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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes the results of a series of experiments in pithed rat, infused with angiotensin II, in order to characterize better vascular selectivity of lacidipine in comparison with other calcium entry blockers, namely amlodipine, verapamil and diltiazem. Lacidipine induced dose-related decreases in blood pressure (ED25% for mean blood pressure = 6 micrograms kg-1) with the appearance of second-degree A-V blocks at 300 micrograms kg-1. A slight decrease in contractile index (CI) was detected only at the highest dose used, 300 micrograms kg-1. The other dihydropyridine, amlodipine, showed a lower degree of vasodilatory activity (ED25% = 330 micrograms kg-1), appearance of second-degree A-V blocks starting from 1,000 micrograms kg-1 and a pronounced decrease in CI at 3,000 micrograms kg-1. Verapamil and diltiazem produced dose-related decreases in blood pressure (ED25% = 32 and 175 micrograms kg-1, respectively) and appearance of second-degree A-V blocks at 300 and 1,000 micrograms kg-1, respectively. Pronounced decreases in CI were detected with verapamil whereas diltiazem induced a more specific negative chronotropic effect. In conclusion, these results confirmed the marked vascular selectivity of lacidipine and give further evidence that this drug may be a suitable agent for the treatment of hypertension.
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PMID:A comparative study on the vascular selectivity of lacidipine in the pithed rat. 157 96

Lacidipine is a calcium antagonist of the dihydropyridine group that is highly selective for vascular tissues. It has been tested during the last few years for the treatment of arterial hypertension. We evaluated the clinical position of this calcium antagonist on the basis of clinical results. From the dose-ranging studies carried out to determine the efficacy of lacidipine, it has been shown that the dose range of 2-6 mg of lacidipine given once daily is effective in reducing blood pressure levels. Lacidipine efficacy (4-6 mg/o.d.) also has been compared with that of the diuretic hydrochlorothiazide, the calcium-antagonist nifedipine, and the beta-blocker atenolol in three different clinical trials according to the same protocol. The results indicated that lacidipine, hydrochlorothiazide, nifedipine, and atenolol caused similar reductions both in systolic and diastolic blood pressure after 1 and 2 months of treatment. Similar blood pressure levels were also reached when another antihypertensive agent (atenolol or hydrochlorothiazide) had been added in nonresponders to monotherapy. Heart rate showed a significant decrease only under atenolol treatment, either monotherapy or associated to the previous treatment. In these comparison studies, tolerability was also evaluated. The incidence of side effects during lacidipine treatment was lower than during nifedipine or atenolol treatment, but higher than during hydrochlorothiazide therapy. Lacidipine did not cause any changes in the laboratory parameters evaluated during the 2-month monotherapy period. From a trial conducted in elderly patients, lacidipine 2 and 4 mg/o.d. has been shown to cause similar diastolic blood pressure reduction after 1 month of treatment, the effect being more gradual with the lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical position of lacidipine, a new dihydropyridine calcium antagonist, in the treatment of hypertension. 172 45

Lacidipine is a long-lasting 1,4-dihydropyridine calcium antagonist that has been reported to protect salt-loaded Dahl-S rats from vascular damage and accelerated mortality when it is administered prophylactically at 0.1 and 0.3 mg/kg p.o. once a day (equivalent to the recommended dose in humans). The aim of this study was to investigate the vasoprotective properties of lacidipine in Dahl-S rats that had already developed sustained hypertension after 4 weeks of a salt-rich diet. Although none of the dosages of lacidipine (0.3, 1, and 3 mg/kg) reduced the elevated values of blood pressure, an almost complete protection from mortality was obtained. Moreover, lacidipine dose-dependently inhibited the development of macroscopic and microscopic alterations in the distal branches of mesenteric arteries and in the brain. A clear regression of vascular damage and cardiac hypertrophy was observed at the highest dose tested (3 mg/kg). These findings further support the assumption that the protective properties of lacidipine are not restricted to a reduction in blood pressure.
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PMID:Lacidipine: prevention of vascular damage induced by hypertension. 172 48

Lacidipine is an orally administered calcium channel blocker of the dihydropyridine class, which shows selectivity for vascular smooth muscle over cardiac tissue and has a long duration of action. In studies using ambulatory blood pressure monitoring, lacidipine 2 to 8mg administered once daily in the morning reduced blood pressure over 24 hours, with the reductions being greater during the day than at night in some studies. 77 to 87% of patients with mild to moderate hypertension had their blood pressure controlled by treatment with lacidipine 2 to 8 mg/day for 1 to 4 months in dose-finding studies. When administered once daily, lacidipine 4 to 6 mg was equivalent in antihypertensive efficacy to hydrochlorothiazide 25 to 50 mg/day, atenolol 50 to 100 mg/day, and the prototype calcium channel blocker nifedipine 20 to 40 mg twice daily (sustained-release formulation). The adverse effects of lacidipine are those common to other dihydropyridine calcium channel blockers, and include headache, flushing, ankle oedema, dizziness and palpitations. The long term effects of lacidipine on cardiovascular morbidity and mortality, and possible additional clinical benefits in terms of its antiatherosclerotic effects, are under investigation; the outcome of these studies will be important in defining the future role of this agent in the treatment of hypertension. Thus, available evidence suggests lacidipine provides a further alternative to the dihydropyridine calcium channel blockers currently available for the treatment of essential hypertension.
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PMID:Lacidipine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of hypertension. 752 28

Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose).
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PMID:Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR. 760 94

Membrane-active drugs can be characterized by direct measurements of their membrane partition coefficients, washout rates from membranes, and washin rates into membranes. There appears to be a correlation between the duration of action of such membrane-active drugs and the membrane partition coefficient in conjunction with the washout rate. Lacidipine has a high membrane partition coefficient compared to other 1,4-dihydropyridine calcium-channel antagonists and a slow washout rate from membranes. Clinically, it also exhibits an extended duration of action. This control at the membrane molecular level may provide an optimal pharmacokinetic profile for lacidipine in the treatment of hypertension. In addition, these same properties may be important for lacidipine as an antiproliferative agent in the treatment of atherosclerosis.
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PMID:The molecular basis for lacidipine's unique pharmacokinetics: optimal hydrophobicity results in membrane interactions that may facilitate the treatment of atherosclerosis. 760 1

Lacidipine is a second-generation 1,4-dihydropyridine calcium antagonist, whose potent and long-lasting antihypertensive properties prompted us to investigate whether its chronic administration to Dahl-S rats prevented salt-induced hypertension, vasculopathy, and accelerated mortality. These studies revealed that lacidipine proved vasoprotective when administered both prophylactically and therapeutically at doses of 0.1 and 0.3 mg/kg p.o. once a day, largely equivalent to the therapeutic doses. A generalized dose-related protection against necrotizing vasculopathy and brain damage was detected, although only the highest dose used (10 mg/kg) controlled the development of hypertension. These protective properties were further confirmed in stroke-prone spontaneously hypertensive rats, which develop accelerated mortality as a result of salt-induced cerebral apoplexy and renal lesions. All untreated controls died within 12 weeks of salt-rich diet, whereas all animals survived during the same period when treated prophylactically with lacidipine at 0.3 and 1 mg/kg p.o. once a day, although a slight reduction in systolic blood pressure was measured only with the highest dose. No cerebral lesions and a clear protection against renal damage were detected in lacidipine-treated animals. In conclusion, these findings reinforce the concept that the beneficial effects of calcium antagonists are not simply restricted to a reduction in blood pressure.
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PMID:Lacidipine: experimental evidence of vasculoprotective properties. 760 15

In our recent review of calcium antagonists for the treatment of patients with cardiovascular disease we concluded that most patients could be managed with formulations of one of the original calcium antagonists, verapamil, diltiazem or nifedipine. Experience is greatest with these drugs, and none of the newer alternatives appeared more effective or better tolerated. Lacidipine (Motens-Boehringer Ingelheim) is the latest calcium antagonist to be marketed for the treatment of patients with mild to moderate hypertension. It is licensed for once-daily use without the need for a modified-release formulation; in this respect it resembles amlodipine. The manufacturer of lacidipine claims that its gradual onset of action "cushions the fall in blood pressure" and "cushions against side effects".
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PMID:Lacidipine--a once-daily calcium antagonist for hypertension. 763 37

Losartan potassium (Cozaar) is an angiotensin II receptor antagonist (AT1 selective) which has undergone extensive clinical trials for the treatment of hypertension. This literature survey will review some of the pre-clinical findings with losartan in models of heart failure, and where appropriate, we will compare the haemodynamic findings in animals with similar studies completed in patients. The major conclusion from these trials is that losartan has clear haemodynamic benefits in patients in heart failure and that the drug appears to be well tolerated, with a low incidence of adverse experiences related to impaired renal function.
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PMID:Losartan in heart failure: preclinical experiences and initial clinical outcomes. 771 3

1. The aim of this randomised, double-blind four way crossover study was to assess the interaction between the new calcium antagonist, lacidipine and atenolol, in patients with mild to moderate hypertension. 2. Sitting blood pressure at 4 h post-dosing with lacidipine (4 mg) and atenolol (100 mg) alone was significantly lower compared with placebo (137/89 +/- 3/3 mmHg; 142/89 +/- 5/3 mmHg; and 154/98 +/- 5/3 mmHg respectively; P < 0.001). Co-administration of both drugs produced a significant additive effect compared with atenolol and lacidipine alone (124/80 +/- 4/2 mmHg; P < 0.002). 3. Heart rate on treatment with lacidipine alone was significantly greater at 4 h compared with placebo (86 +/- 1 beats min-1 and 74 +/- 2 beats min-1 respectively; P < 0.001). When both drugs were used in combination, there was a significant decrease in pulse rate compared with lacidipine alone (58 +/- 1 beats min-1 and 86 +/- 1 beats min-1 respectively; P < 0.001). 4. Home blood pressure recordings confirmed the statistically significant reduction in blood pressure on co-dosing (120/82 +/- 10/2 mmHg) compared with lacidipine (140/92 +/- 5/3 mmHg) and atenolol (146/90 +/- 6/3 mmHg) given alone (P < 0.05). 5. Lacidipine alone produced a significant exercise tachycardia compared with atenolol alone and the atenolol/lacidipine combination (97 +/- 8 beats min-1; 65 +/- 4 beats min-1 and 75 +/- 7 beats min-1 respectively; P < 0.001). Exercise tolerance was not adversely affected by the co-administration of both lacidipine and atenolol.
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PMID:An assessment of lacidipine and atenolol in mild to moderate hypertension. 814 17


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