ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02697.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:In a multicenter randomized double‐blind trial, we compared the antihypertensive effects of 12 weeks of therapy using timolol maleate, a new beta‐adrenergic blocking agent, alone and in combination with hydrochlorothiazide, and hydrochlorothiazide alone in 70 outpatients with mild to moderate uncomplicated essential hypertension (61 of whom completed the study). All three groups showed significant blood pressure reductions in both supine and standing positions which were most marked in the timolol—hydrochlorothiazide group (154/103 → 129/85 mm Hg). A good or excellent therapeutic response was obtained in 20 of 21 patients in the timolol—hydrochlorothiazide group, in 16 of 20 patients receiving timolol alone, and in 10 of 20 receiving hydrochlorothiazide alone. Adverse reactions were minimal in all treatment groups but highest in the hydrochlorothiazide group. It was concluded that timolol—hydrochlorothiazide combination is more effective than either drug alone for management of hypertension and that timolol alone or with hydrochlorothiazide is wel

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02698.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:To study the electrophysiologic mechanisms responsible for the digitalis—quinidine interaction, 27 mongrel dogs were given either quinidine alone, digoxin alone, or digoxin followed by the digoxin—quinidine combination, via the oral route for sufficient time to permit accumulation of steady‐state plasma levels. As anticipated, digoxin levels increased significantly in the presence of quinidine (P<0.05). Whereas digoxin alone had no significant effect on the ECG, quinidine alone prolonged the Q—T interval (P<0.05), and the combination prolonged both the QRS complex and the Q—T interval (P<0.05). Digoxin alone had no significant effect on the Purkinje fiber transmembrane potential, whereas quinidine reduced action potential (AP) amplitude and maximum upstroke velocity (V̇max) significantly. The combination significantly reduced AP amplitude, V̇max, and maximum diastolic potential and prolonged AP duration. The changes induced by the drug combination appeared to be the sum of changes induced by each

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02699.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Sympathetic neuronally released norepinephrine appears to act at intrajunctional α1‐adrenoceptors, whereas administered norepinephrine acts mostly at extra‐junctional α2‐adrenoceptors. We examined the effects of inhibition of neuronal uptake of norepinephrine by desipramine (0.3 mg/kg iv) and cocaine (5 mg/kg iv) on the pressor effects and on plasma norepinephrine levels in pithed rats after the administration of norepinephrine (0.1, 0.3, and 1.0 μg/kg iv) or during stimulation of sympathetic outflow (0.1, 0.3, and 1.0 Hz at 50 V for 1 minute). Desipramine and cocaine potentiated the cardiovascular effects of administered norepinephrine to a greater extent than they potentiated the effects of sympathetic stimulation. Plasma levels of norepinephrine during sympathetic stimulation or after iv administration of norepinephrine were increased significantly after either desipramine or cocaine. The cardiovascular effects of sympathetic stimulation, but not of exogenous norepinephrine, were reduced in adrenomedullectomized rats compared to intact rats. In adrenomedullectomized rats, desipramine potentiates the pressor responses and enhances the increase in plasma norepinephrine levels during sympathetic stimulation to the same extent as in intact pithed rats. The preferential potentiation of administered norepinephrine by uptake inhibition is most likely due to enhancement of accessibility of circulating norepinephrine to otherwise inaccessible intrajunctional α1‐adrenoceptors. The higher concentrations of norepinephrine in the region of the nerve‐ending limit release of the neurotransmitter by feedback inhibition via presynaptic α2‐adrenoceptors, thereby masking potentiation by uptake inhibition of the postsynaptic responses to sympath

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02700.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Loprazolam is a benzodiazepine derivative which possesses, in animals, a potent hypnotic effect. In a double‐blind single‐dose study, three dose levels of loprazolam (0.5, 1.0, and 2.0 mg) were compared to each other as well as to 15 mg flurazepam and placebo in 60 insomniac outpatients. The 0.5‐ and 1.0‐mg doses demonstrated hypnotic potency comparable to that of flurazepam, and all three treatments were superior to placebo. The hypnotic effect of the 2‐mg dose of loprazolam was significantly greater than that of the other treatments, but at this dose, patients experienced significantly more side effects and morning

