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

Calcium channel blockers are widely used in the treatment of ischemic heart disease, hypertension, and supraventricular tachycardia. The prototype agents, verapamil, nifedipine, and diltiazem, represent three classes of calcium channel blockers, each of which has different pharmacologic effects. Nifedipine and the other dihydropyridines primarily are vasodilators and have no clinical effects on cardiac conduction or contractility. Diltiazem and verapamil also are vasodilators, but they possess, to varying degrees, negative inotropic, chronotropic, and dromotropic effects. Side effects of these drugs are relatively rare and usually not serious, with the exception of potential conduction disturbances and heart failure in patients with underlying cardiac disease. To assess patients taking these medications and provide the necessary teaching, the nurse needs an understanding of the pharmacologic properties, clinical indications, and potential adverse effects of the various drugs.
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PMID:Calcium channel blockers. 131 59

Diltiazem administered in drinking water (0.7 mg mL-1) to Goldblatt two kidney-one clip rats over 16 weeks did not prevent the development of hypertension and left ventricular hypertrophy (LVH). When the collagen content of the left ventricles was assayed (as hydroxyproline), it was found that the fibrosis, characteristic of LVH, was inhibited by diltiazem treatment, despite the fact that hypertension and LVH had developed. This study provides some indirect evidence for the notion that the collagen and myocyte compartments of the myocardium are under separate influences during LVH development in renovascular hypertension.
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PMID:Inhibition by diltiazem of left ventricle collagen proliferation during renovascular hypertension development in rats. 135 42

This report describes a case of epinephrine predominant pheochromocytoma successfully managed intraoperatively with an infusion of diltiazem. A 50-yr-old woman with a 10-yr history of diabetes mellitus was admitted to the hospital because of thirst and general fatigue. A cystic left adrenal tumor was found on computed tomographic scan. Although resting plasma catecholamine levels were normal, plasma norepinephrine and epinephrine levels obtained from the left adrenal vein were 1.6 ng.ml-1 (normal, 0.04-0.35) and 6.2 ng.ml-1 (normal, less than 0.12), respectively. Diltiazem was administered i. v. at a rate of 3 micrograms.kg-1.min-1 before induction of anesthesia. Anesthesia was induced with enflurane 2-3% and nitrous oxide in oxygen, followed by tracheal intubation facilitated with vecuronium. Anesthesia was maintained with enflurane 1-3% and nitrous oxide in oxygen. Paralysis was maintained with vecuronium. Hypertension during the manipulation of the tumor was controlled by increasing the inspired concentration of enflurane or by increasing the infusion rate of diltiazem to 5 micrograms.kg-1.min-1. There was no tachyarrhythmia. The infusion of diltiazem was continued until the draining vein from the tumor had been ligated. Hypotension, after removal of the tumor, was treated by the rapid infusion of fluid. Plasma norepinephrine and epinephrine levels during tumor manipulation were 1.18 ng.ml-1 and 6.57 ng.ml-1, respectively.
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PMID:[Use of diltiazem in the anesthetic management of epinephrine predominant pheochromocytoma]. 149 89

Diltiazem is a calcium antagonist widely used in the treatment of angina and hypertension. The contributions of metabolites of diltiazem to the vasorelaxant effects of diltiazem were investigated. The synthesis and spectroscopic characterization of eight major cis-diltiazem metabolites are described. Three of the compounds--N, O-didemethylated metabolite (21), O-demethylated metabolite (22), and diltiazem N-oxide (27)--have been recently reported and have not previously been synthesized. The identities of all eight synthetic metabolites have been verified with samples obtained from human urine using combined LC-MS/MS. The Ca2+ antagonistic activities of diltiazem and its metabolites (except 27) were studied on hamster aorta preparations depolarized with KCl. The order of potencies (IC50 +/- SE, microM) is as follows: diltiazem (0.98 +/- 0.47) greater than 17 (2.46 +/- 0.38) greater than or equal to 23 (3.27 +/- 1.02) greater than 26 (20.2 +/- 10.5) greater than 22 (40.4 +/- 15.4) greater than or equal to 25 (45.5 +/- 18.1) greater than 21 (112.2 +/- 33.2) greater than or equal to 24 (126.7 +/- 24.2). Structure-activity relationships are also discussed.
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PMID:Synthesis, characterization, and Ca2+ antagonistic activity of diltiazem metabolites. 150 10

Although calcium channel blockers were only recently approved for antihypertensive therapy, 10 years of data have demonstrated their beneficial effects. Among the available calcium channel blockers, diltiazem hydrochloride appears to have a highly favorable side-effect profile. A new, extended-release formulation of diltiazem has been developed for the treatment of essential hypertension. The safety and efficacy of various once-daily doses of this new formulation were assessed in two multicenter studies. The first study was a dose-ranging trial of 275 patients with mild-to-moderate hypertension. Patients were randomly assigned to once-daily diltiazem (120, 240, 360, or 480 mg) or placebo for a 4-week, double-blind treatment period. A patient subgroup underwent ambulatory blood pressure monitoring (ABPM) twice. Once-daily diltiazem (dose range, 240-480 mg) significantly lowered trough systolic and diastolic blood pressure in a clearly dose-related fashion. ABPM results demonstrated consistent decreases in systolic and diastolic blood pressure throughout the 24-hour dosing interval. Dosages greater than or equal to 240 mg/day provided trough drug blood levels within the therapeutic range (i.e., greater than or equal to 40 ng/mL). The second study was a forced-escalation trail of 115 patients with mild-to-moderate hypertension. Patients were randomized to treatment with either placebo or escalating dosages of diltiazem (180 mg/day for 2 weeks, 360 mg/day for 2 weeks, and then 540 mg/day for 2 weeks). Statistically significant (p less than 0.01) reductions in supine systolic and diastolic blood pressure were observed with the 360 mg/day and 540 mg/day dosages. Dose escalations resulted in incremental blood pressure reductions and an increase in the percentage of responders. There was a significant correlation between diltiazem peak and trough plasma concentrations and antihypertensive effects in both studies, supporting the 24-hour efficacy of this extended-release formulation. Diltiazem administered once daily was found to be safe and well tolerated by the patients in these studies; adverse events were generally mild, with an incidence similar to placebo. Results indicate that this new extended-release formulation of diltiazem, administered once daily in doses greater than 120 mg, effectively lowers systolic and diastolic blood pressure in patients with mild-to-moderate essential hypertension.
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PMID:Clinical experience with a once-daily, extended-release formulation of diltiazem in the treatment of hypertension. 151 37

Effect of diltiazem on cardiovascular response to laryngoscopy and tracheal intubation was studied in 20 patients without hypertension and 10 patients with hypertension to be operated on under general anesthesia. The patients were divided into three groups: the first group without hypertension (group C, n = 10) received saline as control, the second group without hypertension (group N, n = 10) received bolus injection of diltiazem, and the third group with hypertension (group H, n = 10) received bolus injection of diltiazem. Diltiazem was administered 2 min before intubation at a dose of 0.2 mg.kg-1 as a bolus injection. Changes of mean blood pressure, rate pressure product, pressure rate quotient in group H and N decreased significantly compared with group C. Changes of heart rate were comparable among the three groups. Complications were not remarkable except one case in which systolic pressure decreased to 80 mmHg. The results suggest that bolus injection of diltiazem at a dose of 0.2 mg.kg-1 attenuates cardiovascular response to laryngoscopy and tracheal intubation without serious complications.
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PMID:[Attenuation of cardiovascular response to laryngoscopy and tracheal intubation with bolus injection of diltiazem]. 156 May 74

Recent investigations on the role calcium channels in the activation of vascular muscle suggest that calcium channels act in the capacity of voltage sensors in the excitation-contraction (EC) coupling sequence, rather than acting merely as gateways for calcium influx. In this study, recordings were made of calcium currents under various conditions using voltage-clamp techniques and isolated vascular muscle cells of spontaneously hypertensive rats (SHR) and genetically matched, normotensive Wistar-Kyoto (WKY) rats. Vascular muscle cells from azygos veins showed both transient (T), and long-lasting (L) currents in all of the spontaneously active cells studied. The ratio of L-type to T-type currents was greater in SHR than in WKY controls, even though the cells studied were from the venous side in newborn animals, in which there are no differences in either arterial or venous blood pressure. Data suggest that there are enhanced L-type calcium currents in SHR compared to WKY controls even in the prehypertensive state and that, in this form of gentic hypertension, there are fundamental changes in the membrane signal that triggers contraction. Diltiazem showed a preferential effect on blocking the L-type calcium channels, beginning at 100 pmol/L. At levels of 1 nmol/L to 1 mumol/L, diltiazem blocked L-type calcium current without a detectable effect on gating currents or on T-type calcium current. These findings may indicate fundamental differences between vascular muscle and cardiac muscle channel gating processes.
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PMID:Differences of calcium channels in vascular muscle in hypertension. 165 35

We compared the effects of SD-3211, a novel calcium antagonist, on blood pressure, heart rate, and atrioventricular conduction with those of diltiazem using conscious renal hypertensive dogs (one-kidney, one-clip type). We also examined the combined effects of these calcium antagonists with a beta-adrenoceptor antagonist, propranolol, on these variables. Oral administration of SD-3211 (1.25, 2.5, and 5 mg/kg) resulted in a dose-dependent decrease in blood pressure without affecting heart rate. SD-3211 at all three doses significantly decreased systolic blood pressure. At 2.5 and 5 mg/kg the compound elicited significant decreases in mean blood pressure and diastolic blood pressure. Hypotension obtained with the highest dose of SD-3211 lasted for at least 9 h. No significant alteration in PR interval was observed in electrocardiograms after administration of SD-3211. Diltiazem, given orally at doses of 2.5 and 5 mg/kg but not 1.25 mg/kg, produced significant hypotension with little change in heart rate. The duration of hypotension induced by the highest dose of diltiazem was only 3 h. Diltiazem prolonged PR interval in a dose-dependent manner, causing second-degree atrioventricular block in some dogs. Combined administration of SD-3211 or diltiazem (2.5 mg/kg) with propranolol (30 mg/kg) resulted in enhanced hypotension with no alteration in heart rate. SD-3211 plus propranolol had little effect on the PR interval, whereas diltiazem plus propranolol caused a markedly enhanced prolongation. These results indicate that SD-3211 is an antihypertensive agent with long-lasting action and little effect on heart rate and atrioventricular conduction and, when administered alone or in combination with propranolol, may be useful in the treatment of hypertension.
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PMID:SD-3211, a novel benzothiazine calcium antagonist, alone and in combination with a beta-adrenoceptor antagonist, produces antihypertensive effects without affecting heart rate and atrioventricular conduction in conscious renal hypertensive dogs. 170 42

In 15 randomized, double-blind studies with blood pressure measured at the end of the dosing interval, diltiazem sustained-release or conventional tablets were found to be equal in efficacy to hydrochlorothiazide, beta-blockers, angiotensin-converting enzyme inhibitors, and other calcium-channel antagonists. The total number of patients with adverse effects and those who drop out due to adverse effects are similar for diltiazem and the other drugs. Combination therapy with diltiazem and captopril showed additive effects, and combination of diltiazem with hydrochlorothiazide or atenolol showed additional, but perhaps less than additive, effects. Six studies in older and younger patients have shown no overall effect of age on the antihypertensive effect of diltiazem. Two studies showed no difference in mean antihypertensive response between black and non-black patients. In contrast to diuretics and beta-blockers, diltiazem does not have adverse metabolic effects on electrolytes, carbohydrate metabolism, and lipid metabolism. Diltiazem is an excellent antianginal agent. It has been shown in one study to decrease proteinuria as effectively as lisinopril, and it may have renal protective effects. The antihypertensive efficacy of diltiazem as monotherapy is equal to that of all other antihypertensive classes, and it is tolerated as well or better than most other antihypertensive drugs. Diltiazem is particularly indicated in patients with hypertension and concurrent angina pectoris, diabetes, hyperlipidemias, and, perhaps, chronic renal disease.
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PMID:Diltiazem: its place in the antihypertensive armamentarium. 172 39

In 80 patients with moderate hypertension the effects of nisoldipine 10 mg b.i.d., nifedipine 10 mg and 20 mg t.i.d., diltiazem 60 mg and 120 mg t.i.d., and verapamil 40 mg q.i.d. (all after single dose and 14 days' treatment) on blood pressure; hemodynamic parameters (cardiac output, stroke volume, left ventricular ejection fraction, and total peripheral resistance); and red blood cell and platelet functional state parameters (platelet aggregation, erythrocytal mechanical resistance, and free hemoglobin and ADP levels in plasma) were studied. All of the drugs studied in doses mentioned produced statistically significant hypotensive effects. Nifedipine 20 mg and nisoldipine 10 mg produced the most peripheral vasodilatator activity after a single dose and chronic treatment. Diltiazem had the same effect only in doses of 120 mg and after chronic treatment. However, all the drugs significantly normalized the red blood cell and platelet functional state disturbances in 70-80% of patients with moderate hypertension, even 2 h after a single dose. Disaggregation effect was parallel to clinical improvement. These data make it possible to predict the individual response of most patients to antihypertensive drugs on the basis of acute pharmacological tests, with determination of disaggregation effect.
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PMID:The effects of nisoldipine, diltiazem, nifedipine, and verapamil on hemodynamic parameters and red blood cells-platelet interactions in patients with arterial hypertension. 172 40


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