International journal of clinical pharmacology, therapy, and toxicology
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Int J Clin Pharmacol Ther Toxicol · Oct 1993
Comparative StudyComparison of the bronchodilator efficacy of nebulized pirenzepine and ipratropium bromide in patients with airway obstructive lung disease.
Ipratropium bromide (IB) is a non-selective muscarinic antagonist, whose bronchodilator efficacy has been shown in reversible and irreversible obstructive airway diseases. Pirenzepine is a M1 receptor antagonist and effective in vagally-induced bronchoconstriction. To investigate the bronchodilator efficacy of nebulized pirenzepine, we compared nebulized pirenzepine with nebulized IB and nebulized isotonic saline (placebo). ⋯ IB at the same dose resulted in an increase in FVC in patients with irreversible bronchoconstriction (p < 0.001) and an increase in FEF25-75 in patients with reversible bronchoconstriction (p < 0.0003). Pirenzepine therapy resulted in no significant change in the same parameters. It is concluded that nebulized pirenzepine at a dose of 100 mcg does not have bronchodilator effect in patients with reversible or irreversible bronchoconstriction.
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Int J Clin Pharmacol Ther Toxicol · Apr 1992
"Train-of-four" fade during clinical nondepolarizing neuromuscular block.
Previous clinical studies on the train-of-four (TOF) fade have used different recording techniques, anesthesia agents and muscles for measurement, thus comparison of the results has become difficult. On 49 surgical patients divided into 6 groups, we compared: 1) The TOF fade ratios (T4/T1) produced by d-tubocurarine (dTc), pancuronium (P), atracurium (A), and vecuronium (V) and 2) the influence of previously given suxamethonium on TOF ratios (dTc and P). Neuromuscular block (NMB) was monitored simultaneously by electromyography (EMG) and by mechanomyography (MMG). Differences between the TOF fade ratios of different groups were determined and statistically analyzed by ANOVA of repeated measures, 1) at onset, as compared to spontaneous recovery with the same agent, 2) between NMB agents at (a) onset and (b) during recovery. ⋯ TOF fade was significantly more pronounced during spontaneous recovery than during onset of NMB: a) with all NMB agents, b) with both EMG and MMG responses, with bolus dose administration of the agents, c) the degrees of TOF fade significantly differed between NMB agents during onset, d) the degrees of TOF fade (MMG) were more pronounced during onset when the agents were given in incremental doses following succinylcholine as compared to degrees of fade following single bolus doses in the absence of succinylcholine. During recovery, there was also difference in the TOF fade ratios among the agents: dTc and P produced more fade than A and V.(ABSTRACT TRUNCATED AT 250 WORDS)
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Int J Clin Pharmacol Ther Toxicol · Nov 1991
Comparative StudyHeparin-induced hyperkalemia: a prospective study.
Heparin is frequently used for the prophylaxis and treatment of deep venous thromboembolism and it induces hypoaldosteronism leading to hyperkalemia, an uncommon adverse effect. In an intensive prospective drug monitoring study, 154 inpatients at the Internal Medicine Unit of Hospital Sotero del Río, Santiago, Chile, received heparin in the period between March and November 1990. Mean age of the patients was 65.8 +/- 12.9 years and 56.5% were female. ⋯ Almost all reactions were dose-related. Hyperkalemia was more frequent in patients with diabetes mellitus, metabolic acidosis and long-term heparin therapy. The frequency of hyperkalemia did not correlate with age, sex, renal impairment or with previous use of anti-inflammatory drugs, heparin or aspirin.
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Int J Clin Pharmacol Ther Toxicol · May 1990
Diazepam loading in alcohol withdrawal: clinical pharmacokinetics.
The pharmacokinetics of diazepam and its major active metabolite, desmethyl-diazepam, following a loading dose of diazepam (fixed oral doses of 20 mg) were studied in 16 patients on alcohol withdrawal. No toxic drug levels were measured irrespective of the amount of diazepam needed on the loading (83 +/- 27 mg on average). The mean elimination half-life of diazepam fell within the range observed in healthy persons after the ingestion of therapeutic doses (5), or it was only moderately prolonged (t1/2 49.7 h). ⋯ Standard liver function tests could not predict the length of the elimination half-life of diazepam. Active drug concentrations remained high during the first 48 h of treatment, followed by a steady decline. On the basis of this study, it seems that diazepam can be safely and effectively used in loading doses in the treatment of alcohol withdrawal.
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Int J Clin Pharmacol Ther Toxicol · Jan 1990
Protection from stress of tracheal intubation with midazolam-sufentanil neuroleptanalgesia.
Although diazepam has been shown to reduce the stress response, the protective effect of midazolam, a newer benzodiazepine from a stressful event, tracheal intubation, has not been studied as yet by catecholamine assays in patients undergoing coronary artery bypass surgery, who also receive intravenous sufentanil as a component of the neuroleptanalgesic technique. Therefore, we evaluated the influence of midazolam in combination with sufentanil on the plasma free catecholamines before and after midazolam, after sufentanil and pancuronium and before and after intubation in 15 adult patients undergoing coronary artery surgery. After routine premedication, midazolam 0.14 +/- 0.01 mg.kg-1 i.v. was given over 1 min followed 5 min later by sufentanil in incremental i.v. doses of 1.5 micrograms.kg-1 to a total pre-intubation dose of 4.0-5.0 micrograms.kg-1 injected in 10 min. ⋯ Midazolam administration per se caused a significant decrease in systolic and diastolic blood pressures with a concomitant reduction in systemic vascular resistance. Sufentanil reduced the left ventricular stroke-work index. Tracheal intubation, a strong stressor during anesthesia, elicited no increase in catecholamines and/or adverse hemodynamic responses in contrast to a marked increase in plasma catecholamines routinely observed in patients anesthetized by the commonly used technique of intravenous barbiturates in combination with succinylcholine.