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02701.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The analgesic effect of preoperatively administered ibuprofen was evaluated in 107 dental outpatients undergoing the removal of impacted third molars. Subjects were given 800 mg ibuprofen prior to the procedure and 400 mg ibuprofen 4 and 8 hours later. Comparison was made to groups receiving either placebo at all three doses, 600 mg acetaminophen administered on the same schedule, or preoperatively administered placebo followed by two doses of postoperatively administered 600 mg acetaminophen plus 60 mg codeine. Ibuprofen pretreatment resulted in significantly less pain than placebo or acetaminophen pretreatment as the local anesthetic wore off. Ibuprofen also resulted in less postoperative pain than acetaminophen plus codeine following the second dose. Side effects were similar across drug teatments and placebo with the exception of greater reports of drowsiness following the opiate—analgesic combination. These findings indicate that pretreatment with a nonsteroidal antiinflammatory drug, such as ibuprofen, results in a suppression of postoperative pain when compared to standard therapy without an increase in side effect

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02702.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:In this single‐dose, double‐blind study, the analgesic activity of 400 and 200 mg doxpicomine was compared with 100 and 50 mg meperidine and placebo when given intramuscularly in 102 subject patients experiencing severe postoperative pain. Results indicate that 400 mg doxicomine is similar to 100 mg meperidine in analgesic activity, onset, and duration of action. Side effects were of the same order as those produced by other centrally acting analges

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02703.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The objective was to determine whether deltoid as compared to gluteal injection of morphine and methadone produce differential plasma levels and analgesic effects. Thirty‐two postoperative cancer patients received deltoid and gluteal injections of morphine, 8 and 16 mg, within a double‐blind, twin crossover design. Forty‐four patients received deltoid or gluteal methadone, 10 mg. Deltoid morphine resulted in peak plasma levels 1.8 times (P<0.05) those observed following gluteal morphine. Deltoid methadone resulted in peak levels 2.5 times (P<0.005) those following gluteal injection. Deltoid morphine resulted in an area under the drug level—time (0 to 4 hours) curve 1.4 times (N.S.) the area observed following gluteal injection. Deltoid methadone resulted in an area under the drug level—time (0 to 4 hours) curve 2.2 times (P<0.001) the area observed following gluteal injection. Deltoid methadone, but not morphine, provided greater (1.7‐fold,P<0.05) pain relief than gluteal injection. If more rapid and enhanced analgesia is indicated, then the deltoid site may be preferable over the gluteal site for standard doses of methadone and other lipid soluble analgesics. In addition, the relative potency of compounds of widely differing lipid solubility may depend upon the site of intramuscula

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02704.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:A new renal function test was developed based upon the pharmacologic effects of furosemide to quantify separately the rates of electrolyte and water reabsorption by different segments of the human nephron in vivo. Since furosemide impairs active NaCl transport to Henle's loop and the attendant hypertonicity of the interstitium, osmotic water reabsorption from collecting ducts decreases and the unreabsorbed volume is lost into the urine, causing a rise in flow rate. This volume is computed from the difference in urine flow rate during furosemide with respect to that previously measured during maximal water diuresis alone. Starting from this value, an appropriate set of equations allows the separate calculation of Na reabsorption by the loop of Henle and by the distal tubule. Studies to validate this hypothesis were performed by clearance techniques during maximal water diuresis in 58 normal controls, in 19 patients with liver cirrhosis and ascites, and in 11 patients with chronic renal failure. Measurements were performed before and after the intravenous administration of 50 mg furosemide. The quantitative measurements of segmental solute reabsorption in normal subjects were consistent with results obtained by different methods in man and experimental animals, fully validating this new method. In addition, the data allowed to establish that distal reabsorption is depressed because of reduced proximal delivery in cirrhosis, as a result of impaired transport along Henle's loop in chronic renal disease, while permeability of collecting ducts to water was normal in both conditions. Though still approximate, this new furosemide test represents a considerable improvement over current methods for measuring segmental transport by the human nephron.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02705.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The combination of dextroamphetamine and morphine has been shown to be synergistic for analgesia and antagonistic for most other effects. However, the claim that dextroamphetamine antagonizes the respiratory depression caused by morphine has not been well substantiated. In this double‐blind study, we investigated respiratory effects, including resting respiration, isohypercapnic ventilation, CO2response, dose response, and duration of these effects with dextroamphetamine alone and in combination with morphine. Dextroamphetamine alone (0.215 mg/kg) caused increases in minute ventilation and a leftward shift of the CO2response curve that lasted for less than 2 hours. Dextroamphetamine combined with low‐dose morphine (0.15 mg/kg) antagonized respiratory depression throughout the 5‐hour observation period. Dextroamphetamine combined with high‐dose morphine (0.30 mg/kg) was unable to completely antagonize depressed ventilation, and some residual effects of morphine persisted at

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02706.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY