Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leuprorelin (leuprolide acetate) is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH)] which initially stimulates luteinising hormone (LH) and hence testicular androgen release; continuous administration then results in profound suppression of these hormones. Testosterone levels associated with castration are attained within 3 to 4 weeks. A biodegradable subcutaneous or intramuscular depot formulation of leuprorelin 3.75 or 7.5 mg, which releases the drug at a constant rate over 28 days, is available and may be preferred over daily subcutaneous injections. The progression of previously untreated advanced prostatic cancer is delayed in 70 to 90% of men receiving leuprorelin, with median survival of approximately 2 years. The efficacy of leuprorelin is equivalent to that of estrogen therapy, but the tolerability of the GnRH analogue is far better. In contrast to most other studies of GnRH agonists, a slight survival advantage has been reported for combined treatment with leuprorelin and the antiandrogen flutamide. Small noncomparative trials reveal that leuprorelin also causes regression of benign hyperplastic prostate tissue with corresponding relief of obstructive, but not irritative, symptoms although continuous treatment is necessary to maintain remission. Impotence and flushing occur in most leuprorelin recipients but, unlike diethylstilbestrol (stilboestrol), cardiovascular toxicity and gynaecomastia are not significant problems. Symptom flare, usually manifested as bone pain in prostate cancer patients and exacerbation of obstructive symptoms in those with benign prostatic hypertrophy, can occur in 4 to 29% at the beginning of treatment. Leuprorelin treatment is therefore an established effective palliative measure in men with previously untreated advanced prostatic cancer, and may have a role in those with benign hypertrophy who are unfit for surgery.
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PMID:Leuprorelin. A review of its pharmacology and therapeutic use in prostatic disorders. 179 35

In a controlled, prospective, randomized clinical trial, we evaluated the safety and efficacy of leuprolide, a superactive analog of luteinizing hormone releasing hormone, given in a single subcutaneous injection dose of 1 mg per day, versus diethylstilbestrol (DES) 3 mg per day by mouth in patients with previously untreated Stage D2 prostatic adenocarcinoma. Eleven leuprolide patients and 10 DES patients were evaluated for therapeutic response. Eighty per cent of patients in each group experienced subjective improvement in bone pain and urinary obstructive signs and symptoms. Although the pooled percentages of complete, partial, and stable objective responses were greater for the leuprolide group than the DES group, the sums of the percentages of complete and partial objective responses were comparable for both treatment groups during the first forty-eight and sixty weeks of the study, respectively. In addition, patients not responding to leuprolide generally experienced no benefit with crossover to DES, and vice versa. Serious adverse reactions were more common in the DES group and included fatal myocardial infarction, arrhythmia, deep venous thrombosis, and gynecomastia. Vasomotor flushing, disease flare, and injection site irritation occurred most often in leuprolide patients, but did not require modification or discontinuation of treatment.
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PMID:Comparison of leuprolide and diethylstilbestrol for stage D2 adenocarcinoma of prostate. 392 51

We have carried out a prospective survey of 25 cases of male hypogonadism attending one hospital, and a retrospective study of 73 men attending other endocrine clinics in Manchester. In total, 47 had pituitary disorders, 15 isolated gonadotrophin deficiency (including 4 with Kallmann's syndrome), 10 testicular atrophy of unknown cause, 12 testicular damage, 10 with Klinefelter's syndrome, and 4 had miscellaneous disorders. Our survey emphasises the importance of adequate history and examination. Most patients presented with reduced libido, with marital problems in 62% of married men. Less common problems were facial flushing, osteoporosis and gross obesity. Several patients with pituitary disorders were asymptomatic, even in the presence of visual field defects. Klinefelter's syndrome, and testicular atrophy, may present with infertility or gynaecomastia rather than symptoms of androgen deficiency. On examination, the presence of gynaecomastia or obesity were of no help in differential diagnosis, whereas visual field defects clearly indicated a pituitary cause. Measurement of height/span was of little help. The precise diagnosis was usually established with basal plasma LH, FSH, testosterone and prolactin, with karyotype and pituitary radiology, and without more elaborate dynamic hormone tests. Testosterone esters given by intramuscular injection as "Sustanon 250" was the most commonly used replacement therapy. Improved libido usually resulted. Side-effect occurred in 10%, usually as muscle cramps, pain at the injection sites, acne, or excessive sex drive. One tragic case illustrates the potential dangers of androgen replacement therapy in an unrecognised psychopath, and where doubt exists a psychiatric opinion should be sought before starting therapy.
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PMID:Clinical aspects of androgen deficiency in men. 689 Jul 81

