Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal vascular resistance is increased in essential hypertension, with a consequent reduction in renal plasma flow together with a normal or slightly reduced glomerular filtration rate. Non-specific vasodilators may exacerbate this effect while loop diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium antagonists may increase these renal hemodynamic parameters. We studied the effect of lacidipine, a new long-lasting calcium antagonist, on renal hemodynamics in 11 essential hypertensives. Lacidipine (4 mg once a day) acutely increased renal plasma flow without affecting the glomerular filtration rate. A transient, but non-significant, diuresis and natriuresis occurred. After 4 weeks of lacidipine treatment, all the parameters of renal function returned to basal levels. These results suggest that the well known renal effects of calcium antagonists are, at least in part, related to the onset of the antihypertensive effect being more pronounced with compounds such as nifedipine which have a rapid-onset, blood pressure-lowering effect.
 ...
PMID:The effects of antihypertensive therapy on renal function. 168 83

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.
 ...
PMID:Long-term antihypertensive treatment with lacidipine, a new long-acting calcium antagonist. 172 46

This multicenter study was designed to assess the clinical efficacy and safety of the new once-daily calcium antagonist lacidipine in the treatment of mild-to-moderate essential hypertension. Patients were randomly assigned to receive, double-blind, either lacidipine (n = 180) or hydrochlorothiazide (HCTZ, n = 182) following a 1-month placebo run-in period. Both drugs were titrated after 1 month if blood pressure was not controlled: lacidipine, from 4 to 6 mg once daily; HCTZ, from 25 to 50 mg once daily. Atenolol was added later if necessary to achieve blood pressure control. Lacidipine and HCTZ were equally effective in controlling the blood pressure levels in the majority of patients (approximately 90% after 4 months). Adverse events were those to be expected with these classes of drug and were reported in 48 (26.7%) of the patients receiving lacidipine treatment and in 34 (18.7%) of those receiving HCTZ. The diuretic produced a significantly higher incidence of hypokalemia.
 ...
PMID:A double-blind comparison of the efficacy and safety of lacidipine and hydrochlorothiazide in essential hypertension. The Southern Italy Lacidipine Study Group. 172 4

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.
 ...
PMID:Lacidipine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of hypertension. 752 28

Importance of L-channels for calcium: Calcium L-channels, the specific target of calcium antagonists, appear to be the receptors for these therapeutic agents. Therefore, the accessibility of these channels/receptors to calcium antagonists is a major determinant of the response to these drugs in cardiovascular disorders, including essential hypertension. As with numerous other drugs, the concentration at the receptor level and its time-course largely determine not only the intensity but also the rate of onset and the duration of the drug's effect. Disadvantages of nifedipine: Within the series of dihydropyridine calcium antagonists, the first compound introduced was nifedipine, a relatively hydrophilic drug. Owing to its hydrophilic character the drug rapidly reaches the receptor, thus explaining the rapid onset of its vasodilator action. Accordingly, reflex tachycardia develops, which is not only triggered by the degree of vasodilation but also by the rapidity of its onset. In addition, nifedipine has a short duration of action, requiring the use of special galenic formulations to allow one dose a day. New dihydropyridine calcium antagonists: In view of the disadvantages of the hydrophilic calcium antagonists, attempts have been made to develop dihydropyridines with a slower onset and a longer duration of action. This may be achieved by drugs which are largely in the ionized state at a physiological pH (e.g. amlodipine) and therefore combine slowly with the receptor and bind firmly to various tissue compartments. Another logical approach is the use of highly lipophilic drugs such as lacidipine. Because of its physicochemical properties, the effect in equilibrium is reached very slowly, after up to 5 h in isolated tissues and after more than 2 h after intravenous administration. Lacidipine appears to slowly enter a lipid compartment surrounding the dihydropyridine binding site, which has to be saturated before an equilibrium effect is reached. In addition, the persistence of the drug in this lipid compartment contributes to its long-lasting vasodilator effect.
 ...
PMID:Pharmacology of the dihydropyridine calcium antagonists: relationship between lipophilicity and pharmacodynamic responses. 816 79

The vasoprotective activity of lacidipine has been demonstrated both in animals and humans. Results from several studies indicate that vital organ perfusion is maintained, or even increased, during lacidipine administration. Left ventricular hypertrophy (LVH) represents an independent risk factor for cardiovascular events. Lacidipine has been shown to reduce LVH significantly within 3 months of initiation of treatment. In addition, systolic function, as evaluated by ejection fraction and fractional shortening of the left ventricle, is unchanged after 6 months of treatment with lacidipine. Diastolic function may also be improved by this treatment. In large arteries, lacidipine can reverse the abnormal arterial compliance observed in patients with essential hypertension. Other studies, in spontaneously hypertensive rats, have shown that lacidipine can significantly reduce the elevated media/lumen ratio of small resistance arteries. In conclusion, lacidipine possesses vascular selectivity and its effect in essential hypertension is characterized by vasodilation and by the maintenance, or even improvement, in vital organ perfusion.
 ...
PMID:The cardiac and vascular effects of lacidipine. 885 37

