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 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP< or =90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, spirapril 6 mg, spirapril 3 mg, and placebo were 10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure-lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.
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PMID:Evaluation of the efficacy and tolerability of a low-dose combination of isradipine and spirapril in the first-line treatment of mild to moderate essential hypertension. 949 99

Severe anaphylactoid reactions and even death have been reported in hemodialysis patients using certain membrane dialyzers while receiving angiotensin converting enzyme (ACE) inhibitors. We report mild to moderate anaphylactoid reactions in 4 patients receiving plasmapheresis with on-line membrane filters after being placed on ACE inhibitors. Of 21 patients receiving 497 plasma fractionation procedures, only the 2 patients who were receiving ACE inhibitors developed anaphylactoid reactions. Of 28 patients who had 680 cryofiltration procedures, only 2 of 5 patients who were taking ACE inhibitors developed anaphylactoid reactions. All patients developed facial flushing, increased warmth, bradycardia, and hypotension after approximately 1/2 to 1 L of plasma was processed during the procedures. Only a few procedures caused severe hypotension requiring discontinuation of the procedure. We quantified vasodilatory mediators in 1 patient, who developed pronounced symptoms. Results were obtained for 6-keto PGF1alpha, PGD-M, and methyl histamine in plasma. In addition, in the same patient, 2,3 dinor 6-keto PGF1alpha and methyl histamine were quantified in urine samples. Our results showed that plasma and urinary metabolites were not grossly elevated although they did increase slightly. Mild to moderate anaphylactoid reactions were observed in some patients on ACE inhibitors receiving plasma fractionation or cryofiltration apheresis. This was resolved by discontinuing either the ACE inhibitor, plasma fractionation, or cryofiltration apheresis.
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PMID:Cryofiltration apheresis and plasma fractionation causing anaphylactoid reactions in patients receiving angiotensin converting enzyme inhibitors. 1022 24

Hypertension is an important risk factor for erectile dysfunction (ED). Consequently, there is a high coincidence between hypertension and ED. Oral sildenafil (Viagra) is an effective treatment for ED in patients with treated or untreated hypertension. The most common adverse events of sildenafil (headache, flushing, hypotension) result from its moderate vasodilating properties. The concomitant use of sildenafil and organic nitrates is contraindicated because it may lead to a potentiation of the decreases in blood pressure and thus cause life-threatening hypotension. In contrast, the concomitant use of sildenafil and different classes of antihypertensive agents (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to potentiating blood pressure decreases. Thus, this combination is unlikely to cause clinically significant hypotension or an increased incidence of adverse events. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens.
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PMID:[Interaction between sildenafil and antihypertensive drugs: what is evidence-based?]. 1159 59

Hypocalcemic toxicity accounts for the most common adverse effects of therapeutic plasma exchange. The symptoms can be related to a fall in plasma ionized calcium. Citrate-based anticoagulants, notably sodium citrate and ACD formula A, have been indicated as the major cause of hypocalcemic toxicity, but colloid replacement fluids containing human serum albumin are also at fault. Recognition of the signs and symptoms of hypocalcemic toxicity is important because several clinical measures are available to deal with them and to ensure patient comfort. A typical reactions, characterized by flushing and hypotension during plasma exchange, have been attributed to the effects of angiotensin converting enzyme inhibitors. Both exchange and adsorption apheresis procedures can result in atypical reactions in patients who have been taking this class of drugs within 48 to 72 hours of an apheresis procedure. These reactions are less common than hypocalcemic toxicity, but can be prevented by paying attention to detail.
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PMID:Hypocalcemic toxicity and atypical reactions in therapeutic plasma exchange. 1183 18

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.
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PMID:Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders. 1501 94

