Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In well designed studies in patients with mild to moderate hypertension, combinations of the sustained-release (SR) formulation of the nondihydropyridine calcium channel antagonist verapamil 120 to 240 mg/day and the ACE inhibitor trandolapril 0.5 to 8 mg/day were significantly more effective in reducing sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline than placebo. In most randomised studies, combinations of verapamil SR 120 to 240 mg/day and trandolapril 0.5 to 8 mg/day were significantly more effective in lowering sitting DBP and SBP than the corresponding monotherapies administered at the same dosage. Trandolapril/verapamil SR 2/180 mg/day provided significantly more effective 24-hour ambulatory blood pressure (BP) control than of the corresponding monotherapies. Moreover, trandolapril/verapamil SR reduced BP in patients inadequately controlled with either of the corresponding monotherapies. The antihypertensive efficacy of trandolapril/verapamil SR 2/180 mg/day was generally similar to that of other combinations of antihypertensive agents (metoprolol/hydrochlorothiazide, atenolol/chlorthalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide) in patients with hypertension, including those with type 2 diabetes mellitus. Trandolapril/verapamil SR reduced BP in patients with hypertension and type 2 diabetes or primary renal disease, Black patients and elderly patients. Trandolapril/verapamil SR was more effective than the individual components administered as monotherapy in reducing proteinuria in patients with type 2 diabetes or primary renal disease. Trandolapril/verapamil SR had a neutral or beneficial effect on metabolic parameters (glucose, insulin, lipids) in patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR preserved left ventricular function in patients with heart failure. Fewer cardiac events occurred after therapy with trandolapril/verapamil SR than after trandolapril alone in post-myocardial infarction patients with congestive heart failure. The incidence of adverse events in recipients of trandolapril/verapamil SR was similar to that of the individual components, and that of other combination therapies. In placebo-controlled trials conducted in the US, headache, upper respiratory tract infections, cough, constipation, atrioventricular block (first degree) and dizziness were the most commonly reported adverse events in recipients of combinations of verapamil SR (120 to 240 mg/day) and trandolapril (0.5 to 8 mg/day). In conclusion, the fixed-dose combination of trandolapril/verapamil SR is an effective treatment for patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR tended to be more effective than monotherapy with either verapamil SR or trandolapril, and generally showed antihypertensive efficacy similar to that of other combination antihypertensive therapies. Current data support the use of trandolapril/verapamil SR as an alternative treatment when monotherapy with either agent is not effective. Data from large clinical trials currently being conducted will assist in fully defining the role of trandolapril/verapamil SR as a cardio- and renoprotective agent.
 ...
PMID:Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension. 1242 Nov 12

Alkavervir (Veriloid(R)), a new derivative of veratrum viride was used in the treatment of hypertension in ten children with acute nephritis. The patients had a variety of complications associated with hypertension-heart failure, convulsions, vomiting and headache. In all of them the blood pressure decreased soon after the drug was given.
 ...
PMID:Hypertension in childhood; treatment of acute nephritis with a derivative of veratrum viride. 1331 38

Elevated blood pressure is a risk factor for a variety of cardiovascular disorders, including coronary heart disease, peripheral vascular disease, cardiac failure and cerebrovascular disease. The prevailing view is that an elevated systolic rather than diastolic blood pressure is the major contributor in mortality and morbidity attributed to cardiovascular disorders. Isolated high systolic blood pressure, especially in the elderly, is a major risk factor and should undoubtedly be a target for drug treatment. In the general population, systolic and diastolic blood pressure are highly correlated, and thus it is difficult to dissociate the effects of these two components of the blood pressure and specifically ascribe cardiovascular risk factors to just elevated systolic blood pressure. Therefore, the goal in therapy of an individual with hypertension must be to reduce elevated systolic and diastolic blood pressure in order to reduce mortality and morbidity. ACE and neutral peptidase inhibitors are a new class of drugs that may be beneficial in the treatment of patients with hypertension and heart failure. They may also be useful in the treatment of diabetic patients with hypertension and/or heart failure. Drugs of this class are dual inhibitors of ACE and neutral endopeptidase, and are capable of affecting vascular tone and fluid balance. They are capable of producing vasodilatation by virtue of inhibiting the production of angiotensin II, degradation of natriuretic peptides and bradykinin. They also appear to promote natriuresis and diuresis by amplifying the actions of natriuretic peptidase and reducing aldosterone effects. In addition, they should also attenuate trophogenic actions of the renin angiotensin system and the sympathetic nervous system. Omapatrilat is one drug that appears to be at the advanced stages of clinical development. This drug has been shown to be quite effective in the treatment of hypertension. Evidence also seems to indicate that treatment with omapatrilat results in a higher tendency towards preventing death and worsening heart failure when compared with treatment with a pure ACE inhibitor in patients with advanced heart failure. Overall safety with omapatrilat appears to be good, but like other ACE inhibitors the incidence of cough is higher when compared with placebo. Other common adverse effects noted are headaches, facial flushing/warm sensation, dizziness, nausea and dyspnoea. Of greater concern is the occurrence of angio-oedema, the true incidence of which remains to be fully established as part of the published medical literature.
 ...
PMID:Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders. 1501 94

