en pacientes de bajo riesgo de sangrado, 101 (97,1%). Conclusión: Un alto porcentaje de los pacientes recibió medicación para la prevención del sangrado gastrointestinal. En aproximadamente la mitad de estos no estaba indicada.

Introduction: Anti-ulcer medications are frequently used in hospitalized patients, yet their use is not usually indicated. Objective: To describe the frequency of prescription and indication of medications to prevent gastrointestinal bleeding in hospitalized patients. Materials and methods: A cross-sectional, descriptive, prospective study was carried out in the Internal Medicine service of the Surgery Society of Bogota-San Jose Hospital of Bogota (Colombia). Excluded patients were those with either a gastrointestinal bleeding diagnosis or a history of allergy to anti-ulcer medications. Demographic data and information regarding prescribed medications were collected. It was determined whether the medicine indication was adequate and the type of prescription error was identified. Results: 179 patients were included in the study, 57% (102) of which were women. The average age was 61.3 (±20.2) years old. Infectious disease was the main admission diagnosis (76; 42.4%). A 92.17% (165) of the total number of patients received medications to prevent gastrointestinal bleeding. This indication was adequate for 75 (41.89%) patients. The most frequent error was their use in bleeding low-risk patients (101; 97.1%). Conclusion: A high percentage of patients received medication to prevent gastrointestinal bleeding. However, in about half of these patients it was not indicated.

Hipocalcemia, hipomagnesemia y uso crónico de inhibidores de la bomba de protones / Hypocalcemia, hypomagnesemia, and chronic use of proton pump inhibitors

Introducción: Los inhibidores de la bomba de protones son fármacos usados en múltiples gastropatías. El omeprazol pertenece a este grupo de medicamentos y es aprobado y catalogado como indispensable por la Organización Mundial de la Salud. Esto ha causado que su uso se vuelva constante y hasta cierto punto equívoco. Pese a ser medicamentos seguros muestran efectos secundarios, dentro de los cuales uno ocasional es el trastorno hidroelectrolítico. Objetivo: Presentar un caso clínico en el cual se constató la presencia de efectos secundarios tras el uso de un fármaco de uso constante por la comunidad médica: el omeprazol. Caso clínico: Se presenta a continuación el caso clínico de un paciente masculino con antecedente de hipertensión arterial y gastropatía crónica que muestra uso por 8 años consecutivos de inhibidores de la bomba de protones, al cual se le diagnostica hipomagnesemia e hipocalcemia. Se obtuvieron resultados de laboratorio normales tras administración de suplementos orales y uso de ranitidina con supresión de terapéutica con omeprazol. Conclusiones: Un control constante de los fármacos que usan los pacientes crónicos es fundamental en atención primaria de salud. El uso de inhibidores de la bomba de protones se ha convertido en rutinario y es necesario corroborar siempre la dosis y el tiempo de uso de los fármacos además de la relación con otros medicamentos que use el paciente(AU)

Introduction: Proton-pump inhibitors are drugs used in multiple gastropathies. Omeprazole belongs to this group of medicines; it is approved and classified as essential by the World Health Organization. This has permitted for its use to become constant and, to some extent, misleading. Despite being safe drugs, they show side effects, among which an occasional one is fluid and electrolyte disorders. Objective: To present a clinical case in which the occurrence of side effects was verified after the administration of a drug constantly used by the medical community. Clinical case: The following is a clinical case of a male patient with a history of arterial hypertension and chronic gastropathy, characterized by the usage of proton-pump inhibitors for eight consecutive years, diagnosed with hypomagnesemia and hypocalcemia. Normal laboratory results were obtained after oral supplementation and usage of ranitidine with suppression of omeprazole therapy. Conclusions: Constant control of the drugs used by chronic patients is essential in primary health care. The usage of proton-pump inhibitors has become a routine. It is always necessary to check the dose and time for using the drugs as well as the relationship with other drugs used by the patient(AU)

Efficacy and Safety of AlbisD Compared With Omeprazole 20 mg in Patients With Non-erosive Reflux Disease: A Randomized, Open-label, Active-controlled, Pilot Study

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are frequently used to treat non-erosive reflux disease (NERD), but their effect is limited. It is not known whether a potential alternative, AlbisD, containing ranitidine hydrochloride, sucralfate hydrate, and tripotassium dicitrato bismuthate, is effective and safe in treating NERD. The aim of the study is to evaluate the efficacy and safety of AlbisD compared with omperazole in patients with NERD. METHODS: This was a multicenter, randomized, open-label, parallel-group, non-inferiority comparative study. A total of 126 patients with NERD were randomly allocated to either AlbisD twice daily or omeprazole 20 mg once daily for 4 weeks from February 2016 to August 2016. The study patients had histories of heartburn or regurgitation of moderate severity (> score 2) and a frequency of at least 2 episodes per week, and had no mucosal breaks of the esophagus on endoscopy. The primary efficacy variable was complete cure of heartburn at week 4. Secondary efficacy variables evaluating symptoms of heartburn and acid reflux as well as safety profiles were compared in the 2 groups at week 2 and 4 after treatment. RESULTS: A total of 113 patients completed the study (57 and 56 in AlbisD and omeprazole groups, respectively). The proportion of patients with complete cure of heartburn at week 4 was not significantly different between the AlbisD and omeprazole groups (35.1% vs 32.1% respectively, P = 0.740). There were no significant differences between the 2 groups in the any secondary variables including proportions of days without heartburn or acid reflux over 4 weeks (including daytime and nighttime). Adverse events were similarly reported in the 2 groups (7 [12.3%] vs 6 [10.7%]), and there were no serious adverse events. CONCLUSIONS: The efficacy and safety of AlibsD in treating NERD patients are not inferior to those of omeprazole. Therefore, AlbisD can be an alternative to PPIs for NERD.

