Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 26-year-old female with Bartter's syndrome associated with Graves' disease is reported. This patient had a history of Graves' disease from the age of 22 and anti-thyroid drug (Methimazole) had been administered for 2 years. Thyroid function returned to normal but general fatigue and polyuria continued. Hypokalemia was diagnosed at 25 years of age and she was referred to our hospital for evaluation. Blood pressure was normal and laboratory data revealed normal thyroid function, hypokalemic alkalosis, high plasma renin activity and high plasma aldosterone concentration. She showed normal pressor sensitivity to norepinephrine infusion, grossly diminished pressor sensitivity to exogenous angiotensin II infusion compared with the normal. A renal biopsy specimen showed juxtaglomerular cell hyperplasia. Electron microscopy confirmed lacis cell (agranular cell) proliferation.
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PMID:Bartter's syndrome--case report. 15 51

1. Intravenous infusion of the individual components of the renin-angiotensin system caused drinking in dogs in water balance. 2. Angiotensin II was the most potent and rapidly acting peptide inducing drinking. The minimum effective rate of infusion was between 8.3 and 16.6 X 10(-12) mole kg-1 min-1 which yield blood levels of angiotensin II that fell well within physiological limits for the dog and were mildly pressor. Angiotensin I and synthetic renin substrate caused less drinking than angiotensin II, and angiotensin III was the least effective dipsogen. 3. Renin caused significant drinking when infused I.V. at a rate of 0.5 u. min-1 for 15 min. Drinking was slower in onset and continued for longer than after other components of the renin-angiotensin system. 4. Within the dose range 1875-15,000 X 10(-12) mole of angiotensin II the amount of water drunk depended more on the rate of infusion than on the duration of the infusion. 5. During an I.V. infusion of angiotensin II lasting 2 hr, the rate of drinking was greatest during the first 15 min. After this declined progressively. 6. A delay of 1 hr after the start of an intravenous infusion of angiotensin II before access to water was allowed, did not significantly reduce the amount of water drunk. Nor did infusion of isotonic saline for 105 min reduce drinking in response to a subsequent infusion of angiotensin II. However, a preload of dilute milk approximately equal in volume to the amount of water normally drunk in response to I.V. angiotensin II significantly reduced drinking. Therefore the dog stopped drinking during long-term infusions of angiotensin II owing to the action of satiety mechanisms and not to tachyphylaxis or fatigue. 7. Intracarotid infusion of angiotensin II, angiotensin I, synthetic renin substrate and angiotensin III, at 40 X 10(-12) mole min-1 also caused drinking. Intakes of water were similar to the intakes after I.V. infusion at six times the arterial rate, except that angiotensin I was relatively less effective by intracarotid infusion than by I.V. infusion. 8. Renin, infused at 0.5 u. min-1 for 15 min, was much less effective by intracarotid infusion than by intravenous. 9. These results are compatible with a role for circulating angiotensin II in the thirst of hypovolaemia or moderate extracellular dehydration.
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PMID:Systemic angiotensin-induced drinking in the dog: a physiological phenomenon. 65 Apr 70

Recently there has been extensive development of orally active angiotensin converting enzyme (ACE) inhibitors in addition to those already marketed, for example, captopril, enalapril, lisinopril and ramipril. It was initially thought that ACE inhibitors were likely to be most useful as antihypertensive agents in conditions in which circulating renin and angiotensin II were elevated. However, it is now clear that they can also lower arterial pressure when plasma renin is not high. In addition, they have beneficial effects in cardiac failure. Thus, captopril, enalapril, lisinopril and ramipril can be used in the treatment of mild to moderate hypertension either alone or in conjunction with diuretics or calcium antagonists. Broadly speaking, efficacy appears to be similar to that of beta-blockers or diuretics. Unfortunately, however, there are no long term studies comparing one ACE inhibitor with another or with other classes of antihypertensive agents. Furthermore, there are no prognostic studies which show that use of ACE inhibitors reduces morbidity or mortality in hypertension. Many new ACE inhibitors are undergoing clinical assessment, including alacepril, cilazapril, fosenopril, perindopril, quinapril and ramipril. The drugs vary, in that some exist in the active form whereas others are prodrugs which are converted to the active agent following absorption. In addition they each possess one of several ligands, for example, carboxyl, phosphinyl or sulfhydryl groups, and so vary in their affinity for ACE. Although many of these agents are renally excreted, a small number are metabolised via the liver (e.g. quinapril and spirapril) and this may prove advantageous in the presence of renal impairment. In common with captopril and enalapril, the new ACE inhibitors inhibit the renin-angiotensin system and initial results suggest that they are effective in lowering blood pressure in essential hypertension. Furthermore, they reduce systemic vascular resistance in the absence of a reflex tachycardia. There are a number of adverse effects which are attributable to the pharmacological mechanism of the ACE inhibitors as a group; these include hypotension, particularly in patients with high renin levels, prior diuretic use, renal impairment or in the elderly. Additional adverse effects may relate to chemical structure. The high incidence of adverse effects noted in early studies related to excess dosage and to the presence of a sulfhydryl group, which the more recently developed ACE inhibitors lack. The adverse effects most commonly reported with established and new ACE inhibitors include headache and fatigue, cough, skin rashes, hypotension and diarrhoea. As a group, ACE inhibitors have an acceptable but not negligible adverse effect burden.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin converting enzyme inhibitors and moderate hypertension. 222 19

The renin-angiotensin-aldosterone system plays an important role in the development of congestive heart failure (CHF). In patients with chronic heart failure, angiotensin-converting enzyme (ACE) inhibitors, such as captopril, enalapril, and quinapril, have been shown to improve hemodynamics, reduce symptoms of fatigue and dyspnea, increase exercise capacity, correct hyponatremia, reduce diuretic requirements and ventricular arrhythmias, and conserve potassium and magnesium. ACE inhibitors reduce circulating levels of angiotensin II and aldosterone and may reduce plasma norepinephrine and vasopressin levels. They are equally effective in patients with mild to moderate heart failure and in patients with severe cardiac impairment. ACE inhibitors are at least as beneficial as digitalis in patients with mild heart failure, and they may even be considered as first-line therapy. Promising results have also been obtained in patients with myocardial infarction, in whom long-term therapy with ACE inhibitors has prevented an increase in heart size. ACE inhibitors improve prognosis in patients with severe heart failure and in patients with hyponatremia; the question of effect on survival in mild to moderate heart failure has yet to be answered.
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PMID:ACE inhibitors in congestive heart failure. 267 Feb 20

The effect of the converting enzyme inhibitor captopril as long term treatment was investigated in 14 patients with severe congestive heart failure in a double blind trial. Captopril reduced plasma concentrations of angiotensin II and noradrenaline, with a converse increase in active renin concentration. Effective renal plasma flow increased and renal vascular resistance fell; glomerular filtration rate did not change. Serum urea and creatinine concentrations rose. Both serum and total body potassium contents increased; there were no long term changes in serum concentration or total body content of sodium. Exercise tolerance was appreciably improved, and dyspnoea and fatigue lessened. Left ventricular end systolic and end diastolic dimensions were reduced. There was an appreciable reduction in complex ventricular ectopic rhythms. Adverse effects were few: weight gain and fluid retention were evident in five patients when captopril was introduced and two patients initially experienced mild postural dizziness; rashes in two patients did not recur when the drug was reintroduced at a lower dose; there was a significant reduction in white cell count overall, but the lowest individual white cell count was 4000 X 10(6)/l. Captopril thus seemed to be of considerable value in the long term treatment of severe cardiac failure.
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PMID:Captopril in heart failure. A double blind controlled trial. 638 12

This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered "drug-related" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.
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PMID:Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. 771 81

Valsartan competitively and selectively inhibits the actions of angiotensin II at the AT1 receptor subtype which is responsible for most of the known effects of angiotensin II. In clinical trials in patients with mild to moderate essential hypertension valsartan was as effective as losartan, lisinopril, enalapril, amlodipine and hydrochlorothiazide. Addition of the latter reduced blood pressure in patients who did not respond sufficiently to valsartan monotherapy. Preliminary data also suggest valsartan may be effective in patients with severe essential hypertension. The drug was as effective as lisinopril as treatment for mild to moderate essential hypertension in patients with renal insufficiency and did not worsen renal function. Headache, dizziness and fatigue were the most common adverse events in placebo-controlled studies; the incidence of these adverse events was not significantly different between placebo and valsartan recipients. Compared with ACE inhibitors, valsartan was associated with a significantly lower incidence of dry cough. Thus, valsartan is an effective treatment for mild to moderate essential hypertension and may be particularly useful in patients who experience persistent cough during ACE inhibitor therapy.
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PMID:Valsartan. A review of its pharmacology and therapeutic use in essential hypertension. 925 84

