Gene/Protein Disease Symptom Drug Enzyme Compound
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The effect of bifemelane hydrochloride on dementia in the elderly was studied in thirty-one patients having cerebrovascular disorders. Alzheimer's disease, Parkinsonism and related diseases. The drug (150 mg) was administered orally three times daily for 10 weeks. The final global improvement rating was 77.4% for all patients. The rates of improvement for Alzheimer's disease were higher than those for cerebrovascular disorders, suggesting that this drug affects Alzheimer's disease through a cholinergic potentiating action. Psychotic, neurological and subjective symptoms, and the activity of daily life, were rated before, during and after treatment. All mean rates of improvement were based on observations made in the 4th week after the start of treatment. Improvement rates for global symptoms were more than 80% for emotional incontinence and prejudice or querulous attitudes toward the nurses, and in headache, tinnitus and dizziness among the subjective symptoms. The improvement in intellectual function was evaluated by the dementia rating scale for the elderly (DRSE), and a significant increase was found in DRSE after treatment with this drug. Side effects attributable to the drug were noted in one patient developing urticaria. It is thus suggested that bifemelane hydrochloride is useful in the treatment of different symptoms of dementia.
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PMID:The clinical effect of bifemelane hydrochloride on dementia in aged patients. 179 96

The clinical effectiveness and safety of propiverine hydrochloride (P-4, 20 mg tablet) were studied on 29 patients with nervous pollakisuria, neurogenic bladder or unstable bladder, whose chief complaints were urinary frequency and/or urinary incontinence. The clinical efficacy was "good" or better in 62.1% and "fair" or better in 86.2%. Patients' impressions were "good" or better in 79.3%. There were a total of 4 cases (13.8%) of adverse reactions, namely, two cases of decreased urinary stream, one dry mouth, and one dizziness. These reactions disappeared rapidly after the completion or discontinuance of drug administration, and therefore, did not constitute significant safety problems. The clinical efficacy in the treatment of subjective symptoms was 74.1% for diurnal pollakisuria, 50.0% for nocturnal pollakisuria, 83.3% for urinary incontinence and 69.0% for urgent feeling of micturition. For objective symptoms, P-4 increased significantly the volume of maximum desire to void (MDV); however it did not increase significantly the residual urine volume. The results of this study suggest that propiverine hydrochloride is very useful for the treatment of urinary frequency and/or incontinence.
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PMID:[Experience in the use of propiverine hydrochloride (P-4) for patients suffering from urinary frequency and/or incontinence]. 237 10

We evaluated the effectiveness and side effects of long-term administration of terodiline hydrochloride in patients with chief complaints of pollakisuria or incontinence or both due to unstable bladder or neurogenic bladder associated with uninhibited contraction. The dose was 24 mg once daily. The symptoms such as pollakisuria and incontinence improved in 31 out of 41 patients (76%). Mild side effects were observed in 12 out of 47 patients (26%), which were thirst, dizziness, dysuria, urticaria and gastrointestinal symptoms. An increasing tendency of both maximum desire to void and compliance (p less than 0.10), and significant difference in maximum static pressure (p less than 0.05) were observed on urodynamic examinations before and after administration of this medicine. The results obtained from this study suggest that terodiline hydrochloride may be greatly recommended for patients with such symptoms as pollakisuria and incontinence.
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PMID:[Clinical evaluation of long-term administration of terodiline hydrochloride for the treatment of patients with pollakisuria and incontinence]. 340 May 52

Seven cases of subacute central and peripheral neurologic dysfunction developed in 18 workers employed in the manufacture of reinforced plastic bathtubs. Cases were characterized by weight loss, dizziness, paresthesias, muscle weakness, incontinence, memory loss, and loss of peripheral, color, and night vision. Neuropathies began distally, involved both sensory and motor function, and were associated with prolonged sensory latency, muscle fibrillation, and reduced numbers of functioning motor units. One patient developed posterior lenticular cataracts. Slow improvement occurred on removal from exposure, but residual neuropathies persisted for as long as two years. Epidemiologic investigation disclosed that the first case developed approximately two weeks after introduction of a new plastic foaming agent, 2-t-butylazo-2-hydroxy-5-methylhexane (BHMH). All cases occurred in workers exposed directly to BHMH. No new cases developed after use of BHMH was discontinued. A survey of the firm which produced BHMH and of 68 user firms found two additional clusters of mild neuropathy which may have been caused by BHMH. BHMH was withdrawn from distribution following discovery of these cases. Subsequently, BHMH has been shown in rats to be a potent neurotoxin. Adequate premarket testing could have averted this outbreak.
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PMID:Neurologic dysfunction from exposure to 2-t-butylazo-2-hydroxy-5-methylhexane (BHMH): a new occupational neuropathy. 398 40

Treatment with oestrogens in the perimenopause can regulate dysfunctional uterine bleeding and positively influence unpleasant subjective feelings such as sweating, dizziness, nervousness and lack or incapability of concentration. Oestrogens are especially successful in reactive depression and in the therapy of insomnia. Their positive effect on atrophic changes of the genitalia and in combating urge incontinence is also of therapeutic importance. Of particular socio-medical importance is their beneficial effect on postmenopausal osteoporosis. Side effects like weight gain, increase in blood pressure or changes in coagulation parameters are not observed during therapy with natural oestrogens in the usual doses. The incidence of thrombosis, embolism and myocardial infarction is not increased when oestrogens are given in the perimenopause. The controversy with respect to an increased incidence of endometrial carcinoma after long-term therapy with oestrogens may be based on an incorrect mode of administration as used on the Anglo-American scene. Excess dosage, continuous instead of intermittent therapy, lack of addition of progestational agents and a neglect of contraindications and risk factors may have led to the 3- to 8-fold increased incidence of endometrial carcinoma after oestrogen therapy in the studies from these areas.
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PMID:[Advances and risks in estrogen therapy in the perimenopause]. 665 19

A 53-year-old right-handed woman presented with headaches and dizziness. She had been well for ten years following successful cadaveric renal transplantation and was taking prednisolone and azathioprine. Two months later she had more headaches with transient dominant hemisphere disturbances and then suffered a completed right hemisphere deficit. As this was recovering, she developed an ischemic optic neuropathy, Computerized tomography (CT) was then normal although CSF analysis showed lymphocytosis and high protein. Steroid trial led to dramatic symptomatic and clinical recovery. On tailing off steroids, progressive bilateral hemisphere disturbance occurred. She was bedbound, with fever, headache, incontinence and disturbed consciousness. New evidence of infarction in watershed territories on CT led to temporal lobe biopsy. Cortical arterioles and venules showed proliferation of lymphoid cells staining for leucocyte common antigen and B-cell markers characteristic of Neoplastic Angioendotheliomatosis (NAE). After chemotherapy she regained independence and mobility and CSF protein fell. This is the first case of NAE to our knowledge in association with immunosuppression for renal transplant and is further evidence that NAE is malignant lymphoma. Cerebrovascular disease is common in such patients, the simultaneous events in differing territories is typical of NAE. Response to chemotherapeutic agents occurred although the typical natural history was unchanged.
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PMID:Neoplastic angioendotheliomatosis: a treatable "vascular dementia" occurring in an immunosuppressed transplant patient. 847 50

In a post-marketing surveillance study of 752 patients suffering from urgent incontinence, mixed urgent-stress incontinence, reflex incontinence, urgency and enuresis were treated with propiverine hydrochloride. Clinical efficacy of propiverine hydrochloride was verified by the improvement of symptoms related to detrusor hyperactivity, hypersensitivity and hyperreflexia during a 12-week surveillance period: daytime and overnight urinary incontinence, as well as the frequency, nocturia, urgency in day time and at night decreased. These results are well demonstrated by decreased pad use and statistically significant decrease of Gaudenz urgency score during treatment, confirming the efficacy of propiverine hydrochloride already proved in clinical trials. The safety profile of propiverine hydrochloride displayed characteristic anticholinergic symptoms (dry mouth, accommodation disorders, constipation, tiredness, dizziness) with decreasing incidence during the 12-week treatment period. The residual urine volume decreased also. Serious adverse events were observed rarely and could be explained by the lack of consideration of contraindications, warnings and interactions with other drugs. The positive risk-benefit relationship of propiverine hydrochloride in the treatment of detrusor hyperactivity, hypersensitivity and hyperreflexia was reconfirmed in this post-marketing drug surveillance study.
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PMID:[Tolerance and effectiveness of propiverine hydrochloride in 752 patients with symptoms of detrusor hyperactivity and increased sensitivity and irritability of the urinary bladder: results of a study monitoring drug utilization]. 960 Jan 63

Although drug-drug interactions constitute only a small proportion of adverse drug reactions, they are important because they are often predictable and therefore avoidable or manageable. Their frequency is related to the age of the patient, the number of drugs prescribed, the number of physicians involved in the patient's care and the presence of increasing frailty. The most important mechanisms for drug-drug interactions are the inhibition or induction of drug metabolism, and pharmacodynamic potentiation or antagonism. Interactions involving a loss of action of one of the drugs are at least as frequent as those involving an increased effect. It is likely that only about 10% of potential interactions result in clinically significant events and, while death or serious clinical consequences are rare, low-grade, clinically unspectacular morbidity in the elderly may be much more common. Nonspecific complaints (e.g. confusion, lethargy, weakness, dizziness, incontinence, depression, falling) should all prompt a closer look at the patient's drug list. There are a number of strategies that can be adopted to decrease the risk of potential clinical problems. The number of drugs prescribed for each individual should be limited to as few as is necessary. The use of drugs should be reviewed regularly and unnecessary agents withdrawn if possible, with subsequent monitoring. Patients should be encouraged to engage in a 'prescribing partnership' by alerting physicians, pharmacists and other healthcare professionals to symptoms that occur when new drugs are introduced. Physicians with a responsibility for elderly people in an institutional setting should develop a strategy for monitoring their drug treatment. For those interactions that have come to clinical attention, it is important to review why they happened and to plan for future prevention. Clinicians should also report, via the appropriate postmarketing surveillance scheme, any drug-drug interactions they have encountered. Finally, multidisciplinary education about the nature of physiological aging and its effect on drug handling, and the possible presentations of drug-related disease in older patients, is an important element in reducing interactions in the elderly.
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PMID:Important drug-drug interactions in the elderly. 963 96

Extended-release oxybutynin (Ditropan XL) uses an osmotic system (OROS) to deliver a controlled amount of oxybutynin chloride into the gastrointestinal tract over a 24-hour period when taken once daily. Oxybutynin binds to M3 muscarinic receptors on the detrusor muscle of the bladder, preventing acetylcholinergic activation and relaxing the muscle. Mean peak plasma concentrations are lower with extended-release oxybutynin 15mg once daily than with conventional immediate-release oxybutynin 5mg taken 3 times daily. Relative bioavailabilities of parent drug and metabolite N-desethoxybutynin are 153 and 69%, respectively, for extended-release oxybutynin when compared with immediate-release oxybutynin. In short (< or =6 weeks) randomised, double-blind clinical trials of patients with detrusor instability, extended-release oxybutynin 5 to 30mg once daily significantly reduced the mean weekly number of urge incontinence episodes by 84 to 90%. Extended-release oxybutynin had similar efficacy to immediate-release oxybutynin. Adverse events reported by patients taking extended-release oxybutynin were dose-related anticholinergic effects, most frequently dry mouth, somnolence, constipation, blurred vision and dizziness. A large noncomparative study demonstrated that approximately two thirds of the patients prescribed extended-release oxybutynin for detrusor instability were still taking the medication 6 months later.
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PMID:Extended-release oxybutynin. 1075 30

Medical and surgical options for the treatment of benign prostatic hyperplasia have expanded in recent years. Saw palmetto, the most widely used complementary medication, is less effective than standard medical therapy but has fewer side effects. Although non-selective alpha blockers provide rapid relief of symptoms and are relatively inexpensive, they can cause dizziness and orthostatic hypotension. These effects occur less often with tamsulosin, a more selective alpha blocker. Finasteride, a 5alpha-reductase inhibitor, slowly reduces prostatic volume but is not as effective as alpha blockers, especially in men with a smaller prostate. Dutasteride, a new 5alpha-reductase inhibitor, has recently been labeled for the treatment of benign prostatic hyperplasia. Surgery may be appropriate initial treatment in patients with severe symptoms who are not at high risk for complications. Surgery may also be indicated in patients who have failed medical therapy or have recurrent infection, hematuria, or renal insufficiency. Transurethral resection of the prostate is effective in most patients, but it carries some risk of sexual dysfunction, incontinence, and bleeding. Surgical procedures that use thermal microwave or laser energy to reduce hyperplastic prostate tissue have recently become available. In general, the newer procedures are less expensive than transurethral resection of the prostate and have fewer complications; however, the need for retreatment is somewhat greater with these less invasive techniques.
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PMID:Managing benign prostatic hyperplasia. 1212 35


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