Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR.

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).

An ultrasonographic method to measure the sensitivity of the baroreflex in clinical practice: application to pharmacological studies.

To determine whether it is possible to assess baroreceptor sensitivity by measuring changes in blood velocity in the carotid artery and changes in the heart rate, we performed a series of 108 experiments in 19 hypertensives aged 20-57 years (mean 46.6 +/- 8.6). In each experiment, we took simultaneous measurements of carotid artery blood flow velocity (Doppler technique), the brachial intra-arterial blood pressure and the heart rate, during a rapid and transient increase in blood pressure induced by injections of phenylephrine. We then calculated the maximum slope of the regression lines correlating blood velocity with the heart period (Trieste method) and blood pressure with the heart period (Oxford method). We obtained good accuracy from the Trieste method compared with the Oxford method, as assessed by the mean of the sum of the squares (difference + 5%, NS). After the administration of 4 mg oral lacidipine to 13 essential hypertensives, aged 37-54 years (47.6 +/- 5.3), baroreflex sensitivity was not changed, as assessed by either method (Oxford method 10.1 +/- 5.5 versus 9.8 +/- 6.2 ms/mmHg; Trieste method - 0.57 +/- 0.32 versus - 0.49 +/- 0.31 ms/Hz). The coefficients of variation for the two methods, calculated for the measurements taken before and after the administration of lacidipine, were not statistically different (Oxford method 25.0 +/- 18.4 versus 36.2 +/- 16.0; Trieste method 36.7 +/- 19.2 versus 39.7 +/- 19.2). The new non-invasive Trieste method thus showed the same accuracy and precision as the invasive Oxford method in measuring baroreflex sensitivity and can be used in pharmacological studies.

Efficacy and safety of lacidipine, a new long-lasting calcium antagonist, in elderly hypertensive patients.

Elderly patients are becoming a greater proportion of the hypertensive population. In addition, they may respond differently to drugs, both pharmacodynamically and pharmacokinetically. Therefore, approximately 25% of the patients treated with lacidipine in early studies were over 65 years old. In three double-blind, parallel-group comparative trials, 118 elderly hypertensive patients were treated with lacidipine or comparators, either atenolol, nifedipine SR, or hydrochlorothiazide (HCTZ). Lacidipine was at least as effective in lowering blood pressure as the comparators, as well tolerated as nifedipine SR (but with a significantly lower incidence of edema) and HCTZ, and better tolerated than atenolol. In a double-blind, placebo-controlled, parallel-group, dose-response study of 131 elderly hypertensive patients randomized to receive either lacidipine or placebo, lacidipine significantly reduced the diastolic blood pressure compared with placebo. In the long-term evaluation, more patients required titration with 2 mg of lacidipine than with 4 mg. These results suggest that 4 mg once daily is an effective and well-tolerated antihypertensive treatment in the elderly and, as with the general adult population, represents the optimal long-term maintenance dose.

Clinical pharmacology of lacidipine.

The safety and tolerability of lacidipine was assessed in a volunteer population, and its pharmacodynamic and pharmacokinetic profiles evaluated. In normotensive subjects, single oral doses of 3-5 mg of lacidipine produced a dose-related fall in peripheral vascular resistance. This was accompanied by reflex-mediated increases in heart rate and cardiac output to maintain blood pressure. Adverse events were those typically related to the vasodilatory action of lacidipine, such as flushing and headache. A 4-mg dose of lacidipine elicited a cardiovascular response equivalent to that with 10 mg of nifedipine, given as a single oral dose. Lacidipine did not affect sinoatrial or atrioventricular conduction in the healthy subjects studied. Two specialized electrophysiologic studies in patients confirmed that lacidipine does not affect pacemaker tissue and that it exhibits relative selectivity for the vascular smooth muscle. Lacidipine is eliminated primarily by hepatic metabolism, and extensive first-pass loss occurs after oral dosing. Absolute bioavailability is less than 10%. The systemic availability of lacidipine was increased in healthy elderly subjects and in patients with impaired hepatic function, but not in patients with impaired renal function.

Long-term antihypertensive treatment with lacidipine, a new long-acting calcium antagonist.

Eleven centers in Tuscany, Italy, recruited 96 patients (aged 21-75 years) with mild-to-moderate essential hypertension [diastolic blood pressure (DBP) 95-115 mm Hg; systolic blood pressure (SBP) less than or equal to 200 mm Hg]. After a 4-week, single-blind, placebo run-in period, patients received lacidipine 4 mg once daily. If blood pressure was not controlled after 1 month (control = DBP less than or equal to 90 mm Hg, or less than or equal to 95 mm Hg if reduced by greater than or equal to 15 mm Hg from baseline), the dose was increased to lacidipine 8 mg once daily. Atenolol 50 mg once daily was added after 2 months' monotherapy, if required for blood pressure control. The study continued for 13 months. About 40% of patients were titrated to 8 mg lacidipine; only 7% required addition of atenolol. Lacidipine significantly reduced blood pressure, with 84% of patients showing control of pressure values 24 h after the previous dose on completion of 5 months' monotherapy (63% controlled with lacidipine 4 mg/day; 21% with lacidipine 8 mg/day). There was no clinically relevant difference in the first-dose effect between the two doses of lacidipine (4 mg and 8 mg); both smoothly reduced blood pressure, with maximum effect after 2 h. Lacidipine was well tolerated. Adverse events were those expected with dihydropyridines, were mainly mild and occurred early, disappearing without discontinuation of treatment. Results indicate that 4-8 mg of lacidipine, administered once daily, is effective and well tolerated in mildly to moderately hypertensive patients.

Effect of lacidipine on pituitary function in essential hypertension.

Calcium plays an important role in endocrine reactions such as hormone biosynthesis, release, secretion, and action on target organs. The aim of this study was to evaluate the effects of a new long-lasting calcium-channel blocker, lacidipine, on basal and stimulated anterior pituitary hormone secretion. In a single-blind crossover study comparing lacidipine 4 mg p.o. once daily with placebo, variations in plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH) were evaluated in 10 hypertensive patients. Basal or stimulated anterior pituitary hormone secretion was similar after lacidipine and placebo. Lacidipine treatment significantly reduced blood pressure. It can thus be concluded that lacidipine is an effective calcium antagonist that has no effect on pituitary function.

HLA molecule expression on chronic pancreatitis specimens: is there a role for autoimmunity? A preliminary study.

This study was prospectively carried out in order to clarify if an aberrant expression of HLA-DR molecules could take part in the pathogenesis of chronic pancreatitis. Pancreatic specimens from 12 chronic pancreatitis patients and nine controls were examined. Strong HLA-DR expression was observed in 6/12 chronic pancreatitis patients and in 1/9 controls. Moreover, lymphocytic foci with large numbers of activated cells were found only in chronic pancreatitis. The four HLA-DR - patients had a marked increase of fibrous tissue with small portions of acinar tissue, whereas the six patients with strong positivity had the greatest dilatation and hyperplasia of the ducts. These findings are similar to those observed in immune diseases, such as thyroiditis and primary biliary cirrhosis (PBC), and suggest that autoimmune phenomena are involved in chronic pancreatitis.