Mibefradil: A New Class of Calcium-Channel Antagonists

1998 ◽  
Vol 32 (6) ◽  
pp. 659-671 ◽  
Author(s):  
Sarah J Billups ◽  
Barry L Carter
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Calcium Channel ◽  
Clinical Studies ◽  
Chronic Stable Angina ◽  
Slight Reduction ◽  
Calcium Channel Antagonists ◽  
Once Daily ◽  
New Class ◽  
Reflex Tachycardia

OBJECTIVE: To describe the pharmacology, pharmacokinetics, and clinical efficacy of mibefradil compared with other agents used for hypertension and angina. DATA SOURCES: A MEDLINE search was performed for the period of January 1980 through September 1997 using the key terms mibefradil or Ro 40–5967. All articles written in English were considered for review. STUDY SELECTION AND DATA EXTRACTION: All clinical studies involving mibefradil were evaluated. Preclinical data were included if these data were not adequately represented in clinical (human) studies. DATA SYNTHESIS: Mibefradil is the first member of a new class of calcium-channel antagonists (CCAs) that block the T-type calcium channels. A long elimination half-life makes once-daily dosing feasible, and the drug's lack of negative inotropy and reflex tachycardia distinguishes it from other available CCAs. When administered at recommended dosages (50 or 100 mg once daily), mibefradil reduces blood pressure over 24 hours in patients with hypertension, improves exercise capacity, and relieves anginal symptoms in patients with chronic stable angina pectoris. CONCLUSIONS: Clinical studies have found that the antihypertensive effects of mibefradil are comparable with those of nifedipine, verapamil, and amlodipine, and more effective than those of diltiazem. These effects result from peripheral vasodilation and a slight reduction in heart rate. Selective vasodilation of the coronary vasculature makes it an effective antianginal agent when used alone or added to β-blocker therapy. Mibefradil demonstrates no significant effects on cardiac contractility, and no adrenergic stimulation resulting in reflex tachycardia. Therefore, it may have some advantages over currently available CCAs, especially in patients with congestive heart failure, although such advantages are unproven in published clinical trials. Ongoing clinical studies, including the Mortality Assessment in Congestive Heart Failure Trial (MACH-1) currently in progress, are needed to clarify mibefradil's place in cardiovascular therapy.

The Clinical Studies on Congestive Heart Failure

1979 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Soon Nam Ahn ◽  
Nan Ho Kyung
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Clinical Studies

Torsemide: A Pyridine-Sulfonylurea Loop Diuretic

1995 ◽  
Vol 29 (4) ◽  
pp. 396-402 ◽  
Author(s):  
Jamie S Blose ◽  
Kirkwood F Adams ◽  
J Herbert Patterson
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Renal Disease ◽  
English Language ◽  
Loop Diuretic ◽  
Antihypertensive Agents ◽  
Hepatic Disease ◽  
Loop Diuretics ◽  
Once Daily ◽  
Medline Search

Objective: To review the clinical pharmacology of torsemide and to compare it with currently available loop diuretics, particularly furosemide. Data Sources: An English-language MEDLINE search, 1985 to October 1994, was used to identify pertinent literature, including review articles. Data Extraction: Data from scientific literature were extracted, evaluated, and summarized for presentation. Pivotal and representative studies are discussed relating to the pharmacology, pharmacokinetics, and use of torsemide in patients with congestive heart failure, renal disease, hepatic disease, and hypertension. Data Synthesis: Torsemide is a loop diuretic of the pyridine-sulfonylurea class. The bioavailability of torsemide is approximately 80%, with little first-pass metabolism, and torsemide can be given without regard to meals. The serum concentration reaches its peak within 1 hour after oral administration and diuresis lasts approximately 6—8 hours. Torsemide is eliminated both hepatically (80%) and renally (20%) as unchanged drug with an elimination half-life of about 3.5 hours. Because of the high bioavailability, oral and intravenous doses are therapeutically equivalent. Torsemide, and other loop diuretics such as furosemide, are indicated for the treatment of edema associated with congestive heart failure, renal disease, and hepatic disease. They also are indicated for the treatment of hypertension alone or in combination with other antihypertensive agents. Depending on the indication, the recommended initial adult dosage of torsemide is between 5 and 20 mg once daily orally or intravenously. Special dosage adjustments in the elderly are not necessary. Conclusions: Torsemide is a loop diuretic similar to furosemide, with similar indications. Torsemide is characterized by good bioavailability and once-daily dosing and, compared with furosemide, provides generally equivalent therapeutic efficacy.

Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens.

