ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04676.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

A variety of antihypertensive agents are available for management of elevated arterial pressure. Although these agents all effectively lower arterial pressure, they have somewhat diverse renal hemodynamic proxies. This report reviews the various similarities and differences in renal hemodynamic profiles among the different antihypertensive agents.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04677.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This report concerns the development of an assessment* model (PharmTest)† for further evaluation by academic pharmacologists. The content area chosen for this model is the pharmacology of affective disorders. The components of the PharmTest system are: 1) a cognitive map of the content area used to develop the learning objectives (Figure): 2) both lower‐ and higher‐level objectives developed jointly by basic and clinical faculty; 3) a bank of multiple choice questions (MCQ) judged to be congruent to the objectives by an expert panel; 4) a software program (SP) to manage the testing process; and 5) an annotated self‐study document to aid students in their review after computer self‐testing. PharmTest is designed to assist faculty in producing tests, making possible student self‐testing and study. PharmTest was developed during a 6‐month cooperative project between a faculty member from the University of North Carolina (HJB) and faculty of the University of Dundee. This report presents the learning objectives and cognitive map developed for the model content topic of “Pharmacology of Affective Disorders.” Also it suggests a recipe for development of other content areas of pharmacology based on this project. Also, it presents the development process for PharmTest. Finally a plan for collecting evaluation data from academic pharmacology faculty is presented. Implications of the increased efficiency to faculty in linking learning objectives and testing are discussed, and a suggestion is made for national evaluation of learnin

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04678.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The authors present a new approach for evaluation and counseling of teratogenic risk, The Motherisk program in Toronto presently deals with 60 inquiries per day from the public and health professionals. Most calls are answered through the telephone, and 16–20 women per week are scheduled for our clinic following exposure to known or suspected teratogens, to new drugs with sparse information, to chronic drug therapy, or drugs of abuse. Also seen in clinic are women who want to he counseled or whose physicians want them to meet us due to high levels of anxiety. Since its inception in 1935 the Program has been very effective in preventing unnecessary terminations of otherwise wanted pregnancies. In addition to the clinical service we followup the outcome of these prospectively collected exposures, thus creating a large data base necessary to verify safety/risk of various agents. During the last 2 years Motherisk has completed singly, or in collaboration, large prospective studies on gestational exposure to lithium, antiepileptics, cocaine, and fluexitime. To study the reproductive risks of cocaine we compared first‐trimester exposure to cocaine with two control groups. Infants exposed to cocaine did not have higher rates of any adverse perinatal outcome. Their cognitive function at 16 months of age was identical to the control infants. Meta analysis of all studies assessing gestational risks of cocaine reveals that the results of these studies were dependent on the type of comparison conducted. When babies exposed to cocaine were compared with middle class nonusers, the cocaine groups seemed to he more often different from their controls. Conversely, when cocaine‐exposed infants were compared with babies of women exposed to other drugs of abuse but not cocaine, most of these differences cancelled out, suggesting that clustering of other risk factors may cause some of these adverse ef

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04679.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The development of innovative new drugs is a time‐consuming, expensive, and risky process. Despite these challenges, the pharmaceutical industry has been remarkably successful in developing a broad range of important new medicines. This report examines several aspects of new drug development in the pharmaceutical industry and provides a quantitative evaluation of the role of the drug industry in medical progress. Results indicate that of the 196 new chemical entities approved by the FDA from 1981 through 1990, the source of 92% was the pharmaceutical industry. Within the industry, there was a sizeable increase in the level of clinical research activity (based on the number of investigational new drug [IND] filings) from the mid‐1970s to the mid‐1980s; moreover, for U.S.‐owned firms IND filings increased 46% between 1976 and 1989. Analysis by therapeutic category indicates that much of this clinical research activity was directed towards the development of drugs for cardiovascular disease and mental illness, and more recently towards the treatment of cancer and acquired immunodeficiency syndrome (AIDS). These represent therapeutic areas in which there is an urgent need for new and more effective medicines. The high level of research activity was also reflected in the relative number of drug approvals in these areas. It is hoped that the present findings will contribute to the current debate on drug policy issues and encourage policy‐makers to consider what impact proposed health care policies might have on pharmaceutical i

