Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent observations indicate that angiotensin-converting enzyme (ACE) inhibition corrects renal transplant erythrocytosis (RTE). The mechanism for this association is not known. We examined the effect of ACE inhibition on hematocrit, erythropoietin (EPO), and renin substrate. ACE inhibition has been reported to suppress renin substrate, which is known to stimulate EPO and erythropoiesis. In 15 patients with RTE, hematocrit dropped from 52.8 +/- 0.6 (SEM) to 45.8 +/- 1.4% after 8 weeks of treatment with Enalapril, 2.5-20 mg/day. Serum EPO (normal range: 9-30 mU/ml) was high in one, normal in seven, and low in seven patients. ACE inhibition reduced EPO in patients with initial high or normal levels but induced no change in patients with initial low levels. ACE inhibition had no significant effect on renin substrate. In one patient who rejected his first graft, erythrocytosis recurred following a second, successful transplant. Treatment was discontinued because of cough in two patients and symptomatic drop in blood pressure in one patient. We conclude RTE is not caused by hypererythropoietinemia. In patients with normal circulating EPO, erythrocytosis may result from an increase sensitivity to EPO, and ACE inhibition lowered hematocrit by further reduction of this hormone. However, the finding of erythrocytosis in half our patients with suppressed EPO, suggests the participation of non-EPO-mediated mechanism(s). The recurrence of RTE in a patient after a second transplant raises the additional possibility of patient-specific factors in the pathogenesis of this disorder. In contrast to other reports, we documented side-effects (cough, hypotension) in three (20%) of our patients. Our clinical experience, coupled with prior reports of spontaneous resolution of RTE in some patients, suggests that intermittent courses of ACE-inhibition may be the optimal strategy in the use of this form of therapy for RTE.
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PMID:Angiotensin-converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism. 762 54

Antihypertensive drug therapy can lower blood pressure and prolong life, but many hypertensive patients continue to develop further risk factors and to die prematurely of heart disease. Antihypertensive drugs can also interfere with the patient's quality of life, and many are not compatible with the concomitant medical conditions of the patient and the medications taken to treat them. For these reasons, the antihypertensive therapy selected should meet the specific and complete needs of each patient, not just treat the high blood pressure. An analysis of the drugs that inhibit the renin-angiotensin system suggests that several of these drugs have a more favorable therapeutic profile than other classes of hypotensive agents. The newly developed receptor-site-specific blockers are expected to be tolerated better by hypertensive patients and, consequently, to enhance their quality of life. The first of the new class of nonpeptide blockers of the AT1 receptor, losartan--which has no partial agonist activity--is likely to have the advantages of the angiotensin-converting enzyme inhibitors without their adverse effects, notably cough. In selected patients, the AT1-receptor blockers could become the drugs of first choice for the management of hypertension.
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PMID:Antihypertensive therapy targeted to the needs of the patient: focus on the renin-angiotensin system; older and newer agents. 763 60

1. The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect. 2. Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out. 3. Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made. 4. Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.
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PMID:Reproducibility of angiotensin converting enzyme inhibitor induced cough: a double-blind randomised study. 774 49

The effects of cilazapril on exercise tolerance and neurohumoral factors were investigated in old myocardial infarction (OMI) patients with asymptomatic heart failure and reduced left ventricular ejection fraction. Cilazapril (0.5 mg) was administered once daily to OMI patients (n = 20) [NYHA class I, sinus rhythm, ejection fraction by radionuclide scanning < 50% (36.8 +/- 9.1%, mean +/- SD)]. Two weeks later, five patients were excluded from the study because of cough or hypotension, and 15 patients received 1.0 mg cilazapril once daily for the next 6 weeks. Exercise tolerance, neurohumoral factors and ejection fraction were measured in OMI patients before and after administration of cilazapril. Seven age-matched healthy adults served as the controls. OMI patients had latent heart failure because their exercise tolerance values and aldosterone levels were lower and alpha-atrial natriuretic polypeptide levels were higher than those in healthy subjects. In OMI patients, 8 weeks after cilazapril administration, exercise duration increased from 545 +/- 59 to 590 +/- 74 sec (p < 0.05), anaerobic threshold from 17.5 +/- 3.2 to 20.1 +/- 2.8 ml/min/kg (p < 0.05), peak-VO2 from 23.5 +/- 4.7 to 27.1 +/- 4.4 ml/min/kg (p < 0.05), plasma renin activity from 1.34 +/- 1.13 to 5.82 +/- 5.47 ng/ml/hr (p < 0.01) and alpha-atrial natriuretic polypeptide decreased from 100.7 +/- 44.3 to 80.5 +/- 28.0 pg/ml (p < 0.05). In patients with asymptomatic left ventricular dysfunction after myocardial infarction, 8 week's cilazapril administration improved exercise tolerance and neurohumoral conditions.
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PMID:[Effect of cilazapril on exercise tolerance and neurohumoral factors in patients with asymptomatic chronic heart failure after myocardial infarction]. 852 61

