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

Diltiazem is a widely used calcium channel blocker, and has been found to be effective in the treatment of hypertension, stable, variant and unstable angina, as well as oesophageal spasm. Calcium channel antagonists have been shown to diminish the contractility of gut smooth muscle, but have not as yet been reported to cause clinically significant inhibition of gut motility when used alone. We report a case of reversible functional intestinal obstruction, immediately following diltiazem treatment in a patient with ischaemic heart disease.
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PMID:Paralytic ileus as a result of diltiazem treatment. 820 68

Effects of monatepil ([(+/-)-N-(6,11-dihydrodibenzo[b, e]thiepin-11-yl)-4-(p-fluorophenyl)-1-piperazinebutyramide]m aleate, AJ-2615, CAS 103377-41-9), a novel calcium antagonist, on the cardiac conduction system were compared by electrocardiography with those of the existing calcium antagonists (diltiazem, verapamil and nifedipine) in isolated rabbit heart preparations in vitro and in anesthetized and conscious dogs in vivo. Monatepil (10(-7) mol/l) prolonged the atrio-His bundle conduction time (AH interval) in the Langendorff perfused rabbit heart, like diltiazem, verapamil and nifedipine. This prolongation was decreased to 1/10 in the presence of 3.6% bovine serum albumin. In anesthetized dogs, monatepil (0.1-1.0 mg/kg i.v.), unlike diltiazem and verapamil, did not prolong AH interval. In conscious dogs, monatepil even at 100 mg/kg p.o. did not affect electrocardiograms. At the high dose of 300 mg/kg p.o., only a slight prolongation of the QT interval was found, but the QTc interval was not affected. Diltiazem at 10 mg/kg p.o. caused a prolongation of the PR interval and a disappearance of QRS waves. In conscious renal hypertensive dogs, repeated administration of monatepil (10 mg/kg/d p.o. for 29 days) had little effect on the conduction system of the heart examined by electrocardiograms, albeit a persistent fall in blood pressure continued throughout the administration period. The above results suggest that monatepil is a highly safe drug in the treatment of hypertension.
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PMID:In vitro and in vivo electrocardiographic evaluation of the novel calcium antagonist monatepil on cardiac conduction system. 836 2

Diltiazem is a benzothiazepine derivative calcium antagonist available in several formulations, some of which enable once daily administration. The drug as monotherapy has demonstrated similar efficacy to diuretics in older patients with hypertension. Data comparing diltiazem with beta-blockers and angiotensin converting enzyme inhibitors are more limited, but available studies suggest at least comparable antihypertensive efficacy. Diltiazem as monotherapy or in combination with a beta-adrenoceptor-antagonist, isosorbide dinitrate, or another calcium antagonist, has demonstrated efficacy in patients with effort angina. The drug has also been used intravenously to terminate supraventricular tachycardias and to control the ventricular response to atrial fibrillation or flutter; it also appears to reduce the rate of early reinfarction in patients with non-Q-wave myocardial infarction. The most common adverse events during diltiazem therapy include headache, flushing, peripheral oedema and hypotension. Atrioventricular block although rare, is the most frequent serious adverse event related to diltiazem therapy and may be exacerbated by coadministration of beta-adrenoceptor antagonists, especially in the elderly. Thus, diltiazem appears to be an effective and well tolerated treatment for hypertension and angina in older patients and has shown promise as therapy for supraventricular tachycardias and as prophylaxis against early reinfarction in patients with non-Q-wave myocardial infarction.
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PMID:Diltiazem. A review of its pharmacology and therapeutic use in older patients. 836 96

Diabetes mellitus and cardiovascular disorders are both common disorders, and it could be anticipated that they coexist in many patients. Diltiazem (DZ) is widely used alone or in combination with propranolol (PROP) for the treatment of hypertension and ischemic heart disease. These drugs could interfere with carbohydrate metabolism and impair glucose tolerance. The purpose of this study was to investigate the effect of oral administration of DZ, PROP (100 and 25 mg kg-1, respectively) and their combination on fasting serum glucose and insulin levels in normal and diabetic Wistar rats. Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (60 mg kg-1). In normal animals, serum glucose was significantly increased after DZ, PROP and DZ/PROP treatment compared to the initial values. In diabetic rats, serum glucose was significantly increased after PROP and DZ/PROP treatments, while it was slightly increased after diltiazem treatment compared to the initial values. In normal animals, plasma cAMP is significantly decreased in all treatment groups compared to the control value, while in the plasma of diabetic rats, cAMP was significantly decreased after PROP and DZ/PROP treatments when compared to the control value. Serum potassium of normal rats decreased after the diltiazem and DZ/PROP treatments, and they tend to increase slightly after PROP treatment. Serum potassium of diabetic rats was increased significantly after PROP and DZ/PROP treatments compared to the initial values. Body weight is decreased significantly in all treatment groups in normal rats while this significant decrease was observed only after DZ/PROP treatment in diabetic rats. This investigation suggests that diltiazem alone has no worsening effects on the glycemic control in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of diltiazem and/or propranolol on rat blood glucose levels in normal and diabetic animals. 838 58

