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Biomedical subjects

Domenic A Sica

Publications and source records attributed to Domenic A Sica.

At least 19 recordsLinked to original sources
PubMed2007

Use of diuretics in the treatment of heart failure in the elderly.

Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure, while at the same time decreasing the morbidity and mortality associated with hypertension. Diuretics are currently recommended as first-line therapy for the treatment of hypertension. In addition, they remain an important component of heart failure therapy, in that they improve the symptoms of congestion, which typify the more advanced stages of heart failure. This article reviews the mode of action of the various diuretic classes and the physiologic adaptations that follow; sets up the basis for their use in the treatment of volume-retaining states, particularly as applies to the elderly; and reviews diuretic-related side effects that are normally encountered.

Aged↗
PubMed2007

Combination ACE inhibitor and angiotensin receptor blocker therapy - future considerations.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are regularly prescribed for the management of hypertension. Each of these drug classes has also been shown to provide survival benefits for patients with heart failure, proteinuric chronic kidney disease, and/or a high cardiac risk profile. The individual gains seen with each of these drug classes have led to speculation that their combination might offer additive if not synergistic outcome benefits. The foundation of this hypothesis, although biologically possible, has thus far not been sufficiently well proven to support the everyday use of these 2 drug classes in combination. Additional outcomes trials, which are currently proceeding to their conclusion, may provide the necessary proof to support an expanded use of these 2 drug classes in combination.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Controlled-release carvedilol in the treatment of essential hypertension.

Carvedilol is a beta1-, beta2-, and alpha1-adrenergic blocker that is approved for the treatment of hypertension. A new once-daily, controlled-release (CR) formulation of carvedilol has been shown to be effective in a double-blind, randomized, multicenter, placebo-controlled, parallel-group study. In this article, we summarize the primary results of, and present additional analyses from, that trial. A total of 338 patients with essential hypertension (sitting diastolic blood pressure [DBP] >/=90 and </=109 mm Hg) were randomized to receive carvedilol CR 20, 40, or 80 mg or placebo for 6 weeks. The primary objective was to compare the effects of the 3 carvedilol CR doses with placebo on 24-hour mean blood pressure using ambulatory blood pressure monitoring (ABPM). Mean DBP and systolic BP (SBP) at the drug trough (20-24 hour) blood levels for carvedilol CR and comparison of DBP and SBP at the drug peak (3-7 hour) blood levels for each dose of carvedilol CR and placebo were investigated. The effects of carvedilol CR on heart rate and pulse pressure were also examined. Once-daily administration of carvedilol CR, alone or in combination with other agents, produced clinically and statistically significant reductions compared with placebo for both DBP and SBP after 6 weeks of treatment for the following parameters: trough blood pressure by office cuff or ABPM measurements, peak blood pressure by ABPM, and 24-hour mean blood pressure by ABPM. Placebo-corrected trough-to-peak ratios for DBP were >0.6 for each carvedilol CR dose. Heart rate and pulse pressure were each significantly reduced compared with placebo for each carvedilol CR dose. We conclude that carvedilol CR is a very effective antihypertensive agent with clear dose-related peak blood pressure reduction and continuous 24-hour control.

Administration, Oral↗
PubMed2006

Interaction of grapefruit juice and calcium channel blockers.

Drug-drug interactions are commonly recognized occurrences in the hypertensive population. Drug-nutrient interactions, however, are less well appreciated. The grapefruit juice-calcium channel blocker interaction is one that has been known since 1989. The basis for this interaction has been diligently explored and appears to relate to both flavanoid and nonflavanoid components of grapefruit juice interfering with enterocyte CYP3A4 activity. In the process, presystemic clearance of susceptible drugs decreases and bioavailability increases. A number of calcium channel blockers are prone to this interaction, with the most prominent interaction occurring with felodipine. The calcium channel blocker and grapefruit juice interaction should be incorporated into the knowledge base of rational therapeutics for the prescribing physician.

Beverages↗
PubMed2006

Pharmacotherapy review: calcium channel blockers.

As a drug class, calcium channel blockers encompass a heterogeneous group of compounds with distinctive structures and pharmacologic characteristics. These agents are widely used in the treatment of hypertension, chronic coronary ischemia, and/or supraventricular arrhythmias. Much of the early debate alluding to increased cardiovascular risk associated with calcium channel blocker use has been silenced by an array of outcomes trials that show these drugs to be both safe and effective in reducing hard cardiovascular end points. The most common side effects associated with calcium channel blockers are vasodilatory in nature and include a non-volume-dependent form of peripheral edema, flushing, and headache. Despite the sometimes discomforting side effects seen with calcium channel blocker therapy, their robust blood pressure-lowering effect makes them an important component of most multidrug regimens used for blood pressure control.