The past few decades have seen a remarkable development in the field of pharmacological therapy, one of the most notable examples being the treatment of arterial hypertension. Some of the early anti-hypertensive agents were relatively crude by today's standards, but gradually efficacy, tolerability, or both, of blood pressure-lowering (BP) drugs have been improved. It is presently possible to choose from a number of effective and well-tolerated compounds for the treatment of hypertension. The latest additions to the anti-hypertensive armamentarium are the angiotensin II receptor antagonists, the most advanced of these being losartan. It is perhaps most relevant to compare losartan to the angiotensin converting enzyme (ACE) inhibitors, another class of anti-hypertensive agents which acts mainly by interfering with the renin-angiotensin-aldosterone system (RAAS). Studies have shown that losartan lowers BP at least as effectively as ACE inhibitors. However, the side-effect profile of losartan is more favourable. In particular cough, a relatively common side-effect of ACE inhibitors, has been shown to be significantly less common during losartan treatment. This is probably because losartan does not interfere with bradykinin metabolism, unlike the ACE inhibitors. Regarding the reversal of left ventricular hypertrophy (LVH), a powerful risk indicator for cardiovascular disease, we have shown that losartan is more effective in this regard than treatment with the beta-blocker atenolol. It appears, based on these and other findings, that interference with the RAAS is particularly useful in causing reversal of the cardiovascular hypertrophic changes. The prognostic implications remain to be demonstrated, but it would be logical to expect a benefit from this effect. It was recently shown that polymorphism of the ACE gene is associated with increased risk of coronary heart disease even in the absence of conventional risk factors. If these findings are confirmed the interest in interfering with the RAAS as a therapeutic modality in hypertension would obviously be strengthened. It is not easy to predict the future role of any new therapeutic modality. The positive relation between efficacy and tolerability of losartan, as well as the fact that several observations suggest that interference with the RAAS could be favourable from a prognostic point of view, suggest that losartan may come to play an important role in the future treatment of hypertension.
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PMID:The future role of losartan. 858 83

Pharmacologic agents that attenuate the influence of the renin-angiotensin-aldosterone system are known to reduce systemic arterial blood pressure through vasodilatory action and enhanced renal clearance of sodium and water. Angiotensin-converting enzyme inhibitors are known to antagonize the renin-angiotensin-aldosterone system through their ability to inhibit conversion of angiotensin I to angiotensin II. A new class of antihypertensive agents, angiotensin-II receptor antagonists, has recently been developed. These agents specifically block the receptor for angiotensin II, thereby limiting angiotensin II-mediated vasoconstriction and reducing aldosterone secretion. These effects result in a reduction in systemic arterial blood pressure through reduced vascular tone and enhanced sodium and water clearance. Clinical trials have demonstrated the efficacy of these agents in reducing blood pressure. These new antihypertensive agents also have uricosuric actions and are well tolerated, with a low incidence of cough and angioedema, side effects that are seen with angiotensin-converting enzyme inhibitors. Clinical trials are underway to see if these drugs will be useful in the treatment of diseases other than hypertension, such as congestive heart failure and chronic renal disease.
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PMID:Angiotensin-II receptor antagonists: a new class of antihypertensive agents. 862 40

The renin-angiotensin system, through the effects of angiotensin II, may be involved in the pathogenesis of essential hypertension and associated left ventricular hypertrophy. Treatment with angiotensin-converting enzyme inhibition (ACEI) lowers blood pressure and reduces left ventricular hypertrophy. ACEI, however, may not completely inhibit the production of angiotensin II and its effects, and adverse effects like cough and rise in creatinine have been associated with ACEI and reduced degradation of bradykinin. The first selective antagonist of the angiotensin II-1 (AT1) receptor, losartan, has recently been approved. The LIFE study has been started, in which 8,300 hypertensive patients with left ventricular hypertrophy in Scandinavia and the USA will be randomized to blinded treatment with either atenolol or losartan to compare the effects on cardiovascular morbidity and mortality over a period of five years.
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PMID:[Losartan and the LIFE-study. Antihypertensive treatment with AT1-receptor antagonist]. 864 56