Calcium entry blockers, particularly diltiazem, have been shown to lower not only systemic blood pressure but also improve proteinuria in non-insulin-dependent diabetic patients. The presence of proteinuria is attributed to the loss of glomerular heparan sulfate, which confers a negative charge on the basement membrane. In the present study, we evaluated the efficacy of diltiazem in lowering blood pressure and proteinuria in diabetic rats and also examined the possibility that diltiazem prevents proteinuria through glomerular preservation of heparan sulfate. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg). One group of diabetic rats was treated with diltiazem (25 mg/L) in drinking water for 20 weeks. Another group of diabetic rats and a group of nondiabetic rats were given tap water only. Systolic blood pressure was measured at 4, 8, 12, and 20 weeks. Urinary excretion of albumin was done at 4, 8, 12, 16, and 20 weeks. At the end of 20 weeks, all rats were killed, kidneys were removed, and glomeruli were isolated. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of [35S]sulfate. Diltiazem lowered blood pressure significantly in diabetic rats at 8, 12, and 20 weeks. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from normal rats. Characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. Diltiazem therapy returned not only glomerular synthesis but also various fractions of heparan sulfate to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:Effect of diltiazem on glomerular heparan sulfate and albuminuria in diabetic rats. 850 Aug 60

Receptor binding studies suggest that combinations of calcium channel blockers may result in either enhanced or diminished pharmacological effects, but clinical data in hypertension are incomplete. In this study, we compared blood pressure reductions using nifedipine alone, nifedipine plus diltiazem, and nifedipine plus verapamil and determined whether combinations alter nifedipine pharmacokinetics. After determination of baseline blood pressures. 16 subjects with essential hypertension (12 men, 4 women; mean age, 48 years) received 30 mg/d open-label, sustained release nifedipine for 2 weeks. If still hypertensive (n = 16), they were randomized (double-blind) to receive either additional sustained release diltiazem or sustained release verapamil, both 180 mg/d, for 2 weeks and were then crossed-over for the final 2 weeks of the study. All medications were once-daily, extended-release formulations. Blood pressures and nifedipine plasma concentrations were measured during the final day of each treatment. Overall, each combination lowered mean systolic and diastolic pressures more than nifedipine alone. Mean supine diastolic pressures were significantly lower at 8 hours (77.6 versus 84.6 mm Hg, P = .001) and 12 hours (81.5 versus 87.1 mm Hg, P = .04) with nifedipine plus diltiazem than nifedipine plus verapamil. Mean nifedipine concentrations were inversely correlated with mean blood pressures. Mean nifedipine area under the curve values were greater with diltiazem than verapamil (1430 versus 1134 ng.h/mL, P = .026), with each greater than nifedipine alone (957 ng.h/mL). Nifedipine plus diltiazem had a greater antihypertensive effect than nifedipine plus verapamil. Diltiazem caused greater increases in nifedipine plasma concentrations than did verapamil. These data suggest that combined calcium channel blockers result in additive antihypertensive effects, perhaps because of a pharmacokinetic interaction.
Hypertension 1996 Jul
PMID:Comparison of nifedipine alone and with diltiazem or verapamil in hypertension. 867 49

The objective was to evaluate the dose-related efficacy/tolerance profile of 240, 300, 360, and 420 mg diltiazem slow-release, once-daily (OD) doses, with emphasis on the 300 mg dose. The study was randomized and double-blinded with a 36-week parallel, two-branched, cross-over design after a single-blind, run-in period of 4 weeks on placebo and 6 weeks on 300 mg diltiazem OD. Each branch included six 6-week active treatment periods with 180, 240, and 300 mg tablets, one or two tablets OD. Participants were men and postmenopausal women, aged 40-70 years, with uncomplicated primary hypertension (WHO stages I and II) and a supine diastolic blood pressure of 95-115 mm Hg in the absence of antihypertensive medication. A total of 138 patients from various clinics participated in the study. All were included in the intention to treat analysis, and 117 patients were included in the per protocol analysis. Criteria for evaluation were blood pressure, heart rate, and response rate, as well as plasma diltiazem and metabolite M1 concentration before morning dose. Well-being of the patients and adverse events were recorded. Electrocardiogram and standard laboratory tests were obtained. Analysis of variance was used for statistical calculations. Supine blood pressures and response rates in the per protocol analysis were 161.2/97.0 for placebo (29.1%), 155.2/ 92.8 for 240 mg (54.7%), 153.8/91.6 for 300 mg (55.6%), 155.5/92.0 for 360 mg (59.0%), and 152.0/90.5 for 420 mg (63.2%) of diltiazem OD. The intention to treat analysis was very similar to the per protocol analysis. There was a small but statistically significant decrease in heart rate for all doses of diltiazem OD compared to placebo. A linear relationship existed between the dose and the plasma concentration of both diltiazem and metabolite M1, as well as a dose-response relationship. Diltiazem OD in the dose range 240-420 mg was generally well tolerated and not differently perceived from the placebo treatment except for ankle edema (2-6%). The study shows that OD diltiazem is significantly superior to placebo for mild to moderate hypertension and that the effect is large enough to be clinically valuable. It also shows that there is a linear dose-response relationship for diltiazem between 240 and 420 mg.
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PMID:The Diltiazem Different Doses Study--a dose-response study of once-daily diltiazem therapy for hypertension. 884 61

Diltiazem (DTZ) is a calcium antagonist widely used in the treatment of angina and hypertension. It is extensively metabolized in humans via N-demethylation, O-demethylation, deacetylation, and oxidative deamination, yielding a host of metabolites, some of which have potent pharmacological properties. After our initial identification of O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) as major metabolites of DTZ and our subsequent of identification of their chemical synthesis, an improved high-performance liquid chromatography assay was developed to determine the plasma concentrations of DTZ and seven of its major basic metabolites, including the previously unquantitated Mx and MB. The system consisted of a C18 analytical column protected by a C18 cartridge guard column and a variable wavelength ultraviolet detector set at 237 nm. The mobile phase was a mixture of methanol, 0.04 M ammonium acetate, and acetonitrile (38:36:26) containing 0.08% triethylamine, with final pH of the mobile phase adjusted to 7.5. The system was operated at room temperature isocratically at a flow rate of 1.2 ml/min. Using verapamil as an internal standard, DTZ and the basic metabolites in plasma were determined in young healthy volunteers (n = 21) and in patients with ischemic heart disease (n = 19) at steady state after repeated oral doses of 60 mg DTZ four times daily. Preliminary results show that steady-state plasma concentrations of DTZ and its metabolites were higher in the older patients than in young healthy subjects (p < 0.05).
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PMID:Steady-state plasma concentrations of diltiazem and its metabolites in patients and healthy volunteers. 884 19

Five antihypertensive trials launched outside of the United States have been designed to address one of two vital issues. The first is whether or not there is an optimal level of blood pressure that clinicians should aim for to minimize the risk of cardiovascular disease. This has been addressed by the Swedish Behandla Blodtryck Battre (BBB) Trial and the international Hypertension Optimal Treatment (HOT) Study. The BBB Trial revealed interesting trends, but no definitive conclusions. The ongoing HOT Study will have to be completed before this particular issue can be adequately addressed. However, preliminary analysis of a subgroup study has revealed that the HOT treatment regimens are as effective in the elderly as in younger patients. The second important issue, which is the question of whether traditional antihypertensive agents are more effective than the newer agents in reducing cardiovascular risk, is the current focus of three ongoing studies. Investigators in the Captopril Prevention Project (CAPPP) are comparing captopril to beta-blocker and diuretic regimens. The purpose of the Nordic Diltiazem Study (NORDIL) is to determine if diltiazem is more effective than conventional therapy in reducing cardiovascular risk. The Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-2) has been designed to compare therapy with beta-blockers and diuretics to therapy with calcium antagonists and angiotension converting enzyme inhibitors. All ongoing trials should be completed in the next few years and are expected to yield valuable information that will improve current strategies for the treatment of hypertension.
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PMID:Major antihypertensive intervention trials conducted outside the United States. 886 36

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
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PMID:What, if anything, is controversial about calcium antagonists? 896 30


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