Prostatic cancer is the second most common cause of cancer death in males. Treatment by radical prostatectomy and radiotherapy is useful in the early stages of the disease. Whenever metastases occur, patients are usually treated by surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH) analogue] castration. This form of treatment is, however, associated with unwanted adverse effects, such as flushing, loss of libido and potency and all patients ultimately escape therapy after a delay of 1 to 2 years. For this reason antiandrogens have been developed as another means of endocrine ablation therapy. Antiandrogens fall in 2 groups of which the first group, the steroidal antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at the cellular level but also inhibit testosterone production by their additional gestagenic properties blocking gonadotropin secretion. Except in preventing the flare-up associated with the start of GnRH analogue therapy and in reducing flushing, no evidence exist of any superiority for CPA over classical therapy in terms of adverse effects and survival. The second group, the nonsteroidal or 'pure' antiandrogens, only block androgens at the cellular level without any central effects. In contrast with other forms of castration, patients on pure antiandrogens as monotherapy preserve their sexual function and potency, at the expense of a slightly inferior androgen blockade and gynecomastia. These latter effects are explained by a compensatory rise in androgens as a result of the blockade at the central level, which weakens the androgen blockade, and by peripheral aromatisation of the increased androgens to oestrogens. In addition, some evidence exist that pure antiandrogens improve survival if combined with other forms of castration as they also inhibit the adrenal androgens, the so-called maximal androgen blockade (MAB). If patients escape control under MAB, a trial of stopping the antiandrogen must always be considered, as some tumours have 'learned' to be activated by these drugs. At the moment it is not yet clear if antiandrogens are of any benefit in downstaging the extent of disease before prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens, bicalutamide offers some advantages over flutamide as it possesses a much longer half-life, allowing a once daily regimen, and has advantages over nilutamide in terms of fewer adverse effects.
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PMID:Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer. 959 22

Calcium antagonists (CAs) or calcium-channel blockers, are a common group of antihypertensive medications. These drugs have the property of blocking the calcium channels of the vascular and cardiac smooth-muscle fibers. They have been associated with cutaneous reactions ranging from exanthems to severe adverse events. The frequency of these reactions may be as high as 48 percent. The most common are ankle or pedal edema (up to 30 %), gingival hyperplasia (up to 21 %), and flushing (up to 10 %). Less common are facial or truncal telangiectasia, photosensitivity reactions, new-onset psoriasis (as well as exacerbation of it), purpuric exanthems, pemphigoid manifestations, subacute cutaneous lupus erythematosus, gynecomastia, erythromelalgia, and oral ulcers. Particular adverse manifestations relate to drug potency, degree of vasodilatation, patient age, coexistence of other diseases, co-administration of other cytochrome P450 CYP3A-metabolized medications, fibroblast stimulation, and blood cell effects. Calcium antagonists are associated with a wide range of skin reactions, and the dermatologist should include these in the differential diagnosis of cutaneous diseases.
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PMID:The spectrum of cutaneous reactions associated with calcium antagonists: a review of the literature and the possible etiopathogenic mechanisms. 1499 79

Prostate cancer is the most common cancer among men and androgen deprivation therapy (ADT) is the most effective treatment for this disease. The cornerstone of the treatment of prostate cancer is inhibition of testosterone production which interrupts testosterone-induced growth of the prostate tumor. The dramatic decrease in testosterone levels, however, has several undesirable effects on the metabolic profile and bone metabolism and can also lead to fatigue, loss of libido, gynecomastia, and anemia, provoke vasomotor flushing, and generally affect the quality of life. Due to the long-term survival rates of patients with prostate cancer, treatment-related adverse effects are highly relevant and thus, in each clinical setting, the benefits of ADT must be weighed against treatment-related adverse effects. The current review focuses on the more recently described metabolic complications of androgen deprivation therapy, including obesity, diabetes, lipid alterations, metabolic syndrome, and cardiovascular disease. In addition, it provides practical management recommendations drawn from the available guidelines issued by the American Diabetes Association and American Heart Association.
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PMID:Adverse effects of androgen deprivation therapy in patients with prostate cancer: focus on metabolic complications. 2874

Androgen deprivation therapy (ADT) is the mainstay of treatment of patients with relapsed or metastatic hormone-sensitive prostatic carcinoma. The dramatic reduction of serum testosterone levels induced by ADT produces multiple side effects as vasomotor flushing, sexual dysfunction, fatigue, impairment of cognitive function, reduced quality of sleep, gynecomastia and anemia, that are able to decrease health-related quality of life (QoL). In addition, hormonal therapy can interfere with bone metabolism and induce metabolic and cardiovascular complications. Recently, new-generation hormonal therapies, such as abiraterone and enzalutamide, have been tested and approved in castration resistant prostatic cancer patients and current studies are moving forward to the earlier use of these two drugs. In this evolving scenario, the management of hormonal therapy toxicity, given the long duration of treatment and the potentially high impact of side effects on patients' functional status and quality of life, is a critical challenge for clinicians. A correct information of patients before the initiation of treatment, together with the adoption of preventive measures, could help to ameliorate their quality of life. The aim of this review is to describe the impact on quality of life of endocrine treatment side effects and analyze possible interventions to alleviate them.
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PMID:Hormonal treatment and quality of life of prostate cancer patients: new evidence. 2924 13