Losartan is a novel orally active nonpeptidal antihypertensive agent that specifically blocks the angiotensin II type 1 receptor. This paper compares the short- and long-term safety and tolerability of losartan with those of placebo. Approximately 3800 patients with mild-to-severe essential hypertension were enrolled in 16 double-masked and 4 open clinical trials worldwide. Of these, approximately 2900 were treated with losartan either alone or in combination with other antihypertensive drugs. These trials included patients with diabetes mellitus (n = 133). An additional 5 trials enrolled hypertensive patients with compromised renal function (n = 115) or heart failure (n = 220). Losartan dosages primarily ranged from 10 to 150 mg once daily, with most patients receiving 50 to 100 mg per day. Hypertension trials generally lasted 12 weeks. The most frequently reported adverse events were headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurred more frequently (> or = 1%) in the losartan-treated groups. Cough occurred in 3.1% of patients treated with losartan and 2.6% of patients treated with placebo. The overall incidence of clinical and laboratory adverse events in the losartan- and placebo-treated groups was similar among patients with hypertension and either diabetes mellitus, renal impairment, or heart failure. The data suggest that losartan can be safely administered in hypertensive patients with concomitant illnesses. It can be considered for first-line therapy and is suitable as an alternative therapy in patients already experiencing side effects with other agents.
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PMID:Clinical safety and tolerability of losartan. 937 6

Prostacyclin (or epoprostenol), an arachidonic acid metabolite, is an effective treatment for patients with primary pulmonary hypertension. Interruption of chronic prostacyclin infusion can result in recurrent symptoms of dyspnea and fatigue. The etiology of this phenomenon is unknown. We hypothesized that sympathoadrenal activation could lead to increased vascular tone after abrupt termination of the infusion. To evaluate this effect, we monitored six chronically instrumented, awake sheep during and after infusion of prostacyclin. Prostacyclin decreased mean arterial pressure (MAP) by 14% and increased cardiac output by 33%. After the infusion ceased, MAP rebounded 23% above baseline, and cardiac output decreased by 28% from peak values within 10 min. We were unable to demonstrate an increase in norepinephrine levels after cessation of prostacyclin, nor did alpha-adrenergic blockade affect postinfusion hemodynamics. However, plasma renin activity increased >10-fold at peak infusion and remained elevated for up to 2 h after discontinuation of prostacyclin. Coinfusion of the angiotensin II-receptor antagonist L-158,809 resulted in complete abrogation of the postcessation rise in MAP. We conclude that renin-angiotensin system activation is primarily responsible for systemic hypertension occurring after abrupt cessation of prostacyclin infusion in sheep and that angiotensin II receptor blockade prevents this response. Our data do not support a role for sympathetic nervous system activation in the systemic pressor response after prostacyclin infusion.
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PMID:Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep. 968 53

Valsartan/hydrochlorothiazide (HCTZ) combines an angiotensin II AT1 receptor blocker with a thiazide diuretic to produce additive blood pressure reductions without major effects on heart rate. HCTZ did not significantly alter valsartan pharmacokinetics; during combination therapy, HCTZ pharmacokinetics differed from those seen with HCTZ monotherapy. In clinical trials in patients with essential hypertension, adding HCTZ 12.5 or 25 mg/day to valsartan 80 mg/day resulted in a greater blood pressure reduction than increasing the valsartan dosage from 80 to 160 mg/day. The valsartan/HCTZ combination was generally more effective than either drug given alone. Efficacy of the combination was maintained during up to 3 years of treatment. Valsartan/HCTZ was well tolerated in both short and long term trials. The most common adverse events were dizziness, headache and fatigue. The overall incidence of adverse events with the combination was similar to that with placebo. HCTZ-induced hypokalaemia was less common during combination therapy.
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PMID:Valsartan/hydrochlorothiazide. 1035


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