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)

Angiotensin II type 1 (AT1) receptor antagonists inhibit the renin-angiotensin system more completely than ACE inhibitors, and do not increase bradykinin levels as ACE inhibitors do. ACE inhibitors have been proven to increase survival and improve quality of life in patients with congestive heart failure (CHF). At the 48-week follow-up of the Evaluation of Losartan in the Elderly (ELITE) Study, the AT1 receptor antagonist losartan (at a dosage of 50 mg/day) was found to be superior to captopril 50 mg 3 times daily in terms of its effects on total mortality, total mortality and/or hospitalisation for CHF, and hospitalisation for any reason. Hospitalisation for CHF was the same for both drugs. Adverse effects occurred in 12 and 21% of those receiving losartan and captopril, respectively. Cough, rash, angioedema or taste disturbances/reduced appetite prompted the cessation of drug treatment in 0 and 7% of those receiving losartan and captopril, respectively. Until additional data are available, this author recommends that elderly patients with CHF and an abnormal or normal left ventricular ejection fraction, and who are unable to tolerate ACE inhibitors, should receive losartan 50 mg/day.
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PMID:The ELITE Study. What are its implications for the drug treatment of heart failure? Evaluation of Losartan in the Elderly Study. 963 91

Understanding the mechanism of action and the pharmacokinetic properties of vasodilatory drugs facilitates optimal use in clinical practice. It should be kept in mind that a drug belongs to a class but is a distinct entity, sometimes derived from a prototype to achieve a specific effect. The most common pharmacokinetic drug improvement is the development of a drug with a half-life sufficiently long to allow an adequate once-daily dosage. Developing a controlled release preparation can increase the apparent half-life of a drug. Altering the molecular structure may also increase the half-life of a prototype drug. Another desirable improvement is increasing the specificity of a drug, which may result in fewer adverse effects, or more efficacy at the target site. This is especially important for vasodilatory drugs which may be administered over decades for the treatment of hypertension, which usually does not interfere with subjective well-being. Compliance is greatly increased with once-daily dosing. Vasodilatory agents cause relaxation by either a decrease in cytoplasmic calcium, an increase in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors, angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids and NO donors. Despite chemical differences, the pharmacokinetic properties of calcium antagonists are similar. Absorption from the gastrointestinal tract is high, with all substances undergoing considerable first-pass metabolism by the liver, resulting in low bioavailability and pronounced individual variation in pharmacokinetics. Renal impairment has little effect on pharmacokinetics since renal elimination of these agents is minimal. Except for the newer drugs of the dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine, nisoldipine and nitrendipine, the half-life of calcium antagonists is short. Maintaining an effective drug concentration for the remainder of these agents requires multiple daily dosing, in some cases even with controlled release formulations. However, a coat-core preparation of nifedipine has been developed to allow once-daily administration. Adverse effects are directly correlated to the potency of the individual calcium antagonists. Treatment with the potassium channel opener minoxidil is reserved for patients with moderately severe to severe hypertension which is refractory to other treatment. Diazoxide and hydralazine are chiefly used to treat severe hypertensive emergencies, primary pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors prevent conversion of angiotensin-I to angiotensin-II and are most effective when renin production is increased. Since ACE is identical to kininase-II, which inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and cardioreparative effects by preventing and reversing cardiac fibrosis and ventricular hypertrophy in animal models. The predominant elimination pathway of most ACE inhibitors is via renal excretion. Therefore, renal impairment is associated with reduced elimination and a dosage reduction of 25 to 50% is recommended in patients with moderate to severe renal impairment. Separating angiotensin-II inhibition from bradykinin potentiation has been the goal in developing angiotensin-II receptor antagonists. The incidence of adverse effects of such an agent, losartan, is comparable to that encountered with placebo treatment, and the troublesome cough associated with ACE inhibitors is absent.
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PMID:Clinical pharmacokinetics of vasodilators. Part I. 964 8

