Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diuretics can result in various undesired biochemical changes, such as impotence, skin rashes, nausea, dizziness and lethargy as well as subjective side effects. The side effects are mostly predictable, their effects depending on both the circulatory blood volume and on the transport of water and solute in the renal tubules. Two of the commonest side effects are mild hypovolaemia, when any diuretic is used, and mild hypokalaemia when the non-potassium-sparing diuretics, such as thiazides and frusemide are used. Its occurrence is dose dependent and can be corrected by potassium supplements, but potassium-retaining diuretics, which also correct the often associated fall in serum magnesium, are preferable. Many reports link hypokalaemia with cardiac arrhythmias, but some dispute this association in the absence of the concomitant use of digoxin. Hyponatraemia rarely occurs, but can be life threatening. Calcium excretion is markedly reduced, but unlike other electrolyte disturbances from diuretics, this may be valuable: some suggest diuretics have an anti-osteoporotic action. Diuretics increase glucose and insulin resistance and should be used sparingly in diabetics. They rarely cause a non-ketotic hyperosmolar coma. Urate is raised, but clinical gout is not common. Cholesterol elevation has been reported in some studies, but long-term studies indicate that lipid changes are minor. Other rare side effects are not predictable from their pharmacological actions and these include the occurrence of skin rashes, thrombocytopenia, pancreatitis and interstitial nephritis; and ototoxicity from frusemide.
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PMID:Adverse reactions to diuretics. 148 14

A large hypertensive population of patients in general practice was used to assess the tolerability of nifedipine in previously untreated patients and was compared with other antihypertensive drugs in previously treated patients. A total of 3972 patients with a sitting diastolic blood pressure between 95 and 115 mmHg were treated with 20 mg nifedipine twice daily for 1 month. In non-responders the dose was increased to 40 mg twice daily for a second month; responders continued to take 20 mg twice daily. A total of 2772 patients had been previously untreated for hypertension, whereas 857 had previously been treated with beta-blockers alone or in combination and 346 had received diuretics alone or in combination. Adverse events were recorded for 28 days prior to treatment being initiated with or changed to nifedipine and for two 28-day nifedipine treatment periods. Flushing and headache, which diminished with time, occurred during nifedipine treatment. Ankle oedema did not diminish with time. Reductions were seen in occurrences of dyspnoea, impotence, lethargy and cold extremities.
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PMID:General practice data derived tolerability assessment of antihypertensive drugs. 280 16

Although beta blockers are effective for the treatment of angina pectoris, chronic adverse effects produced by these agents--including lethargy, fatigue, and male impotence--can adversely affect patient acceptance and treatment compliance. To assess the clinical effects of switching from anti-anginal treatment with beta blocker only (phase I) to half-dose beta blocker plus the calcium blocker nifedipine (phase II) or nifedipine alone (phase III), 18 patients with chronic stable angina pectoris and side effects to beta blockers were evaluated in a 12-week, open-label trial. Three patients did not complete the study, one secondary to new unstable angina and two secondary to nifedipine side effects. Of the 15 patients completing the trial (13 men and two women; mean age, 54 +/- 5 [SEM] years), all sequentially participated in the one-month phases. Weekly angina frequency assessed from patient diaries was significantly less for treatment with nifedipine only (phase III) as compared with beta blocker (phase I) (1.7 +/- 1 versus 3.9 +/- 1 episodes per week), while phase II was not significantly different. Exercise test time was maintained throughout all phases (phase I, 457 +/- 39; phase II, 458 +/- 40; and phase III, 498 +/- 48 seconds, p not significant). All 15 patients in phase I (100 percent) had side effects to beta blockers, but these side effects were lessened in 12 patients (80 percent) in phase II and 13 patients (86 percent) in phase III, with total alleviation of symptoms in two patients (13 percent) in phase II, and eight patients (53 percent) in phase III. Thus, in patients with side effects to beta blockers, switching to nifedipine is associated with a significant reduction in beta blocker adverse symptoms and equal anti-anginal efficacy.
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PMID:Alternative medical treatment for patients with angina pectoris and adverse reactions to beta blockers. Usefulness of nifedipine. 287 34