Calcium antagonists (calcium channel blockers) are widely used in the treatment of hypertension and other cardiovascular diseases. The results of a large number of clinical trials have demonstrated that calcium antagonists are as efficacious as other classes of antihypertensive agents in decreasing blood pressure in the elderly patients. Large clinical trials have shown the effectiveness of calcium antagonists (with long duration of action) in reducing cardiovascular and cerebrovascular morbidity and mortality in elderly hypertensive patients. The calcium antagonists are a chemically, pharmacologically and therapeutically heterogeneous group of agents. Among themselves, they differ in vasoselectivity, effect on cardiac conduction, sympathetic activation, adverse effect profile, ability to protect against target organ damage, suitability for patients with co-morbid conditions, and pharmacodynamic characteristics. The calcium antagonists can be used as single agents or in combination with other antihypertensive drugs. These drugs should not be used as first-line drugs in treating high blood pressure in patients with heart failure, since drugs in other classes provide more benefits. The dihydropyridine calcium antagonists should not be used in post-myocardial infarction patients or in patients with unstable angina; however, non-dihydropyridines may be used in such patients. The adverse effects of dihydropyridines include peripheral and ankle edema, flushing and headache. The short-acting preparations of the older calcium antagonists are no longer used, because of the potential for adverse cardiovascular outcome.
 ...
PMID:The use of calcium antagonists in the therapy of hypertension in the elderly. 1462 75

DEFINITION, PATHOPHYSIOLOGY, THERAPY: The hypertensive crisis is characterized by a massive, acute rise in blood pressure. Patients with underlying hypertensive disease usually have an increase in systolic blood pressure values > 220 mmHg and diastolic values > 120 mmHg. The severity of the condition, however, is not determined by the absolute blood pressure level but by the magnitude of the acute increase in blood pressure. Thus, in the presence of primarily normotensive baseline values (such as those in eclampsia), even a systolic blood pressure > 170 mmHg may lead to a life-threatening condition. The most important causes are non-compliance (reduction or interruption of therapy), inadequate therapy, endocrine disease, renal (vessel) disease, pregnancy and intoxication (drugs). The management of this condition greatly depends on whether the patient has a hypertensive crisis with organ manifestation (hypertensive emergency) or a crisis without organ manifestation (hypertensive urgency). By documenting the medical history, the medical status and by simple diagnostic procedures, the differential diagnosis can be established at the emergency site within a very short period of time. In the absence of organ manifestations (hypertensive urgency) the patient may have non-specific symptoms such as palpitations, headache, malaise and a general feeling of illness in addition to the increase in blood pressure. In a hypertensive urgency the patient's blood pressure should not be reduced within a few minutes but within a period of 24 to 48 hours. Such adjustment can be achieved on an out-patient basis, however, only if the patient can be followed up adequately for early detection of a renewed attack. In the absence of follow-up facilities, the patient's blood pressure should be reduced over a period of 4 to 6 hours, if necessary in an out-patient emergency service. While intravenous medication is given preference when a rapid effect is desired, oral medication may be used for gradual reduction on an out-patient basis, depending on the patient's medical history and on any underlying chronic disease. Organ manifestations in the course of a hypertensive emergency concern the cardiovascular system and are associated with the symptoms of acute left-ventricular heart failure, the acute coronary syndrome or acute aortic dissection. In the brain the patient may have symptoms of hypertensive encephalopathy, hemorrhage, ischemia; in the kidney he/she may develop acute failure. The patient's blood pressure should be reduced rapidly during the treatment. It should not be reduced to the normal value, but by approximately 20-30% of the baseline value. The reason for a stepwise reduction in blood pressure is the fact that patients with chronic hypertension have an altered autoregulation curve. Acute normotension would lead to hypoperfusion in these patients. Those with aortic dissection or pulmonary edema are excepted from the rule of gradual blood pressure reduction. In the presence of these diseases, blood pressure must be reduced rapidly to normal values. Patients with a hypertensive emergency should always be admitted to the hospital. Parenteral treatment is given preference, since the effect of the treatment is rapid and occurs within a calculable period of time. Thus, parenteral treatment can also be better regulated than medication administered orally or by the sublingual route. Several antihypertensives are available for this purpose. The selection of the substance greatly depends on the existing organ failure as well as the reliable effectiveness and the regulability of the applied antihypertensive.
 ...
PMID:[Hypertensive emergency and urgence]. 1468 6

