The Protective Effect of Lercanidipine on Indomethacin-Induced Gastric Ulcers in Rats

Abstract Nonsteroidal anti-inflammatory drugs (NSAID) are among the aggressive factors causing gastric ulcer. They cause oxidative damage in the gastric tissue and lead to intracellular calcium deposition. Lercanidipine is a calcium channel blocker derived from the third generation dihydropyridine. The aim of this study is to analyse the effect of lercanidipine on indomethacin-induced gastric ulcers. A total of 24 albino Wistar male rats were divided into four groups; those who received indomethacin 25 mg/kg (IND), 5 mg mg/kg lercanidipine +25 mg/kg indomethacin (LC-5), 10 mg/kg lercanidipine+25mg/kg indomethacin (LC-10) and healthy rats who received 0.5 mL distilled water. Six hours after the application of indomethacin, the animals were sacrificed by high dose thiopental sodium. The stomachs of the animals were excised to perform a macroscopic analysis and the ulcerous region was measured on millimeter paper. All the stomachs were subjected to a biochemical analysis. Macroscopic analysis revealed hyperaemia on the gastric surface of the indomethacin group. Ulcerous tissues formed by oval, circular or irregular mucosal defects in varying diameters and depths were observed on the whole surface of the stomach. Hyperaemia was lower and ulcerous region was smaller in groups LC-5 and LC-10 compared to IND group. Malondialdehyde and myeloperoxidase levels were significantly lower and total glutathione and cyclooxygenase-1 activity were higher in groups LC-5 and LC-10. Lercanidipine did not change the cyclooxygenase-2 activity. Lercanidipine in doses 10 mg/kg is more effective compared to 5 mg/kg. Lercanidipinine can be useful in the treatment of NSAID-induced gastric damage.

Practice of Indian Physicians Towards Use of Calcium Channel Blockers in the Management of Hypertension : A Paper Based Questionnaire Survey.

Hypertension is a prevalent condition. Improving blood pressure control would depend on understanding concerns and limitations of physicians. Objective: Understanding practice of calcium channel blockers use among physicians. Material and methods: A cross-sectional, observational paper based questionnaire survey among 218 Indian physicians. Results: According to 55.83% of physicians (n=218), prevalence of hypertension ranges between 21-40%. Sixty percent physicians get referred cases mostly from the general physicians (69.48%). More than 20% patients have concomitant illness according to 33.81% physicians, most common being diabetes (33.44%).According to 96.30% physicians, due to asymptomatic nature, hypertension remains undiagnosed, untreated and uncontrolled. Stress (32.35%), obesity (23.13%), physical inactivity (22.78%) and smoking (20.52%) are responsible for sympathetic over activity. Calcium channel blockers (CCBs) (37.19%), beta blockers (30.43%), angiotensin receptor blocker (ARB) (12.14%) and angiotensin converting enzyme (ACE) inhibitors (4.02%) are used as first choice in patients with sympathetic over activity. Ischemic event, stroke, heart failure and renal failure occur due to ignoring sympathetic over activity according to 30.91%, 25.39%, 20.97% and 22.30% physicians respectively. According to 51.63% of physicians, patient compliance to antihypertensive therapy is > 70%. Lack of awareness (40.5%) and dosage frequency (24%) are two most common reasons for noncompliance. According to 89.72% of physicians, the current CCBs primarily inhibit L-type calcium channels but cause sympathetic over activity. A total of 48.34% physicians, >10% patients complain of pedal edema with amlodipine. In physicians opinion, blockage of L and N type of calcium channels (56.47%), unique mode of action (11.76%), arteriolar and venous dilation (9.41%) and inhibition of reninangiotensin- aldosterone (RAS) system (7.06%) are responsible for less pedal edema with cilnidipine. A total of 98.7% and 99.54% physicians rated efficacy and safety of cilnidipine as “good-very good” compared to other CCB respectively. Conclusion: In hypertension, sympathetic over activity may cause many complications. As per the physicians opinion survey, cilnidipine because of its unique mechanism of action offers multiple benefits in hypertensive patients and can be preferred over amlodipine.

Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers

PURPOSE: Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements. MATERIALS AND METHODS: We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure. RESULTS: Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1+/-74.1 vs. 215.0+/-69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU> or =275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype. CONCLUSION: CCBs inhibit the antiplatelet activity of clopidogrel.