In the United States, the drugs most commonly used to treat peptic ulcer disease are antacids and the H2-receptor antagonists cimetidine and ranitidine. Other available agents include anticholinergics and the coating agent sucralfate. Investigational drugs such as colloidal bismuth, carbenoxolone, prostaglandins, the tricyclic compound pirenzepine, and substituted benzimidazoles are not available for use in the United States. Most of the commercially available and investigational compounds have similar efficacy; therefore the optimal drug may be the one associated with the fewest adverse effects and the most convenient dosing regimen. Cimetidine causes a small number of adverse effects, including neuropsychiatric disorders, gynecomastia, impotence, loss of libido, elevation of serum creatinine and serum transaminases concentrations, and drug interactions. Some of these reactions have been of clinical significance. Presently, there are rare reports of gynecomastia, bradycardia, inhibition of acetylcholinesterase, headache, lethargy, diarrhea, and rash in patients receiving ranitidine. Antacids can produce either diarrhea or constipation and have been associated with low serum phosphorus concentrations, and metabolic alkalosis. Anticholinergics, especially in elderly or debilitated patients, can cause central nervous system disorders, intestinal atony, or urinary retention. Sucralfate may cause constipation, diarrhea, nausea, and headache. The investigational agents have their own side effect profiles. The adverse effects of anticholinergics make them unattractive therapeutic choices, and antacids and sucralfate have inconvenient dosing requirements compared with some equally efficacious alternatives. In addition, clinical experience with sucralfate in the United States is limited. The safety record of cimetidine is admirable. As clinical experience with ranitidine increases, currently unrecognized adverse effects may be reported. However, based on current data, ranitidine is as effective as cimetidine and is associated with a lower incidence of side effects.
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PMID:Problems associated with medical treatment of peptic ulcer disease. 609 62

Nadolol (N) titrated from 80 to 240 mg or bendroflumethiazide (B) 5 to 10 mg, or the combination (B + N), were randomly assigned double-blind to 365 men with pretreatment diastolic blood pressures (BP) of 95 to 114 mm Hg. After 12 weeks of treatment, a diastolic BP of less than 90 mm Hg was achieved in 49% who received N, 46% who received B and 85% who received B + N. With N, the diastolic BP decreased more in whites than in blacks; with B, this racial trend was reversed. Side effects were infrequent; the most common were impotence, lethargy, weakness and postural dizziness, which occurred more often with B than with N. Addition of hydralazine, 25 to 100 mg twice daily, controlled diastolic BP at a level of less than 90 mm Hg in approximately 60% of those previously uncontrolled. N, and especially B + N, provided an efficacious once-daily treatment for systemic hypertension, and addition of hydralazine was effective in most nonresponders.
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PMID:Efficacy of nadolol alone and combined with bendroflumethiazide and hydralazine for systemic hypertension. 635 51

The benefit of any medical intervention, particularly drug therapy, must be weighed against its cost. These costs are not only dollar expenditures but effects on lifestyle and overall health. Diuretic therapy for hypertension has been in use long enough to allow long-term clinical evaluation. It is clear from the numerous prospective drug intervention trials involving hypertensive patients that diuretic therapy is not free of "costs." Aside from the fact that 15 to 20% of diuretic-treated patients reportedly drop out of trials because of side effects, including exertional dyspnea, fatigability, lethargy and impotence, numerous metabolic derangements have been reported with these drugs, i.e., potassium, uric acid, lipid, sodium, glucose and magnesium alterations. Perhaps most important are the changes in lipid fractions, which may be responsible for the failure of antihypertensive therapy to decrease the risk of coronary heart disease. Thus, although diuretics are somewhat less expensive than other antihypertensive drugs in terms of dollars, their overall costs are high. The major alternatives, such as the alpha-blocker prazosin or the central nervous system agent clonidine, are preferable, do not impair a patient's lifestyle and are recommended to be used along with changes in diet and an exercise program for control of mild to moderate hypertension.
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PMID:Diuretic therapy for mild hypertension: the "real" cost of treatment. 642 Nov 37

