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 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Hydration status and the effects of hypohydration have been the topic of much public and scientific debate in recent years. While many physiological responses to hypohydration have been studied extensively, the subjective responses to hypohydration have largely been ignored. The present investigation was designed to investigate the physiological responses and subjective feelings resulting from 13, 24 and 37 h of fluid restriction (FR) and to compare these with a euhydration (EU) trial of the same duration in fifteen healthy volunteers. The volunteers were nine men and six women of mean age 30 (sd 12) years and body mass 71.5 (sd 13.4) kg. Urine and blood samples were collected and subjective feelings recorded on a 100 mm verbally anchored questionnaire at intervals throughout the investigation. In the EU trial the subjects maintained their normal diet. Body mass decreased by 2.7 (sd 0.6) % at 37 h in the FR trial and did not change significantly in the EU trial. Food intake in the FR trial (n 10) provided an estimated water intake of 487 (sd 335) ml and urinary losses (n 15) amounted to 1.37 (sd 0.39) litres. This is in comparison with an estimated water intake of 3168 (sd 1167) ml and a urinary loss of 2.76 (sd 1.11) litres in the EU trial. Plasma osmolality and angiotensin II concentrations increased from 0-37 h with FR. Plasma volume decreased linearly throughout the FR trial amounting to a 6.2 (sd 5.1) % reduction by 37 h. Thirst increased from 0-13 h of FR then did not increase further (P>0.05). The subjects reported feelings of headache during the FR trial and also that their ability to concentrate and their alertness were reduced.
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PMID:The effects of fluid restriction on hydration status and subjective feelings in man. 1518 98

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.
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PMID:Candesartan. 1559 74

Raynaud's phenomenon is a common disorder with vasospasm of the digital arteries causing pallor with cyanosis and/or rubor. It can be primary (idiopathic), where it is not associated with other diseases, or secondary to several diseases or conditions, including connective tissue diseases, such as scleroderma and systemic lupus erythematosus. Raynaud's is often mild enough to not require treatment; however, with secondary Raynaud's there is not only vasospasm but also fixed blood vessel defects so the ischaemia can be more severe. Complications can include digital ulcers and could, rarely, lead to amputation. Treatment is often non-pharmacological including avoiding cold and smoking cessation. Calcium channel antagonists, such as nifedipine, are often considered when treatment is needed; however, adverse effects of these drugs can include hypotension, vasodilatation, peripheral oedema and headaches. Other treatments have been studied in randomised, controlled trials including classes of drugs, such as angiotensin II inhibitors, selective serotonin reuptake inhibitors, phosphodiesterase-5 inhibitors (e.g. sildenafil), nitrates (topical or oral; the latter can be limited by adverse effects, such as flushing, headache and hypotension), and for more serious Raynaud's or its complications prostacyclin agonists may be used. There are two large studies that demonstrate that endothelin receptor blockade with bosentan can reduce the number of new digital ulcers in scleroderma patients. However, it does not affect the healing period. Thus, Raynaud's is common and often requires non-pharmacological treatment. When secondary Raynaud's is suspected, such as Raynaud's with an older age at onset or other features of connective tissue disease, then an appropriate history, physical examination and laboratory tests may be indicated to reach an appropriate diagnosis. There have been advances in pharmacological treatment, but some of the treatments are limited by adverse effects.
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PMID:The diagnosis and treatment of Raynaud's phenomenon: a practical approach. 1735 12

In the Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS) trial, the combination of acetylsalicylic acid (50 mg) and extended-release dipyridamole (400 mg) (ASA+Dip) was compared with clopidogrel (75 mg) in patients with a recent transient ischaemic attack (TIA) or minor disabling stroke. In the same patients, the selective type I angiotensin II-receptor blocker telmisartan (80 mg) was compared with placebo. Both comparisons did not show any benefit or harm from any of the treatments evaluated. Therefore, ASA+Dip and clopidogrel should be considered effective in secondary stroke prevention following TIA or minor disabling stroke. ASA+Dip caused headache in 6% of patients. Clopidogrel can cause severe haematological side effects in rare cases; its use is hampered mainly by its high cost. Telmisartan was well tolerated in patients with a recent TIA or minor disabling stroke but should not be used for indications other than lowering blood pressure.
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PMID:[Inhibition of platelet aggregation and angiotensin II-receptor blockade following TIA; the unexpected results of the Prevention Regimen For Effectively Avoiding Second Strokes (PROFESS) trial]. 1880 78

Aliskiren is the first member of the new class of orally active direct renin inhibitors to receive approval from the United States Food and Drug Administration for the treatment of hypertension. In patients with hypertension, aliskiren can be used either as monotherapy or in combination with other antihypertensive agents. By inhibiting renin, aliskiren blocks the conversion of angiotensinogen to angiotensin I, which subsequently results in a reduction in angiotensin II concentrations. Unlike the angiotensin-converting enzyme inhibitors and the angiotensin II receptor blockers (ARBs), which reactively stimulate an increase in plasma renin activity, aliskiren suppresses the effects of renin and leads to a reduction in plasma renin activity. In clinical trials involving patients with mild-to-moderate hypertension, aliskiren provided antihypertensive efficacy that was comparable to that of an ARB. Combination therapy with aliskiren and an ARB may provide additional blood pressure-lowering effects compared with the respective monotherapies with each of the agents. The results from surrogate outcome studies have also alluded to the potential for aliskiren to prevent target organ damage. Because aliskiren does not significantly affect the cytochrome P450 system, it has been associated with few drug interactions. In clinical studies, aliskiren was well tolerated, and its adverse-effect profile was similar to that of placebo. Fatigue, headache, dizziness, diarrhea, nasopharyngitis, and back pain were the most commonly reported adverse events. Overall, aliskiren appears to be a reasonable treatment option for patients with mild-to-moderate hypertension who are intolerant of first-line antihypertensive therapies. Aliskiren may also be a promising renoprotective strategy in patients with concomitant hypertension and diabetes mellitus. Its potential as a first-line antihypertensive agent will have to be further examined once studies evaluating its effects on long-term clinical outcomes are completed.
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PMID:Aliskiren: an oral direct renin inhibitor for the treatment of hypertension. 1917 May 89