Fixed combinations of calcium channel blockers and angiotensin converting enzyme inhibitors represent an alternative to diuretic-based combination therapy. The aim of the present study was to compare the antihypertensive efficacy of the combination enalapril 10 mg/nitrendipine 20 mg (E/N) vs losartan 50 mg/hydrochlorothiazide 12.5 mg (L/H), assessed by 24-h ambulatory blood pressure monitoring. This multicentre, double-blind, parallel study included 97 hypertensive patients (office diastolic blood pressure (DBP) 90-109 mmHg and daytime DBP > 85 mmHg). After a 2- to 3-week period of single-blind placebo, they were randomized to receive double-blind treatment with E/N (n = 48) or L/H (n = 49) for a 4-week period. The primary outcome measure was the difference in 24-h DBP reduction between treatments from randomization to the end of the double-blind period. Secondary efficacy variables included differences in 24-h systolic (S) BP reduction, daytime, night-time and office SBP and DBP reduction, proportion of responders and controlled patients, trough-to-peak ratio and smoothness indexes. Safety was assessed by the proportion of patients with adverse events and the detection of laboratory abnormalities. No significant differences were observed in the primary outcome measure. The group receiving E/N tended to show greater reductions in most measures (24 h, daytime and office SBP and DBP) and higher BP control rates, but only the difference in the rate of office SBP control (< 140 mmHg) reached statistical significance (42.2 vs 22.4%; P = 0.048). The trough-to-peak ratios and smoothness indexes were similar in both groups. The incidence of adverse events related to the treatment was 27.1% (95% CI 14.5-39.6%) in E/N-treated patients and 14.3% (95% CI 4.5-45.8%) in the L/H group, but differences were not significant. The kind of event more frequently observed were flushing and headache in E/N, and dizziness and asthenia in L/H; all observed adverse events were mild. We conclude that E/N and L/H have a similar antihypertensive efficacy, assessed by office or ambulatory blood pressure monitoring. E/N achieved a significantly higher office SBP control rate, but this was accompanied by an apparently higher proportion of mild adverse events.
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PMID:Comparison of the antihypertensive effects of the fixed dose combination enalapril 10 mg/nitrendipine 20 mg vs losartan 50 mg/hydrochlorothiazide 12.5 mg, assessed by 24-h ambulatory blood pressure monitoring, in essential hypertensive patients. 1497 17

The fixed-dose combination of enalapril 10mg with nitrendipine 20mg combines an ACE inhibitor with a calcium channel antagonist (CCA) and is indicated for the treatment of patients with mild-to-moderate hypertension whose blood pressure (BP) is inadequately controlled with enalapril or nitrendipine monotherapy. In randomised, double-blind clinical trials, enalapril/nitrendipine 10/20 mg/day was significantly more effective than its individual components in reducing diastolic BP (DBP) in patients with mild-to-moderate hypertension inadequately controlled with enalapril 10 mg/day or nitrendipine 20 mg/day. The fixed-dose combination was similar in efficacy at reducing DBP to amlodipine 10 mg/day in patients who failed to achieve BP control with amlodipine 5 mg/day, and to losartan/hydrochlorothiazide 50/12.5 mg/day in patients who received the combinations as first-line therapy. Enalapril/nitrendipine 10/20 mg produced a consistent antihypertensive effect that persisted for the entire 24-hour dosage interval as shown by ambulatory BP monitoring. Enalapril/nitrendipine 10/20 mg was well tolerated in clinical trials where it was administered to patients with mild-to-moderate hypertension for up to 12 weeks. The adverse events were those expected of ACE inhibitors and CCAs and included cough, headache and flushing. Evidence from clinical trials, including a pooled analysis, suggests that the incidence of oedema may be significantly lower with the fixed-dose combination than with CCA monotherapy. In conclusion, enalapril/nitrendipine 10/20 mg is a well tolerated fixed-dose combination of two established antihypertensive agents administered once daily that effectively lowers BP throughout the 24-hour dosage interval. Importantly, the fixed-dose combination may have a lower incidence of oedema than CCA monotherapy. Enalapril/nitrendipine 10/20 mg provides an additional treatment option for patients with mild-to-moderate hypertension for whom combination therapy is appropriate.
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PMID:Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension. 1513 92