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04680.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The authors compared the relative safety and efficacy of changing treatment from once‐daily atenolol to metoprolol in patients with essential hypertension. A parallel‐group randomized clinical trial was conducted in two phases: a 4‐week baseline single‐blind phase using atenolol 50 mg, followed by a 4‐week randomized double‐blind treatment phase using either atenolol 50 mg or metoprolol 100 mg administered once daily at noontime. Patients with well‐controlled hypertension already prescribed 50 mg of atenolol (with or without the addition of a diuretic) for control of hypertension were selected for participation from the outpatient hypertension clinic of the Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania. Seated blood pressure (BP) and pulse were obtained during the baseline phase and during the randomized treatment phase. Twenty‐four‐hour ambulatory BP monitoring was performed once during the baseline phase and once during the randomized treatment phase, near the end of each 4‐week period. There were no within‐ and between‐treatment differences in office systolic and diastolic BP. There was a slight increase in pulse (average = 5.2 beats/minute; P = .02) for those participants treated with metoprolol. For within‐treatment groups, the ambulatory BP data showed no significant differences in systolic and diastolic BPs, except for an increase in morning diastolic BP for those randomized to metoprolol (average = 6.2 mm Hg; P = .01). For between‐treatment groups, the metoprolol arm had a higher morning systolic BP (P = .01), a higher morning diastolic BP (P = .03), and a higher nighttime heart rate (P = .01). There were no study withdrawals due to adverse events. Once‐daily administration of both atenolol and metoprolol appear to control BP as measured by office and ambulatory monitoring techniques, but atenolol appears to maintain BP control more effectively than metoprolol during t

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04681.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The effect of rigid blood pressure control on renal function is an unsettled issue. This study describes a retrospective analysis on the relationships between blood pressure control, hematocrit levels, and renal function in 97 treated hypertensive patients. Data analysis was done on systolic and diastolic blood pressure, hematocrit levels, renal function assessed by serum urea nitrogen (SUN), serum creatinine (Scr), and hydrochlorothiazide (HCTZ) dose at entry and at four anniversary dates thereafter. The patients were divided into two groups: group I and group II on the basis of HCTZ dose. Group I received an average of 100 mg HCTZ daily, whereas group II received an average of 50 mg HCTZ daily. In group I, the decrement in both systolic and diastolic blood pressure over time was highly significant (P<.0001); however, no change in renal function was noted. In group II, systolic blood pressure decreased significantly (P<.01) from entry to year 1, then leveled off. In year 4, systolic blood pressure was not different from that of entry. Conversely, the difference between entry and year 4 diastolic blood pressure was highly significant (P<.0001). In group II, significant decreases were noted between entry and year 4, SUN (16.5 ± 5.7 versus 14.9 ± 4.1 mg/dL; P<.0012) and Scr (1.29 ± .23 versus 1.24 ± .19 mg/dL; P<.0192). Hematocrit showed diverse responses; in group I, hematocrit significantly increased from entry to year 4 (44.8 ± 2.5 versus 47.2 ± 3.9%; P<.01); whereas, in group II, hematocrit significantly decreased (47.7 ± 3.8 versus 44.9 ± 3.4%; P<.001). A separate analysis between blacks and whites showed that black patients did better with high‐dose (very high dose according to current concept) of HCTZ in both blood pressure and renal function controls, whereas white subjects tend to do better with low‐dose (high dose according to current concepts) of HCTZ. This study concludes that high‐dose (or very high dose) HCTZ is beneficial for black hypertensives, however, low‐dose (or high‐dose) HCTZ appears to be unive

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04682.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

It is the current opinion that an ideal antihypertensive drug should reduce blood pressure (BP) not only at rest but also during stressful situations. The current study was aimed to compare the effects of the selective α1‐adrenergic blocker terazosin (5 mg once daily) and of the angiotensin‐converting enzyme inhibitor enalapril (20 mg once daily) on cardiovascular response to a set of standardized laboratory stressors, such as mental arithmetic, handgrip test and cycle ergometry, in a group of 16 essential hypertensive patients. The study was a randomized, double‐blind, cross‐over trial preceded by a placebo run‐in period. Terazosin and enalapril had a comparable effect on resting BP, reducing systolic (SBP) and diastolic (DBP) blood pressure from 159.5 ± 13.9/101.6 ± 8.8 mm Hg during placebo by 7.8%/6.7% and by 11.3%/10.2%, respectively. The “response” rate to the two treatments was approximately the same, being 69% and 75% after terazosin and enalapril, respectively. During mental arithmetic, from an average of 181.6 ± 17.8/118.6 ± 11.5 mm Hg during placebo, BP was reduced by 11.5%/7.9% after terazosin and by 13.6%/8.5% after enalapril; during handgrip test, BP decreased from 207.2 ± 22.2/142.2 ± 13.6 mm Hg by 7.3%/8.4% after terazosin and by 7.7%/7.1% after enalapril; finally, during cycle ergometry, terazosin and enalapril lowered BP by 5.4%/6.7% and 7%/3.1%, respectively, from a placebo value of 215.5 ± 17.3/127.6 ± 11.2. No significant difference in antihypertensive efficacy was observed between the two drugs, either at rest and during stress testing. Neither terazosin nor enalapril induced any significant change in resting and stress testing heart rate. Our data suggest that doses of terazosin and enalapril able to reduce resting BP are also effective in lowering BP during a variety of stressful situations, and thereby are potentially able to ameliorate the impact of recurring stress‐induced increases of BP on t

