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)

Diseases of the respiratory organs comprise almost 4% of the adverse drug reactions reported to the Spontaneous Adverse Drug Reactions Center, SANZ (169 of the 4415 reports collected between 1981 and 1990). The most frequent reports were coughing caused by ACE inhibitors, attack of bronchial asthma induced by nonsteroidal anti-inflammatory drugs and beta-blocking agents, interstitial pneumopathy caused by amiodarone and sulfonamides, and respiratory depression due to benzodiazepines. The spontaneous reporting system does not allow one to determine the incidence, the reports are only of a signal-generating function. Classical semiology and special diagnostic techniques in assessing adverse drug reactions are discussed. A precise analysis of the case, temporal correlation with reaction and exposure time as well as comparisons with similar cases, together with a critical study of the literature on adverse drug reactions, remain the most important diagnostic procedures.
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PMID:[Drug side effects on the bronchi and lung]. 837 63

Perindopril erbumine, a new long-acting, non-sulfhydryl-containing angiotensin converting enzyme inhibitor, was evaluated in 289 patients with hypertension in a 16-week, double-blind, placebo-controlled dose-ranging study. After 4 weeks of single-blind placebo treatment, patients with supine diastolic arterial pressures from 95 to 114 mm Hg were randomized to receive placebo, 4 mg perindopril once daily, or 2 mg perindopril twice daily. The daily dose of perindopril was increased by 4 mg every 4 weeks to a maximum of 16 mg per day. Mean decreases in systolic and diastolic arterial pressure were greater with perindopril than with placebo (p < 0.05). The dose-response curve flattened after 8 mg per day, and there was no difference in arterial pressure reduction or in the percentage of responders between once- and twice-daily administration of perindopril. Adverse reactions with perindopril were generally mild and, with the exception of cough, were similar with placebo. The findings of this study indicate that perindopril is effective, well tolerated, and suitable for once-daily administration for the treatment of hypertension.
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PMID:Perindopril as monotherapy in hypertension: a multicenter comparison of two dosing regimens. The Perindopril Study Group. 847 65

The Hypertension Optimal Treatment (HOT) Study is an ongoing prospective, randomized, multicenter trial conducted in 26 countries. Its two main aims are to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and the incidence of cardiovascular morbidity and mortality in hypertensive patients and the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) compared with placebo. Altogether 19,193 patients have been recruited and randomized and one-year data are now available for all patients. This is a report on the blood pressures achieved, the tolerability and other available data after 12 months of follow-up of all patients. Special reference will be given to the subgroup of elderly patients (> or = 65 years, n = 6,113) as compared to younger patients (< 65 years, n = 13,080). On average, the target group < or = 90 mmHg in diastolic blood pressure has reached 86 mmHg, the target group < or = 85 mmHg has reached 83 mmHg and the target group < or = 80 mmHg has reached 81 mmHg. The percentage of patients that has obtained their target blood pressures is 84% in the target group < or = 90 mmHg, 72% in the target group < or = 85 mmHg and 57% in the target group < or = 80 mmHg at 12 months of follow-up. In the elderly subgroup (> or = 65 years of age) the percentage of patients at target is higher for all target groups, being 86, 76 and 61%, respectively, at 12 months. Antihypertensive treatment is initiated with a calcium antagonist, felodipine, at a dose of 5 mg once daily. If target blood pressure is not reached, additional antihypertensive therapy, with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent, is given. Further dose adjustments are made in accordance with a set protocol. As a fifth and final step a diuretic may be added. Side effects have been relatively few in this large multinational series of intensively treated hypertensive patients. Only ankle edema, 2.6% and 3.0%, and coughing, 1.3% and 0.8%, in young and elderly patients, respectively, exceed a frequency of 1%, and 88% of all patients are still taking their baseline therapy felodipine after one year. The one-year data presented here indicate that it should be possible to fulfill the primary aims of the HOT Study.
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PMID:The Hypertension Optimal Treatment (HOT) Study: 12-month data on blood pressure and tolerability. With special reference to age and gender. 853 54

A one-year open study was focused on the therapeutic effect and tolerance of spirapril in 171 patients with mild to moderate hypertension in 11 centres in the Czech and Slovak Republic. The antihypertensive effectiveness was investigated after four weeks, after 12 weeks and after 52 weeks. Only the results recorded after one year are reported. The study was completed after one year by 139 patients, incl. 120 (86.3%) with a normal diastolic pressure of 90 mmHg or less. The study was not completed by 32 patients (18.8%): because treatment was not effective--9.4%, because of undesirable effects--4.7%, 3.5% were eliminated by the investigators for various reasons (change of domicile, poor collaboration) and 1.2% because the protocol was not respected. According to the analysis "intention to treat" the diastolic pressure was normalized by monotherapy with spirapril in 25.1% of the baseline group; combination of spirapril with bopindolol led to normalization of the pressure in another 38.0% patients and in 7.0% patients normal diastolic pressure was achieved by a combination of spirapril with a hydrochlorothiazide; i.e. a total of 70.1% of the baseline group had a normal diastolic pressure after one year of treatment. In another 9.4% of the baseline group the diastolic pressure declined by 10 mmHg or more but not to normal levels. Thus normalization or effective control of pressure was achieved after one year in 79.6% patients according to the analysis "intention to treat". The combination of spirapril and bopindolol proved very effective. Patients where it was necessary to combine spirapril with bopindolol or hydrochlorothiazide had significantly higher baseline readings of blood pressure. During treatment the authors did not record in any of the groups a change of lipids, potassium, uric acid, the haemogram, liver tests or creatinine. Treatment was well tolerated and undesirable effects were rare (most frequent side effects: cough 3.5%, vertigo also 3.5%). The results of the study indicate that spirapril is an effective and well tolerated ACE inhibitor in the treatment of hypertension and its combination with bopindolol is equally suitable as the combination of spirapril with hydrochlorothiazide.
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PMID:[Spirapril in the therapy of mild and moderately severe hypertension. A Czech and Slovak multicenter study]. 855 92

Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective in reducing morbidity and mortality in patients with heart failure or post-myocardial infarction left ventricular dysfunction. Despite evidence from several large-scale randomized trials, the use of ACE-I in patients with heart failure remains relatively low. In part, the failure to achieve more widespread use of ACE-I in patients with heart failure may be due to physician's perceptions of the side effects associated with ACE-I, such as angioedema, renal dysfunction, cough, and hypotension. Many of these side effects are thought to be due to ACE-I-induced bradykinin accumulation. It is possible to inhibit the effect of angiotensin II without increasing bradykinin levels using an angiotensin II type I blocking agent such as losartan. How effective losartan is compared with an ACE-I is uncertain, however. Some of the beneficial effects of ACE-I have been attributed to bradykinin accumulation, and therefore ACE-I might have an advantage compared with an angiotensin II type I receptor antagonist such as losartan. On the other hand, angiotensin II may be produced by non-ACE-I-dependent mechanisms, which would suggest that an angiotensin II type I receptor blocking agent would be advantageous. To determine the relative safety and efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of angiotensin II, versus an angiotensin II type I receptor blocking agent, which does not result in bradykinin accumulation, we have begun the Evaluation of Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy of captopril and losartan in elderly patients with heart failure.
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PMID:Angiotensin II receptor antagonists in heart failure: rationale and design of the evaluation of losartan in the elderly (ELITE) trial. 857 52

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 purpose of this study was to evaluate the long-term safety and efficacy of moexipril, a non-sulphydryl angiotensin converting enzyme inhibitor, alone or in combination with hydrochlorothiazide in older patients with hypertension. One hundred and seventy two hypertensive men and women, 65-80 years old, with seated DBP between 95 and 114 mm Hg were studied. The study was a 2 year, multicentre (12 centres), open-label protocol of moexipril monotherapy or combination therapy (with hydrochlorothiazide). Blood pressure, pulse rate, weight, adverse effects and laboratory studies were assessed following moexipril at 7.5 or 15 mg once daily or 7.5 or 15 mg daily in combination with 25 mg of hydrochlorothiazide if the seated DBP remained > or = 90 mm Hg on moexipril monotherapy. The primary measure of efficacy was a change from baseline in seated DBP. Secondary outcome measures included changes in seated DBP, pulse rate, laboratory parameters and adverse side-effects. Following 1 year of therapy in 135 patients, the BP fell 16/14 mm Hg among patients receiving moexipril monotherapy and 27/17 mm Hg for those receiving combined therapy compared with baseline (P < 0.001 for both). After 2 years of treatment, reductions were similar in 120 patients. Nineteen patients (11%) were prematurely withdrawn from the study because of inadequate therapeutic response and 28 (16%) because of adverse experiences. There were no significant changes in pulse rate or postural reductions in BP on either moexipril monotherapy or combination treatment. Three adverse side-effects occurred at a frequency exceeding 2% that were possibly or probably attributable to moexipril or combination therapy: hypotension (2%), dizziness (6%) and increased cough (12%). There were no clinically relevant mean group changes from baseline laboratory values in the treatment groups. In conclusion, these long-term data demonstrate that moexipril, either alone or in combination with hydrochlorothiazide, has long-term anti-hypertensive efficacy and is generally well tolerated in elderly patients with hypertension.
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PMID:Long-term safety and efficacy of moexipril alone and in combination with hydrochlorothiazide in elderly patients with hypertension. 858 66

One hundred and thirty five non-smoking hypertensive patients with ACE inhibitor cough confirmed by lisinopril rechallenge and placebo dechallenge were recruited into a double-blind random parallel-group comparison of losartan 50 mg, lisinopril 20 mg and hydrochlorothiazide 25 mg each given once daily for a maximum of 8 weeks. The aim of the study was to compare the incidence of cough with the angiotensin II antagonist losartan, the ACE inhibitor lisinopril and the hydrochlorothiazide in hypertensive patients with previous ACE inhibitor cough. Cough detected by self-administered questionnaire was the primary end-point, and cough frequency by visual analogue scale a secondary end-point. The incidence of cough with losartan (29%) was lower than that for lisinopril (72%, P < 0.01) and similar to that for hydrochlorothiazide (34%). Cough frequency by visual analogue scale was lower for losartan than lisinopril (P < 0.01) and similar to that for hydrochlorothiazide. The specific selective AT1 angiotensin II receptor antagonist losartan is significantly less likely than lisinopril to cause cough in patients who previously have had ACE inhibitor cough. ACE inhibitor cough is likely to be related to non-specific kininase II inhibition.
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PMID:ACE inhibitors, angiotensin II antagonists and cough. The Losartan Cough Study Group. 858 82

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

C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough.
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PMID:Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients. 868 42


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