1991 ◽  
Vol 9 (7) ◽  
pp. 1215-1223 ◽  
Author(s):  
A C Braverman ◽  
J H Antin ◽  
M T Plappert ◽  
E F Cook ◽  
R T Lee
Keyword(s):  
Heart Failure ◽  
Bone Marrow ◽  
Congestive Heart Failure ◽  
Bone Marrow Transplantation ◽  
Left Ventricular Mass ◽  
Marrow Transplantation ◽  
Dose Group ◽  
Left Ventricular ◽  
Once Daily ◽  
Dosing Regimens

Cyclophosphamide (CY) cardiotoxicity may be a lethal complication of bone marrow transplantation. Previous echocardiographic studies have reported that left ventricular dysfunction due to CY occurs in over 50% of patients undergoing transplantation. To evaluate the cardiotoxicity of new dosing protocols that included twice-daily rather than once-daily CY, 44 bone marrow transplantation patients were prospectively evaluated with serial ECGs and echocardiograms. Twenty-six patients received a once-daily lower-dose protocol (mean total 87 +/- 11 mg/kg), and 18 patients received a twice-daily higher-dose (mean total 174 +/- 34 mg/kg) CY regimen. In the higher-dose CY group, significant reductions in summed ECG voltage (-20%) (P less than .01) and increases in left ventricular mass index (LVMI) (+10%) (P less than .05) were detected in the first week following therapy. These changes resolved by the third week following CY and were significantly greater than the changes noted in the lower-dose group. However, left ventricular ejection fraction (EF) did not change significantly in either group. Five patients developed clinical cardiotoxicity (four, pericarditis; one, congestive heart failure); four of the five patients were in the higher-dose group (P = .14). Only a prior history of congestive heart failure or a baseline EF less than 50% was an independent correlate of clinical cardiotoxicity (P less than .05). Thus, dose-dependent cardiotoxicity following the use of CY for bone marrow transplantation is evident as reversible decreases in ECG voltage and increases in left ventricular mass, possibly reflecting myocardial edema or hemorrhage. However, systolic dysfunction is much less common with these new twice-daily dosing regimens when compared with earlier studies of high-dose once-daily CY.

Defining the Role of Calcium Channel Antagonists in Heart Failure Due to Systolic Dysfunction

2003 ◽  
Vol 3 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Isabelle Mah?? ◽  
Olivier Chassany ◽  
Anne-Sophie Grenard ◽  
Charles Caulin ◽  
Jean-Fran??ois Bergmann
Keyword(s):  
Heart Failure ◽  
Calcium Channel ◽  
Systolic Dysfunction ◽  
Calcium Channel Antagonists

Once Daily Dosing of Enalapril in Congestive Heart Failure

2009 ◽  
Vol 223 (4) ◽  
pp. 313-320 ◽  
Author(s):  
JOHAN AHLNER ◽  
BJÖRN BERGDAHL ◽  
ULF DAHLSTRÖM ◽  
JAN OHLSSON
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Once Daily

Magnesium Homeostasis and Clinical Disorders of Magnesium Deficiency

1994 ◽  
Vol 28 (2) ◽  
pp. 220-226 ◽  
Author(s):  
Robert Whang ◽  
Edward M. Hampton ◽  
David D. Whang
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Congestive Heart Failure ◽  
Critically Ill ◽  
Clinical Studies ◽  
Magnesium Deficiency ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Digitalis Toxicity ◽  
Mg Deficiency

OBJECTIVE: To survey the causes of clinical hypomagnesemia and Mg deficiency. The relationship of hypomagnesemia to digitalis toxicity, congestive heart failure, arrhythmias, and acute myocardial infarction is discussed, as is the clinical interrelationship of Mg and K concentrations, the principal intracellular cations. DATA SOURCES: A MEDLINE search and retrieval was used to identify relevant references. STUDY SELECTION: Clinical reports, as well as studies, were selected for this review. DATA EXTRACTION: There were very few placebo-controlled clinical studies. Clinical observations were related primarily to compilation of series in which Mg was administered and clinical results reported. In addition, conclusions derived from review articles on the subject of clinical Mg depletion were used. DATA SYNTHESIS: Clinical diagnosis of Mg deficiency is ascertained most expeditiously by estimating serum Mg concentrations. Although available on order by physicians, the lack of routine serum Mg analysis as part of the “electrolyte panel” impedes the diagnosis of clinical Mg deficiency. Renal loss of Mg resulting from the widespread use of loop diuretics is responsible for significant numbers of patients with Mg deficiency and hypomagnesemia. Life threatening cardiac arrhythmias and seizures represent the most serious manifestations of clinical hypomagnesemia and Mg depletion. In the most critically ill patients, treatment with intravenous Mg is recommended. Oral repletion of Mg is reserved for the less critically ill hospitalized patients and ambulatory patients. Close attention must be paid to optimizing K replenishment in hypokalemic patients by concurrent treatment of any accompanying hypomagnesemia to avoid the problem of refractory K repletion. CONCLUSIONS: Hypomagnesemia is one of the most frequent serum electrolyte abnormalities in current clinical practice. Routine inclusion of serum Mg analysis in the electrolyte panel will enhance the clinical recognition and treatment of hypomagnesemic Mg-depleted patients. Failure to respond to treatment of recurrent ventricular tachycardia/fibrillation to usual antiarrhythmic therapy in patients with acute myocardial infarction, idiopathic dilated cardiomyopathy, and congestive heart failure should alert the clinician to consider administering intravenous Mg. Repair of coexisting hypomagnesemia in hypokalemic patients is essentialto avoid the problem of refractory K repletion caused by coexisting Mg depletion. More controlled clinical studies of Mg deficiency are necessary to ascertain the cost-effectiveness of Mg replacement therapy.

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