A case of nizatidine-induced immediate hypersensitivity

Nizatidine is a histamine H₂ receptor antagonist that inhibits stomach acid production and is commonly used in the treatment of peptic ulcer and gastroesophageal reflux. H₂ receptor antagonists are typically well tolerated, and hypersensitivity reactions are rare. A 19-year-old woman developed urticaria 30 minutes after taking a drug containing nizatidine. Allergic reactions to nizatidine were confirmed via skin prick test, which also revealed cross-reactions to ranitidine. We believe that this is the first case report on immediate hypersensitivity to nizatidine in Korea.

Symmetrical Drug-Related Intertriginous and Flexural Exanthema: Two Cases and Brief Literature Review

It has been reported that there are a range of causative drugs related to symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The causative drugs reported so far include the following: antibiotics, intravenous immunoglobulin, chemotherapeutic agents, and biologics. In this study, we report two cases of SDRIFE and a review of the previous literature. We believe that our study makes a significant contribution to the literature because it demonstrates that intradermal injection of the Chinese herbal ball, and not its topical application, elicited a reaction that predicted the occurrence of SDRIFE. This finding is important for the diagnosis of SDRIFE in future studies. Our findings also provide evidence for a SDRIFE reaction after exposure to ranitidine and mosapride.

Seguridad en anestesia: error en la administración de fármacos LASA / Safety in anesthesia: an error in the administration of LASA drugs / Segurança na anestesia: um erro na administração de drogas LASA

La seguridad del paciente es prioritaria en el ámbito anestésico quirúrgico. El error en la administración de fármacos es una causa frecuente de incidentes críticos en el perioperatorio. Una forma de error, es la administración del medicamento equivocado debido a las presentaciones similares. El objetivo de este trabajo es la descripción de fallas en las barreras de prevención de incidentes críticos con medicamentos, en base al estudio de un caso clínico y al análisis de sus consecuencias. Metodología : Descripción de un caso clínico y estudio sistemático de la situación de riesgo en base al análisis taxonómico del paciente, individuo, tarea, equipo humano, lugar de trabajo y organización (PITELO) sugerido por el Sistema Español de Notificación en Seguridad en Anestesia y Reanimación (SENSAR). Resultados : Mujer sana que presentó paro respiratorio luego de la administración intravenosa de un fármaco en el postoperatorio. Se requirió 24 hs de terapia intensiva y múltiples estudios, luego de lo cual se diagnosticó un error en la administración de fármaco. La confusión se presentó con una dupla de ampollas LASA (del inglés: look-alike, sound-alike) de los fármacos atracurio y ranitidina. La documentación fotográfica evidencia la similitud y el diagrama identifica fallas latentes del sistema. Se estimaron los costos del error y se realizaron propuestas de mejora. Discusión y conclusiones : Se evidencia una falla en las barreras de prevención de eventos adversos y en el sistema de reporte de los mismos. Es necesario incrementar la cultura de seguridad en todos los niveles del sistema: regulatorio, institucional y personal.

Patient safety is a priority in the surgical anesthetic area, and errors in drug administration area frequent cause of critical incidents in the perioperative period. One type of error is the administration of the wrong medication due to similar presentations. The objective of this study is to describe the failure of barriers to prevent critical drug incidents; this is based on the study of a clinical case and an analysis of its consequences. Methodology . Description of a clinical case and systematic study of the risk situation based on the taxonomic analysis of the patient, individual, task, human team, workplace, and organization (PITELO), as suggested by the Spanish System of Safety Notification in Anesthesia and Resuscitation (SENSAR). Results . A healthy woman presented in respiratory arrest after the intravenous administration of a drug in the postoperative period. It took 24 hours of intensive care and multiple studies before an error in drug administration was diagnosed. The confusion was presented with a pair of LASA (look-alike, sound-alike) ampoules of atracurium and ranitidine drugs. Photographic documentation evidences the similarity of the ampoules themselves, and the diagram identifies latent system failures. The costs of the error are estimated and proposals for improvement are provided. Discussion and Conclusions . There is evidence of a failure in the barriers to the prevention of adverse events and in the reporting system. It is necessary to increase the safety culture at all levels of the system: regulatory, institutional, and personal.

