摘要:

Comprehension and recall of the information contained in the informed consent statement was tested in clinically hypertensive patients entering a controlled trial comparing hydrochlorothiazide and propranolol. The consent statement was the primary vehicle for conveying the information to the patient. The average of correct answers to a multiple‐choice quiz was 71.6% at 2 hr and 61.2% at 3 mo after the consent procedure. The effectiveness of recall did not correlate with level of education. Patients exhibited greater comprehension of the action of the drugs than of their side effects. Nearly all patients indicated their belief that they would receive the best possible care. While 95% wanted to be informed about the trial, 75% stated they would have given their consent even without this information.Clinical Pharmacology and Therapeutics(1980)27,435–440; doi:10.1038/clpt.198

ISSN:0009-9236    

DOI:10.1038/clpt.1980.60

年代:1980

数据来源: WILEY

摘要:

Five patients with moderate hypertension were given placebo and at least 3 single oral doses (25, 50, 75, 100, or 150 mg) of metoprolol as well as multiple doses at at least 2 dose levels (25, 50, or 100 mg thrice daily). Blood pressure, pulse rate at rest, plasma renin activity, and drug plasma concentration were intensively monitored during 7.5 hr after each dose. Pulse rate, systolic blood pressure, and plasma renin activity decreased after the single oral doses, but diastolic blood pressure did not decrease consistently. The correlation coefficients between percentage decrease in systolic blood pressure and pulse rate and total plasma concentrations were higher individually than in the group. The corresponding regression equations were different between individuals and for systolic blood pressure there was a 700% difference in regression coefficients. The acute changes in diastolic blood pressure and plasma renin activity were not related to metoprolol plasma concentrations. The decrease in systolic blood pressure and pulse rate on multiple doses could not be predicted from the response after single doses.Clinical Pharmacology and Therapeutics(1980)27,441–449; doi:10.1038/clpt.1980.

ISSN:0009-9236    

DOI:10.1038/clpt.1980.61

年代:1980

数据来源: WILEY

摘要:

The kinetics of quinidine and propranolol, administered singly and in combination, were evaluated in 5 healthy subjects. The orally administered doses resulted in plasma concentrations within the therapeutic range. For each drug the average steady‐slate plasma concentration, maximal plasma concentration, and time of maximum plasma concentration were not altered by the presence of the other drug. This study shows no kinetic interaction between quinidine and propranolol in normal subjects.Clinical Pharmacology and Therapeutics(1980)27,450–453; doi:10.1038/clpt.198

ISSN:0009-9236    

DOI:10.1038/clpt.1980.62

年代:1980

数据来源: WILEY

摘要:

Organ selectivity of beta sympathetic blockade with propranolol was studied in 6 normal men by comparing the cardiovascular and respiration responses during isoproterenol infusions before and after propranolol. Beta sympathetic blockade was achieved with propranolol and was considered present when there was no heart rate (HR) response to isoproterenol during an infusion tenfold greater than that which raised HR 25% during a control period. During blockade there was no change in HR or systolic or diastolic blood pressure during isoproterenol infusions. There was a consistent (p<0.05) rise in resting ventilation (+17%), oxygen consumption (+9%), and carbon dioxide production (+15%) with low‐dose (raised HR 10% before blockade) isoproterenol infusion during blockade. These respiratory effects of low‐dose isoproterenol during cardiovascular blockade were quantitatively similar to that before blockade. With infusion that raised HR 25%, there was a further increase in V̇E, V̇O2, and V̇CO2before blockade but no further increase during beta blockade. Changes in acid‐base status did not explain the increase in V̇Eduring blockade. We conclude that there are differences between effectiveness of propranolol blockade of the cardiovascular system and of the respiratory system.Clinical Pharmacology and Therapeutics(1980)27,454–459; doi:10.1038/

ISSN:0009-9236    

DOI:10.1038/clpt.1980.63

年代:1980

数据来源: WILEY

摘要:

To assess the effects of acebutolol and propranolol on resting left ventricular function, 21 patients with coronary artery disease were studied. A baseline echocardiogram was obtained on day 1, and in a double‐blind, randomized, crossover study the patients received 40 mg propranolol every 8 hr for 1 wk, 300 mg acebutolol every 8 hr for 1 wk, and 1 capsule placebo every 8 hr for 1 wk. On days 8, 15, and 22, after an echocardiogram at 7:30 A.M. (i.e., 7.5 hr after the midnight dose), they received double‐blind randomized, crossover medications (acebutolol 300 mg, propranolol 40 mg, or placebo). The echocardiogram was repeated at 1, 2, and 4 hr after placebo or propranolol and at 2, 3, and 5 hr after acebutolol. The left ventricular end diastolic dimension, left ventricular end systolic dimension, percent systolic shortening of the left ventricular minor axis, and ejection fraction were determined. We found that there was no significant difference between control values for any of the above parameters and those obtained at 1, 2, 4, or 7.5 hr after propranolol or placebo and at 2, 3, 5, or 7.5 hr after acebutolol. We conclude that in the doses used, acebutolol and propranolol do not induce depression of resting left ventricular function in patients with coronary artery disease who have normal or near normal left ventricular function at rest.Clinical Pharmacology and Therapeutics(1980)27,460–463; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1980.64

年代:1980

数据来源: WILEY

摘要:

