Drugs
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Review Comparative Study
Milrinone. A preliminary review of its pharmacological properties and therapeutic use.
Milrinone is a bipyridine derivative of amrinone, with approximately 10 to 75 times greater positive inotropic potency, and separate direct vasodilatory properties. As with amrinone, the relative importance of these properties to treatment of congestive heart failure still remain controversial. The mode of action of milrinone appears to be due in part to selective inhibition of a specific cardiac phosphodiesterase with a subsequent increase in intracellular cyclic adenosine monophosphate and alteration in intracellular and extracellular calcium transport. ⋯ One small study suggests that short term effects of intravenous milrinone may be superior to those of oral captopril, and it appears that the addition of captopril to milrinone therapy may produce a synergistic haemodynamic effect. Preliminary long term studies suggest that tolerance to the haemodynamic effects of milrinone does not occur, and that the drug is well tolerated and without the thrombocytopenic effects, fever and gastrointestinal complications observed with amrinone. However, it has not been demonstrated that milrinone improves the prognosis of the disease or the overall mortality and its propensity to produce arrhythmias has not been fully agreed upon.(ABSTRACT TRUNCATED AT 400 WORDS)
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Small spinal (intrathecal or extrathecal) doses of opioids induce a long-lasting and regional analgesic effect in various experimental animal models. Nowadays extrathecal morphine administration is considered an established method of controlling postoperative and cancer-induced pain conditions. The potency of morphine applied by the spinal route is higher than when the drug is applied by the intravenous (IV) route. ⋯ There are risks in replacing opioid administration by the oral or IV route with spinal opioids. Morphine should only be used in selected cases until the advantage of spinal opioid analgesia to control postoperative and cancer pain has been clearly defined in well-designed clinical studies. Spinal morphine dosages must be individualised according to the intensity of the nociceptive stimuli and should take into account intra-individual variability in drug responses due to pharmacokinetic and pharmacodynamic factors.
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Randomized Controlled Trial Clinical Trial
The pharmacodynamics and pharmacokinetics of multiple doses of the new H2-receptor antagonist, roxatidine acetate, in healthy men.
Roxatidine acetate (HOE 760, TZU 0460) is a new H2-receptor antagonist which is more potent than cimetidine and ranitidine. A randomised, double-blind, placebo-controlled study was conducted in healthy men to determine the effects of multiple oral doses of roxatidine acetate on unstimulated gastric acid secretion, and to assess the preliminary multiple-dose pharmacokinetics of its active desacetyl metabolite. The subjects were randomised to receive either roxatidine acetate 150 mg or placebo daily at 9 pm for 14 days. ⋯ The gastric pH increased with the mean plasma concentrations of the desacetyl metabolite. Mean plasma levels at steady state were attained between the 4th and 7th days after which there was no evidence of appreciable accumulation of the desacetyl metabolite. Roxatidine acetate 150 mg administered orally at 9 pm for 14 days to healthy men was safe, well tolerated, and produced clinically relevant increases in gastric pH, and decreases in gastric acid concentration, without affecting gastric fluid volume.
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Comparative Study
Haemodynamic effects of new beta-blockers with vasodilatory properties in essential hypertension.
Six weeks of treatment with carvedilol, N-696, celiprolol, dilevalol, acebutolol, urapidil, doxazosin and altiopril reduced blood pressure with various changes in heart rate. Cardiac index decreased and total peripheral resistance index (TPRI) stayed at the pretreatment levels in the carvedilol, N-696 and acebutolol groups, whereas TPRI tended to decrease in the celiprolol (p less than 0.05), dilevalol (p less than 0.05), urapidil, doxazosin (p less than 0.05) and altiopril groups; cardiac index was unchanged in these groups. ⋯ These results indicate that ISA on vascular beta 2-receptors may induce vasodilatation and ISA on cardiac beta 2-receptors may counteract cardiac beta 2-blockade. Differences in haemodynamic responses between these drugs with ISA and vasodilators such as alpha-blocking agents (urapidil and doxazosin) and an ACE inhibitor, altiopril, may be attributable to manifestation of cardiac beta-blockade as observed in the drugs with ISA.
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Randomized Controlled Trial Comparative Study Clinical Trial
The effects of roxatidine acetate on 24-hour intragastric acidity. Investigations in healthy volunteers and comparison with ranitidine and placebo.
In a series of double-blind randomised studies in normal volunteers with continuous intragastric pH monitoring, the effects of different dosage regimens of roxatidine acetate, a new H2-receptor antagonist, were compared with placebo and ranitidine. Roxatidine acetate 75 mg twice daily decreased median 24-hour gastric acidity from pH 1.6 to 3.2 and median nocturnal acidity from 1.5 to 3.0. ⋯ However, when drugs were taken after the evening meal (post cenam nocte; PCN) roxatidine acetate 150 mg was less potent than ranitidine 300 mg, with median night-time pH rising from 1.3 to 3.2 and 4.0, respectively, in 28 volunteers. Roxatidine acetate 300 mg PCN produced the greatest rise of pH, to 4.9, suggesting that the true potency ratio of the 2 drugs is between 1 and 2.