Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses.

OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. RESULTS: Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.

Role of prostaglandins in hypertension.

The role of prostaglandins (PGs) in hypertension (HT) is reviewed, emphasising their biochemical characteristics, physiological effects and functions, especially in the cardiovascular area, and the current evidence of their participation in the antihypertensive activity of a balanced mechanism to maintain normal blood pressure. Also, the clinical use of PGs and the future of such autacoids in the treatment of HT and other diseases or conditions is mentioned.

Successful pregnancy in a severe hypertensive patient treated with nitrendipine. Case report.

Nitrendipine (NIT), a new potent calcium channel blocking agent, was administered to a patient with essential severe (191/119 mm Hg), refractory, and resistant hypertension (HT) to conventional triple drug regime. Three previous pregnancies had been unsuccessful in the past 4 years because of uncontrollable HT and repeated hypertensive crises. NIT (20 mg tablets) was given PO as a single morning dose and 15 months after BP control, she became pregnant again. With a 20 mg/day dose of NIT throughout pregnancy, a healthy 2400 g, 47 cm male boy was delivered by a non-emergency cesarean section at 37 weeks' pregnancy. Both mother and son remain normal months after birth. The results suggest NIT may be considered as an alternative for this type of patients and should be studied in clinical trials.

Effects of doxazosin on blood pressure, renin-angiotensin-aldosterone and urinary kallikrein.

Doxazosin, a new quinazoline-derivative postsynaptic alpha 1-adrenoceptor antagonist, was studied in this randomized, double-blind, placebo-controlled 12-week study. Its effects on blood pressure (BP), heart rate, metabolic functions and renal hormones were analyzed after administration of a single oral morning dose in a 3-phase fashion when administered to 17 patients (11 women, 6 men, 21 to 59 years) with mild to moderate uncomplicated essential hypertension. After titrating the antihypertensive effective dose biweekly from 1 to 8 mg/day and a mean end titration-point dose of 4.14 +/- 0.1 mg (mean +/- standard error of the mean) at week 8 of treatment, it was adjusted to maintain diastolic BP at levels less than or equal to 90 mm Hg for up to 12 weeks of treatment when, at a final mean dose of 4.35 +/- 0.2 mg/day, BP decreased in all patients by a mean 31 +/- 3/17 +/- 2 (supine) and 39 +/- 3/15 +/- 3 (standing) mm Hg (p less than 0.005) with no increase in heart rate and no "first-dose phenomenon." Neither the renin-aldosterone system nor electrolyte excretion was significantly affected. Renal function and metabolic parameters also remained unchanged. Urinary kallikrein excretion was augmented 2.47-fold (p less than 0.002). There was good tolerance; 1 patient discontinued the study because of dry nose. These results suggest that long-term monotherapy with doxazosin is an effective and safe antihypertensive agent for mild to moderate essential hypertension that stimulates urinary kallikrein excretion.

Long-term (3 years) sustained antihypertensive and metabolic actions of nitrendipine in severe, complicated, and resistant hypertension.

The antihypertensive efficacy of once-daily nitrendipine was studied in 18 patients with severe, resistant, refractory, and complicated hypertension. The dose range was 20-120 mg/day adjusted weekly for a total treatment period of 3 years. Nitrendipine produced a significant reduction in blood pressure compared to pretreatment baseline values with no significant effects on heart rate. Renal function was preserved and there was an increase in urine flow, urinary excretions of Na+, kallikrein, and prostaglandin E2, and plasma renin. Some patients experienced known calcium antagonist side effects but the drug was otherwise well tolerated.

Usos clinicos de los inhibidores de la enzima convertidora. Revision. / Clinical uses of converting-enzyme inhibitors: a review

Se hizo una revision y actualizacion de las drogas del grupo anti-hipertensivas que actuan inhibiendo la enzima convertidora de la angiotensina I, introducidas recientemente en el tratamiento de la hipertension arterial y otras enfermedades.Se definieron algunas caracteristicas, su mecanismo de accion y las indicaciones clinicas en algunos estados patologicos ademas de algunos tipos de hipertension arterial humana (hipertension arterial renovascular, hipertension arterial esencial y refractaria a la terapia convencional), en insuficiencia cardiaca congestiva, hipertension arterial en pacientes en hemodialisis. Tambien se describieron sus usos en enfermedades tales como: edema idiopatico, crisis hipertensiva que acompana a la escleroderma con vasculitis, en el sindrome nefritico agudo y la hipertension pulmonar. Por ultimo, se describieron sus efectos secundarios e interacciones con otras drogas

Urinary excretion of prostaglandins (PGE2 and PGF2 alpha) and kallikrein in acute glomerulonephritis.

We studied prostaglandins and kallikrein urinary excretion in 14 children with acute poststreptococcal glomerulonephritis within 48 hours of hospital admission (period A), and again, 4-6 weeks later, when they were clinically recovered (period B). Seventeen apparently healthy children were studied as controls. The results (mean +/- SEM) indicate that PGE2 urinary excretion (ng/kg/day) was diminished during both periods of study (control group = 2.06 +/- 0.43, patients = period A 0.91 +/- 0.28 [P less than 0.02], period B 0.92 +/- 0.21 [P less than 0.02]). PGF2 alpha urinary excretion (ng/kg/day) was also suppressed during period A, but not during period B when large individual variability existed (control group = 7.10 +/- 1.07, patients period A 3.56 +/- 0.66 [P less than 0.001], period B 10.51 +/- 5.01 [NS]). Kallikrein urinary excretion (EU/kg/day) was also depressed during the acute phase and remained low during convalescence (control group = 0.492 +/- 0.1, patients period A 0.143 +/- 0.044 [P less than 0.001], period B 0.265 +/- 0.093 [P less than 0.02]). There was no difference in PGE/PGF ratio between controls and patients in the periods of study (control 0.328 +/- 0.055, period A 0.395 +/- 0.144, period B 0.384 +/- 0.128). Urine volume (ml/day) was lower in period A (582 +/- 75.8) but comparable in period B (1020 +/- 140.2) and control children (1210 +/- 80.2). No correlation could be found between the urinary excretion of PGE2, PGF2 alpha and kallikrein with any of the following parameters: urinary or serum sodium and potassium, serum or urinary osmolality, Cosm, urine flow, plasma renin activity, plasma or urinary aldosterone, hypertension or fluid retention.(ABSTRACT TRUNCATED AT 250 WORDS)