A segurança do paciente é prioritária no âmbito anestésico cirúrgico. O erro na administração de fármacos é uma causa frequente de incidentes críticos no perioperatório. Uma forma de erro é a administração de medicação errada devido a uma apresentação similar. O objetivo deste trabalho é a descrição de falhas nas barreiras de prevenção de incidentes críticos com medicamentos, em base no estudo de um caso clínico e ao análise de suas consequências. Metodologia . Descrição de um caso clínico e estudo sistemático da situação de risco em base ao análises taxonômico do doente, tarefa, equipamento humano, lugar de trabalho e organização (PITELO) sugerido pelo Sistema Espanhol de Notificação em Segurança em Anestesia e Reanimação (SENSAR). Resultados . Mulher sem patologia que apresentou paro respiratório a pois a administração intravenosa de um fármacos no pós-operatório. Requereu-se de 24 hs na UTI e múltiplos estudos, logo dos quais foi diagnosticado um erro na administração do fármaco. A confusão se apresentou como causa deduplas ampolas LASA (do inglês: aparência parecida com o som) dos fármacos atracurio y ranitidina. A documentação fotográfica evidencia a similitude e o diagrama identificafalhas latentes no sistema. Foram analisados os custos do erro e realizou-se propostas de melhora. Discussão y conclusões . Evidencia-se uma falla nas barreiras de prevenção de eventos adversos e no sistema de reporte dos mesmos. É necessário incrementar a cultura de segurança em todos os níveis do sistema: regulatório, institucional e pessoal.

Pantoprazole Does Not Reduce the Antiplatelet Effect of Clopidogrel: A Randomized Controlled Trial in Korea

BACKGROUND/AIMS: Concerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea. METHODS: Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction restriction fragment length polymorphism. RESULTS: After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism. CONCLUSIONS: This study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).

Clinical Features of Serious Adverse Drug Reactions in a Tertiary Care Hospital in Korea / 대한내과학회지

BACKGROUND/AIMS: Several studies have reported on the clinical aspects of adverse drug reactions (ADRs). To date, no study has evaluated serious adverse drug reactions (SADRs) in Korea. The current study evaluates the clinical expression of SADRs in a Korean hospital. METHODS: We reviewed a total of 3,386 cases of SADR occurring between March 2012 and November 2015 in a single tertiary care institution (Regional Pharmacovigilance Center). RESULTS: When classified by organ system, the most common SADRs were white cell and reticuloendothelial system disorders (n = 511). Skin/appendage (n = 296) and gastrointestinal (n = 216) disorders were the fourth- and eighth-most common SADRs, respectively. The three most common single symptoms were leukopenia (n = 499 events), hypotension (n = 444) and anaphylaxis (n = 215). Leukopenia was mainly caused by anti-tumor drugs, followed by piperacilin/tazobactam (n = 28), vancomycin (n = 10) and methimazole (n = 6). Hypotension was most often caused by propacetamol injection (n = 145), while anaphylaxis was mainly caused by cefaclor (n = 19), ranitidine (n = 12), iopamidol (n = 10) and multi-vitamin infusion (n = 9). CONCLUSIONS: Significant differences were noted in the clinical aspects of ADRs and SADRs. Additional studies are warranted to further assess SADRs in response to frequently used causative drugs.

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.

RESUMO Contexto Anti-inflamatórios não esteroidais induzem lesões da mucosa gástrica devido às suas propriedades ácidas. Ranitidina, um antagonista dos receptores H2, revelou-se benéfico em pacientes com úlceras gástricas. Objetivo - O presente estudo foi realizado para avaliar o efeito da administração de ranitidina em gastropatia induzida por anti-inflamatórios não esteroidais (diclofenaco, nimesulida) e seu efeito sobre a histopatologia do estômago, dos rins e fígado. Métodos Diclofenaco, nimesulida e ranitidina foram administradas em doses de 2, 4 e 6 mg/kg, p.o. uma vez diariamente por 14 dias e seu efeito sobre o volume gástrico, acidez, significam o número de úlcera e o pH gástrico. Além disso, o exame histopatológico também foi realizado em seções do estômago, dos rins e fígado. Resultados Após a administração de diclofenaco ou nimesulida, todos os parâmetros gástricos foram significativamente alterados assim como a histopatologia do estômago, fígado e rim. No grupo controle, as seções renais mostraram glomérulos normais sem espessamento da membrana basal glomerular, enquanto em diclofenaco isolado, nimesulida isolado e grupos com ranitidina e nimesulida, foi observado espessamento da membrana basal glomerular. Estas alterações observou-se serem revertidas no grupo ranitidina com diclofenaco. As seções do fígado, o grupo controle mostrou placas e cordões de hepatócitos cuboidais anastomosados com núcleos bem demarcados e citoplasma abundante. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, leve dilatação dos sinusoides é vista acoplados com proeminência de veia central. Nos grupos diclofenaco e nimesulida sozinhos, túbulos proximais e distais contorcidos mostram necrose tubular focal leve. Nas secções gástricas, o grupo controle mostrou várias dobras formando vilosidades e a superfície do revestimento epitelial da mucosa. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, o duodeno mostrou dispersas células inflamatórias predominantemente compostas por linfócitos. Nos grupos diclofenaco e nimesulida sozinhos, as secções de áreas gástricas mostraram necrose parcial e inflamação crônica moderada respectivamente. Conclusão - O estudo, portanto, forneceu o fundamento terapêutico para administração simultânea de bloqueador de receptor H2 (ranitidina) com diclofenaco, sendo mais benéfica em comparação com ranitidina com nimesulida para minimizar a intolerância gástrica de diclofenaco no tratamento a longo prazo de condições inflamatórias.

