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)

A dry, tickly and often bothersome cough is the most common adverse effect of ACE inhibitors. Recent studies indicate that cough may develop in around 10% of the patients treated with ACE inhibitors. In half of these patients, the ACE inhibitor has to be discontinued. Cough has emerged as a class effect occurring with all ACE inhibitors with no clear difference between the single substances. While ACE inhibition is safe in the vast majority of patients with obstructive airways disease, asthmatic symptoms or exacerbation of asthma as well as a rise in bronchial reactivity have been occasionally reported. ACE inhibition increases the cough reflex. The mechanisms underlying ACE inhibitor-induced cough are probably linked to suppression of kininase II activity, which may be followed by an accumulation of kinins, substance P and prostaglandins. Physicians should be aware that a dry cough is the most common adverse effect of ACE inhibitors and that this symptom may occur not necessarily shortly after institution of therapy but months or even a year later. Replacement by another ACE inhibitor should not be tried, since the cough will almost always recur on rechallenge with the same or another ACE inhibitor. After withdrawal of the ACE inhibitor, which is the treatment of choice, cough will resolve usually within a few days.
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PMID:ACE inhibitor-induced cough and bronchospasm. Incidence, mechanisms and management. 906 25

Between 1991 and 1995 about 3% of the unwanted drug-induced side effects reported to the Swiss Drug Monitoring Center (SANZ) concerned pulmonary disturbances (144 out of a total of 4824 reports). The most frequent reports were those about cough and taste disorders caused by ACE-inhibitors, smell disorders caused by antimicotics, and asthma attacks caused by nonsteroidal antirheumatics or betablocking eye drops. 33% of these unwanted side effects have been classified as severe. By spontaneous reporting a correct calculation of incidence is not possible. The reports, however, have signal function. Precise case analysis, temporary correlations (reaction and exposure time and onset of reaction), exclusion of other causes for the disease, comparisons between similar cases and critical study of literature concerning drug-related side effects are still the most important foundations for diagnosis.
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PMID:[Side effects of drugs on the respiratory tract: experiences of the Swiss Drug Monitoring Center from 1991 to 1995]. 896 44

The ACE inhibitors have been found effective in reducing the morbidity and mortality of both post-infarction patients and those with chronic systolic left ventricular dysfunction. However, their use is limited--particularly in elderly patients because of poor tolerance partly due to bradykinin-induced side-effects such as renal dysfunction, first-dose hypotension, and cough. Thus, the introduction of the angiotensin II type I receptor antagonists--that block the effects of angiotensin II without increasing bradykinin concentration--may be particularly important in the treatment of elderly patients. The role of the angiotensin II type I receptor antagonists in patients with systolic left ventricular dysfunction is currently being explored in direct comparison with and in conjunction with the ACE inhibitors. Furthermore, important questions about the most effective dose of ACE inhibitor and ACE inhibitor use in conjunction with aspirin and the NSAIDs still have to be answered. Thus, although we have learnt much about the role of ACE inhibitors in heart failure treatment, we are still at an early stage in the application of this knowledge, particularly in elderly patients.
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PMID:ACE inhibitor use in elderly patients with systolic left ventricular dysfunction: problems and opportunities. 899 96

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

Combination therapy with the new ACE inhibitor moexipril plus hydrochlorothiazide (HCTZ) results in significant blood pressure (BP) reductions. This study compares the efficacy and safety of moexipril plus HCTZ to that of a standard combination treatment in patients with mild-to-moderate hypertension. After a 1 month placebo run-in period, 140 hypertensive patients whose sitting diastolic BP (DBP) averaged 95-114 mm Hg were randomized to receive either once daily moexipril 7.5 mg/HCTZ 12.5 mg or metoprolol 100 mg/HCTZ 12.5 mg for the following 12-week double-blind treatment period. At biweekly visits BP was controlled sphygmomanometrically and the occurrence of adverse events (AE) was documented. At study endpoint adjusted mean reductions in sitting systolic/diastolic BP seen with both combinations were -17.6 mm Hg/-12.8 mm Hg and -17.2 mm Hg/-13.9 mm Hg in the moexipril/HCTZ and metoprolol/HCTZ groups, respectively. The response rate to both kinds of combinations were very similar, 69% and 74% in the moexipril/HCTZ and metoprolol/HCTZ groups, respectively. The percentage of patients which experienced one or more AEs were 46% in the moexipril/HCTZ and 61% in the metoprolol/HCTZ group. Headache and cough which are the most frequently reported AEs after treatment with ACE inhibitors were seen in 9% and 10% of the patients in the moexipril/HCTZ group compared to 10% and 4% in the metoprolol/HCTZ group. The study indicates that the combination of moexipril 7.5 mg plus HCTZ 12.5 mg is as efficacious and safe as metoprolol 100 mg plus HCTZ 12.5 mg in the treatment of mild-to-moderate hypertension.
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PMID:Antihypertensive treatment with moexipril plus HCTZ vs metoprolol plus HCTZ in patients with mild-to-moderate hypertension. 914 Aug 1

