Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to identify differences in the patterns of efficacy and duration of effect by diltiazem given in different dosage forms and schedules. Blood pressure (BP) and heart rate (HR) were monitored before and after treatment by ambulatory blood pressure monitoring for 48 h every 30 min. Patients were divided for treatment assignment into 4 groups -nocturnal BP dippers and nondippers. In dipper hypertension, diltiazem-retard at 08:00 (n = 7) had the most marked antihypertensive effects during nighttime rest (SBP; 136 +/- 14/118 +/- 9 mmHg, p < 0.01 before vs. after treatment). Diltiazem-retard at 19:00 (n = 6) exerted greatest effect during daytime activity (152 +/- 7/139 +/- 6, p < 0.01) with inhibition of the morning BP rise. Diltiazem (t.i.d., n = 5) had the best effect during daytime activity (151 +/- 16/136 +/- 9, p < 0.05). However, in nondipper hypertensive patients, diltiazem (t.i.d., n = 8) had the most pronounced antihypertensive effects during nightly rest (144 +/- 12/127 +/- 12, p < 0.05). Evening medication with diltiazem retard appears to be more efficacious than the other dosage schedules.
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PMID:Administration-time-dependent effects of diltiazem on the 24-hour blood pressure profile of essential hypertension patients. 904 53

Diltiazem is a calcium antagonist widely used for the treatment of angina and hypertension. Previous studies in patients have shown that the haemodynamic effects of diltiazem are greater after parenteral rather than oral administration. The rat has been used as an animal model to determine the effect of the route of administration on the pharmacokinetic and haemodynamic effects of diltiazem. The results showed that plasma concentrations of diltiazem were more than 10 times higher after the intra-arterial dose. The plasma concentrations of the major metabolites were also higher after intra-arterial administration, although only for deacetyl diltiazem (M1) did the difference reach statistical significance (P < 0.05). The haemodynamic effects (on blood pressure and heart rate) of diltiazem were considerably greater after intra-arterial administration; this was attributed mainly to the much higher plasma concentrations of diltiazem. The hypotensive and chronotropic effects of diltiazem were similar; Emax and EC50 for diastolic blood pressure were 72+/-19% and 4.4+/-5.9 microg mL(-1); for heart rate they were 77+/-32% and 10.0+/-11.7 microg mL(-1), respectively. The haemodynamic effects of diltiazem are much greater after intra-arterial administration, mainly because of the much higher plasma concentrations of the drug. The contribution by the metabolites would be minimal after this route of administration.
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PMID:Pharmacokinetics and haemodynamic effect of diltiazem in rats: effect of route of administration. 953 Sep 86

31 male and female patients, between the ages of 18 and 65 years, presenting mild-to-moderate hypertension (DBP between 95 and 114 mmHg) and stable chronic renal failure (creatinine clearance between 60 and 25 ml/min) after a preinclusion placebo phase were included in a multicentre open study designed to evaluate the clinical, electrocardiographic and laboratory safety, as well as the antihypertensive efficacy of Diltiazem 300 mg Retard, as monotherapy for 3 months, or combined with a diuretic (furosemide) or angiotensin converting enzyme inhibitor (captopril) for 45 days. After an 8-day placebo run-in period, the study consisted of a 45-day phase of strict monotherapy with Diltiazem 300 mg Retard, followed by a final 45-day phase during which either monotherapy was continued (if safety was satisfactory and supine DBP < or = 90 mmHg), or two-agent combination therapy was instituted (when supine DBP was between 91 and 115 mmHg), 6 clinical evaluations were performed during the 3 months of this trial. Overall, 21 patients (mean age: 50 +/- 14 years) completed the study until the 3rd month: 13 remained on monotherapy, and 8 required two-agent combination therapy. Supine and standing systolic and diastolic blood pressures and heart rate were significantly decreased. The number of responding patients controlled (supine DBP < or = 90 mmHg) progressed between D10 (40%) and D90 (57%). The observed adverse events and reasons for drop-outs from the trial for adverse events were mostly related to the vasodilator effects of Diltiazem. The cardiac safety was good, with no significant variation of the PR interval on the ECG (0.15 +/- 0.03 sec on D-8, 0.17 +/- 0.02 sec on D90). No marked modification of blood and urinary laboratory constants (serum electrolytes, blood glucose, liver function tests) was observed during this trial. Renal function, evaluated by creatinine clearance, was not altered by treatment (40.5 +/- 15.2 ml/min on D0, 41.7 +/- 16.9 ml/min on D90). Overall, this study confirmed the good clinical, laboratory and electrocardiographic safety as well as the antihypertensive efficacy of Diltiazem 300 mg Retard administered as monotherapy for 3 months or possibly in combination for 45 days, in hypertensive patients with chronic renal failure.
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PMID:[Evaluation of the tolerance and effectiveness of Diltiazem LP 300 mg in hypertensive patients with chronic renal insufficiency]. 980 45

-To assess cellular mechanisms mediating myogenic responses of interlobular artery (ILA), experiments were performed with the use of isolated perfused hydronephrotic kidneys. ILAs were divided into 3 groups according to their basal diameters: proximal (>60 microm), intermediate (40 to 60 microm), and distal (<40 microm) ILAs. Myogenic responses were obtained by stepwise increase in perfusion pressure. Greater myogenic responsiveness was observed in ILAs with smaller diameters. Diltiazem (10 micromol/L) inhibited myogenic responses of all segments of ILAs. Furthermore, gadolinium (10 micromol/L), a mechanosensitive cation channel blocker, abolished myogenic responses of distal but not proximal ILA. In contrast, 2-nitro-4-carboxyphenyl-N, N-diphenyl-carbamate (200 micromol/L), an inhibitor of phospholipase C, prevented myogenic responses of proximal but not distal ILA. Finally, basal proximal ILA diameters were increased by treatment with 50 nmol/L of staurosporine (P<0.05), and subsequent addition of thapsigargin (1 micromol/L) blocked myogenic contraction of proximal ILAs. Myogenic responses of intermediate ILAs exhibited characteristics between those of distal and proximal ILAs. Our data indicate that underlying mechanisms for myogenic responses differ in distinct segments of ILAs. The present results suggest that mechanosensitive cation channels are involved in myogenic constriction of distal ILAs. Finally, our findings provide evidence that the stimulation of phospholipase C mediates myogenic contraction of proximal ILAs.
Hypertension 1998 Dec
PMID:Biophysical signals underlying myogenic responses in rat interlobular artery. 985 74

In 1998 the final results were presented of two large intervention trials in hypertension, the Hypertension Optimal Treatment Study (HOT) and the Captopril Prevention Project (CAPPP). Both were initiated from Sweden although the HOT Study was conducted in 26 countries worldwide and the CAPPP Study in Finland and Sweden. The HOT and CAPPP trials and their principal results will be reviewed briefly here. In addition a brief up-date will be provided of three ongoing intervention trials in hypertension that were also initiated from Sweden: the Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-), the Nordic Diltiazem (NORDIL) Study and the Study on Cognition and Prognosis in Elderly Hypertensives (SCOPE).
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PMID:Recent intervention trials in hypertension initiated in Sweden--HOT, CAPPP and others. Hypertension Optimal Treatment Study. Captopril Prevention Project. 1042 77

Calcium antagonists, particularly the newer, longer-acting agents, are clearly effective in reducing elevated blood pressure with minimal to modest adverse effect profiles, and are therefore used extensively. The goal of antihypertensive therapy, however, is not simply to reduce blood pressure, but also to reduce vascular injury due to hypertension. Prospective controlled clinical trials evaluating cardiovascular morbidity and mortality are needed to test calcium antagonists in patients with hypertension. This review summarises the design and, in some cases, the results of 7 trials (5 of them still ongoing) that have provided insight into the effects of moderate- to long-acting calcium antagonists on mortality and target-organ damage in patients with hypertension. The Systolic Hypertension in Europe (Syst-Eur) trial studied 4695 elderly patients with isolated systolic hypertension, and demonstrated significant reductions in stroke and all fatal and nonfatal cardiac end-points in patients randomised to nitrendipine versus placebo. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compares the effects of standard diuretic treatment with 3 alternatives (amlodipine, lisinopril, and doxazosin) on the incidence of fatal coronary artery disease and nonfatal myocardial infarction in more than 42,000 hypertensive patients with additional cardiovascular risk factors. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) compares the effects of amlodipine +/- perindopril with atenolol +/- bendrofluazide on fatal coronary artery disease and nonfatal myocardial infarction in 18,000 high risk patients. The Controlled ONset Verapamil INvestigation of Cardiovascular End-points (CONVINCE) study is assessing the incidence of fatal or nonfatal myocardial infarction and stroke, and cardiovascular disease-related death in patients on controlled-onset extended-release verapamil compared with a standard regimen of hydrochlorothiazide or atenolol. The Nordic Diltiazem Study (NORDIL) also compares a calcium antagonist (diltiazem) with conventional antihypertensive drug treatment (diuretics or beta-blockers) with add-on therapy as needed, in preventing cardiovascular mortality or morbidity. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) tests a similar hypothesis, examining the effects of amlodipine on atherosclerotic lesions. The African-American Study of Kidney Disease (AASK) trial is evaluating the effects of amlodipine in hypertensive patients with renal disease. These important clinical trials of different classes of antihypertensive agents are critical for optimising the treatment of hypertensive patients in order to prevent coronary artery disease and other vascular diseases in this new millennium. Importantly, these randomised trials are free of the major problems of observational studies, i.e., confounding by indication, and should fully address the concerns raised by observational studies and small, under-powered, randomised trials that calcium antagonists may have adverse effects on myocardial infarction, bleeding and cancer. To date, these trials in progress have provided no evidence to support these concerns.
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PMID:[Calcium antagonists in cardiovascular disease. Clinical evidence from morbidity and mortality trials]. 1100 56