Efficacy of proton pump inhibitors and H2 blocker in the treatment of symptomatic gastroesophageal reflux disease in infants / 소아과

PURPOSE: Gastroesophageal reflux disease (GERD) occurs in pediatric patients when reflux of gastric contents presents with troublesome symptoms. The present study compared the effects of omeprazole and ranitidine for the treatment of symptomatic GERD in infants of 2-12 months. METHODS: This study was a clinical randomized double-blind trial and parallel-group comparison of omeprazole and ranitidine performed at Children Training Hospital in Tabriz, Iran. Patients received a standard treatment for 2 weeks. After 2 weeks, the patients with persistent symptoms were enrolled in this randomized study. RESULTS: We enrolled 76 patients in the present study and excluded 16 patients. Thirty patients each were included in group A (ranitidine) and in group B (omeprazole). GERD symptom score for groups A and B was 47.17±5.62 and 51.93±5.42, respectively, with a P value of 0.54, before the treatment and 2.47±0.58 and 2.43±1.15, respectively, after the treatment (P=0.98). No statistically significant differences were found between ranitidine and omeprazole in their efficacy for the treatment of GERD. CONCLUSION: The safety and efficacy of ranitidine and omeprazole have been demonstrated in infants. Both groups of infants showed a statistically significant decrease in the score of clinical variables after the treatment.

Uso de inhibidores de la bomba de protones y antagonistas de los receptores H2 de histamina como profilaxis en úlceras por estrés: ¿una práctica justificada? / Use of proton pump inhibitors and Histamine-2 receptor antagonists in stress ulcers: a justified practice? / Uso de inibidores da bomba de prótons e antagonistas dos receptores H2 de histamina como profilaxia em úlceras por estresse: uma prática justificada?

La introducción de los moduladores de acidez gástrica como profilaxis contra las úlceras por estrés en pacientes críticos se ha \r\nido convirtiendo en una práctica de rutina tanto en la unidad de cuidados intensivos como fuera de esta; sin embargo, el desco\r\n-\r\nnocimiento de la fisiopatología de la enfermedad, las indicaciones de uso de moduladores de pH como profilácticos, los riesgos \r\nasociados a la prescripción indiscriminada y de las guías disponibles sobre esta práctica han llevado a un uso descontrolado \r\nde medicamentos como omeprazol y ranitidina, lo cual aumenta los costos para los hospitales y predispone a los pacientes a \r\npresentar enfermedades como neumonía. Con el objetivo de revisar los factores de riesgo asociados a esta patología, la eficacia \r\nde esta medida, sus indicaciones y posibles complicaciones tanto dentro como fuera de las unidades de cuidados intensivos, se \r\nrealizó una revisión de la literatura. Esta incluyó artículos disponibles en diferentes bases de datos que hicieran referencia al manejo \r\nprofiláctico de úlceras por estrés desde 1980 hasta 2014. Se encontró que, según la literatura actual, el uso de la profilaxis contra \r\núlceras por estrés es una práctica muy debatida en el caso de los pacientes críticos y, lo que es más importante, en los no críticos \r\naún no existen recomendaciones de uso o factores de riesgo establecidos. Por esta razón, la extrapolación de esta conducta a \r\npacientes fuera de la unidad de cuidados intensivos es injustificada hasta el momento.

The introduction of acid gastric modulators in critical patients \r\nas prophylaxis against stress ulcers has increasingly become \r\na routine practice both in the intensive care unit and outside \r\nof it. However, lack of knowledge about topics including \r\nthe physiopathology of the disease, directions for use of pH \r\nmodulators as a prophylactic, the associated risk of over-pre\r\n-\r\nscription, and guidelines available about this practice has led \r\nto an overuse of drugs like omeprazole and ranitidine, making \r\nhospitalization more expensive and predisposing patients \r\nto diseases like pneumonia. The objective of this article is \r\nto review the risk factors associated with this pathology, the \r\nefficacy of this action, and the complications and indications \r\ninside and outside of intensive care units using all available \r\ndata through 2014. In the end we conclude that at this time \r\nand with the new evidence, the use of prophylaxis against \r\nstress ulcers in critical patients is a widely debated practice and \r\nmore importantly there are no recommendations for its use or \r\nestablished risk factors in the non-critical population, leading \r\nus to conclude that extrapolation to patients outside of inten\r\n-\r\nsive care is not justified up to date.