There are several theories on the cause of ACE inhibitor-induced cough, but the exact mechanism is not known. In many patients, if cough develops, the ACE inhibitor can be discontinued and a drug in another therapeutic class used in its place. However, in patients with CHF, diabetic nephropathy, and patients who have experienced a myocardial infarction, discontinuing the ACE inhibitor may not be in the best interest of the patient. In this patient population it would be reasonable to try cromolyn sodium to treat cough, while continuing the ACE inhibitor. Data are not available to support the efficacy of cromolyn sodium to treat cough in patients with diabetic nephropathy, but these patients clearly benefit from the use of an ACE inhibitor. Other factors not addressed in the case reports and the clinical trial such as patient adherence, cost, and quality of life should also play a role in the decision to use cromolyn sodium. Cromolyn sodium has been effective for the treatment of ACE inhibitor-induced cough in many case reports and has had mild success in one small clinical trial. Although none of the reports adequately assessed adverse effects, studies examining cromolyn for other indications have demonstrated a relatively benign adverse effect profile. It is difficult to recommend an exact dose to use because of the dosing variability in the case reports. The majority of the case reports and the one clinical trial used dosages similar to recommendations for bronchial asthma (i.e., 2 puffs [1.6 mg] 4 times daily via MDI or 20-mg capsules 4 times daily via breath-activated inhalation). At this time, the use of cromolyn sodium is a viable option, but more controlled studies are needed to fully elucidate its role in the treatment of ACE inhibitor-induced cough.
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PMID:Cromolyn sodium for ACE inhibitor-induced cough. 918 21

Raised blood pressure in the elderly is not a normal consequences of aging, but is a major risk factor for cardiovascular disease. Cardiac and cerebrovascular disease account for > 50% of deaths among people aged > 65 years. Because the percentage of elderly people in most populations is rising, blood pressure control in this group is becoming increasingly important. Several large intervention studies in the elderly have demonstrated that antihypertensive medication reduces cardiovascular morbidity and mortality. In addition, the absolute benefits of blood pressure reduction are higher in elderly compared with younger patients. ACE inhibitors are effective and well tolerated in the treatment of hypertension in the elderly. Their success led to interest in alternative ways of blocking the renin angiotensin system, and the subsequent development of angiotensin II (AII) receptor antagonists. Losartan was the first drug in this class to become commercially available. Since then, valsartan has been launched in some markets and others are likely to be launched in the near future. Losartan is effective in the treatment of essential hypertension and has a low incidence of adverse effects. First-dose hypotension is very uncommon and, at the present time, cough does not appear to be an adverse effect of these drugs, although long term tolerability studies are needed to confirm this. Angioedema, a rare but life-threatening adverse effect of ACE inhibitors, has also been associated with losartan. Current data suggest that All receptor antagonists are effective in elderly hypertensive patients, although further data are needed to confirm these findings. At present, All receptor antagonists are likely to be used in hypertensive patients who are intolerant of ACE inhibitors, although this may change with the availability of long term tolerability and clinical outcomes data.
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PMID:Angiotensin II receptor antagonists. Potential in elderly patients with cardiovascular disease. 920 48

ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine > or = 2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develop cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety and efficacy of an ACE inhibitor compared with an angiotensin II type 1 receptor blocking agent is being explored in a prospective randomized trial (Evaluation of Losartan In The Elderly [ELITE]), as well as the safety and pharmacological effectiveness of adding an angiotensin II receptor antagonist to an ACE inhibitor (Randomized Angiotensin receptor antagonists-ACE-inhibitor Study [RAAS]). There may also be a role for the combination of an aldosterone receptor antagonists and an ACE inhibitor in patients with left ventricular systolic dysfunction. Once an ACE inhibitor is administered to a patient with left ventricular systolic dysfunction it should be continued indefinitely. ACE inhibitors may be of value not only in preventing the progression of heart failure but also in reversing endothelial dysfunction and preventing the development of atherosclerosis and its consequences, such as myocardial infarction.
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PMID:ACE inhibitors in heart failure: prospects and limitations. 921 Oct 22

Fosinopril is the prodrug of the active diacid ACE inhibitor fosinoprilat. In patients with heart failure, fosinopril reduces pulmonary capillary wedge pressure, mean arterial blood pressure, mean right atrial pressure and heart rate, and increases stroke volume index and cardiac index. The drug has compensatory dual elimination routes via renal and hepatic systems and accumulates to a lesser extent than enalapril and lisinopril in patients with chronic renal insufficiency with or without heart failure. Comparative studies of 3 or 6 months' duration with fosinopril 10 to 40 mg/day have demonstrated clinical efficacy significantly superior to that of placebo in patients with heart failure [mostly New York Heart Association (NYHA) functional class II or III]. Fosinopril treatment consistently increased exercise duration and improved heart failure symptoms in these patients. Significantly fewer fosinopril than placebo recipients withdrew or were hospitalised because of worsening heart failure. Additionally, significantly more fosinopril than placebo recipients showed improvement, and fewer patients had deteriorated, in terms of NYHA functional class. Fosinopril and enalapril showed similar clinical efficacy over 6 and 12 months' treatment in patients with NYHA functional class II to IV heart failure. As yet, there are no data showing a mortality benefit with fosinopril. Fosinopril was well tolerated in clinical trials in patients with heart failure. Dizziness (11.9 vs 5.4% for placebo), cough (9.7 vs 5.1%) and hypotension (4.4 vs 0.8%) were the most commonly reported adverse events. In 6- or 12-month comparative studies, fosinopril therapy was associated with a lower incidence of dizziness and hypotension, but a higher incidence of vertigo, than enalapril therapy. 0.8% of patients discontinued the drug because of cough, which occurred to a similar extent with fosinopril and enalapril. Thus, based on available clinical evidence, fosinopril is an effective and well tolerated option for the management of patients with heart failure. Although clinical data are limited, fosinopril may be especially useful in patients with renal or hepatic impairment.
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PMID:Fosinopril. A review of its pharmacology and clinical efficacy in the management of heart failure. 921 Oct 84

Postinfectious cough has been drawing attention as a factor involved in the etiology of chronic cough in the United States. In Japan, clinical features of postinfectious chronic cough (PICC) have not been described in detail. We investigated 22 patients with PICC diagnosed by the established criteria (Jpn. J. Allergol. 1995; 44: 1418). All patients were nonsmokers and none received ACE inhibitors. None had a history of atopy or sinus diseases. There were four men and 18 women with a median age of 65 years. These 22 patients underwent clinical examinations including chest roentgenograms, respiratory function tests, eosinophil counts in venous blood, serum IgE titers, antibody titers to Mycoplasma pneumoniae, sputum cytologic findings taken from ten patients, and histological features of bronchial biopsy specimens obtained from two patients; all findings were within normal limits. Clinical course of cough in 20 of the patients with PICC was evaluated using a cough diary. One patient did not keep a cough diary. Ten patients improved with dextromethorphan hydrobromide (D) and oxatomide (O). Three of the remaining 9 patients improved with Bakumondo-to (B) only, 4 with D+O+B, and 2 with D+O+B+ozagrel hydrochloride. The duration of cough before treatment showed a significant correlation with the time from the start of treatment to recovery (r = 0.47, p < 0.05). These results indicate that PICC tends to occur in elderly women and to improve with treatment combining with D, O, and B. We hope to establish a standard therapy for postinfectious chronic cough.
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PMID:[Clinical features of postinfectious chronic cough]. 923 11


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