Antibacterial & antitoxic effects of the cardiovascular drug lacidipine in an animal model.

Background & objectives: Vibrio cholerae produces acute infection by liberating potent enterotoxin, called cholera toxin in human intestine. Cardiovascular drug lacidipine possessing powerful in vitro action against V. cholerae was tested to determine its possible activity against a toxigenic V. cholerae strain in an established animal model. Methods: In the rabbit intestine four loops were constructed, 3 of which were injected with over night grown V. cholerae 569B culture. Of these, two loops were simultaneously given graded doses (100, 200 μg) of lacidipine, one was left as such for a positive control. The first loop received sterile medium (negative control). After 18 h, contents of all the loops were examined for accumulation of fluid and number of viable cells. Results: Lacidipine when administrated with live V. cholerae 569B, caused a reduction in the number of viable bacteria along with amount of fluid in the loops. The amount of fluid and number of viable cells were much reduced in the loop that had 200 μg of lacidipine than the loop that received 100 μg of the drug. Interpretation & conclusions: Lacidipine has distinct inhibitory action against V. cholerae 569B with respect to both viability and production of cholera toxin in the rabbit ileum. Structural modifications of this compound may possibly lead to procurement of new potent antimicrobial drugs.

Avaliaçäo da eficácia da lercanidipina comparada à nifedipina oros no tratamento da hipertensäo arterial primária leve e moderada pela monitorizaçäo ambulatorial de 24 horas (MAPA) / Evaluation of efficacy of lercanidipine compared to nifedipine oros in treatment of mild and moderate primary arterial hypertension by ambulatorial 24 hours monitoring

A eficácia anti-hipertensiva da lercanidipina foi avaliada de forma comparativa e simples-cega com a nifedipina oros no tratamento da hipertensão primária leve a moderada nas 24 horas. Empregou-se a monitorização ambulatorial da pressão arterial nas 24 horas (MAPA) em 18 pacientes hipertensos leves a moderados, de ambos os sexos, sendo que a metade recebeu lercanidipina 10 mg/dia e os demais nifedipina oros 30 mg por 4 semanas. Os pacientes que não apresentaram a pressão arterial (PA) normalizada, sendo o critério PAS > 140 mmHg e/ou PAD > 90 mmHg, tiveram a dose duplicada; nos demais pacientes foi mantida e todos foram acompanhados por mais 4 semanas. Foi realizada a MAPA de 24 horas antes e após a primeira dose de cada medicação, ao final das 8 semanas do estudo e após 48 horas da administração da última dose da lercanidipina ou nifedipina oros. Foram observadas reduções semelhantes da PA nos dois grupos em todos os momentos durante a MAPA após a primeira dose e ao final das 8 semanas de tratamento durante as 48 horas após a última tomada. A persistência do efeito anti-hipertensivo 48 horas após a última dose foi mantida sem diferença quando se comparou os dois fármacos. A eficácia anti-hipertensiva da lercanidipina foi semelhante à da nifedipina oros nos hipertensos primários leves a moderados nas 24 horas, havendo persistência do efeito anti-hipertensivo, verificado com ambas as drogas durante o tratamento crônico, por um período de até 48 horas após a última tomada.

Estudo multicêntrico brasileiro de eficácia e tolerabilidade da associaçäo de anlodipino e enalapril em formulaçäo galênica única no tratamento da hipertensäo arterial leve a moderada / Brazilian multicente study the efficacy and tolerability the association in anlodipino and enalapril in galenic fomulation in treatment arterial hypertension mild-to-mderate

