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

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.
 ...
PMID:Problems associated with medical treatment of peptic ulcer disease. 609 62

Thirty-eight metastatic breast cancer patients were treated with aminoglutethimide. All patients had progressive metastatic disease following initial response to Tamoxifen therapy. Thirty-two patients were evaluable for response, of these, two patients (6%) had complete remission, 13 patients (41%) had partial response, and six patients (19%) had stable disease. Eleven patients (34%) had progressive disease. The most common side effects were transient skin rash, lethargy or dizziness. Four patients' (11%) treatment was discontinued because of either skin rash or dizziness within the first two weeks of the study. These data show that aminoglutethimide is an effective agent following tamoxifen therapy.
 ...
PMID:Treatment of advanced breast cancer with aminoglutethimide after therapy with tamoxifen. 618 Aug 20

Two hundred and thirteen unselected postmenopausal women with advanced breast cancer were treated with aminoglutethimide and hydrocortisone. There were 6 complete responses (CR), 47 partial responses (PR), 25 stable disease (SD) and 3 mixed response. Overall objective response rate was 28%, and with SD 41%. Median duration of objective response was 14 months. Years after menopause, age and tumour-free interval did not affect response rates. Main side-effects were drowsiness and lethargy (33%), rash (23%) and nausea (15%). Eleven patients (5%) stopped treatment because of toxicity. Median survival from start of treatment was 28 months and was the same for CRs, PRs and SD, compared with 10 months for progressive disease (P less than 0.001). Median survival from first metastasis was 43 months for PR/CR, 40 months for SD (not significantly different) and 22 months for progressive disease (P less than 0.001). Aminoglutethimide is an effective endocrine therapy in advanced postmenopausal breast cancer, particularly for bone deposits. Disease stabilization is associated with symptomatic and survival benefit similar to CR/PR.
 ...
PMID:Aminoglutethimide for the treatment of advanced postmenopausal breast cancer. 668 69

Altogether 117 patients with advanced breast cancer were treated with either tamoxifen 10 mg by mouth twice daily or aminoglutethimide 250 mg by mouth four times daily with hydrocortisone 20 mg twice daily in a randomised cross-over trial in which patients who failed to respond to the first treatment or relapsed while receiving it were switched to the other. Eighteen (30%) out of 60 patients initially treated with tamoxifen achieved an objective response and 11 (18%) showed stable disease. Seventeen (30%) out of 57 patients treated initially with aminoglutethimide achieved an objective response and 13 (23%) achieved stable disease. Objective responses in bone metastases were achieved more commonly with aminoglutethimide (11 patients (35%)) than with tamoxifen (five (17%)). The predicted median duration of response for tamoxifen was 15 months and for aminoglutethimide over 15 months (no significant difference). Five (15%) out of 34 patients who failed to respond to tamoxifen and four out of six patients who relapsed after responding to tamoxifen subsequently responded to aminoglutethimide. In contrast, only two (6%) out of 31 patients who failed to respond to aminoglutethimide and none out of four patients who relapsed while receiving aminoglutethimide subsequently responded to tamoxifen. The main side effects occurring in the 97 patients who received aminoglutethimide as first- or second-line treatment were lethargy and drowsiness (36 patients) and rash (29); seven patients had to stop treatment because of side effects. In contrast, side effects were rare and mild with tamoxifen and no patient had to stop treatment because of them. Both tamoxifen and aminoglutethimide appeared from this study to be equally effective in the medical endocrine treatment of advanced breast cancer.
 ...
PMID:Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. 679 71

In a control randomized cross-over trial, 117 patients with advanced breast cancer were treated initially either with tamoxifen (10 mg p.o. twice daily) or aminoglutethimide (250 mg p.o. 4 times daily) with hydrocortisone (20 mg twice daily). Patients failing to respond or relapsing were switched to the alternative treatment. Eighteen (30%) of the 60 patients initially treated with tamoxifen achieved an objective response, and 11 (18%) achieved stable disease. Seventeen (30%) of the 57 patients treated initially with aminoglutethimide achieved an objective response, and 13 (23%) achieved stable disease. Aminoglutethimide achieved a 35% objective response and a further 26% subjective bone pain relief in patients with bone metastases (overall, 61%) compared with a 17% objective response and a further 17% objective bone pain relief with tamoxifen (total, 34%). None of six premenopausal patients responded to aminoglutethimide compared with two of four responding to tamoxifen. The median response duration to aminoglutethimide was 16 months compared with 20 months for tamoxifen. Side effects for aminoglutethimide (including lethargy, rash, and depression) were more common than for tamoxifen, and 7% of aminoglutethimide-treated patients had to discontinue treatment because of these compared with 0% on tamoxifen. In cross-over studies, 6 of 12 tamoxifen responders who relapsed achieved a second response to aminoglutethimide (50%), as did 6 of 29 patients who initially failed to respond to tamoxifen (21%). In contrast, none of 11 patients relapsing after response to aminoglutethimide achieved a second response to tamoxifen; only 1 of 18 nonresponders to aminoglutethimide subsequently responded to tamoxifen (6%). In a subsequent study in which 62 patients were treated with combined tamoxifen and aminoglutethimide, the overall response rate of 37% was not significantly better than that for either agent used alone.
 ...
PMID:Tamoxifen versus aminoglutethimide versus combined tamoxifen and aminoglutethimide in the treatment of advanced breast carcinoma. 704 25

A progress report is presented on two on-going clinical trials in women with advanced breast cancer. In Trial I to date, 56 patients have been randomized to tamoxifen (TAM) alone or TAM plus aminoglutethimide (AG) (plus hydrocortisone). Patients failing TAM can then receive AG. The two groups are reasonably well balanced with respect to prior hormonal therapy exposure (TAM, 19%; TAM plus AG, 17%), age, disease-free interval, performance score, and estrogen receptor status. The TAM plus AG group has a higher incidence of visceral dominant disease (41 versus 26%) and prior chemotherapy exposure (41 versus 33%). Responses have been observed in 7 of 27 (26%) patients on TAM and 11 of 28 (39%) on TAM plus AG. Median times to treatment failure (defined as disease progression, unacceptable toxicity, or patient refusal) are 211 and 123 days, respectively (log-rank on time to treatment failure, p = 0.87). Toxicity is greater for TAM plus AG with a higher incidence of skin rash, lethargy, and dizziness. Thrombotic events were seen in one patient on TAM and two patients on TAM plus AG. One patient on TAM plus AG developed leukopenia and sepsis. The data are too preliminary for one to draw firm conclusions regarding relative efficacy. In TRial II to date, 35 patients with prior tamoxifen exposure have received AG. The mean number of prior systemic therapies is 3.2 (range, 1 to 7). The response rate is 20% and similar with (21%) or without (19%) prior chemotherapy exposure. The median time to treatment failure is 92 days. One patient developed leukopenia and sepsis. Additional patient accrual is necessary to allow characterization of potential efficacy within prognostically important subsets.
 ...
PMID:Progress report on two clinical trials in women with advanced breast cancer. Trial I: tamoxifen versus tamoxifen plus aminoglutethimide. Trial II: aminoglutethimide in patients with prior tamoxifen exposure. 704 29

Aminoglutethimide in combination with dexamethasone has been used in 44 patients with metastatic breast cancer who had prior response to hormonal manipulation and/or positive estrogen receptors. Objective tumor response (complete response plus partial response) has been achieved in 19 of 44 patients. Responses were seen in soft tissue, bone, and pleura. Eleven of 44 patients had stable disease, and 14 patients had progressive disease. The median duration of response was 8 months. Side effects were moderate, including lethargy, rash, fever, and Cushingoid facies. This treatment is well tolerated and is an effective hormone manipulation in postmenopausal patients with metastatic breast carcinoma.
 ...
PMID:Aminoglutethimide in the treatment of metastatic breast cancer. 708 6

Forty-six patients with progressive metastatic disease following initial response to tamoxifen therapy were treated with aminoglutethimide. Three patients (6%) achieved complete remission, 15 patients (33%) had partial response, and eight patients (17%) had stable disease. Twenty patients (44%) had progressive disease. The most common side effects were transient skin rash, lethargy, or dizziness. In four patients (7%), treatment was discontinued because of undesirable side effects within the first 2 weeks of the study. These data show that aminoglutethimide is an effective agent following tamoxifen therapy.
 ...
PMID:Aminoglutethimide after tamoxifen therapy in advanced breast cancer: M. D. Anderson Hospital experience. 708 9

The clinical signs and gross and microscopic lesions of Lassa virus infection in the rhesus monkey are described. Of 17 monkeys infected with Lassa virus, nine died or were killed when moribund. The clinical signs were lethargy, aphagia, constipation, fever, conjunctivitis, and skin rash. Pulmonary congestion, pleural effusion, pericardial edema, hydropericardium, and a few visceral hemorrhages were present grossly. Major microscopic lesions were necrotizing hepatitis and interstitial pneumonia. Other microscopic changes were present in the heart, small intestine, spleen, lymph nodes, kidney, urinary bladder, adrenal glands, and central nervous system; however, most of these lesions were mild. In fact, death could not always be attributed to the morphologic changes; therefore, function alterations must be examined.
 ...
PMID:Pathology of Lassa virus infection in the rhesus monkey. 712 56

Aminoglutethimide (Elipten), at a dosage between 250 and 1500 mg/d by mouth, was administered in a clinical phase II study to 17 patients with metastasizing carcinoma of the breast resistant to hormones and cytostatic drugs. Results of this treatment were available for 14 patients. Nine women were given the drug alone, eight in combination with cytostatic drugs. In 11 women the drug significantly decreased pain within 3-14 days. Used alone aminoglutethimide produced objective regression of the metastases in two women, two further instances of regression occurred when the drug was combined with cytostatic agents. Five women developed urticarial rash, while six had somnolence and nausea or lethargy. Aminoglutethimide is suitable for symptomatic treatment of metastasizing treatment-resistant carcinoma of the breast, either alone or in combination with cytostatic drugs.
 ...
PMID:[Aminoglutethimide in metastasizing carcinoma of the breast resistant to hormonal and cytostatic treatment (author's transl)]. 727 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>