Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin system has a wide range of physiological actions, and thus interference with the system has attractive therapeutic potential. The orally active angiotensin converting enzyme (ACE) inhibitors have so far been the most successful drugs in this area. They lower arterial pressure both in renovascular and essential hypertension, and their effects are enhanced by concomitant diuretic therapy or dietary salt restriction. Since, in renovascular hypertension, the affected kidney depends on enhanced local generation of angiotensin II to help preserve its function, the circulation and excretory capacity of this kidney may be compromised with ACE inhibition. ACE inhibitors can improve exercise tolerance and diminish cardiac ventricular arrhythmias in patients with heart failure. Because these drugs lower plasma aldosterone, they tend to correct potassium deficiency and hypokalemia, which may have been induced by diuretic treatment. Hypotension can occur with the first dose of ACE inhibitor, especially in sodium-depleted subjects; in patients on prior antihypertensive therapy, particularly if this includes a diuretic; and in the elderly. Not all of the actions of ACE inhibitors are necessarily due to lowering of plasma angiotensin II: accumulation of kinins may be responsible for some of the effects and side effects. Common to all ACE inhibitors are occasional rashes, cough, and, more rarely, angioedema. Apparently peculiar to captopril, and less often seen with the lower doses now employed, are taste disturbance, proteinuria, and marrow depression. ACE inhibitors, should not be used in pregnant women.
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PMID:Converting enzyme inhibitors in the treatment of hypertension. 248 62

Angiotensin-converting enzyme inhibitors (ACEI) constitute an effective and well tolerated class of drugs for the treatment of arterial hypertension. Yet they have been blamed for the occurrence of side-effects the most frequently reported of which are renal function impairment, hypotension and cough. For this reason, the renal function of hypertensive patients has been evaluated after short - and long - term treatment with perindopril. In patients with normal renal function on short-term treatment (1 and 5 days) perindopril produced an increase of renal plasma flow without change in glomerular filtration. In long-term treatment (up to 18 months), no significant change in plasma creatinine level was observed. In old age hypertensive patients or in patients with chronic renal failure glomerular filtration was also preserved, apart from rare cases of creatinine clearance reduction, notably after addition of hydrochlorothiazide. A very slight and clinically not significant rise of kaliemia was noted when perindopril was used as single-drug treatment. Cases of symptomatic hypotension were rare (0.2 p. 100), even in situations of water and salt depletion. Among the other side-effects of ACEI, cough, which has more recently been described, has carefully been looked for. Its incidence has been determined in a double-blind trial comparing perindopril (1.2 p. 100) with captopril (2.4 p. 100). It has also been evaluated in a long-term study involving 632 hypertensive patients, 391 of whom were treated for 1 year; its incidence then was 2.9 p. 100, and drug withdrawal was required in 8 cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Tolerance and safety of the use of perindopril]. 250 18

Ten patients (mean age 53 years; range 37-65 years) with hypertension refractory to standard triple treatment were selected for measurement of blood pressure and echocardiographic evaluation of the left ventricular dimensions before and after 3, 6 and 12 months of captopril therapy. In each patient the dose of captopril was titrated to a maximum of 150 mg t.d.s. (range 25 to 150 mg t.d.s.) with a therapeutic goal of less than or equal to 90 mm Hg diastolic blood pressure. Most patients had added diuretic therapy. Four patients were unable to complete the study, two because of insufficient response to captopril therapy, and two because of side-effects (skin rash and cough). A significant fall in blood pressure was seen after three months of treatment and a reduced blood pressure was still maintained after 12 months. Over the same period, the average number of drugs was reduced from 3.6 to 2.1 per patient. A gradual reduction of septal and posterior wall thickness were noted, from 12.8 and 11.5 mm to 10.0 and 8.5 mm, respectively, after 12 months. Calculated left ventricular muscle mass was insignificantly reduced from 281 to 243 g after 12 months. The present study suggests that in hypertension resistant to conventional multiple therapy, captopril can reduce the blood pressure, and, in the long run it can also induce reversal of left ventricular wall thickening without causing deterioration of left ventricular function.
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PMID:Regression of left ventricular hypertrophy on long-term treatment with captopril of severe hypertensives refractory to standard triple treatment. 253 76

Seventeen patients using angiotensin-converting enzyme (ACE) inhibitors for hypertension were evaluated with baseline spirometry followed by determination of bronchial reactivity by challenge with methacholine. There were nine coughers and eight noncoughers in the study. Among the nine coughers, eight demonstrated bronchial hyperreactivity. Conversely, none of the noncoughers disclosed bronchial hyperreactivity. Eight of the nine coughers were rechallenged two to six months following cessation of ACE inhibitor therapy. Six of these eight showed persistent bronchial hyperreactivity. We conclude that cough is associated with the use of ACE inhibitors in patients with underlying bronchial hyperreactivity. The findings indicate caution in administration of ACE inhibitors in asthmatic patients and those with known bronchial hyperreactivity.
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PMID:Bronchial hyperreactivity and cough due to angiotensin-converting enzyme inhibitors. 253 9