A introdução dos moduladores de acidez gástrica como \r\nprofilaxia contra as úlceras por estresse em pacientes críticos \r\nconverteu-se em prática de rotina tanto na unidade de cuidados \r\nintensivos como fora desta. No entanto, o desconhecimento \r\nda fisiopatologia da doença, as indicações de uso de modula\r\n-\r\ndores de pH como profiláticos, os riscos associados à prescrição \r\nindiscriminada e as orientações disponíveis sobre esta prática \r\nlevaram a um uso descontrolado de medicamentos como \r\nomeprazol e ranitidina, aumentando o custo para os hospi\r\n-\r\ntais e predispondo os pacientes a doenças como pneumonia. \r\nCom o objetivo de revisar os fatores de risco associados a esta \r\npatologia, a eficácia desta medida, suas indicações e possí\r\n-\r\nveis complicações tanto dentro como fora das unidades de \r\ncuidado intensivo, foi realizada uma revisão da literatura. Esta \r\nincluiu artigos disponíveis em diferentes bancos de dados que \r\nse referiram ao manuseio profilático de úlceras por estresse, \r\ndesde 1980 até 2014. Descobriu-se que, segundo a literatura \r\natual, o uso de profilaxia contra úlceras por estresse é uma \r\nprática muito debatida no caso dos pacientes críticos e, o que \r\né mais importante, para os não críticos ainda não existem reco\r\n-\r\nmendações de uso ou fatores de risco estabelecidos. Por este \r\nmotivo, a extrapolação desta conduta com pacientes fora da \r\nunidade de cuidados intensivos é injustificada até o momento.

Comparação entre a ranitidina e o omeprazol em relação a possíveis interações medicamentosas com o clopidogrel em pacientes portadores de doenças arterial coronária estável / Possible drug interaction between clopidogrel and ranitidin or omeprazole in patients with stable coronary artery disease: a comparative study

INTRODUÇÃO: Os Inibidores de Bombas de Prótons (IBP´s) são comumente prescritos a pacientes em uso de dupla antiagregação plaquetária (DAP) com ácido acetilsalicílico (AAS) e clopidogrel. Entretanto, esta classe de medicamentos, especialmente o omeprazol, tem sido associada à redução da potência antiplaquetária do clopidogrel, levando em muitos casos ao uso de ranitidina como alternativa. MÉTODOS: Foram analisados pacientes com doença arterial coronária (DAC) estável em uso de AAS 100 mg uma vez ao dia. A agregabilidade plaquetária foi medida no momento basal e após uma semana de terapia com clopidogrel na dose de 75 mg uma vez ao dia. Após essa fase inicial, os participantes foram randomizados de modo duplo-cego e duplo-mascarado para omeprazol 20 mg duas vezes dia ou ranitidina 150 mg duas vezes ao dia, sendo os testes de agregação plaquetária novamente repetidos após uma semana. A agregabilidade foi avaliada com a utilização dos seguintes métodos: VerifyNow P2Y12® (Accumetrics - San Diego, CA, EUA, meta principal do estudo), utilizando-se Unidades de Reatividade ao P2Y12 ("P2Y12 Reactivity Units" - PRU) e Inibição Percentual da Agregabilidade (IPA) na descrição da agregabilidade; agregometria de sangue total (AST) por bioimpedância utilizando os reagentes ADP e colágeno, sendo a agregabilidade medida em Ohms; "Platelet Function Analyser" 100® (Siemens Healthcare Diagnostics®, Newark, Delaware, EUA) utilizando o cartucho de colágeno/ADP, com a agregabilidade avaliada pelo tempo de fechamento do orifício em segundos. Além disso, foi feita dosagem de tromboxano B2 (TXB2) sérico na última visita a fim de se avaliar o efeito do AAS. RESULTADOS: Oitenta e cinco pacientes foram incluídos na análise final, sendo 41 no grupo omeprazol e 44 no grupo ranitidina. Houve redução significativa da IPA após o acréscimo de omeprazol (de 26,3 ± 32,9% para 17,4 ± 33,1%; P = 0,025), enquanto o grupo ranitidina não demonstrou modificação significativa (de 32,6 ± 28,9% para...

BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed to patients taking dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and clopidogrel. However, this class of medication, especially omeprazole, has been associated with a reduction of clopidogrel efficacy, leading many to substitute omeprazole with ranitidine. METHODS: The present study analyzed patients with stable coronary artery disease (CAD) in use of ASA 100 mg daily. Platelet aggregability was measured at baseline and after one week of clopidogrel 75 mg daily. Then, the subjects were randomized, in a double-blinded, doubledummy fashion, to omeprazole 20 mg twice a day or ranitidine 150 mg twice a day. After one more week, aggregability tests were repeated. Platelet aggregability was evaluated by the following methods: VerifyNow P2Y12TM (Accumetrics - San Diego, California, USA, main endpoint of the study), with aggregability depicted as percent Inhibition of Platelet Aggregation (IPA) and as P2Y12 Reactivity Units (PRU); whole blood aggregometry by bioimpendance using ADP and collagen with aggregability measured in Ohms; and Platelet Function Analyser 100TM (Siemens Healthcare Diagnostics, Newark, Delaware, USA) using collagen/ADP cartridge with aggregability measured in time to closure in seconds. Besides that, serum thromboxane B2 dosage was done on the last visit to evaluate ASA effect. RESULTS: Eighty-five patients were included in final analysis (41 in the omeprazole group and 44 in the ranitidine group). IPA was significantly decreased after addition of omeprazole (from 26.3% ± 32.9 to 17.4% ± 33,1; P = 0.025), with no significant changes being observed in the ranitidine group (from 32.6% ± 28.9 to 30.1% ± 31.3; P = 0.310). When taking into account PRU values, there was a numerical, but statistically non-significant increase in the omeprazole group (from 159.73 ± 83.06 to 173.54 ± 72.29; P = 0.116), with a very slight difference in the ranitidine group (from 153.61 ±...

