Drugs
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This review will discuss the safety profiles of the angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril and lisinopril in patients with hypertension. In general, the safety profiles of ACE inhibitors compare favourably with those of other agents used for the treatment of hypertension. Adverse effects are not common when ACE inhibitors are used at the currently recommended doses. ⋯ Other adverse effects such as cough and angioedema also occur with all ACE inhibitors. The mechanisms are poorly understood, making it difficult to predict in which patients they will occur. Adverse effects such as rash, dysgeusia, neutropenia and proteinuria, which were reported relatively frequently in the early experience with captopril, are reported less frequently with lower doses of captopril and do not appear to be a problem with other ACE inhibitors such as enalapril and lisinopril.
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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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The newer neuromuscular blocking drugs include vecuronium and atracurium. Vecuronium is a competitive neuromuscular blocking drug with a steroid nucleus. A dose of 0.1 mg/kg has an onset time of 2 minutes and provides surgical paralysis for 20 minutes. ⋯ The dose needed to induce sleep varies widely (0.15 to 0.5 mg/kg); onset is slow (1.5 to 5 minutes), and recovery may be prolonged. Midazolam is also used in lower doses as a sedative. Ketamine, an intravenous induction agent, has recently been used intrathecally and extradurally to provide analgesia.
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Nausea and vomiting continue to be critical problems in cancer chemotherapy, although considerable progress has been made toward understanding the neuropharmacological mechanisms of vomiting and how chemotherapeutic agents and antiemetics affect these mechanisms. The principles of behavioural psychology have also been applied in an effort to understand and effectively manage these complications which have potentially serious consequences. For example, there is now some degree of rationality to our use of metoclopramide for cisplatin-induced nausea and vomiting, the use of combination antiemetic regimens, and use of lorazepam for the prevention (albeit unproven) of anticipatory nausea and vomiting. ⋯ The role of behavioural therapies, which have been shown to be effective particularly in children and in anticipatory nausea and vomiting, needs to be more firmly established. Rather than recommending a given antiemetic programme for any particular chemotherapy, it is preferable to think in terms of initial approaches and how they can be modified. No one antiemetic programme is effective or safe in all situations.