Calcium Channel Blockers↗
PubMed2006

Angiotensin receptor blockers: new considerations in their mechanism of action.

Angiotensin receptor blockers are one of several drug classes that act by hindering activity of the renin-angiotensin axis. Angiotensin receptor blockers act by selectively blocking the binding of angiotensin II to the angiotensin type 1 receptor but not the angiotensin type 2 receptor. Compounds in this class are as effective as most other antihypertensive drug classes in reducing blood pressure in the patient with hypertension. The mechanism of action of an angiotensin receptor blocker, which seemed a straightforward proposition early on, has of late become more convoluted with a host of class and compound-specific concerns having emerged. As the mechanistic basis for the action(s) of angiotensin receptor blockers more completely unfolds, added credence may ultimately be lent to widely touted and often overstated intraclass differences.

Aldosterone↗
PubMed2006

Antihypertensive therapy and its effects on potassium homeostasis.

The role of potassium in cardiovascular disease and the importance of preserving potassium balance have emerged as clinical hot points, particularly as they relate to cardioprotective and renoprotective therapies that secondarily promote potassium retention. Antihypertensive medications that most commonly influence serum potassium levels and/or total body potassium include beta blockers and potassium-wasting and potassium-sparing diuretics as well as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Uncertainty exists as to the best way to monitor potassium levels when any of these drug therapies are used, particularly in the setting of chronic kidney disease and/or heart failure. Guidelines for the monitoring of serum potassium levels in the setting of antihypertensive therapy are at best makeshift and often drawn from the know-how of the treating physician.

Adrenergic beta-Antagonists↗
PubMed2006

Efficacy of a once-daily formulation of carvedilol for the treatment of hypertension.

Beta-blockers with pharmacologic effects that differ from conventional agents might add to antihypertensive treatment options. This study evaluated a new once-daily formulation of the beta-/alpha1-blocker, carvedilol controlled-release (CR), in hypertensive patients off treatment or while still taking up to 2 (non-beta-blocker) agents. After a 4-week run-in phase, patients were randomized either to placebo (n=76) or carvedilol CR 20 mg (n=82), 40 mg (n=76), or 80 mg (n=86) once daily. After 6 weeks of treatment, ambulatory blood pressure monitoring was repeated to measure the primary end point of changes in mean 24-hour diastolic blood pressure. During treatment, 24-hour diastolic blood pressure fell in the placebo and carvedilol CR 20-mg, 40-mg, and 80-mg groups by (mean +/- SE) 0.4+/-0.9, 4.4+/-0.9, 7.9+/-0.9, and 9.6+/-0.9 mm Hg, respectively (P< or =.001, trend test for all carvedilol CR doses with placebo). Corresponding 24-hour systolic blood pressure changes were 0.6+/-1.4, 6.8+/-1.3, 10.1+/-1.4, and 12.5+/-1.3 mm Hg, respectively (P< or =.001, trend test). Diastolic blood pressure trough-to-peak ratios (placebo-corrected) based on ambulatory blood pressure monitoring (trough = mean of 20- to 24-hour post-dose readings; peak = mean of 3- to 7-hour post-dose readings) for 20-mg, 40-mg, and 80-mg doses were 0.73, 0.64, and 0.65, respectively. Adverse events, including clinical chemistry values, were similar in the drug-treated and placebo groups. Carvedilol CR has a clinically meaningful defined dose-dependent antihypertensive effect that persists throughout a 24-hour period.

Aged↗
PubMed2006

Baroreflex activation for the treatment of hypertension: principles and practice.

This article reviews the history and current status of an innovative nonpharmacological approach for the treatment of resistant hypertension - chronic electrical activation of the afferent limb of the carotid baroreflex. Recent studies in both normotensive and hypertensive canine models have unambiguously demonstrated sustained and clinically relevant reductions in arterial pressure and sympathetic activity in the course of prolonged baroreflex activation. Clinical trials designed to evaluate the efficacy and safety of this therapy in patients with resistant hypertension are now underway in both Europe and the USA.

Animals↗