A 65-year-old woman started taking enalapril 2.5 mg daily for hypertension. Twelve days later she complained of a persistent, dry cough. Due to the coughing and a preexisting cystocele, she developed stress incontinence and a marked decline in her functional status. The coughing and incontinence resolved with the discontinuation of enalapril. During a subsequent hospitalization the patient received captopril 6.25 mg twice daily for congestive heart failure. Within 24 hours the dry cough recurred. It resolved with the discontinuation of the drug. Cough is a symptom that is generally not recognized as a drug side effect. However, increasing numbers of case reports document angiotensin-converting enzyme inhibitor-induced cough. Although the actual frequency and mechanism are currently unknown, the dry cough typically begins early in the course of therapy. It may be specific to this pharmacologic class rather than to one individual agent. Age and sex may be contributing factors. While cough has been considered a minor side effect, unnecessary hospitalizations and inappropriate treatments may easily result. Even minor adverse reactions may have an impact on a patient's quality of life.
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PMID:Angiotensin-converting enzyme inhibitor-induced cough. 254 8

We report a 68 yr old woman with hypertension who developed a dry cough on enalapril but not on captopril therapy. Pulmonary function tests, methacholine inhalation challenges, total blood eosinophil counts, and changes in plasma concentrations of prostaglandin E2 and thromboxane B2 did not explain the difference in the adverse reaction between these two angiotensin converting enzyme inhibitors.
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PMID:Cough induced by enalapril but not by captopril. 254 98

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.
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PMID:Clinical experience with lisinopril. Observations on safety and tolerability. 255 Jun 41

A retrospective analysis of records from an outpatient medical practice was undertaken to determine the incidence and features of cough resulting from the use of enalapril maleate. Of 209 patients taking enalapril, 22 (10.5%) required discontinuation of therapy because of an intractable, dry cough. Cough was more than twice as common in women; 16 (14.6%) of 109 women and 6 (6%) of 100 men stopped taking enalapril because of cough. The cough resolved in 21 of 22 patients within 2 weeks of discontinuation of enalapril therapy. When the patients with cough were compared with the others, there was no significant difference in age, smoking status, creatinine levels, enalapril dosage, associated cardiopulmonary disease, or concomitant administration of medications. Among the 187 study patients who did not discontinue taking enalapril because of cough, many developed a persistent, dry cough that to date has not been severe enough to require discontinuation of therapy, after a mean follow-up period of 16 months. The enalapril-induced cough is insidious, dry, persistent, benign, and reversible on discontinuation of therapy. It is important to distinguish enalapril-induced cough from cough resulting from acute illness, reactive airway disease, and congestive heart failure. Optimal clinical application of enalapril in the treatment of hypertension and congestive heart failure will require increased awareness of this incessant cough, which requires discontinuation of the therapy in about 10% of patients.
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PMID:Enalapril-induced cough. 255 77

The respective prevalence of hypertension and asthma is sufficient for their combined existence to be far from rare. The effects of certain antihypertensive drugs, e.g., alpha 2-adrenoceptor agonists, on the bronchi may be either harmful or beneficial. When inhaled, alpha 2-agonists reduce the immediate bronchial response to allergens, whereas when ingested they aggravate the bronchial response to histamine and all the more so when their effect on the central nervous system is greater. Therefore, there has been much interest in agents such as the new oxazoline derivative, rilmenidine, which has less central effects than clonidine, an imidazoline compound of reference. Calcium antagonists inhibit smooth muscle contraction and release of mast cell inflammatory mediators. In asthmatic subjects, their short-term administration leads to a modest improvement in spontaneous bronchial obstruction, has only a partial protective action against various nonspecific or allergenic stimuli, and slightly reinforces the beneficial effect of beta 2-agonists. Beta-adrenoceptor antagonists aggravate bronchial obstruction and nonspecific bronchial hyperreactivity in asthmatic subjects. These harmful effects are dose-dependent, have even been reported after the administration of eyedrops, and are common to all beta-blockers. Angiotensin-converting enzyme inhibitors increase bronchial hyperreactivity in patients who develop cough during treatment and may, in certain cases, worsen or even induce asthma, probably by opposing inactivation by hydrolysis of tachykinins and of bradykinins.
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PMID:Bronchial effects of alpha 2-adrenoceptor agonists and of other antihypertensive agents in asthma. 257 Dec 93

To establish the role of angiotensin converting enzyme inhibitors in the management of hypertension in the elderly, 16 patients were treated with captopril in a randomized double-blind placebo-controlled cross-over study. Clinic blood pressure, ambulatory blood pressure, renal function and mental performance, with emphasis on mood and psychological well-being, were assessed. Twelve patients, aged 73 (+/- 4.4) years, completed the study. The doses of captopril used were 50 mg (11 patients) and 25 mg (one patient) twice daily for 4 weeks. Mean (+/- s.e.m.) clinic sitting blood pressure during captopril therapy was significantly lower than during administration of placebo (172 +/- 4.5/83 +/- 25 versus 188 +/- 4.4/89 +/- 3.4 mmHg; P less than 0.001/P less than 0.05). Mean ambulatory blood pressure was also significantly lower on captopril treatment than during administration of placebo (166 +/- 5.3/87 +/- 1.6 versus 179 +/- 5.1/94 +/- 2.4 mmHg; P less than 0.02/P less than 0.02) and this effect was sustained over the dosing interval. Renal blood flow and mental performance were unaltered by treatment. Gastrointestinal discomfort occurred in two patients, one of whom was withdrawn and cough developed in one patient. We conclude that captopril is effective as monotherapy in lowering blood pressure in the elderly.
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PMID:A double-blind evaluation of captopril in elderly hypertensives. 265 60


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