Reserpine in different doses was assigned in random, double-blind fashion to 329 patients with mild to moderate hypertension who had not achieved normotension with chlorthalidone therapy alone. The additional reduction of BP averaged 11.0/10.4 mm Hg with chlorthalidone, 50 mg, plus reserpine, 0.25 mg (C 50+R 0.25); 9.5/9.4 mm Hg with C 50+R 0.125; 6.4/8.5 mm Hg with C 50+R 0.05; and 9.9/9.6 mm Hg with C 25+R 0.125. The percentage of patients in whom control was achieved at diastolic BP less than 90 mm Hg and at least 5 mm Hg below baseline with either chorthalidone alone or with reserpine added was 65% with C 50+R 0.25, 69% with C 50+R 0.125, 58% with C 50+R 0.05, and 56% with C 25+R 0.125. Side effects of lethargy and impotence noted by patients with the 0.05-mg dose of reserpine were only one third of those noted with the 0.25-mg dose, although the incidence of other side effects did not differ. These results indicate that hypertension in many persons can be controlled by less than customary doses of reserpine in combination with a diuretic.
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PMID:Low doses v standard dose of reserpine. A randomized, double-blind, multiclinic trial in patients taking chlorthalidone. 675 48

More than 1200 patients who received pindolol for the treatment of hypertension, angina pectoris, and various arrhythmias in studies conducted in the United States were included in the New Drug Application submitted to the FDA. Nearly 1000 of these patients received pindolol as monotherapy. The side effects reported were generally transient and of mild or moderate severity. The most frequently reported side effects seen after pindolol administration, compared to those seen after placebo, were in decreasing order of incidence: headache, dizziness, insomnia, muscle pain, fatigue, weakness, nervousness, joint pain, edema, nausea, and muscle cramps. Other side effects that occurred more frequently with pindolol than with placebo but at a rather low incidence induced weight gain, bizarre dreams, visual disturbances, lethargy, and diarrhea. Nasal congestion, throat discomfort, nocturia, impotence, pruritus, anxiety, hypotension, bradycardia, and heart failure occurred only rarely. Of the 323 patients who received pindolol alone for the treatment of mild to moderate hypertension, only 20 (6.2%) were withdrawn from the study because of side effects. Overall, 3.4% of the patients treated with pindolol were withdrawn because of side effects, most of which involved the central nervous system, that is, insomnia, anxiety, dizziness, and headache. However, a few patients manifested some edema and weight gain while receiving pindolol alone. Review of the side effects data did not reveal a tendency for the incidence of side effects to be dose related. One placebo-controlled, double-blind study designed to evaluate the fixed dosages of 15, 30, and 60 mg in the treatment of mild to moderate hypertension suggested that only the incidences of insomnia and nervousness increased with increasing doses. However, these side effects were generally transient and of mild or moderate severity. The evidence indicates that pindolol has an acceptable safety profile and that any side effects that appear are generally well tolerated and disappear with continued treatment.
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PMID:Adverse reactions to pindolol administration. 704 82

Haemochromatosis is one of the most common inborn errors of metabolism. In prospective epidemiological studies the frequency of haemochromatosis is 0.0037 (76/20333 subjects) for homozygotes which corresponds to a gene frequency of 0.061 and a frequency of heterozygotes of 0.115. Abnormality in liver function tests, weakness and lethargy, skin hyperpigmentation, diabetes mellitus, arthralgia, impotence and ECG abnormalities are the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. Survival analyses in long-term studies showed that in the absence of cirrhosis and diabetes, iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Patients with massive and long-lasting iron overload had a worse prognosis than those with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence insulin-dependent diabetes. Most deaths in patients with hereditary haemochromatosis were caused by liver cancers which often occurred many years after complete iron removal. In patients with haemochromatosis, liver cirrhosis, cardiomyopathy, and diabetes mellitus are also significantly more frequent causes of deaths when compared with the general population. Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.
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PMID:Clinical spectrum and management of haemochromatosis. 788 Nov 58

The goa-1 gene encoding the alpha subunit of the heterotrimeric guanosine triphosphate-binding protein (G protein) Go from Caenorhabditis elegans is expressed in most neurons, and in the muscles involved in egg laying and male mating. Reduction-of-function mutations in goa-1 caused a variety of behavioral defects including hyperactive movement, premature egg laying, and male impotence. Expression of the activated Go alpha subunit (G alpha o) in transgenic nematodes resulted in lethargic movement, delayed egg laying, and reduced mating efficiency. Induced expression of activated G alpha o in adults was sufficient to cause these phenotypes, indicating that G alpha o mediates behavior through its role in neuronal function and the functioning of specialized muscles.
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PMID:Participation of the protein Go in multiple aspects of behavior in C. elegans. 788 45


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