Drug-Induced Anaphylaxis in a Single Korean Tertiary Hospital / 대한내과학회지

BACKGROUND/AIMS: Drug-induced anaphylaxis (DIA) is a severe, acute, and potentially life-threatening condition. In Korea, only a few well-documented cases of DIA have been described. Therefore, the aim of this study was to investigate the clinical characteristics, causes, and management of DIA in a single Korean medical institute. METHODS: This was a retrospective medical record review of all DIA patients who visited the in-patient, out-patient, and emergency departments of our hospital from January 1 2006 to October 30 2013. RESULTS: Among 605 cases of anaphylaxis, 167 were drug-induced. The culprit drugs were contrast agents (43 cases, 25.7%), antibiotics (38, 22.8%), non-steroidal anti-inflammatory drugs (35, 21.0%), anti-cancer drugs (22, 13.2%), parenteral vitamins (9, 5.4%), ranitidine (6, 3.6%), and neuromuscular blockers (3, 1.8%). The most common organ-specific symptoms/signs were cardiovascular (74.3%), cutaneous (71.3%), respiratory (55.7%), and gastrointestinal manifestations (19.2%). In most cases, DIA was treated with antihistamines (77.2%) and systemic corticosteroids (76.5%); the use of epinephrine was considerably less frequent (35.3%). CONCLUSIONS: In our institution, contrast agents were the leading cause of DIA. Although epinephrine is the drug of choice in the treatment of acute anaphylaxis, fewer than 50% of the study patients received epinephrine to treat DIA.

Metabolic profile and ruminal and abomasal pH in sheep subjected to intravenous ranitidine / Perfil metabólico ruminal e pH abomasal em ovinos tratados com ranitidina por via intravenosa

Brazilian sheep production has intensified, predisposing sheep to an increased incidence of digestive disorders, such as abomasal ulcers. Ranitidine is used to prevent and treat this disease; however, there is little information on the parenteral use of this drug in adult ruminants. Few data exist on the concomitant metabolic changes and the behavior of the digestive system associated with its use. For this study, five healthy male sheep with ruminal and abomasal cannulas were used. A 5x5 Latin square experiment with a 2x2+1 factorial arrangement of the treatments was performed. Sheep treated with drug doses of 1 or 2mg/kg ranitidine administered intravenously every 8 or 12 hours were compared with the control group, was treated intravenously with 1 mL of physiological solution per 25 kg every 12 hours. Higher total protein concentrations, hemoglobin levels, as well as increased aspartate aminotransferase activity and increased abomasal pH for up to 150 min following drug administration were observed in all animals that received the drug, regardless of dose and frequency. The animals treated every 12 hours showed a decrease in leukocyte number compared with the control group and with the animals treated every 8 hours. Increased serum creatinine concentrations were observed in the animals treated every 8 hours. Treatments of 1mg/kg every 8 hours and 2mg/kg every 12 hours increased the red blood cell count and decreased the serum pepsinogen. All protocols studied were safe for healthy sheep, but 1mg/kg ranitidine every 8 hours and 2mg/kg ranitidine every 12 hours were the most effective protocols for gastric protection.(AU)

A ovinocultura brasileira tem se intensificado, o que predispõe os animais à maior incidência de transtornos digestivos, como a úlcera de abomaso. A ranitidina é utilizada na prevenção e tratamento desta afecção, no entanto há pouca informação sobre a indicação parenteral deste fármaco para ruminantes adultos. São escassas as informações a respeito das alterações metabólicas e do comportamento do sistema digestório associados ao seu uso. Para este estudo foram utilizados cinco ovinos, machos, hígidos, providos de cânula ruminal e abomasal. O delineamento foi Quadrado Latino 5x5 com arranjo fatorial de tratamentos 2x2+1. Os ovinos tratados com as doses de 1 e 2mg/kg de ranitidina administrada por via intravenosa a cada 8 ou 12 horas foram comparados aos animais do grupo controle, tratados por via intravenosa com 1mL de solução fisiológica por 25 kg a cada 12 horas. Maiores concentrações de proteína total e hemoglobina, maiores atividades de AST e aumento do pH abomasal por até 150 minutos foram observados em todos os animais que receberam o fármaco, independentemente de dose e frequência. Os animais tratados a cada 12 horas mostraram diminuição do número de leucócitos comparados aos animais tratados a cada 8 horas e aos animais do grupo controle. Observou-se aumento das concentrações de creatinina nos animais tratados a cada 8 horas. Os tratamentos 1mg/kg a cada 8 horas e 2mg/kg a cada 12 horas aumentaram o número de hemácias e diminuíram as concentrações séricas de pepsinogênio. Todos os protocolos estudados foram seguros para ovinos sadios, porém 1mg/kg de ranitidina a cada 8 horas e 2mg/kg a cada 12 horas mostraram-se mais eficientes quanto à proteção gástrica.

