摘要:

The reversal of acute alcohol intoxication by naloxone is controversial. Naloxone increases cortisol secretion but there are no reports of this effect during acute alcohol intoxication. This study examines the effect of 20 mg naloxone on alcohol‐induced intoxication using a balanced placebo design to investigate the role of cortisol, participant expectancy of treatment, and possible pharmacokinetic interactions during intoxication. Our results show differences in the time course of subjective self‐evaluation of drunkenness in the presence of naloxone. Also, changes are observed in naloxone pharmacokinetic parameters with the ingestion of alcohol, specifically a decrease in plasma clearance. Whereas the cortisol response induced by naloxone was greater in the subgroup of participants with positive expectancy, in the presence of alcohol the naloxone effect on cortisol response was not observed. These observations may help explain the observed reversal of alcohol‐induced coma by naloxone in a subgroup of patients.Clinical Pharmacology and Therapeutics(1988)43, 599–604; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1988.82

年代:1988

数据来源: WILEY

摘要:

In a study of serotonin (5‐HT) function in patients with eating disorders and healthy control subjects, severe headaches with features of common migraine occurred unexpectedly in 28 of 52 subjects (54%) 8 to 12 hours after receiving a single oral dose of the 5‐HT receptor agonistm‐chlorophenylpiperazine (m‐CPP), 0.5 mg/kg. None of the same subjects developed similar late‐occurring headaches after placebo or the 5‐HT precursor, L‐tryptophan, 100 mg/kg given intravenously. The frequency of these migrainelike headaches was not significantly different between patients with bulimia or anorexia nervosa and control subjects, but incidence of headaches was significantly greater in subjects with a personal or family history of migraine, with almost all predisposed individuals (18 of 20, 90%) developing severe symptoms. Headache ratings were also significantly correlated (rho = 0.70;p<0.0001) with peak concentrations ofm‐CPP in plasma. These observations indicate thatm‐CPP may provide a novel probe for studies of the pathophysiology of migraine headaches.Clinical Pharmacology and Therapeutics(1988)43, 605–609; doi:

ISSN:0009-9236    

DOI:10.1038/clpt.1988.83

年代:1988

数据来源: WILEY

摘要:

A meta‐analysis was performed to reevaluate the efficacy of dipyridamole for prophylaxis of angina pectoris. We found 10 articles that reported 11 randomized control trials published between 1960 and 1970. Three trials found a statistically significant benefit for the drug vs placebo, four showed a positive trend, two found no difference, and two showed a slight trend favoring placebo. When the results of all 11 trials were combined, two different statistical methods showed a statistically significant benefit from the drug. These combined results must be interpreted cautiously because of excluded patients and other methodologic variations in the studies, as well as evidence from other studies that dipyridamole may aggravate angina. Nevertheless, we conclude that there is some evidence for efficacy of the drug and believe the question should be restudied in larger and better‐designed trials.Clinical Pharmacology and Therapeutics(1988)43, 610–615; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1988.84

年代:1988

数据来源: WILEY

摘要:

Low‐dose angiotensin‐converting enzyme inhibition is thought to completely block the renin‐angiotensin system. This study examined the hemodynamic and hormonal responses to initial low‐ and higher dose converting‐enzyme inhibitor (lisinopril or captopril) at rest compared with the response during subsequent chronic therapy while treadmill exercise testing was performed in nine patients with chronic heart failure. At rest, similar changes in systemic arterial pressure, plasma renin activity, and plasma aldosterone concentration were found with initial low and higher doses. However, after at least 4 weeks of therapy, dose‐dependent increases in plasma renin activity and decreases in plasma aldosterone concentration were noted during exercise without significant differences in exercise systemic arterial pressure or heart rate. This discrepancy suggests that initial low‐dose converting enzyme inhibition does completely block the enzyme, but higher dose therapy is required for complete blockade during subsequent exercise in chronic heart failure.Clinical Pharmacology and Therapeutics(1988)43, 616–622; doi:10.1

ISSN:0009-9236    

DOI:10.1038/clpt.1988.85

年代:1988

数据来源: WILEY

摘要:

Trough serum methadone concentration was measured in 43 patients under treatment for heroin addiction and complaining of withdrawal symptoms. Low serum levels were noted only in patients taking very low doses and in 10 patients who were concomitantly using enzyme‐inducing drugs. The 27 patients in the maintenance program who had trough levels greater than 100 ng/ml were given no dose increase and were followed up prospectively. Alternate explanations for the patient's symptoms were well accepted in almost all cases, and subsequent performance in the treatment program appeared to be independent of serum level. We conclude that a trough serum level of 100 ng/ml is adequate for effective methadone maintenance. Measurement of serum levels can be a valuable intervention in patients with difficulties.Clinical Pharmacology and Therapeutics(1988)43, 623–629; doi:10.1038/clpt.198

ISSN:0009-9236    

DOI:10.1038/clpt.1988.86

年代:1988

数据来源: WILEY

摘要:

The rate of formation of the three initial metabolites of cyclosporine metabolism has been determined in liver microsomes of 15 kidney transplant donors. Interindividual variation in metabolite formation was considerable but all three metabolites varied in parallel. An antiserum raised against a steroid‐inducible rat cytochrome P‐450 (P‐450 PCN) strongly inhibited the formation of these metabolites. Immunoquantitation of the protein recognized by a monoclonal antibody reacting with human cytochromes P‐450 of the P‐450III gene family, homologues of rat P‐450 PCN and rabbit P‐4503C, revealed a high degree of correlation with microsomal cyclosporine metabolism. The data suggest that this cytochrome P‐450 is the major cyclosporine‐metabolizing enzyme in human liver. The substrate specificity and the known inducers and inhibitors of this cytochrome P‐450 explain several clinically observed drug interactions with cyclosporine.Clinical Pharmacology and Therapeutics(1988)43, 630–635; do

ISSN:0009-9236    

DOI:10.1038/clpt.1988.87

年代:1988

数据来源: WILEY

摘要:

We examined the hypothesis that excess accumulation of major quinidine metabolites or the commercial impurity dihydroquinidine contributes to the development of polymorphic ventricular tachycardia (torsades de pointes, [TdP]) in patients taking quinidine. Total and free plasma concentrations of these compounds were measured by reverse‐phase HPLC with fluorescence detection and equilibrium dialysis in 19 patients with TdP and 38 control patients tolerating quinidine therapy without toxicity. No significant differences were found between the two groups of patients. Ratios of metabolite or dihydroquinidine to quinidine varied up to tenfold among patients but were similarly distributed in the TdP and control groups. Only the metabolite 3‐hydroxyquinidine was present at free plasma concentrations that exceeded free concentrations of quinidine. We conclude that although quinidine metabolism is highly variable, there does not appear to be any correlation between the plasma concentrations of quinidine, its metabolites or dihydroquinidine, and the subsequent development of TdP.Clinical Pharmacology and Therapeutics(1988)43, 636–642; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1988.88

年代:1988

数据来源: WILEY

摘要:

We have studied the effect on serum gastrin concentrations of weekly 3‐day courses of 20 mg/day omeprazole followed by a 4‐day period without medication (weekend therapy) for 4 weeks in 10 patients with duodenal ulcer. Basal and postprandial serum gastrin concentrations were measured in week 1, before (day 1) and immediately after the 3‐day omeprazole course (day 4), and further on day 6 and day 8, immediately before the next course, and at similar intervals in week 4 (days 22, 25, 27, and 29). Basal serum gastrin concentrations were not significantly different from day 1, but postprandial peak gastrin concentrations on days 6, 8, 22, 25, 27, and 29 and integrated postprandial gastrin secretion on days 25 and 27 were significantly increased (p<0.01 top<0.05). However, the increases in serum gastrin concentration were modest and clinically irrelevant. It is concluded that this intermittent weekend schedule of omeprazole therapy does not induce marked hypergastrinemia and may therefore be suitable for long‐term therapy with this drug.Clinical Pharmacology and Therapeutics(1988)43, 643–647; doi:10.1038/cl

ISSN:0009-9236    

DOI:10.1038/clpt.1988.89

年代:1988

数据来源: WILEY

摘要:

Clonidine can produce symptomatic sinus bradycardia or atrioventricular (AV) block in some patients. Electrophysiologic studies have been performed after intravenous clonidine in patients showing such side effects; these have demonstrated variable depression of sinus and AV nodal function. We have evaluated the electrophysiologic and hemodynamic effects of chronic oral treatment with either clonidine (0.2 to 0.5 mg every 12 hours; n = 7) or another centrally active α2‐agonist, tiamenidine (0.5 to 1.5 mg every 12 hours; n = 7), in otherwise healthy hypertensive human volunteers. At dosages that modestly lowered diastolic blood pressure, both agents significantly slowed sinus rate and increased the atrial pacing rate producing AV nodal Wenckebach. Clonidine also significantly increased corrected sinus node recovery time and lowered cardiac output while similar (but statistically insignificant) trends were seen with tiamenidine. We conclude that chronic oral treatment with these α2‐agonists depresses sinus and AV nodal function in virtually all subjects, including those without manifest conduction system disease.Clinical Pharmacology and Therapeutics(1988)43, 648–654; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1988.90

年代:1988

数据来源: WILEY

摘要:

The effects of nadolol (20 and 80 mg) on blood pressure and sleep parameters were assessed in six patients with mild hypertension. A 32‐night experimental protocol in the sleep laboratory was instituted consisting of four placebo‐baseline nights followed by 4 weeks of drug administration. Both doses of nadolol had a clear‐cut and consistent lowering effect on blood pressure throughout the night and during the day, with a greater reduction noted with the 80 mg dose. In fact, blood pressure values were reduced to normotensive levels. Neither dose had a disrupting effect on sleep, whereas the 80 mg dose improved sleep efficiency and also had a rapid eye movement‐enhancing effect. This absence of sleep‐disrupting effects is attributed to nadolol's low level of lipophilicity and lack of intrinsic sympathomimetic activity. The clinical significance of the lack of sleep disruption and possible improvement of sleep with nadolol is discussed in light of the well‐recognized sleep disturbances produced by other β‐blockers.Clinical Pharmacology and Therapeutics(1988)43, 655–662; doi:10.

ISSN:0009-9236    

DOI:10.1038/clpt.1988.91

年代:1988

数据来源: WILEY