Calcium channel blockers have come into worldwide use for treating hypertension and other circulatory disorders. In recent years, results of several observational studies have suggested that these drugs may not be as safe or effective as other available therapies, such as diuretics and beta-blockers, in the prevention of cardiovascular events. The Nordic Diltiazem (NORDIL) and the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) studies were the first two randomized interventional trials in hypertensive patients that directly compared the effects of therapy based on calcium antagonists with those of diuretic and beta-blocker-based treatment on major cardiovascular endpoints. Both studies found that the effectiveness of calcium antagonist therapy was similar to that of diuretic and beta-blocker therapy for preventing the composite primary endpoint of fatal and nonfatal stroke, myocardial infarction, and other cardiovascular death. The two studies shared several nonsignificant trends for cause-specific events, including greater stroke prevention and lesser coronary event prevention in the calcium antagonist groups compared with the diuretic and beta-blocker groups. There is not yet sufficient evidence to prove whether cause-specific differences exist. Results of the NORDIL and INSIGHT studies support incorporating calcium antagonist-based therapy as an additional safe and effective approach for preventing blood pressure-related illness and death.
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PMID:The INSIGHT and NORDIL trials: Are calcium antagonists equivalent to established drug therapies for cardiovascular protection? 1147 11

A novel diltiazem HCl extended-release (ER) tablet formulation was developed for evening administration in the management of angina and hypertension. Pharmacokinetics of the formulation were evaluated to identify variations in morning (7 a.m. or 8 a.m.) versus evening (10 p.m.) drug administration. Single-dose (360 mg) and multiple-dose (360 mg once daily for 7 days), open-label, randomized, two-way crossover studies of the new diltiazem HCl ER tablets were completed in 48 healthy volunteers. Serial plasma samples were collected via direct venipuncture up to 48 hours postdose and analyzed for diltiazem and its two major metabolites by high-performance liquid chromatography (HPLC). The primary parameters used to assess the data were AUC0- infinity, AUC0-tau, AUC6 a.m.-12 p.m., Cmax, and tmax. Statistical comparisons using ANOVA were evaluated after logarithmic transformation of dose-dependent parameters. Diltiazem HCl ER tablets administered in the evening exhibited 17% and 22% greater bioavailability compared to morning administration under single-dose and steady-state conditions, respectively. The two times of drug administration were bioinequivalent in both studies. The evening schedule also provided more than twofold higher plasma diltiazem levels in the critical morning hours, when both blood pressure and the incidence of cardiovascular events are the highest.
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PMID:Pharmacokinetics of a novel diltiazem HCl extended-release tablet formulation for evening administration. 1451 97

We determined tissue distribution of diltiazem after it was used to treat hypertension in two cases. The postmortem interval was 16 h in both cases. Diltiazem was isolated using liquid-liquid extraction, and it was identified and quantitated using gas chromatography-mass spectrometry (GC-MS) and GC, respectively. In one case, diltiazem concentrations in the lungs and pulmonary vessel blood were 62-82 and 27-30 times higher than right femoral blood, respectively. Although blood was not obtained from the left cardiac chambers, aortic blood showed a 10-times higher level of diltiazem than right femoral venous blood. Diltiazem concentration in blood in the right cardiac chambers was 3.6 times higher than that in right femoral venous blood. In another case, diltiazem concentrations in the lungs were 7.4-7.6 times higher than right femoral venous blood. Blood in the pulmonary arteries, pulmonary veins, left cardiac chambers, and aorta showed 2.0-3.1 times higher levels of diltiazem than right femoral venous blood. Blood in the right cardiac chambers displayed only 1.3 times higher level of diltiazem than right femoral venous blood. Our results strongly suggest that diltiazem accumulated in the lungs and was rapidly redistributed into pulmonary venous blood and then into the left cardiac chambers.
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PMID:Redistribution of diltiazem in the early postmortem period. 1518 79

A 55-year-old woman with pulmonary tumor was scheduled for tumor resection. Preoperatively, her episode of paroxysmal hypertension suggested the existence of pheochromocytoma, but MIBG (metaiodo-benzylguanidine) scintigraphy revealed no local accumulation. Therefore, physicians and surgeons denied the possibility of pheochromocytoma. During epidural catheterization, hypertension occurred, which was controlled by diltiazem 2 mg. Anesthesia was induced with midazolam 10 mg, propofol 70 mg and fentanyl 300 microg and maintained with propofol 4-7 mg x kg(-1) x hr(-1), epidural block with 1% mepivacaine and nitrous oxide 66% in oxygen. Manipulation of the tumor induced hypertension. Diltiazem 1-2 microg x kg(-1) x min(-1) and nicardipine 0.4-4 microg x kg(-1) x min(-1) were administered. After tumor resection, blood pressure decreased to 82/42 mmHg and norepinephrine 0.05-0.25 microg x kg(-1) x min(-1) was infused. Norepinephrine infusion was continued for 24 hours after surgery. She was discharged from the recovery room on the third postoperative day without any complications. A case of ectopic pheochromocytoma of pulmonary origin was managed with midazolam, propofol, fentanyl and continuous epidural block. Diltiazem, nicardipine and norepinephrine were administered to control blood pressure.
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PMID:[A case of ectopic pheochromocytoma of pulmonary origin]. 1519 38


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