Inhaled beta(2)-adrenoceptor agonists (beta(2)-agonists) are the most commonly used asthma medications in many Western countries. Minor adverse effects such as palpitations, tremor, headache and metabolic effects are predictable and dose related. Time series studies suggested an association between the relatively nonselective beta-agonist fenoterol and asthma deaths. Three case-control studies confirmed that among patients prescribed fenoterol, the risk of death was significantly elevated even after controlling for the severity of asthma. The Saskatchewan study not only found an increased risk of death among patients dispensed fenoterol, but also suggested this might be a class effect of beta(2)-agonists. However, in subsequent studies, the long-acting beta(2)-agonist salmeterol was not associated with increased asthma mortality. In a case-control study blood albuterol (salbutamol) concentrations were found to be 2.5 times higher among patients who died of asthma compared with controls. It is speculated that such toxic concentrations could cause tachyarrhythmias under conditions of hypoxia and hypokalemia. The risk of asthma exacerbations and near-fatal attacks may also be increased among patients dispensed fenoterol, but this association may be largely due to confounding by severity. Although salmeterol does not appear to increase the risk of near-fatal attacks, there is a consistent association with the use of nebulized beta(2)-agonists. Nebulized and oral beta(2)-agonists are also associated with an increased risk of cardiovascular death, ischemic heart disease and cardiac failure. Caution should be exercised when first prescribing a beta-agonist for patients with cardiovascular disease. A potential mechanism for adverse effects with regular use of beta(2)-agonists is tachyphylaxis. Tachyphylaxis to the bronchodilator effects of long-acting beta(2)-agonists can occur, but has been consistently demonstrated only for formoterol (eformoterol) a full agonist, rather than salmeterol, a partial agonist. Tachyphylaxis to protection against induced bronchospasm occurs with both full and partial beta(2)-agonists, and probably within a matter of days at most. Underlying airway responsiveness to directly acting bronchoconstricting agents is not increased when the bronchodilator effect of the regular beta(2)-agonist has been allowed to wear off, although there may be an increase in responsiveness to indirectly acting agents. While there has been speculation that underlying airway inflammation in asthma may be made worse by regular use of short-acting beta(2)-agonists, in contradistinction, a number of studies have shown that long-acting beta(2)-agonists have positive anti-inflammatory effects. An Australian Cochrane Airways Group systematic review of the randomized, controlled trials of short-acting beta-agonists found only minimal and clinically unimportant differences between regular use and use as needed. Regular short-acting treatment was better than placebo. However, a subsequent systematic review has found that regular use of long-acting beta-agonists had significant advantages over regular use of short-acting beta-agonists. More studies and data are needed on the regular use of beta(2)-agonists in patients not taking inhaled corticosteroids, and in potentially vulnerable groups, such as the elderly and those with particular genotypes for the beta-receptor, who might be more prone to adverse effects.
 ...
PMID:Adverse effects of beta-agonists: are they clinically relevant? 1471 95

The release of Adalat Oros 60 on the Belgian market was justified since it has been clearly demonstrated that the dosage of 60 mg significantly increases the proportion of responders to nifedipine monotherapy. This gives us the opportunity to briefly review the history of nifedipine and to describe the original and ingenious galenic controlled-release formulation known as Oros (Gastrointestinal Therapeutic System, or GITS in the anglo-saxon world). Cleary, nifedipine is a potent calcium antagonist the action of which is now smooth and devoid of the usual ups and downs observed with the regular capsules, even in their Retard form. These abrupt changes in plasma concentrations, with the subsequent variations in heart rate and blood pressure, were dangerous and bothersome. Oros allows plasma concentrations of nifedipine to plateau for at least 24 hours after oral administration. This reduces the incidence of side-effects which remain those classically attributable to calcium antagonists (i.e.: flushes, headaches); interestingly, they tend to appear early after treatment initiation which allows to easily ascribe them to the drug and to quickly assess tolerance. The INSIGHT trial compared the effects on nifedipine Oros to those of a classical diuretic combination (hydrochlorothiazide-amiloride) in 6321 hypertensives who had at least one additional risk factor for cardiovascular disease. The rate of the primary outcome (a composite of cardiovascular death, myocardial infarction, heart failure, stroke) was similar in the two treatment groups, but nifedipine was superior among the subgroup of diabetics. Substudies suggested that nifedipine slows the progression of atherosclerotic lesions (carotid and coronary arteries), preserves renal function, and prevents the development of new diabetes.
 ...
PMID:[Medication of the month. Adalat Oros 60 mg]. 1513 4

