Introduction:Blood pressure (BP) reduction is the major determinant of benefit provided by antihypertensive treatment. Although different drugs reduce peripheral BP to some extent, there may be a significant difference in their effect on central BP reduction. It has been shown that beta-blockers are efficient in reducing peripheral, but not central BP. This study was done to assess the effect of beta-1-blocker, nebivolol, in patients with essential hypertension on central aortic pressures and arterial stiffness.Materials and Methods:In this single arm, open-labeled study, 13 patients were given nebivolol, 5 mg orally once daily for 15 days. Primary outcome was change in central aortic pressure, and other measures of efficacy included changes in brachial BP, augmentation index (AIx%), AIx%@75 HR, augmentation pressure (AP), heart rate (HR), and carotid femoral pulse wave velocity (PWVcf).Results:Nebivolol 5 mg significantly reduced central aortic pressures [systolic BP, 131.5–111.6 mmHg; diastolic BP, 96.3–81.7 mmHg; Mean Arterial Pressure (MAP), 111.3–94.0 mmHg (all P<0.0001), and Pulse Pressure (PP), 35.2-29.7 mmHg (P<0.01)]. AIx%@75 HR reduced from 29 to 21.6 (P<0.001) and PWVcf reduced from 8.6 to 7.2 m/s (P<0.001). One subject was lost to followup.Conclusion:Nebivolol 5 mg demonstrated antihypertensive efficacy in patients with essential hypertension by reducing not only peripheral brachial pressures, but also significantly reducing central aortic pressures, augmentation index, and carotid femoral pulse wave velocity, which is the marker of arterial stiffness.

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Angiotensin converting enzyme (ACE) inhibitors and dihydropyridine calcium antagonists are well established and widely used as monotherapy in patients with mild to moderate essential hypertension. Earlier studies combining short acting drugs from these classes require multiple dosing and were associated with poor compliance. Availability of longer acting compounds allows once daily administration to avoid the inconvenience of a multiple daily dose. It was decided to perform a randomised double blind, crossover study with the long acting calcium channel blocker amlodipine and the long acting ACE inhibitor lisinopril, given either alone or in combination in essential hypertension. Twenty four patients with diastolic blood pressure (DBP) between 95 and 104 mm Hg received amlodipine 2.5 mg and 5 mg, lisinopril 5 mg and 10 mg, and their combination as per a prior randomisation schedule. Supine and standing blood pressure and heart rate were recorded at weekly intervals. Higher doses of both the drugs individually or in combination were used if the target supine DBP below 90 mm Hg was not achieved. There was a significant additional blood pressure lowering eVect with the combination when compared either with amlodipine or lisinopril alone. Five mg amlodipine and 10 mg lisinopril monotherapy achieved the target blood pressure in 71% and 72% patients respectively. The combination of 2.5 mg amlodipine with 5 mg lisinopril produced a much more significant lowering of blood pressure in a higher percentage of patients than that with an individual low dose. (Postgrad Med J 2000;76:350-353)

In this study of healthy male volunteers, the 2 tablet preparations of clopidogrel showed bioequivalence. However, the sample size was smaller than that generally recommended for a bioequivalence study, and additional studies with larger sample sizes are needed.

The newly developed pain model produces a type of experimental pain that is responsive to analgesic effects of tramadol at clinically relevant doses. The model might be useful in early screening of new therapeutic agents before proceeding to expensive clinical trials in acute and chronic pain sufferers.

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Aim:An experimental pain model which is sensitive and reproducible would be a useful pharmacological tool both for existing and new drugs. The aim of the present study was to establish a simple and reliable method of producing experimental pain which can be used for screening of analgesic agents.Materials and Methods:The method was standardized by recording pain threshold and pain tolerance values in 24 healthy volunteers. Reproducibility of the test procedure was evaluated by recording the pain threshold and pain tolerance values by a single observer on two sessions (inter-day reproducibility), and second observer in one session (inter-observer reproducibility), separately. Validity of the model was further tested by evaluating the analgesic effect of tramadol in 12 healthy volunteers.Results:Cold pain model was found to produce low variability with coefficient of variation less than 15%. Inter-observer and inter-day reproducibility was very good as shown by Bland – Altman plot with most of the values within ± 2SD. Analgesic activity by Tramadol was statistically different from placebo (P < 0.05).Conclusion:The newly developed pain model offers a stable and sensitive method for the early assessment of analgesic activity.

Aims:The aim of the present study was to quantify the changes in pharmacodynamic response during cold stimulation-induced pain. Materials and Methods: In the present study we evaluated the effect of cold stimulation (immersion of hand into cold water, 1 ± 0.5°C) in 24 healthy human subjects. Change in skin conductance (in the form of galvanic skin response), skin temperature, and heart rate were recorded using the Data Acquisition System (Biopac mp 150). Results: There was significant increase in skin conductance (P<0.001) from 0.22 ± 0.19 microSiemens to 0.32 ± 0.27 microSiemens, with 58.3% increase from the baseline. The heart rate also significantly increased by 8.3% (P<0.001) from 85.6 ± 15.1 bpm to 92.2 ± 14.2 bpm. There was no significant change in skin temperature. Conclusion: The findings of this study showed that an increase in skin conductance seemed to be a good indicator of acute pain. The changes in skin conductance were influenced by acute pain; therefore, monitoring skin conductance could be used as a pharmacodynamic parameter in the evaluation of analgesic agents. Optimized content for mobile and hand-held devicesHTML pages have been optimized for mobile and other hand-held devices (such as iPad, Kindle, iPod) for faster browsing speed. Click on [Mobile Full text] from Table of Contents page. This is simple HTML version for faster download on mobiles (if viewed on desktop, it will be automatically redirected to full HTML version)