Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Feb 2001
Role of bradykinin and tachykinins in the potentiation by enalapril of coughing induced by citric acid in pigs.
Angiotensin-converting enzyme (ACE) inhibitors are among the first-choice drugs for treating hypertension and congestive heart disease. It has been reported, however, that these drugs could induce chronic cough and airway hyperresponsiveness. The aim of this work was to assess in pigs the effects of bradykinin and tachykinins on citric-acid-induced coughing after ACE inhibitor pretreatment. ⋯ When enalapril was combined with the three tachykinin receptor antagonists SR 140333 (NK1 receptor antagonist), SR 48968 (NK2 receptor antagonist) and SR 142801 (NK3 receptor antagonist), a significant decrease was observed as compared with control value obtained on day 1; the percentage of variation was also significantly different as compared with those observed in enalapril groups at both doses. These data suggest that ACE-inhibitor-induced enhancement of the cough reflex is mainly due to tachykinins and not to bradykinin in our pig model. Bradykinin, however, plays a major role in coughing induced by citric acid alone.
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Fundam Clin Pharmacol · Jul 2000
Randomized Controlled Trial Comparative Study Clinical TrialActivity of ebastine (10 and 20 mg) and cetirizine at 24 hours of a steady state treatment in the skin of healthy volunteers.
We have compared the inhibitory effects of ebastine (10 mg), ebastine (20 mg) and cetirizine (10 mg) on histamine-induced wheal and flare skin reactions 24 h following a 6-day-long treatment. This was a double-blind, randomised, crossover, placebo-controlled study involving 24 healthy volunteers (18-65 years) with negative skin prick tests and the absence of specific IgEs to common allergens. Subjects were randomised to receive each of the following treatments once daily for 6 days: ebastine (10 mg), ebastine (20 mg), cetirizine (10 mg) or placebo with a washout period of 5 days. ⋯ Our results clearly indicate that ebastine, at either recommended dosage of 10 and 20 mg, and cetirizine produced significant inhibition of the histamine-induced wheal and flare reaction compared to placebo for up to 24 h. A superior efficacy of 20 mg of ebastine is observed compared with 10 mg of ebastine and 10 mg of cetirizine on the skin wheal response 24 h after the last dose of a 6-day-long treatment. This study clearly proves ebastine to be an effective, truly once-daily antihistamine.
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Fundam Clin Pharmacol · Jul 2000
Tramadol relieves thermal hyperalgesia in rats with chronic constriction injury of the sciatic nerve.
The present study was designed to test whether tramadol is effective in the control of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve was induced over the left hind limb in male Sprague-Dawley rats. Identical surgery was performed on the opposite side except that the sciatic nerve was not ligated (sham surgery). ⋯ Tramadol also resulted in a decreased sensitivity to thermal stimulus on the sham limb both in acute and semi-chronic administration. We conclude that both acute and semi-chronic tramadol treatment relieves thermal hyperalgesia effectively in rats with CCI of the sciatic nerve. This indicates that tramadol shows promise as a potential treatment for relief of neuropathic pain in humans.
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Fundam Clin Pharmacol · Jul 2000
Additivity of bupivacaine and morphine for peripheral analgesia in rats.
Infiltration of the surgical wound is a classical technique for post-operative analgesia. Recent studies have suggested that local anaesthetic may be combined with other drugs such as opioids. This study has evaluated, in rat, the infiltration with morphine, bupivacaine and their combination. ⋯ The isobolographic analysis revealed only additivity between bupivacaine and morphine. The infiltration with morphine offers a peripheral analgesic effect which is additive with the effect of bupivacaine. An anti-inflammatory effect of morphine participates in this peripheral analgesic effect.
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Fundam Clin Pharmacol · May 2000
Comparative StudyEmitted doses of salbutamol pressurized metered-dose inhaler from five different plastic spacer devices.
In a recent clinical study we have demonstrated that the bronchodilator effect of 200 microg salbutamol (Ventoline) was spacer device-dependent in 100 tested asthmatic children, with the Babyhaler providing greater efficacy for improving peak expiratory flow rate compared to Aeroscopic, Nebuhaler, Aerochamber and Volumatic. The aim of this present study was to correlate our clinical results to in vitro determinations of the emitted dose (ED) of Ventoline administered via these five different plastic spacer devices. ED was determined from the mean of single doses collected in unit dose sampling tubes using a constant suction flow of 28.3 L/min. ⋯ Despite a greater ED from the Babyhaler, in vitro results do not fully explain the in vivo results. However, the previously described clinical improvement seen with the Babyhaler may be due to the quantitatively different aerosol production in a more 'useful' size range, as well as the different breathing patterns of the children tested. The results of this present study question the relevance of mouthpiece filter collection studies using a constant sampling in predicting clinical or physiological outcomes.