Several cellular and molecular mechanisms have been implicated in migraine pathophysiology including abnormal neuronal excitability and vascular events. Drugs from different pharmacological classes are used for migraine prophylaxis. These agents may normalize neuronal excitability by modulating distinct ionic channels and various neurotransmitter systems. They can also block cortical spreading depression, prevent peripheral and/or central pain sensitization, and normalize brainstem function. Most of the drugs recently used in migraine prophylaxis have been identified by serendipidy and they have been originally approved for other indications. Subsequently, their use has been extended to migraine prevention, according to their putative mechanisms of action. More recently, trials on adequate samples of migraine patients have been conducted for several drugs. In the present review, we will present and discuss the pathophysiological bases for the use of antidepressants, beta-adrenergic blockers, calcium channel blockers and antiepileptic drugs in migraine prevention. Currently, the major classes of conventional migraine preventive drugs include the antidepressant amitriptyline, the beta-adrenergic blocker propranolol, and the antiepileptic drugs topiramate and valproic acid. Promising results have recently been obtained for angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers. Some limited clinical findings have also been reported for atypical antipsychotic agents, nutritional supplements and also botulinum toxin. Targets of migraine preventive treatment are to reduce frequency and intensity of attacks and to decrease disability related to chronic headache.
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PMID:Pathophysiological basis of migraine prophylaxis. 1965 35

A pregnant young woman with a severe migraine is prescribed candesartan, an angiotensin II type 1 receptor antagonist (AT II antagonists). This has a positive effect-except for severe maldevelopment of her fetus. There is an increase in the use of the fetotoxic drugs, AT II antagonists and angiotensin-converting enzyme inhibitors, as prophylactic treatment of migraines, in addition to their use as hypertensives.
J Headache Pain 2010 Apr
PMID:Angiotensin II receptor antagonists against migraine in pregnancy: fatal outcome. 2006 32

Valsartan is a potent antagonist of the type 1 angiotensin receptor (AT(1)). By blocking the actions of angiotensin II on the AT(1), it inhibits vasoconstriction and synthesis of aldosterone thus lowering systemic blood pressure. Valsartan has been approved by the FDA for the treatment of hypertension in children aged 6 years and older. Valsartan can be dosed once a day with a sustained 24-hour effect on blood pressure reduction. The starting dose recommended in children is 1.3 mg/kg once daily (maximum 40 mg) which needs adjustment according to blood pressure response (dose range 1.3-2.7 mg/kg daily; up to 160 mg). A suspension form (4 mg/mL) is available for children who cannot swallow tablets. In patients aged 6 to 16 years, valsartan treatment (from a low dose of 10-20 mg to a high dose of 80-160 mg) resulted in dose-dependent reductions of 7.9-11.5 mmHg in systolic blood pressure and 4.6-7.4 mmHg in diastolic blood pressure. In 1- to 5-year-olds, valsartan (from a low dose of 5-10 mg to a high dose of 40-80 mg) reduced the systolic blood pressure by 8.4-8.6 mmHg and the diastolic blood pressure by 5.5 mmHg. Similar to adults and other antihypertensive medications, the most frequent side effect in children subsequent to valsartan use is headache. Current studies have not shown adverse effects on linear growth, weight gain, head growth, or development in children aged 1 to 5 years subsequent to valsartan use. Based on limited pediatric data, valsartan appears to be well tolerated and efficacious in reducing elevated blood pressure.
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PMID:Clinical utility of valsartan in the treatment of hypertension in children and adolescents. 2157 45

Renin inhibitors are antihypertensive drugs that block the first step in the renin-angiotensin system. Their mechanism of action differs from that of the angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists, but like these drugs, renin inhibitors interrupt the negative feedback effects of angiotensin II on renin secretion. The renin-angiotensin-aldosterone system (RAAS) has long been recognized to play a significant role in hypertension pathophysiology. Certain agents that modify the RAAS can control blood pressure and improve cardiovascular outcomes. Optimization of this compound by Novartis led to the development of aliskiren - the only direct renin inhibitor which is clinically used as an antihypertensive drug. Aliskiren is the first of a new class of antihypertensive agents. Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing. In short-term studies, it was effective in lowering blood pressure either alone or in combination with valsartan and hydrochlorothiazide, and had a low incidence of serious adverse effects. It was approved by the Food and Drug Administration in 2007 for the use as a monotherapy or in combination with other antihypertensives. Greater reductions in blood pressure have been achieved when aliskiren was used in combination with hydrochlorothiazide or an angiotensin-receptor blocker. The most common adverse effects reported in clinical trials were headache, fatigue, dizziness, diarrhea, and nasopharyngitis. Aliskiren has not been studied in patients with moderate renal dysfunction; as an RAAS-acting drug, it should be prescribed for such patients only with caution.
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PMID:Aliskiren: An orally active renin inhibitor. 2168 46


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