A new class I antiarrhythmic, flecainide, was investigated in 10 patients to assess short‐term efficacy and safety. All patients were hospitalized for 3 days; no antiarrhythmics were given on days 1 and 3. On day 2 flecainide 1 mg/kg was given intravenously over 5 min. If the predrug arrhythmia(s) was not completely suppressed, additional boluses of 0.5 mg/kg were injected at 30‐ to 60‐min intervals to a maximum of 2 mg/kg. Seven patients received 2 mg/kg, and 3 patients received 1 mg/kg. Before drug 5 patients had premature ventricular contractions (PVCs) (more than 4 per min); 2 patients had atrial fibrillation (AF) with PVCs; 1 patient had both PVCs and premature atrial contractions (PACs); and 2 patients had only PACs. One patient with PVCs failed to respond to flecainide; he was unresponsive to all available antiarrhythmic drugs. In the other 7 patients PVCs were suppressed for an average of 13 hr (range 6 to 24 hr), AF was not affected, and PACs were suppressed. Flecainide did not induce significant changes in P‐R, QRS, or Q‐T intervals. Side effects were negligible and included a tingling sensation and feeling of skin warmth for 15 min after drug in one patient.Clinical Pharmacology and Therapeutics(1980)27,464–470; doi:10.1038/

ISSN:0009-9236    

DOI:10.1038/clpt.1980.65

年代:1980

数据来源: WILEY

摘要:

Timolol is a beta adrenergic antagonist in 0.25% or 0.5% eyedrop solution for glaucoma. In a double‐blind crossover study in healthy males we measured systemic beta blockade, intraocular pressure, and timolol kinetics after the first and ninth 12‐hourly dose of a 0.5% ophthalmic solution. Timolol ophthalmic and placebo were each given as 2 drops to each eye with precautions to prevent the normal loss of drug in tears and overflow (high dose) and as 1 drop to each eye with no special precautions (standard therapeutic dose). Exercise tachycardia, measured at 70 and 255 min after administration of drug, was lower at both levels. Postexercise 1‐sec forced expiratory volume (FEV1) was not affected. Intraocular pressure measured at 3 and 8 hr after drug was lower at both dose levels. Timolol was consistently present in urine but was not detectable in most plasma samples. Dynamic effects were not greater after the ninth than after the first dose, and the urinary excretion data provided no evidence of drug cumulation.Clinical Pharmacology and Therapeutics(1980)27,471–477; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1980.66

年代:1980

数据来源: WILEY

摘要:

The respiratory depressant capacities of intravenous nalbuphine, a potent analgesic of the narcotic antagonist type, and of morphine were compared in 23 healthy subjects using displacement of CO2response by a steady‐state method as the index of respiratory depression. At equianalgesic doses of 10 mg/70 kg, respiratory depression by nalbuphine was equal to that by morphine. When increments of 10 mg/70 kg were given hourly the dose‐effect curve for respiratory depression by nalbuphine was flatter than that of morphine, and maximum respiratory depression occurred after 30 mg/70 kg. In a separate study of 10 subjects nalbuphine was administered in 10 mg/70 kg increments to a total dose of 60 mg/70 kg; doses in excess of 30 mg/70 kg failed to increase respiratory depression beyond that induced by morphine 20 mg/70 kg. A ceiling effect for respiratory depression previously known to exist only for nalorphine was thereby demonstrated to apply to nalbuphine. The respiratory depression of nalbuphine was readily antagonized by naloxone 0.4 mg, nalorphine 10 mg, and levallorphan 1.0 mg. Subjective effects of nalbuphine were milder than those of morphine, and dysphoria suggestive of the psychotomimetic effects of narcotic antagonists was reported only 4 times in 24 subject exposures. The ceiling effect for respiratory depression by nalbuphine provides a unique safety factor among potent analgesics.Clinical Pharmacology and Therapeutics(1980)27,478–485; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1980.67

年代:1980

数据来源: WILEY

摘要:

Whether meperidine metabolism is affected by pregnancy or immaturity has not been clearly established. This is of interest because meperidine is commonly given during labor for pain relief and the fetus receives the drug in utero. Moreover, animal studies suggest that the hormones of pregnancy contribute to decreased activity of the drug‐metabolizing enzymes. In our study gas chromatography was used to determine the concentrations of meperidine and normeperidine in the plasma and urine of pregnant and nonpregnant women and in the urine of neonates. Plasma samples were collected for at least 3 hr after a dose of meperidine intravenously to calculate the kinetic parameters of meperidine disposition; urine samples were collected for 3 days. In contrast to reports on animals, we found that pregnant and nonpregnant women readily metabolize meperidine to normeperidine and excrete both in a similar manner. No significant differences were demonstrated between any of the kinetic constants for peripartum and nonpregnant subjects. The neonate was found to metabolize and excrete these drugs less rapidly.Clinical Pharmacology and Therapeutics(1980)27,486–491; doi:10.1038/clpt.198

ISSN:0009-9236    

DOI:10.1038/clpt.1980.68

年代:1980

数据来源: WILEY

摘要:

Naloxone tests for opiate dependence were given to 296 applicants for treatment with the surrogate opiate levomethadyl acetate (LAAM, levo‐alpha‐acetylmethadol) and to 103 applicants for treatment with the opiate antagonist naltrexone. Thirty‐five of the 296 LAAM applicants applied first for LAAM, then following detoxification, for naltrexone. There was a dramatic decrease in withdrawal signs and symptoms when the subject went from an opiate‐dependent to a nondependent state. From our experience, we devised a scoring guide and testing procedure based on objective signs. We propose a 2‐step test, with an initial intramuscular dose, then (if necessary) an intravenous dose, to determine an applicant's eligibility for surrogate opiate or narcotic antagonist treatment.Clinical Pharmacology and Therapeutics(1980)27,492–501; doi:10.1038/

ISSN:0009-9236    

DOI:10.1038/clpt.1980.69

年代:1980

数据来源: WILEY