Domenic A Sica

..This article is the first in a series describing important pharmacotherapeutic considerations of the individual drug classes used in the treatment of hypertension...

..As such, steps should be taken to lessen the likelihood of its occurring if therapy is being contemplated with agents in this class...

..Such novel pharmacologic approaches offer useful options for treatment in the otherwise difficult to control hypertensive patient...

..This is more apt to occur with spironolactone due to the very long half-life of several of its active metabolites...

..The specific risk:benefit ratio for individual cardiovascular medications should be more routinely considered in the context of gender...

..Despite the potential for side effects with CCBs, their potent blood pressure-lowering effect makes them a prerequisite for blood pressure control in many patients...

..Non-DHP CCBs could potentially attenuate sympathetic activity and reduce protein excretion in patients with CKD...

..Calcium channel blockers are distinctive for their potent blood pressure-lowering effects, and novel strategies such as chronotherapeutic dosing of these agents has further improved upon the flexibility of their use...

..The neutral findings in this trial add a new wrinkle to the concept of class effect for cardiovascular protection with angiotensin-converting enzyme inhibitors in patients with coronary artery disease...

..Understanding these issues is important to the effective use of these compounds...

..The frequency of such scrutiny should be patient-specific and based on the constellation of risk factors for hyperkalemia...

..A number of questions still remain unanswered in the pharmacotherapy of chronic kidney disease, including the optimal dose for these drugs as well as what represents the most favorable achieved blood pressure...

..This article reviews the commonly encountered side effects with the various diuretic classes. Where indicated, the mechanistic basis and treatment of such side effects is further discussed...

..This review discusses the physiologic and non-physiologic basis for side effects with ACE inhibition...

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..Losartan, like other angiotensin-receptor antagonists, is devoid of significant adverse effects...

..Hyperkalemia should be considered as a possibility in any patient receiving these medications and as such is best addressed preemptively...

..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...

..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...

..provides data from INVEST (INternational VErapamil-Trandolapril STudy), which shows the particular utility of a CCB and ACE inhibitor combination in bringing elderly hypertensive patients with CAD to goal BP when monotherapy..

..The calcium channel blocker and grapefruit juice interaction should be incorporated into the knowledge base of rational therapeutics for the prescribing physician...

..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...

..Vasopressin receptor antagonists will redefine the treatment of heart failure-related hyponatremia and may possibly evolve as adjunct therapies to loop diuretics in diuretic-resistant patients...

..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...

..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...

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..Results from a series of outcomes trials increasingly support the use of drugs in this class as cardioprotective and renoprotective agents in patients with heart failure, diabetic nephropathy, and post-myocardial infarction...

..The recent availability of vasopressin receptor antagonists, however, offers a different approach to the management of this complex electrolyte disturbance, but one that is still evolving as to the scope of its clinical benefits...

..The not infrequent development of a dermatitis, together with a substantially greater cost than oral clonidine, have been the major undoings for transdermal clonidine...

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..The future of this drug class remains bright. Other drug classes, such as angiotensin receptor blockers, have narrowed-but not entirely closed-the outcomes gap that exists between these two drug classes...

..There is, however, a place for minoxidil in the treatment of resistant hypertension especially in patients with advanced renal disease...

..Propranolol CR is an effective antihypertensive formulation that may reduce blood pressure during the morning period of maximum cardiovascular risk...

..Additional studies of an integrative nature will be necessary to obtain more complete definition of the dynamic interplay between nutrition and various neurohumoral axes in determining how nocturnal blood pressure patterns are expressed...

..The need to reduce renin-angiotensin aldosterone system activity in a heart failure patient would seem to justify the small risk of angioedema with ARB therapy in a patient having previously experienced ACE inhibitor-related angioedema...

..Time and additional clinical experience with eplerenone will establish its safety profile and determine if the original label for this compound was correct...

..Such justification might include the presence of heart failure or proteinuric nephropathic states among other considerations...

..Polypharmacy and altered drug metabolism increase the risk of myotoxicity, albeit to an ill-defined degree, in this population. Many factors should enter into the choice of a statin in the multiply medicated renal failure patient...

..A valued member of our therapeutic armamentarium need not be laid entirely to rest; rather, doxazosin should now be viewed as a secondary or tertiary antihypertensive therapy pending a more complete review of the ALLHAT data...

..Early termination of a clinical trial can have important clinical implications and, in particular, can redirect patterns of clinical practice...

..An evidence-based therapeutic approach derived from these trials would argue for ARBs to be the foundation of therapy in the patient with type 2 diabetes and nephropathy...

..Physicians must take many factors into account when selecting a member of the HMG-CoA reductase inhibitor class, particularly as relates to their use in the multiply medicated elderly patient...

..This may provide an explanation for the differential effect on systolic blood pressure exhibited by this compound...

..Omapatrilat, a vasopeptidase inhibitor, preserves natriuretic peptides and inhibits the renin angiotensin aldosterone system by simultaneously inhibiting neutral endopeptidase and angiotensin-converting enzyme...

..In addition, for some agents clinical trials that demonstrate decreased morbidity or mortality are currently lacking...

..Losartan is a selective angiotensin AT1 receptor antagonist currently employed in the management of essential hypertension. This compound is in common use in populations with renal failure and end-stage renal disease (ESRD)...

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..These attributes would favour the increased use of ARBs in this population...

..To characterize the pharmacokinetics and pharmacodynamics of the different calcium-channel blockers...

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..Additional clarifying studies are required to establish whether specific patient subsets exist that might benefit from such combination therapy...

..However, the exact role of torsemide in the outpatient management of congestive heart failure remains to be determined...

..Discontinuing the CCB and switching to an alternative antihypertensive therapy will resolve the edema...

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..It remains to be determined if this represents a class effect for all angiotensin-converting enzyme inhibitors...

..The temptation should be avoided to simply reduce the doses of either metolazone or the loop diuretic as a means to controlling an active diuresis...

..Bioavailability was similar for both formulations of propranolol. Propranolol CR exhibited appropriate pharmacokinetics for a chronotherapeutic approach to the treatment of hypertension...

..Eplerenone has not been studied in ESRD in a therapeutic or safety capacity. Additional studies are needed with these compounds in the ESRD population before their use can be considered safe...

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..Escalating doses of drugs in this class often give rise to salt and water retention, in which case diuretic therapy becomes a valuable adjunctive therapy...

..These new pulmonary observations in patients afflicted with an ACE inhibitor-related cough should revive interest in this bothersome side effect...

..If made truly cost-competitive, it will gain an increasing share of the hypertensive market. If not, market forces will relegate it to a secondary role for hypertension treatment...

..The results of this trial are both interesting and relevant to what is an expanding use of angiotensin-receptor blockers in the hypertensive population...

..Moreover, this drug class is devoid of relevant class-specific side effects. These features provide some of the basis for the excellent tolerance of drugs in this class...

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..Furthermore, AKT (activated via alpha1A receptors), as well as increased alpha1A receptors and their agonist NE, might contribute to the observed hypertrophy...

..To evaluate the preoperative relationships of hypertension and diabetes mellitus in severe obesity and the effects of gastric bypass (GBP)-induced weight loss...

..Additional clarifying studies are needed to establish whether specific patient subsets exist that might benefit from such combination therapy...

..Like most matters in the clinical sector the approach to a disease in this case hypertension should remain highly individualised and cognisant of what can be significant cost considerations...

..Because of the complexity of this topic, issues of hyperkalemia will be addressed in a forthcoming manuscript...