Comparar o emprego de uma formulaçäo galêmica única da associaçäo do antagonista de cálcio dihidropiridínico nlodipino com o inibidor da enzima de conversäo enalapril, em duas dosagens diferentes, com a utilizaçäo isilada de cada um dos componentes da associaçäo notratamento de pacientes hipertensos essenciais leves a moderados. Utilizou-se um estudo multicêntrico, duplo cego, randomizado e paralelo. Foi avaliada a eficácia anti-hipertensiva com medida da pressäo arterial no consultório e monitorizaçäo ambulatorial da pressäo arterial (MAPA), a tolerabilidade, a segurança clínica por exames clínico-aboratoriais, os efeitos nos metabolismos glicídico e lipídico e na morfometria e funçäo cardíada. Visando avaliar de forma objetiva e temporal o desenvolvimento eventual do adverso do edema de membros inferiores, foi determinado de modo seriado o volume das pernas dos pacientes pela técnicaque utiliza o princípio de Arquimedes. O estudo teve duraçäo de 24 semanas e foram incluídos 99 pacientes com pressäo darterial diastólica entre 90 e 115 mm Hg após três semanas de retirada da medicaçäo anti-hipertensiva. Os esquemas terapêuticos mostraram-se seguros e adquados ao tratamento. A associaçäo galênica de anlodipino e enalapril nas duas doses empregadas apresentou, pela medida da pressäo arterial no consultório e por MAPA, eficácia anti-hipertensiva semelhante ao emprego de anlodipino isolado e superior à observada com uso exlusivo do enalapril. Ressalta-se que a eficácia da associaçäo foi obtida com doses menores que as empregadas com cada droga isolada. As duas dosagens da associaçäo mostraram perfil de tolerabilidade superior ao do anlodipino ou do enalapril isolados, com reduçäo significativa da incidência de tosse e de edema de membros inferiores, que foi acompanhada de um menor aumento no volume da perna. O tratamento com a associaçäo näo modificou os parâmetros metabólicos e determinou reduçäo nos 1ndices da morfometria do ventrículo esquerdo. A formulaçäo galêmica de anlodipino e enalapril é segura, útil, de alta eficácia e de melhor tolerabilidade que o emprego de cada componente isolado no tratamento de pacientes com hipertensäo essencial leve `a moderada

Dihydropyridine group of calcium channel antagonist in epilepsy.

Effects of intraperitoneally administered dihydropyridine calcium channel blocker-nifedipine (NIF) 5 mg/kg and diphenylhydantoin (DPH) 5 mg/kg were studied on hippocampal kindling and maximum electro shock thresholds (MEST). All the NIF injected rats showed complete suppression of behavioral seizure after the 3rd injection. Few of the DPH rats had increased epileptic activity for two days and others--absence of Grade--5 seizure after the 5th DPH injection. However, all showed partial seizure suppression subsequently. Neither NIF nor DPH could suppress the after discharge (AD). MEST were not affected by NIF although DPH showed a complete suppression of posterior limb extensor tone in all the rats.

Tratamiento con Amlodipina de la hipertensión arterial esencial leve/moderada / Treatment of the essencial arterial hypertension with Amlodipina

Se estudiaron 20 pacientes con el diagnóstico de hipertensión arterial esencial leve a moderada, con el objeto de investigar la eficacia y seguridad de la Amlodipina, como medicamento única o en combinación, en el tratamiento de la hipertensión esencial leve a moderada en la práctica clínica. Del total de 20 pacientes, 12 eran mujeres (60 por ciento ) y 8 hombres (40 por ciento ); la edad promedio fue de 51 años, con un peso medio de 66.26 Kg. Las cifras promedio de presión arterial al inicio del estudio fueron 164/103 mmHg. Se inició tratamiento con una dosis oral diaria de 5 mg de Amlodipina y al final de la sexta semana se realizó un ajuste de la dosis (10 mg/día) en nueve pacientes cuya presión arterial diastólica era mayor de 90 mmHg. Las cifras promedio de presión arterial a la décima semana fueron 151/88 mmHg, lo que representa un 100 por ciento de efectividad del medicamento en el control de la hipertensión arterial en el grupo de pacientes sujeto a estudio. Los efectos secundarios detectados durante el estudio fue un caso de edema de miembros inferiores leve, el cual se toleró sin necesidad de omitir el medicamento y que luego desapareció; los pacientes restantes tuvieron una excelente tolerancia a la droga

Novos diidropiridínicos bloqueadores do canal de cálcio / New dihydropyridine calcium channel blockers

Trata-se de uma revisäo sucinta do tratamento da hipertensäo e dos novos antihipertensivos diidropiridínicos bloqueadores do canal de cálcio, bem como das relaçöes estrutura química - atividade biológica e mecanismo de açäo destes fármacos