All currently available antihypertensive drugs can cause adverse drug reactions. Potential adverse drug reactions should already be taken into account when a new antihypertensive regimen is started. It is furthermore important to ask at follow-up visits specifically about common adverse reactions. The aims of this article are therefore to shortly summarise common and typical adverse drug reactions of antihypertensives. All antihypertensives may cause dizziness, hypotension, allergies, rashes, gastrointestinal complaints and dry mouth. Thiazide diuretics furthermore may cause electrolyte disturbances, dehydration and hyperuricemia, betablockers may cause bronchospasm, bradycardia, cold extremities and sleep disturbances and calcium antagonists may cause flushing, ankle oedema and gingival hyperplasia. Concerning potential lethal adverse drug reactions, it is important to know that ACE inhibitors and angiotensin receptor antagonists are contraindicated in all patients with a history of angioedema. However, angiotensin receptor antagonists are well-suited alternatives for patients with ACE inhibitor-induced cough or hypogeusia. Rare adverse drug reactions are commonly recognised only after drug approval based on spontaneous reporting. This demonstrates the importance of considering medications as potential causes of new complaints and symptoms and to reports such suspected adverse drug reactions to the national pharmacovigilance centres. Only the local or international accumulation of comparable spontaneous reports allows the drug regulation agencies to recognise new and unexpected adverse drug reactions early and to initiate appropriate measures.
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PMID:[Antihypertensives--which adverse drug reactions are clinically relevant?]. 1519 39

A previous article on the safety of amlodipine reviewed data from over 4,000 subjects who participated in clinical trials sponsored by Pfizer Central Research. Once-daily amlodipine was shown to be a well-tolerated treatment of hypertension and myocardial ischemia. Although amlodipine is a potent vasodilator, there was a low incidence of side effects such as headache, flushing, and dizziness. Amlodipine was not associated with adverse effects on hematologic or biochemical safety parameters nor on serum cholesterol or triglyceride levels. Amlodipine did not alter electrical conduction in the heart. Amlodipine had a favorable safety profile in comparative trials vs. beta-blockers. The data base of comparative trials vs. other calcium antagonists was small but the toleration of amlodipine was similar to that of verapamil and diltiazem. No data from comparative trials vs. another calcium antagonist of the dihydropyridine class have been available. This article reviews data from recently completed trials vs. nitrendipine and from trials in which amlodipine was used in combination with other agents. Amlodipine was better tolerated than nitrendipine and had a much lower incidence of side effects usually related to vasodilatation. This difference in side-effect profile was especially marked during the first days of treatment. Amlodipine was well tolerated when used in combination with beta-blockers, diuretics, ACE inhibitors, and nitrates. The gradual onset of action and relatively long half-life of amlodipine are the probable cause for the improved toleration in comparison with other dihydropyridines. Besides the low incidence of trivial side effects, increasing clinical experience with amlodipine provides no evidence that amlodipine is a cause of rare but serious adverse effects. It is concluded that amlodipine is an antihypertensive and anti-ischemic agent that has the combined advantages of a good safety profile with once-daily dosage and a smooth onset and long duration of action.
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PMID:An update on the safety of amlodipine. 1629 14

The dihydropyridine calcium channel blocker lercanidipine and the ACE inhibitor enalapril are frequently used in the treatment of hypertensive patients. In April 2007, a fixed-dose combination of the two drugs was approved in Germany for the treatment of patients not responding to monotherapy. It is expected that the drug will soon be available in the other European Union markets. In this review the present literature is summarized. Two doses will be available with 10 mg lercanidipine each and 10 or 20 mg enalapril. The medication should be taken once daily, optimally =15 minutes before a meal and the consumption of grapefruit juice should be avoided. The fixed-dose combination of the two drugs has a stronger blood pressure-lowering effect than monotherapy with 20 mg enalapril or 10 mg lercanidipine. The combination is well tolerated and few patients stopped the treatment because of side effects. As expected, the most common side effects reported are cough, peripheral edema, flushing, dizziness and vertigo, occurring in 1-5% of patients. This new fixed-dose combination is a useful adjunct to the present treatment and should increase compliance and help reduce hypertension-related costs.
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PMID:Fixed-dose lercanidipine/enalapril for hypertension. 1853 84


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