The effects of 2 fixed antihypertensive combination drugs on blood pressure and aortic elastic properties were compared in 2 parallel groups. Twenty-six patients for 6 months received a calcium antagonist plus ACE inhibitor (verapamil SR 180 mg/trandolapril 1 mg (Vera/Tran)) and 25 patients a beta-adrenoceptor antagonist plus diuretic (metoprolol 100 mg/hydrochlorothiazide 12.5 mg (Meto/HCTZ)). In addition to blood pressure (SBP, DBP), carotidofemoral pulse wave velocity (PWV) was assessed non-invasively. Total peripheral resistance (TPR) was determined from cardiac output derived by electrical impedance cardiography. Sitting DBP decreased for -14.4 mmHg following Vera/Tran compared with -9.2 mmHg following Meto/HCTZ (p = 0.02 for difference between treatments). Blood pressure was normalized (i.e. DBP < 90 mmHg) in 69% of patients with Vera/Tran and in 52% with Meto/HCTZ. PWV was lowered with Vera/Tran to a higher extent than with Meto/HCTZ (differences between group means -0.46 to -0.98 m/sec, statistically not significant). Vera/Tran induced a decrease in TPR of about 15% of baseline values, whereas Meto/HCTZ showed no influence. Treatment-related adverse events following Meto/HCTZ were bradycardia and associated symptoms; following Vera/Tran these were cough and edema in 1 case each. In the Meto/HCTZ group, there were more withdrawals/drop-outs (9/25) than in the Vera/Tran group (2/26). The somewhat more intense reduction in PWV with Vera/Tran is indicative of an increase in aortic elastic properties associated with the more potent decrease in BP. In the present study, the combination of calcium antagonist plus ACE inhibitor was found to be an effective and well tolerated antihypertensive regimen and in these respects appears to have some advantages compared with a combination of beta-blocker plus diuretic.
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PMID:Blood pressure and aortic elastic properties--verapamil SR/trandolapril compared to a metoprolol/hydrochlorothiazide combination therapy. 972 95

The present study investigated the effect of the new ACE-inhibitor moexipril versus the beta 1-adrenergic blocker atenolol on metabolic parameters, adverse events (AEs) and sitting systolic (SSBP) and sitting diastolic blood pressure (SDBP) in obese postmenopausal women with hypertension (stage I and II). After a 4-week placebo run-in phase, 116 obese, postmenopausal women with primary hypertension were randomised into two treatment groups receiving once daily dosages of either moexipril 7.5 mg or atenolol 25 mg initially (mean age: 57 +/- 7 years in both groups; mean weight: 94 kg in the moexipril group and 89 kg in the atenolol group, corresponding to a body mass index (BMI) of 35.2 kg/m2 and 34.1 kg/m2 in both groups, respectively). After 4 and 8 weeks, the dosages were uptitrated to moexipril 15 mg, or if necessary to moexipril 15 mg/hydrochlorothiazide (HCTZ) 25 mg, or to atenolol 50 mg and atenolol 50 mg/HCTZ 25 mg, in patients whose blood pressure was not sufficiently controlled. At endpoint, metabolic parameters (total cholesterol, triglycerides, LDL, HDL, glucose, insulin) were not significantly altered in either treatment group. Most frequent adverse events under monotherapy (moexipril/atenolol) were asthenia (5.3/13.0%), headache (13.2/21.7%), cough (7.9/6.5%), pharyngitis (21.1/8.7%) and peripheral oedema (5.3/13.0%). Overall at least one AE was reported in 66% of the patients treated with moexipril and in 78% of those treated with atenolol. Reduction of SSBP/SDBP at endpoint was 14.7 +/- 1.9/10.0 +/- 1.1 and 8.7 +/- 1.9/8.4 +/- 1.1 mmHg after treatment with moexipril and atenolol, respectively. The results showed that moexipril and atenolol are equally effective in reducing blood pressure without adversely affecting blood lipids and carbohydrate metabolism.
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PMID:Comparison between moexipril and atenolol in obese postmenopausal women with hypertension. 981 86

Most antihypertensives have advantages and disadvantages. The ideal antihypertensive drug should be effective in lowering blood pressure, well tolerated, safe in the long term, and easy to use. Ideally, it should be relatively inexpensive. Most importantly it should reduce the risk of the adverse effects of high blood pressure, such as myocardial infarction, sudden death, stroke, heart failure, renal damage, and retinal changes. Most antihypertensive drugs effectively reduce blood pressure, are available as once daily preparations, and are safe long-term. Unfortunately, most antihypertensive drugs cause adverse effects in some patients and for few drugs is there good evidence that they protect the heart, the brain, the kidney, and the eye? Reducing the effects of Angiotensin II (using an ACE inhibitor) has been shown to reduce the incidence of coronary events, sudden death, heart failure, renal damage, and fundal changes. AT1 blocking drugs offer the same pharmacological advantages but also very good tolerability, in particular no cough. Therefore, they have the potential to meet all the criteria for an ideal antihypertensive drug.
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PMID:Therapeutic advantages of AT1 blockers in hypertension. 983 62