Prevalencia de reacciones adversas neuropsiquiátricas a los medicamentosen pacientes hospitalizados en los serviciosde clínica, cirugía, pediatría y ginecología-obstetricia del Hospital Vicente Corral Moscoso 2014 / Prevalence of adverse neuropsiquiatric reactions to drugs, in hospitalized patients in the services of clinic, surgery, pediatrics and gynecology-obstetrics of Hospital Vicente Corral 2014

La prevalencia de reacciones adversas a los medicamentos (RAM) de tipo neuropsiquiátricas se encuentra alrededor del 11,4% del total de las reacciones adversas registradas según la mayoría de estudios. En nuestro medio carecemos de datos.Objetivo: Determinar la prevalencia de RAM de tipo neuropsiquiátricas en pacientes internados en los servicios de pediatría, clínica, cirugía y ginecología-obstetricia del Hospital Vicente Corral Moscoso (HVCM) de la ciudad de Cuenca.Método y materiales: Se realizó un estudio descriptivo a partir del mes de enero de 2014, hasta completar la muestra. La muestra fue de 336 casos y por conglomerados. La información se obtuvo mediante notificación espontánea, con una encuesta basada en la tarjeta amarilla modificada por los autores.Resultados: Se obtuvo una prevalencia de 39,6% casos con posibles RAM de tipo neurop-siquiátricas; el sexo femenino es el más afectado, en una razón de 3 a 1; la edad de mayor afectación está entre los 20 a 29 años; el ser-vicio de atención en donde se encontró una mayor frecuencia fue el de Ginecología-Obstetricia con un 19,96% de los casos; el tipo más frecuente fue la cefalea con un 21,4%; el diag-nóstico asociado con mayor frecuencia fue la neumonía adquirida en la comunidad con un 59,09%; el fármaco que con mayor frecuencia se asoció a RAM fue la Metoclopramida con un 53,84% (la RAM que con mayor frecuencia se asoció con Metoclopramida fue el mareo con 26%). Conclusión: La presencia de RAM tipo neurop-siquiátricas en el Hospital Vicente Corral Mos-coso presenta una prevalencia alta.

The prevalence of adverse drug reactions (ADRs) of neuropsychiatric type reactions is around 11.4% of all adverse reactions reported by most studies. In our lack of data.Objective: To determine the prevalence of neuropsychiatric RAM type inpatient pediatric services, clinic, surgery and obstetrics and gy-necology of Vicente Corral Moscoso Hospital (HVCM) of the city of Cuenca.Method and Materials: A descriptive study was conducted from January 2014 to complete the sample. The sample was 336 and conglomera-tes. The information was obtained by sponta-neous reporting, with a survey based on yellow card modified by the authors.Results: A prevalence of 39.6% of cases with possible neuropsychiatric RAM type was ob-tained; female gender is most affected, in a ratio of 3-1; most affected age is between 20 to 29 years; the service where a higher fre-quency was found Obstetrics-Gynecology with 19.96% of the cases; type headache was more frequent with 21.4%; diagnosis was more frequently associated with pneumonia acqui-red in the community with a 59.09%; the drug most often associated with metoclopramide RAM was a 53.84%% (the RAM that is most of-ten associated with metoclopramide was dizzi-ness 26%).Conclusion: The presence of neuropsychiatric RAM type Vicente Corral Moscoso in the hospi-tal has a high prevalence.

Incidence of postoperative dyspepsia is not associated with prophylactic use of drugs / Incidência de dispepsia pós-operatória não está associada com uso profilático de medicamentos

CONTEXT AND OBJECTIVE: Preoperative fasting guidelines do not recommend H2 receptor antagonists or proton pump inhibitors. This study investigated prophylactic use of gastric protection and the incidence of dyspeptic symptoms in the immediate postoperative period. DESIGN AND SETTING: Non-randomized observational investigation in a post-anesthesia care unit. METHODS: American Society of Anesthesiologists risk classification ASAP1 and ASAP2 patients over 18 years of age were evaluated to identify dyspeptic symptoms during post-anesthesia care for up to 48 hours, after receiving or not receiving prophylactic gastric protection during anesthesia. History of dyspeptic symptoms and previous use of such medications were exclusion criteria. The odds ratio for incidence of dyspeptic symptoms with use of these medications was obtained. RESULTS: This investigation studied 188 patients: 71% women; 50.5% ASAP1 patients. Most patients received general anesthesia (68%). Gastric protection was widely used (n = 164; 87.2%), comprising omeprazole (n = 126; 76.8%) or ranitidine (n = 38; 23.2%). Only a few patients did not receive any prophylaxis (n = 24; 12.8%). During the observation, 24 patients (12.8%) reported some dyspeptic symptoms but without any relationship with prophylaxis (relative risk, RR = 0.56; 95% confidence interval, CI: 0.23-1.35; P = 0.17; number needed to treat, NNT = 11). Omeprazole, compared with ranitidine, did not reduce the chance of having symptoms (RR = 0.65; 95% CI: 0.27-1.60; P = 0.26; NNT = 19). CONCLUSION: This study suggests that prophylactic use of proton pump inhibitors or H2 receptor antagonists was routine for asymptomatic patients and was not associated with postoperative protection against dyspeptic symptoms. .