Candesartan cilexetil is the prodrug of candesartan, an angiotensin II receptor antagonist. Candesartan binds selectively and non-competitively to the angiotensin II receptor type 1, thus preventing the actions of angiotensin II. Clinical trials have demonstrated its efficacy at a dose range of 2 to 32 mg once daily in hypertension of all grades, heart failure, in reducing urinary albumin excretion in diabetes mellitus and in coexisting hypertension and renal failure. Pharmacokinetic properties of candesartan cilexetil in elderly patients are not significantly different from those in younger individuals. Hepatic impairment does not change pharmacokinetics of candesartan cilexetil at doses up to 12 mg/day. No dose adjustment is necessary in patients with mild or moderate renal impairment. Tolerability of candesartan cilexetil is not much different from that of placebo. All adverse events are usually of mild to moderate severity and not dose-related. The most common adverse events were headache, upper respiratory tract infection, back pain, and dizziness. The incidence of these adverse effects, as well as of cough, was similar in patients treated with candesartan cilexetil or placebo. The incidence of adverse events in long-term trials was not different from that in short-term trials. Tolerability of candesartan cilexetil does not differ with either age or gender.
 ...
PMID:Candesartan. 1559 74

Decompensated heart failure continues to significantly impact the economics of our healthcare system. In recent years, the focus on management of decompensated heart failure has changed from solely improving hemodynamics to modifying neurohormones. Endothelin (ET) is one of the important mediators in heart failure. This article reviews the clinical pharmacology, clinical efficacy, and tolerability of tezosentan, a dual-action ET-1 receptor antagonist. Using the search term tezosentan, a literature review was conducted to identify peer-reviewed articles and abstracts in MEDLINE (1966 to April 2004) and Current Content (1966 to April 2004) databases. Citations from available articles were also reviewed for additional references. When given as an intravenous infusion, tezosentan achieves steady-state concentration within the first 6 hours. Tezosentan is excreted almost entirely through the bile (>95%) and has a terminal elimination half-life of 3 hours. The side effects of tezosentan include headache, nausea, and hypotension. Clinical studies demonstrated mixed results for tezosentan regarding its efficacy and tolerability in the management of decompensated heart failure. The role or tezosentan in treating heart failure is yet to be defined.
 ...
PMID:Tezosentan in the management of decompensated heart failure. 1559 26

Levosimendan is a new calcium sensitizer developed for the treatment of congestive heart failure. Experimental studies indicate that levosimendan increases myocardial contractility and dilates both the peripheral and coronary vessels. Its positive inotropic effect is based on calcium-dependent binding of the drug to cardiac troponin C. It also acts as an opener of ATP-dependent potassium channels in vascular smooth muscle, thus inducing vasodilation. Although levosimendan acts preferentially as a calcium sensitizer it has also demonstrated selective phosphodiesterase III inhibitory effects in vitro. However, this selective inhibition does not seem to contribute to the positive action at pharmacologically relevant concentrations. Levosimendan has an active metabolite, OR-1896. Similarly to levosimendan, the metabolite exerts its positive inotropic and vasodilatory effects on myocardium and vasculature. The elimination half-life of levosimendan is about 1 hour. Thus, with intravenous administration, the parent drug rapidly disappears from the circulation after the infusion is stopped. The active metabolite, however, has a half-life of approximately 80 hours, and can be detected in circulation up to 2 weeks after stopping a 24-hour infusion of levosimendan. The intravenous formulation of levosimendan has been studied in several randomized comparative studies in patients with decompensated heart failure. Both patients with ischemic and non-ischemic etiology have participated in the studies. Levosimendan produces significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in PCWP, mean blood pressure, mean pulmonary artery pressure, mean right atrial pressure and total peripheral resistance. With a loading dose, the effects on PCWP and cardiac ouput are seen within few minutes. There is no sign of development of tolerance even with a prolonged infusion up to 48 hours. Cardiac performance is improved with no significant increases in oxygen consumption or potentially malignant rhythm disorders. Due to the formation of an active metabolite, the hemodynamic effects are maintained up to several days after stopping levosimendan infusion. Compared to dobutamine, levosimendan produces similar increase in cardiac output but profoundly greater decrease in pulmonary capillary wedge pressure. On the contrary to dobutamine, the hemodynamic effects are not attenuated with concomitant beta-blocker use. Levosimendan has been shown to have favourable effects on symptoms of heart failure superior to placebo and at least comparable to dobutamine. Mortality and morbidity in levosimendan treated patients has been shown to be significantly lower when compared to dobutamine or placebo treated patients. The most common adverse events associated with levosimendan treatment are headache and hypotension, as a likely consequence of the vasodilating properties of the compound. In conclusion, levosimendan offers a new effective option for the treatment of acutely decompensated heart failure. Unlike traditional inotropes, levosimendan seems also to be safe in terms of morbidity and mortality.
 ...
PMID:Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. 1572 64


<< Previous 1 2 3 4 5 6 7 8 9 10