A number of new classes of antihypertensive drugs have become available in the recent years which appear to hold therapeutic potential for better management of hypertension. Losartan, an angiotensin II receptor antagonist, does not produce cough which is classically seen with ACE inhibitors. Fenoldopam, a dopamine D1-receptor agonist, has a rapid and short duration of action and is ideally suited by intravenous infusion for quick control of BP in hypertensive emergencies. Kentaserin, a serotonin (5-HT2A) receptor antagonist, has a long duration of action and can be given once daily. It has the added benefit of having antiplatelet effect. Monatepil, a dual alpha-receptor and calcium channel blocker, has potent antihypertensive effect, lowers serum cholesterol and also has antiatherosclerotic effect. Dual ACE and endopeptidase inhibitor, such as alatriopril, has a "broad spectrum" antihypertensive effect and may be effective in majority of hypertensive patients. Many other classes of antihypertensive drugs are still in the investigative stage, and their therapeutic potentials and safety need to be ascertained in long-term controlled clinical trials.
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PMID:New classes of antihypertensive drugs: therapeutic potentials. 1005 49

Fourteen cases (13 pleural and one intrapulmonary) of solitary fibrous tumors (SFTs) (the so-called fibrous mesothelioma) were studied. The lesions occurred more in females (nine cases) than males (five cases). The age of patients ranged from 44 to 73 years old (median 60 years). The tumors presented as cough with or without blood-tinged sputum, exertional dyspnea, chest pain, nausea, body weight loss, fever, or as asymptomatic masses detected by routine chest radiograph. Two patients with huge (tumor larger than 20 cm) malignant tumors had accompanying pleural effusion and one associated with hypoglycemia. Ten benign tumors measured 2-11 cm (median size 7 cm) while the remaining four histologically malignant ones measured 20-30 cm in size. All of them were well circumscribed and thinly encapsulated. Hemorrhage and necrosis were more frequently seen in the malignant tumors. Histologically, these lesions were characterized by 'patternless pattern' with occasional hemangiopericytic features (three cases). The tumor cells were all immunoreactive for vimentin, CD 34, and focally actin-positive in one case, but not for keratin, desmin, S-100 protein, carcinoembryonic antigen, alpha 1-ACT and F VIII-related antigen, supported a primitive mesenchymal origin. p53 protein was expressed in two of the malignant cases. Proliferating cell nuclear antigen stain was positive with 50 and 80% of the labeling index in the benign and malignant tumors, respectively, but retinoblastoma gene protein was negative in all tumors. This analysis confirmed the relationship between histological malignant SFTs and tumor size, cellularity, mitotic activity, necrosis and tumor suppressor gene expression. However, the clinical behavior was unpredictable. Complete respectability seemed to be the most important indicator of clinical outcome in the less aggressive tumors.
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PMID:Thoracic solitary fibrous tumor: clinical and pathological diversity. 1010 Jan 46

In cancer and rheumatoid arthritis, granulocytosis is often observed and indicates the progress of disease. We developed a granulocytapheresis system to permit granulocyte reduction. Cellulose acetate was found to be a selective and effective adsorbent. In an in vivo study using an acetate bead column, 9.2 x 10(8) leukocytes were collected. Initially, granulocytapheresis was applied to terminal patients or those with stage IV cancer. Pain, cough and bloody sputum were reduced in spite of no decrease in tumor size. Granulocytapheresis appears to prevent inflammatory damage in or around the tumor site. This granulocyte reduction technique was also applied to patients with rheumatoid arthritis. The Lansbury index markedly improved after treatment. As cytokines and adhesion molecules might contribute to symptoms, granulocytapheresis may be useful in improving the "Quality of Life" in these diseases.
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PMID:Extracorporeal granulocytapheresis for cancer and rheumatoid arthritis. 1016 55

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the patients under and over 65 years of age recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final 6 weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). Similar mean changes in blood pressure from baseline were evident with each treatment. The elderly subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and safe in elderly hypertensive patients. The combination of eprosartan and HCTZ is also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. Compared with eprosartan enalapril was associated with an increased risk of cough. These results suggest that, irrespective of age, patients may be less likely to discontinue treatment with eprosartan than with an ACE inhibitor.
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PMID:Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group. 1021 6

Dry cough is a troublesome side-effect associated with certain antihypertensive agents that act by modulating aspects of the renin-angiotensin-aldosterone system. The incidence of dry cough associated with two of these therapies, the novel All receptor antagonist telmisartan and the ACE inhibitor lisinopril, was assessed in a multicentre, randomised, parallel-group, double-blind, placebo-controlled, 8-week study of 88 patients with mild to moderate hypertension who previously demonstrated ACE inhibitor-related cough. Patients received either telmisartan 80 mg, lisinopril 20 mg, or placebo once daily. Cough incidence, measured at each visit by a self-administered symptom assessment questionnaire, was significantly higher with lisinopril (60%) than with telmisartan (15.6%) or placebo (9.7%). A visual analogue scale demonstrated a similar trend for cough frequency. Thus the incidence of cough with telmisartan 80 mg is significantly less than that seen with lisinopril 20 mg and is comparable to placebo.
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PMID:The incidence of cough: a comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. Telmisartan Cough Study Group. 1034 43


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