CONTEXTO E OBJETIVO: Diretrizes para jejum pré-operatório não recomendam antagonistas dos receptores H2 ou inibidores da bomba de prótons. Este estudo investigou o uso profilático de proteção gástrica e a incidência de sintomas dispépticos no período pós-operatório imediato. TIPO DE ESTUDO E LOCAL: Estudo observacional não aleatorizado em unidade de recuperação pós-anestésica. MÉTODOS: Pacientes ASAP1 e ASAP2, classificação de risco da American Society of Anesthesiologists, com mais de 18 anos de idade, foram avaliados para identificar sintomas dispépticos durante a recuperação pós-anestésica em até 48 horas, tendo ou não recebido proteção gástrica profilática durante a anestesia. História de sintomas dispépticos e uso prévio de tais medicamentos foram critérios de exclusão. A razão de chances para incidência de sintomas dispépticos com uso desses medicamentos foi obtida. RESULTADOS: Foram estudados 188 pacientes, 71% mulheres, 50,5% dos pacientes ASAP1. A maioria dos pacientes recebeu anestesia geral (68%). Proteção gástrica foi amplamente usada (n = 164; 87,2%), consistindo de omeprazol (n = 126; 76,8%) ou ranitidina (n = 38; 23,2%). Poucos pacientes não receberam qualquer profilaxia (n = 24; 12,8%). Durante a observação, 24 pacientes (12,8%) relataram alguns sintomas dispépticos, porém sem relação com profilaxia (risco relativo, RR = 0,56; intervalo de confiança, IC 95% 0,23-1,35, P = 0,17; número necessário para tratar, NNT = 11). Omeprazol, comparado à ranitidina, não reduziu a chance de ter sintomas (RR = 0,65; IC 95% 0,27-1,60; P = 0,26; NNT = 19). CONCLUSÃO: Este estudo sugere que o uso profilático de inibidores da bomba de prótons ...

Test of dissolution and comparison of in vitro dissolution profiles of coated ranitidine tablets marketed in Bahia, Brazil

Ranitidine is an antisecretory drug with H2 antagonist action useful in treating gastric and duodenal disorders. The dissolution test is used to obtain and compare dissolution profiles and establish similarities of pharmaceutical forms. The aim of this study was to compare the dissolution profiles of 150-mg coated ranitidine tablets of a reference drug (product A) and a generic (product B) and a similar (product C) drug marketed in Bahia, Brazil using a simple, fast and inexpensive ultraviolet method. Dissolution was determined using a USP type 2 apparatus at 50 rpm with 900 mL of distilled water at 37.0 ± 0.5 oC for 1h. The dissolution test was performed in compliance with the American Pharmacopoeia (USP-32). Dissolution efficiency and difference (f1) and similarity (f2) factors were calculated and evaluated. The proposed quantification methodology for drug dissolution test was validated, presenting accuracy, linearity and precision within the acceptance criteria. Products A, B and C showed dissolution efficiency values of 59.29, 73.59 and 66.67%, respectively. Factors f1 and f2 were calculated and showed that the profiles of products A, B and C were dissimilar. However, all the products released ranitidine satisfactorily, with at least 80% of the drug dissolved within 30 min.

A ranitidina é um fármaco antissecretor, antagonista H2, usado no tratamento de desordens gástricas e duodenais. O teste de dissolução é utilizado para obter e comparar perfis de dissolução, estabelecendo semelhança de formas farmacêuticas. Este estudo tem por objetivo comparar perfis de dissolução de comprimidos revestidos contendo 150 mg de ranitidina, em medicamentos de referência (produto A), genérico (produto B) e similar (produto C) comercializados na Bahia-Brasil, usando um método ultravioleta simples, rápido e de baixo custo. As condições que permitiram a determinação da dissolução foram: aparelho USP tipo 2 a 50 rpm, contendo 900 mL de água destilada mantida a 37,0 ± 0,5 °C, durante 1 h. O teste de dissolução foi realizado em conformidade com a Farmacopeia Americana (USP-32). Cálculo da eficiência de dissolução e fatores de diferença (f1) e semelhança (f2) foram avaliados. A metodologia proposta para a quantificação do fármaco no ensaio de dissolução foi validada apresentando precisão, linearidade e exatidão dentro dos critérios de aceitação. Os produtos A, B e C mostraram eficiência de dissolução de 59,29, 73,59 e 66,67%, respectivamente. Calcularam-se os fatores f1 e f2 e mostrou-se que os perfis não foram semelhantes para os comprimidos de produtos A, B e C. No entanto, todos os produtos liberaram o fármaco satisfatoriamente, pois, pelo menos, 80% de ranitidina foram dissolvidos em 30 min.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

The Modulatory Role of Spinally Located Histamine Receptors in the Regulation of the Blood Glucose Level in D-Glucose-Fed Mice

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (alpha-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with alpha-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, alpha-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.