The use of ACE inhibitors in patients with myocardial infarction (MI) has been the subject of several studies conducted during recent years. These studies have demonstrated the capacity of these agents to improve both survival and morbidity of patients with MI. However, the use of ACE inhibitors in patients with MI has been shown to reduce blood pressure (BP) and so could jeopardise the ischaemic myocardium. A significant reduction in systemic BP has been demonstrated by all the studies of ACE inhibitors in patients with MI, but no relationship has been found between the occurrence of hypotension and a worse clinical outcome. An increased risk of death has been observed exclusively in association with severe and sudden hypotension, the occurrence of which can be largely prevented by the administration of the ACE inhibitor according to an increasing dose-titration scheme. Conversely, a certain degree of long term BP reduction could result in some beneficial effect in patients with MI and contribute to the lower incidence of re-infarction observed in patients with acute MI undergoing long term treatment with captopril. Since the renin-angiotensin system is strictly related to kidney function, its blockade by an ACE inhibitor could result in some degree of renal dysfunction, particularly in patients with MI and impaired ventricular function. The available results from large-scale studies suggest that abnormalities in kidney function (namely an increase in serum creatinine) are observed in 0.9 to 2.4% of patients with MI who, nevertheless, experience some benefit from treatment with ACE inhibitors. Interestingly, the administration of ACE inhibitors does not seem to further compromise severely impaired renal function, and may also represent a useful tool for the treatment of patients with renal dysfunction associated with MI. The use of ACE inhibitors in patients with MI is associated with a satisfactory clinical and laboratory safety profile. The occurrence of significant adverse effects seems to be very low and mainly attributable to a rather modest prevalence of cough (2.4 to 6.8%). Discontinuation of treatment because of biochemical and haematological abnormalities has been observed in less than 1% of treated patients. Thus, the beneficial effects of ACE inhibitor treatment seem to outweigh safety concerns, thereby reinforcing the role of ACE inhibition as a suitable therapeutic strategy in the treatment of patients with MI.
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PMID:A risk-benefit assessment of ACE inhibitor therapy post-myocardial infarction. 880 Jun 25

Despite the availability of safe and efficacious antihypertensive agents, hypertension continues to be a major source of morbidity and mortality in the United States. Losartan, the first of a new class of agents, the angiotensin II receptor antagonists, can be administered as monotherapy in the treatment of hypertension or to complement existing therapy. The angiotensin II receptor antagonists block the effects of angiotensin II through preferential binding to angiotensin II receptor subtype AT1 on the cell membrane. Compared with angiotensin-converting enzyme inhibitors, they may provide more complete blockade of the renin-angiotensin system and be associated with a lower frequency of cough as a side effect.
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PMID:A new class of antihypertensive therapy: angiotensin II receptor antagonists. 888 79

Angiotensin receptor antagonists represent a new class of drugs for the treatment of patients with hypertension. Reduction of blood pressure in patients with essential hypertension requires increased activity of the renin-angiotensin system. Losartan, the first orally active, nonpeptide angiotensin antagonist, specifically competes with angiotensin II (Ang II) for the AT1 receptor and reversibly alters the receptor. Maximum blood pressure reductions occur after doses of approximately 50 mg, although some patients will require 100 mg; the parent compound and a metabolite are responsible for a smooth 24-hour effect on blood pressure. Once-daily dosing with losartan has been documented to be safe. The drug's safety has been evaluated in 4,058 patients; of these patients, more than 1,200 were treated for longer than 6 months and more than 800 were treated for longer than 1 year with doses of 10 mg to 150 mg. Overall, no hypertensive patients were withdrawn from treatment because of elevated serum creatinine or potassium levels, and there were no reports of angioedema. In addition, some reductions in plasma uric acid levels were noted. Cough occurred significantly less often in patients treated with losartan than in those treated with hydrochlorothiazide or lisinopril. In contrast to angiotensin-converting enzyme (ACE) inhibitors, losartan does not activate bradykinin-nitric oxide-prostanoid vasodilation.
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PMID:Losartan: first of a new class of angiotensin antagonists for the management of hypertension. 893 38


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