摘要:

ObjectivesTo investigate a possible relationship between the time courses of action of various calcium antagonists and their lipophilicity, characterized as logP-values.MethodsThe functional experiments were performedin vitroin human small subcutaneous arteries (internal diameter 591 ± 51 μm,n= 7 for each concentration), obtained from cosmetic surgery (mamma reduction and abdominoplasty). The vessels were investigated in an isometric wire myograph. The vasodilator effect of the calcium antagonists was quantified by means of log IC50-values, and the onset of the vasodilator effect for each concentration studied was expressed as time to Eeq90-values (time to reach 90% of the maximal effect).ResultsLog IC50-values were −8.46 ± 0.09, −8.33 ± 0.25 and −8.72 ± 0.16 for nifedipine, felodipine and (S)-lercanidipine, respectively (not significant). On average, nifedipine reached time to Eeq90in 11 ± 1 min. For felodipine and (S)-lercanidipine the corresponding values were 60 ± 11min and 99 ± 9 min, respectively. The differences between these values were statistically significant (P< 0.01). In spite of these differences in the invitro human vascular model, the three calcium antagonists are equipotent with regard to their vasodilator effects. Linear regression analysis of the correlation between the logarithm of the membrane partition coefficient (logP-values) of the calcium antagonists tested [2.50, 4.46 and 6.88 for nifedipine, felodipine and (S)-lercanidipine, respectively] and their respective values found for time to Eeq90was highly significant.ConclusionsIt appears that a higher logP-value is correlated with a slower onset of action.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundA high pulse pressure is an independent cardiovascular risk factor. It has therefore been suggested that antihypertensive treatment should not only reduce systolic blood pressure (SBP) and diastolic blood pressure (DBP), but should also decrease pulse pressure (SBP minus DBP). In a previous analysis, we showed that two angiotensin II type 1 (AT1)-receptor blockers, candesartan cilexetil and losartan, differed in their effects in reducing SBP and DBP.ObjectiveTo compare the efficacy of candesartan cilexetil and losartan according to a new approach—their effect on pulse pressure–and to describe the dose—effect relationship for SBP, DBP and pulse pressure, in a placebo-controlled study.MethodsAfter a 4-week placebo run-in period, 268 patients with mild-to-moderate hypertension were allocated randomly to groups to receive placebo, candesartan cilexetil (8 mg once daily) or losartan (50 mg once daily), for 4 weeks. The doses were then doubled to 16 and 100 mg, respectively, for the final 4 weeks of the study. Clinic blood pressure was measured 24 and 48 h after each dose of drug or placebo, and ambulatory blood pressure was monitored from 0 to 36 h after each dose, at baseline and after 4 and 8 weeks of treatment.ResultsCandesartan cilexetil decreased ambulatory pulse pressure significantly (P< 0.05) more than did losartan during both daytime and night-time, and over the 24 h period after the previous dose. A different dose—effect relationship on SBP, DBP and pulse pressure was observed. The duration of action of candesartan cilexetil was greater than that of losartan. After a missed dose (i.e. approximately 24–36 h after the previous dose), mean ambulatory pulse pressure values after 4 and 8 weeks of treatment with candesartan cilexetil were lower than those observed with losartan (P< 0.005). Clinic pulse pressure measurements were consistent with these ambulatory measurements.ConclusionsAT1-receptor blockers differ both in their ability to reduce pulse pressure and in their duration of effect, candesartan cilexetil having a greater and more sustained effect than losartan. Different dose—effect relationships on SBP, DBP or pulse pressure were observed. Further prospective studies based on pulse pressure are needed to analyse the mechanism of reduction of pulse pressure and to determine its prognostic value.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo collect statistically significant information on patterns of antihypertensive therapy in medical practice, with particular attention to the drugs used in the pharmacological management of hypertensive patients and the reasons for the limited achievement of therapeutic goals during treatment.DesignA survey conducted among general practitioners, specialists, and hypertensive patients.MethodsA total of 28 000 physicians were contacted by letter and 3394 declared their willingness to participate and received a questionnaire. Subsequently, 1255 questionnaires suitable for analysis (corresponding to 37.0% of adhering physicians) were received. In addition, 4612 questionnaires completed by patients were pooled and evaluated. The prevalence of hypertension was calculated from a base of 254 192 patients, seen by general practitioners.ResultsThe prevalence of hypertension, defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥95 mmHg, or current treatment, was 19.7%. The average number of hypertensive patients in each general practitioner's file, covering the previous 12 months, was approximately 230. Physicians reported a 66% rate of discontinuation of treatment or switching to another drug. Physicians and patients both considered inadequate blood pressure control and side effects to be the two main reasons for switching antihypertensive therapy, but in opposite order. Furthermore, physicians indicated a prevalence of drug side effects between 10 and 20%, according to class of drug used, whereas 69% of patients reported to have experienced side effects. In the doctors' opinions, there were many reasons for poor patient adherence: complexity of the drug regimen, appearance of side effects, forgetfulness, reduced patient understanding of the need for long-term continuation of treatment, and refusal to accept a chronic pathological condition.ConclusionsThe survey showed awareness of the disease among physicians and provides a representation of the experiences of both general practitioners and specialists, in addition to that of their patients. During antihypertensive therapy, a disconcerting degree of discontinuation and switching of drugs occurred. Insufficient blood pressure control and side effects accounted for most of the observed treatment changes. This survey revealed the existence of a gap between the physicians' perception of tolerability and the real experience of patients, a clear need for greater tolerability of treatments, and a need for an enhancement of patient-physician communication.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID