UMLS:C0010200 - FACTA Search

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)

The aim of this 3-month double-blind study was to assess the antihypertensive effect and acceptability of perindopril in comparison with enalapril in patients with mild to moderate essential hypertension. After a 4-week placebo run-in period, 161 patients with supine diastolic blood pressure (DBP) between 95 and 115 mmHg were randomized to receive perindopril 4 mg or enalapril 10 mg once daily. If supine DBP was higher than 90 mmHg, treatment was adjusted monthly, first by doubling the dose and then by addition of hydrochlorothiazide 12.5 mg. After 3 months of active treatment the decrease in supine and standing blood pressures was statistically significant within both groups but was not statistically different between groups. The percentage of patients (65%) who achieved supine DBP of < or = 90 mmHg in the perindopril group was not significantly different from the enalapril group (73%). Monotherapy resulted in control of supine DBP in 56% of the perindopril group and 58% of the enalapril group; the addition of hydrochlorothiazide resulted in control of supine DBP in 6% and 15% respectively. The number of withdrawals for adverse events was statistically significant between groups (0 in the perindopril group and 7 in the enalapril group, p = 0.01). During active treatment the most frequently reported complaints were headaches and cough; there was not statistically difference between groups. Changes in laboratory parameters were minor and not significantly different between the two groups except for serum glucose, potassium, and triglyceride levels. In conclusion, there was no significance between perindopril and enalapril in terms of efficacy. Clinical acceptability seems to be better in the perindopril group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical acceptability of ACE inhibitor therapy in mild to moderate hypertension, a comparison between perindopril and enalapril. 852 53

The pharmacokinetics and pharmacodynamics of enalapril, an angiotensin converting enzyme inhibitor, are reported to vary with the time of administration. The present study was undertaken to examine whether the effect of enalapril on plasma bradykinin (BK), substance P and prostaglandin E2 (PGE2), which are likely to be involved in the mechanism of enalapril-induced cough, might also be affected by its time of administration. Enalapril 5 mg or placebo was given orally at 10:00 h (day trial) or 22:00 h (night trial) to 12 patients with essential hypertension. Serum concentrations of total drug (enalapril + enalaprilat, its active metabolite) during the day and night trials did not differ significantly at any time. However, serum enalaprilat tended to be higher and its maximum concentration greater in the day trial than in the night trial. Blood pressure 24 h after administration of enalapril was reduced at 22:00 h, but not at 10:00 h. Plasma BK tended to increase following enalapril administration at 10:00 h, but not at 22:00 h. Remarkable increases in plasma BK were observed in two patients in the day trial and one of them also complained of cough. However, no such increase in plasma BK or subsequent adverse effect were recorded in the night trial. Plasma substance P and PGE2 did not change significantly following enalapril administration either in the day or night trial. The results suggest that the response of BK to enalapril is affected by the time of administration. In patients who complain of cough during treatment with enalapril during the daytime, this adverse effect might be diminished or eliminated by a switch to night-time administration.
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PMID:Chronopharmacology of enalapril in hypertensive patients. 858 61

The antihypertensive effects and the tolerability of losartan and enalapril given alone or in combination with hydrochlorothiazide (HCTZ) were compared in a multicenter, double-blind, randomized, parallel-group, 16-week clinical trial. The study consisted of a 4-week placebo washout phase and a 12-week active treatment phase. Patients with mild-to-moderate, uncomplicated essential hypertension were considered for participation in the study. To enter the treatment phase of the study, a mean sitting diastolic blood pressure (SiDBP) > or = 95 and < or = 115 mm Hg was required. Patients received either 50-mg losartan once daily or 5-mg enalapril once daily at randomization. The dose of enalapril could be titrated to 10 mg after 4 weeks and 25 mg of HCTZ could be added after 8 weeks, based on measurements of SiDBP at clinic visits. The dose of losartan remained at 50 mg; 12.5 mg of HCTZ could be added after 8 weeks. Changes in the treatment regimen at each step were required if SiDBP remained > or = mm Hg. Doses of the diuretic were chosen based on commercially available forms of the test agents in combination with HCTZ. Trough blood pressure, heart rate, and safety parameters were measured at 4-week intervals during the treatment phase of the study. Significant reductions in mean SiDBP and mean sitting systolic blood pressure (SiSBP) were achieved at all time points (4, 8, and 12 weeks) with both treatments. No significant differences between treatment groups for mean changes in SiDBP or SiSBP were observed overall. At study end, patients receiving the losartan regimen had a mean reduction in SiDBP of 10.3 mm Hg, whereas patients in the enalapril regimen had a mean reduction of 9.8 mm Hg. Likewise, the percentage of patients reaching goal blood pressure reduction was not significantly different between groups. The mean reduction in SiDBP-- but not SiSBP--in black patients was slightly greater in the losartan group than in the enalapril group (SiDBP, 10.0 mm Hg losartan vs 8.0 mm Hg enalapril; P = 0.02). Similarly, losartan patients aged 65 years and older had a slightly greater decrease in SiDBP than comparable enalapril patients (12.7 mm Hg vs 8.7 mm Hg; P = 0.03). The importance of these differences between subgroups must be clarified by additional studies. Overall, both treatments were well tolerated. A regimen of losartan alone or in combination with HCTZ was effective in treating patients with essential hypertension and was comparable to a regimen of enalapril alone or in combination with HCTZ. However, treatment with losartan was associated with a lower incidence of cough.
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PMID:Efficacy and tolerability of losartan versus enalapril alone or in combination with hydrochlorothiazide in patients with essential hypertension. 859 43

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

We describe a rare case of ACE inhibitor-induced angioedema during long-term therapy in a 51-year-old male patient with essential hypertension; and this is the third case reported of this adverse reaction in Japan. The patient received enalapril for 66 months, and complained of a dry cough which was mild and tolerable. Recently, he noted tenderness of his mouth, face, swelling of lips and tongue for 3 to 4 h after taking his morning dose of enalapril. These symptoms abated spontaneously, so he continued taking the drugs. He again noted similar episodes of angioedema 29 days after the first experience. He had no further episodes of angioedema or dry cough after cessation of enalapril. This case of angioedema developed during long-term therapy with enalapril administered as 19,930 mg of enalapril maleate. We emphasize that angioedema may occur at any time during the use of enalapril.
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PMID:A case report of angioedema during long-term (66 months) angiotensin converting enzyme inhibition therapy with enalapril. 874 Dec 42

Losartan potassium is an orally active, nonpeptide angiotensin II (AII) receptor antagonist. It is the first of a new class of drugs to be introduced for clinical use in hypertension. This novel agent binds competitively and selectively to the AII subtype 1 (AT(1)) receptor, thereby blocking AII-induced physiological effects. An active metabolite, E3174, contributes substantially to its antihypertensive effect, which persists throughout 24 hours after once-daily administration. In patients with mild to moderate hypertension, losartan potassium 50 to 100mg once daily as monotherapy lowers blood pressure to a similar degree to enalapril, atenolol and felodipine extended release (ER). Losartan potassium combined with hydrochlorothiazide reduces blood pressure further than either drug given separately. About one-third of patients with severe hypertension have responded to the combination product. Losartan potassium appears to be effective in elderly patients. Losartan potassium is very well tolerated. In clinical trials, dizziness was the only drug-related event reported more frequently with losartan potassium monotherapy than with placebo. First-dose hypotension is uncommon. An aspect of the drug's tolerability profile which may prove to be particularly advantageous is that it is associated with a similar incidence of cough to placebo in patients with a history of ACE inhibitor-related cough. Additionally, clinically relevant adverse metabolic effects or laboratory abnormalities have not been documented during losartan potassium therapy and renal function is preserved in patients with or without renal insufficiency. The adverse effect profile of the losartan potassium-hydrochlorothiazide combination resembles those for losartan potassium monotherapy and placebo. Long term tolerability data are limited (<2 years) but support the very good tolerability profile in shorter studies. Elements of the drug's profile yet to be assessed or reported fully in the literature include long term efficacy; potential to favourably influence cardiovascular and renovascular systems (and ultimately mortality) in patients with hypertension and, lastly, cost effectiveness and influence on quality of life. In summary, losartan potassium is the first AT(1)+ receptor antagonist to become available for the management of hypertension and, as such, it is an important new antihypertensive agent. Pending long term data as outlined above, it is likely to find initial use in patients with mild to severe hypertension who are unresponsive to, or intolerant of their current therapy. However, with its novel mechanism of action, good efficacy and favourable tolerability profile, losartan potassium is well placed to claim a prominent position in the management of patients with essential hypertension in the future.
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PMID:Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. 886 49

The clinical efficacy and tolerability of losartan were studied in clinical trials in Japanese patients with essential hypertension. In a short-term trial, losartan (25 to 100 mg once daily) provided good control of blood pressure for 24 h without affecting the patient's own diurnal blood pressure profile. In a double-blind study, the efficacy and tolerability of losartan (25 to 50 mg once daily) were compared to enalapril (5 to 10 mg) in Japanese patients with mild to moderate essential hypertension. Losartan, 25 to 50 mg given once daily, produced an antihypertensive effect comparable to enalapril, 5 to 10 mg, in these patients. The incidence of adverse reactions in the losartan group was 9.0% (13/144), which was lower than that observed in the enalapril group, 20.3% (29/143). The incidence of cough in the losartan group (0.7%) was lower than that of the enalapril group (13.3%). No discontinuation due to cough was observed in the losartan group: however, seven patients were discontinued from the enalapril group. Losartan exhibited antihypertensive efficacy comparable to enalapril and a tolerability profile superior to enalapril in this study. The efficacy and tolerability of losartan were also investigated in 29 hypertensive patients with renal impairment. When losartan (25 to 100 mg) once daily was used, blood pressure was controlled in 62.1% (18/29) of patients. The rate of cases assessed as "useful" was 58.3% when the pretreatment serum creatinine level was less than 3.0 mg/dL. No cases, however, were assessed as "useful" in patients in which the level was 3.0 mg/dL or higher. In a trial with hypertensive diabetic patients, losartan did not adversely affect glucose tolerance and lipid metabolism. Losartan was associated with a decreased total cholesterol (p < 0.01) and LDL cholesterol (p < 0.01) without significantly changing HDL cholesterol in patients with total serum cholesterol of > 220 mg/dL. In summary, losartan, the first angiotensin II antagonist, is an effective antihypertensive agent with an excellent tolerability profile.
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PMID:The clinical efficacy and tolerability of the angiotensin II-receptor antagonist losartan in Japanese patients with hypertension. 891 45

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

Losartan potassium is the first of a new class of orally active antihypertensive drugs which antagonise the action of angiotensin (AT) II at the AT1 receptor subtype. Losartan potassium is converted by the liver to the active metabolite E-3174, which is a more potent antagonist at the AT1 receptor. E-3174 is responsible for most of the pharmacological effects of losartan potassium, and its long half-life contributes to the extended duration of action of the drug. Losartan potassium is effective as a once-daily antihypertensive agent. In mild to moderate hypertension, losartan potassium has similar efficacy to enalapril, atenolol and felodipine extended release. When losartan potassium is combined with hydrochlorothiazide there is a further reduction in blood pressure. Losartan potassium is well tolerated in mild, moderate and severe essential hypertension, with dizziness being reported as the only drug-related adverse effect. The overall rate of patient withdrawal from therapy due to adverse experiences with losartan potassium is lower (2.3%) than that of placebo (3.7%). First-dose hypotension is uncommon, perhaps due to the slower onset of action of the drug, and cough does not appear to be a significant problem. A number of areas concerning the safety and efficacy of losartan potassium remain to be clarified. In particular, long term tolerability studies are needed; cough only became apparent as an adverse effect of ACE inhibitors after 3 to 4 years of use. Postmarketing surveillance has shown that angioedema, a rare but life-threatening adverse effect of ACE inhibitors, also occurs with losartan potassium. Further data are needed on the use of losartan potassium in patients with renal impairment before accepting the recommendation that dosage adjustment is not necessary. The pharmacokinetics and pharmacodynamics of losartan potassium in patients with hepatic disease also require further investigation. Losartan potassium increases uric acid secretion and lowers plasma uric acid levels, which may be of benefit when losartan potassium is combined with a thiazide diuretic, but which may otherwise lead to uric acid stone formation and possibly to nephropathy. Simple control of blood pressure is no longer an adequate goal in the management of hypertension. Any new antihypertensive agent should also reduce cardiovascular events, prevent or cause regression of end-organ damage such as left ventricular hypertrophy, atherosclerosis and renal failure, and should not impair quality of life. Such data on losartan potassium are not currently available. Losartan potassium is likely to be used in patients who are intolerant of ACE inhibitors, but its future in the management of hypertension will depend on long term tolerability studies and data on its effects beyond simple blood pressure control.
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PMID:A risk-benefit assessment of losartan potassium in the treatment of hypertension. 901 Jun 43

The primary goal of combination therapy is to enhance efficacy without compromising safety. In this multicenter study, the efficacy and tolerability of perindopril added to continuing hydrochlorothiazide therapy were evaluated in patients with mild to moderate (stage I and II), essential hypertension. Two hundred fifty-two patients with supine diastolic blood pressure of 95 mmHg to 114 mmHg were treated for 4 weeks with open-label hydrochlorothiazide at 25 mg/day. The 208 patients whose supine diastolic blood pressure was > or = 90 mmHg at the end of hydrochlorothiazide monotherapy entered a 12-week, double-blind treatment, where placebo or perindopril were added to the 25-mg/ day hydrochlorothiazide therapy as follows: placebo (n = 50) and doses of perindopril at 2 mg/day (n = 52), 4 mg/day (n = 53), and 8 mg/day (n = 53). The perindopril-hydrochlorothiazide combinations decreased both supine systolic blood pressure and supine diastolic blood pressure by 10.3/6.7, 9.6/8.0, and 9.3/6.3 mmHg, for perindopril doses of 2, 4, and 8 mg/day, respectively; there was no difference among the three drug groups. Placebo decreased blood pressure by 1.6/2.0 mmHg, an effect that was significantly lower compared with perindopril-hydrochlorothiazide combinations. Adverse events were mild and similar among all treatment groups, except cough, which was 4.0%, 3.9%, 7.6%, and 13.2% for placebo and perindopril doses of 2, 4, and 8 mg, respectively. The results of this multicenter study indicate that the combination of perindopril and hydrochlorothiazide is safe and effective in lowering blood pressure. The findings also demonstrate that lower doses of perindopril are as effective as higher doses when combined with hydrochlorothiazide.
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PMID:Perindopril/hydrochlorothiazide dose combinations for the treatment of hypertension: a multicenter study. 904 72

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