In an open, multicenter study, the calcium antagonist lacidipine was tested for efficacy and safety, particularly with respect to any influence on lipid and carbohydrate metabolism. The study was performed in 2,127 patients with essential hypertension. The patients were treated orally, with lacidipine in a dosage of 2-6 mg once daily for 48 weeks. Lacidipine significantly reduced both systolic and diastolic blood pressure by 20 +/- 17 mm Hg and 14 +/- 10 mm Hg, respectively, from baseline values (both p < 0.0001). Decreases in blood pressure were achieved without any adverse effects on lipid and carbohydrate metabolism, either in the total group or in subsets of diabetic or hyperlipidemic patients. It is concluded that lacidipine is a safe and effective drug in the long-term antihypertensive treatment of patients with essential hypertension and with concomitant metabolic disorders such as diabetes mellitus or dyslipidemia.
 ...
PMID:The impact of lacidipine, a novel dihydropyridine calcium antagonist, on carbohydrate and lipid metabolism. 885 41

Thirty patients with mild to moderate essential hypertension had received four weeks treatment with Lacidipine and serum lipid peroxide (LPO), superoxide dismutase (SOD) and insulin levels were measured before and after treatment. The results showed: (1) there were decreased in SOD activity and increased Lpo content the patients group (P < 0.01); (2) after treated with Lacidipine, the SOD acitvity increased and Lpo content decreased (P < 0.01); (3) Lacidipine had obvious antihypertensive effect with no significant changes in heart rate; (4) Lacidipine had no significant effects on insulin, blood glucose and lipids. The results suggest that lacidipine is a safe and effective antihypertensive agent and can improve the metabolic balances in free radical system.
 ...
PMID:[Effects of lacidipine on serum oxygen free radicals and fasting levels of insulin in patients with essential hypertension]. 986 30

Diuretics and calcium blockers are particularly effective in the treatment of hypertension in Blacks, who, characteristically, have low-renin hypertension. The efficacy and tolerable of lacidipine (a calcium) blocker of the dihydropyridine class) and hydrochlorothiazide (a diuretic) were compared in a 12 week double-blind randomised parallel group study of Nigerians with essential hypertension. Lacidipine was given at a starting dose of 4 mg daily by mouth and increased to 6 mg if there was no satisfactory response at 4 weeks, and hydrochlorothiazide was stared at 25 mg daily by mouth and increased to 50 mg if necessary. Twenty-four patients (8 male) in the lacidipine group and 17 (5 male) in the hydrochlorothiazide group were evaluable at the end of the trial. In the lacidipine group, SBP was significantly reduced from 157 +/- 14 mmHg to 146 +/- 24 mmHg (P < 0.00001) and DBP from 90 +/- 9 mmHG to 87 +/- 15 mmHg (P < 0.00001) with BP normalisation rates of 67% and 79% at 4 weeks and 12 weeks, respectively. In the hydrochlorothiazide group, SBP was significantly reduced from 16.4 +/- 19 mmHg to 141 +/- 17 mmHg (P < 0.00001) and DBP from 102 +/- 6 mmHG to 89 +/- 7 mmHg (P < 0.00001) with normalisation rates of 77% and 82% at 4 weeks and 12 weeks respectively. The groups did not differ in BP reduction nor normalisation rates. There were no reported side effects.
 ...
PMID:Evaluation of lacidipine (a calcium blocker) in the treatment of hypertension in black African people: a double-blind comparison with hydrochlorothiazide. 1045 35

An increasing amount of data suggests that systolic blood pressure (SBP) and pulse pressure (PP) may more closely relate to and thus favour the atherogenic process than does diastolic blood pressure (DBP). The baseline data from the ongoing European Lacidipine Study on Atherosclerosis (ELSA) recently indicated that carotid artery atherosclerosis in normocholesterolaemic patients with mild or moderate essential hypertension is more closely related to SBP and more so PP than to DBP and lipid variables. Other new data point to the effects of hypertension on arterial compliance, as well as the effects of 24-h blood pressure variability on arterial compliance and distensibility. When viewed in their entirety, these data present a compelling case for the closer monitoring of SBP and PP with respect to arterial compliance, and the need for aggressive blood pressure treatment to control and perhaps reverse the underlying pathological changes in arterial structure and function in hypertensive patients.
 ...
PMID:Systolic blood pressure and pulse pressure: role of 24-h mean values and variability in the determination of organ damage. 1070 28


1 2 Next >>