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04683.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This study was designed to determine the pharmacokinetics and dose proportionality of clentiazem (CLZ) after single doses (SD) of 20, 40, and 80 mg and multiple dose administration (SS) of 40, 80, and 160 mg/day for 5 days. The study was an open‐label, randomized four‐period complete crossover design. Twenty‐four healthy male volunteers participated in the study, and blood samples were drawn over 48 hours after both SD and SS. Plasma samples were analyzed for CLZ and three metabolites by high‐pressure liquid chromatography. After SD, the area under the plasma concentration‐time curve (AUC0‐∞) and maximum concentration (Cmax) increased disproportionately with the increase in dose. At steady‐state, a twofold increase in dose (20 to 40 mg twice daily and 40 to 80 mg twice daily) resulted in an increase in AUCssof 2.14‐ and 2.51‐fold, respectively. Oral clearance of CLZ decreased (203.8 L/h at 40 mg/d to 140.2 L/h at 160 mg/d) and bioavailability increased (0.35 at 40 mg/d to 0.50 at 160 mg/d) with increasing doses. The terminal half‐life of CLZ remained unchanged with increasing doses (13.7–15.5 hours). The ratios of AUCssto AUC0‐∞at SD ranged from 1.13 to 1.27, indicating no significant accumulation of CLZ (P>.05). The AUC ratio of N‐desmethyl CLZ to that of CLZ remained constant after SD. On SS, however, there was a small decrease in this ratio with increasing dose (0.77 at 40 mg/d to 0.61 at 160 mg/d). These results indicate that the degree of nonlinearity observed with CLZ pharmacokinetics may largely be due to sa

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04684.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The use‐dependent effects of cibenzoline, a new anti‐arrhythmic drug, on the maximal rate of rise (V̇max) of the action potential and on conduction velocity, and their corresponding recovery kinetics were studied in isolated papillary muscles of guinea pigs under normal and hypoxic conditions. Standard microelectrode techniques were applied to monitor the action potential of the muscles and their conduction. Under control conditions, the amount of use‐dependent block of V̇max, conduction velocity, and square of conduction velocity, induced by 10 μmol/L cibenzoline were 26.5 ± 3.9, 13.8 ± 1.4, and 25.6 ± 2.4%, respectively; under hypoxic conditions, these values increased to 32.3 ± 4.8, 19.7 ± 1.2, and 35.5 ± 2.0%, respectively. In the presence of 10 μmol/L cibenzoline, the mean values of time constants for the onset of the use‐dependent inhibition of V̇max, conduction velocity, and the square of conduction velocity, during a 2‐Hz stimulation, were 3.65 ± 0.27, 2.77 ± 0.33, and 2.56 ± 0.26 seconds, respectively. Under hypoxic conditions, these values changed to 5.10 ± 0.96, 3.05 ± 0.44, and 2.84 ± 0.39 seconds, respectively. The recovery time constants averaged 14.72 ± 4.08 seconds (for V̇max), 22.23 ± 3.78 seconds (for conduction velocity), and 23.17 ± 13.38 seconds (for the square of conduction velocity) in the presence of 10 μmol/L cibenzoline, and 17.19 ± 8.59 seconds (for V̇max), 15.77 ± 2.37 seconds (for conduction velocity), and 16.82 ± 2.61 seconds (for the square of conduction velocity) under hypoxic conditions. These results showed that the characteristics of the use‐dependent inhibition of V̇max and conduction velocity induced by cibenzoline are similar to those of the intermediate (slow) kinetic drugs, and that the amount of the use‐dependent block increases under hypoxic conditions, whereas the time constants of onset and recovery from the use‐dependent

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04685.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY