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)

Menopause and the accompanying reduction in estrogen production may cause a number of symptoms in women which include hot flushes, sweating, mood and sleep disturbances, fatigue and urogenital dysfunction. The effectiveness of estrogen-based hormone replacement therapy (HRT) in ameliorating these symptoms, and in preventing long term sequelae such as osteoporosis, is well established. Comparative trials indicate that oral conjugated estrogens 0.625mg, oral ethinyl estradiol 0.02mg and transdermal estradiol 0.05mg have equivalent efficacy in relief of mild to moderate menopausal symptoms and prevention of bone mineral loss. Concomitant progestogen therapy is usually prescribed for women with intact uteri to protect against endometrial hyperplasia and carcinoma. The addition of progestogen maintains and may even enhance the bone-conserving effects of estrogen, and continuous regimens appear to reduce the incidence of irregular menses. Adverse reactions are predominantly local skin irritation with transdermal preparations (14% of patients) and systemic effects common to most forms of HRT including breast tenderness, flushing, headache and irregular bleeding, occurring in less than or equal to 2% of patients. Data concerning the effect of HRT on quality of life are limited, but most analyses have assigned utility values of 0.99 for mild and 0.95 for severe menopausal symptoms. However, recent clinical data suggest that these utility values may underestimate the impact of menopausal symptoms on quality of life. The cost benefit and cost effectiveness of HRT in the treatment of menopausal symptoms have not been fully researched, although preliminary results suggest that conjugated estrogens and transdermal estradiol compare well with alternative therapies such as veralipride and Chinese medicines. A Swedish study using a prevalence-based approach estimated that estriol treatment in all women with urinary incontinence aged greater than or equal to 65 years resulted in monetary savings compared with treating 20% of women. Cost-utility data indicated that the change in quality-adjusted life years (QALYs) with HRT was always positive, but the degree of change was determined by the baseline assumptions. Estimated changes in QALYs with HRT ranged from 0.006 for 5 years of treatment with unopposed estrogen in women with intact uteri, to 0.5 for 10 years of the same treatment in women with severe menopausal symptoms following hysterectomy. Compliance with HRT is suboptimal as 5 to 50% of women withdraw from therapy, thereby increasing costs per year of life saved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone replacement therapy: I. A pharmacoeconomic appraisal of its therapeutic use in menopausal symptoms and urogenital estrogen deficiency. 1014 33

Preclinical studies indicate that dihydropyridine-type calcium channel antagonists modulate dopamine neurotransmitter function and can reduce cocaine-reinforced behaviors. Amlodipine, a long-acting dihydropyridine-type calcium channel antagonist related to isradipine and nifedipine, was administered in open label fashion for 12 weeks to 26 cocaine-dependent patients. In subjects expressing cocaine craving, craving significantly declined during the course of the 12 weeks. Five individuals reported flushing, headache, fatigue, nocturia, nausea, and lightheadedness. No conclusions regarding efficacy can be made due to the small number of subjects and the open-label design.
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PMID:Amlodipine treatment of cocaine dependence. 1043 93

We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07+/-0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%-50% every 5-7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29+/-0.11 mg/kg per day for those < 13 years, 0.16+/-0.11 mg/kg per day for those > or = 13 years, 0.23+/-0.14 mg/kg per day for essential, hypertension and 0.24+/-0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.
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PMID:Efficacy of amlodipine in pediatric patients with hypertension. 1045 79

The main objective of fixed dose combination therapy for hypertension is to improve blood pressure (BP) control with lower, better tolerated dosages of 2 antihypertensives rather than higher dosages of a single agent. Felodipine and metoprolol lower BP via different, but complementary, mechanisms and controlled release formulations of these 2 drugs are available as a fixed dose combination, felodipine/metoprolol. In clinical trials in patients with hypertension, felodipine/metoprolol was significantly more effective than placebo and the respective monotherapies administered at the same dosages. Mean BP was reduced to < 155/90 mm Hg in patients treated with combination therapy and controlled in approximately 70% of patients. In one study that titrated dosages to effect, fewer felodipine/metoprolol than felodipine or metoprolol monotherapy recipients required dosage increases to achieve BP control (45 vs 60 and 67%, respectively). Data from double blind comparative studies show that the antihypertensive efficacy of felodipine/metoprolol 5 to 10/50 to 100 mg/day is significantly greater than that of enalapril monotherapy or captopril plus hydrochlorothiazide and equivalent to nifedipine/atenolol and amlodipine. In comparisons with enalapril, fewer felodipine/metoprolol than enalapril recipients required dosage titration to achieve BP control. Compared with amlodipine, felodipine/metoprolol significantly reduced mean 24-hour average BP (8.9/5.5 vs 14.4/9.5 mm Hg after 6 weeks; p < 0.001). Both treatments preserved diurnal rhythm. Long term follow-up studies show that the antihypertensive effect of felodipine/metoprolol occurs mostly during the first month of treatment with small additional decreases in BP being observed in the second and third months, and a relatively constant effect thereafter. According to a validated questionnaire, quality of life was relatively similar during 12 weeks treatment with felodipine/metoprolol, enalapril or placebo. In a retrospective pharmacoeconomic analysis conducted in Sweden, felodipine/metoprolol was more cost effective than enalapril as initial treatment for hypertension. Peripheral oedema, headache and flushing were the most commonly reported adverse events with felodipine/metoprolol and felodipine monotherapy, whereas dizziness, fatigue, headache and respiratory infection were more frequent with metoprolol monotherapy. Dose-dependent adverse events such as oedema may occur less often in patients taking lower dosages in combination than in those taking higher dosages of felodipine monotherapy. Thus, patients with hypertension treated with felodipine/metoprolol experience greater control of BP, with less need for dosage titration, than those treated with felodipine, metoprolol or enalapril monotherapy. Importantly this greater efficacy does not appear to be associated with a higher incidence of adverse events relative to monotherapy. Additionally, in short term studies felodipine/metoprolol had a similar (minimal) effect on QOL to enalapril monotherapy but was more cost effective.
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PMID:Felodipine/metoprolol: a review of the fixed dose controlled release formulation in the management of essential hypertension. 1071 4

Somatostatin analogs are promising agents in the treatment of medullary thyroid carcinoma. We have evaluated the effects of the slow release somatostatin analog lanreotide in combination with interferon-alpha2b in seven patients with advanced and symptomatic medullary thyroid carcinoma. The frequency and intensity of daily flushing episodes and bowel movements, the intensity of fatigue, weight, performance status, calcitonin levels, and change in tumor masses were recorded before and during treatment. No objective complete or partial responses were recorded. However, disease stabilization and minor tumor regression were observed in three of seven and two of seven patients, respectively. The number and intensity of bowel movements and flushing episodes decreased in five of six and two of two patients, respectively. Decrease in fatigue and improvement in performance status were observed in five of seven and six of seven patients, respectively. Weight gain was recorded in three of four patients. Plasma levels of calcitonin decreased significantly in six of seven patients. Clinical benefit, evaluated by a structured algorithm, was achieved in six of seven patients and was coupled with a decrease of 50% or more in serum calcitonin levels in three of seven patients. In conclusion, the combination of lanreotide with interferon had a major impact on clinical symptoms and was well tolerated.
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PMID:Slow release lanreotide in combination with interferon-alpha2b in the treatment of symptomatic advanced medullary thyroid carcinoma. 1072 27

The safety and efficacy of Amlodipine (AML) for mild to moderate hypertension was evaluated in a "real life" setting. This open non-comparative trial included 123 men and 143 women (age 30-91 years, mean 59.4). All had sitting diastolic blood pressure (DBP) between 95 and 115 mmHg, confirmed in most by 2 baseline measurements, 2 weeks apart. Eligible patients were given AML 5 mg daily as add-on or monotherapy and were evaluated 4 weeks later. If DBP was then > 90 mmHg, the daily dose was raised to 10 mg; those with < 90 mmHg remained on 5 mg. AML was continued for 8 weeks. Other BP-lowering drugs were unchanged. Of the original 266 patients 22 (8.2%) withdrew due to adverse events (AE), and others were protocol violators, lost to follow-up or withdrew, leaving 211 available for efficacy analysis. In this major group BP was reduced from 165 +/- 15/101 +/- 4 to 139 +/- 11/83 +/- 5 after 12 weeks of AML (p < 0.05). The reduction was greater in those under 70 years, from 173 +/- 12/100 +/- 5 to 142 +/- 12/80 +/- 4 (p < 0.05). In those with BMI > 30 kg/m2, BP decreased from 165 +/- 15/101 +/- 5 to 140 +/- 12/83 +/- 5 (p < 0.05). Mean change in heart rate was -1.5 bpm (p < 0.05). Mean final AML dose was 5.5 mg/day. The most common AML-related AE requiring cessation of the drug was pedal edema in 2.6% of the 266 patients; in 3.7% it persisted during therapy. Other AE occurring in > 1% were dizziness in 1.8%, headache 1.5%, flushing 1.1% and fatigue 1.1%. We conclude that AML is an effective and well-tolerated antihypertensive suitable for most hypertensive patients.
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PMID:[Multicenter community-based trial of amlodipine in hypertension in Israel]. 1095 90

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.
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PMID:Treatment of hypertensive children with amlodipine. 1104 Nov 59

A double-blind, randomized, placebo controlled study was conducted to determine the efficacy of a promising immunoadsorption treatment device containing staphylococcal protein A (Prosorba Immunoadsorption Column, Cypress Bioscience, Inc., San Diego, CA, U.S.A.) in patients with refractory rheumatoid arthritis (RA). Eligibility criteria required adult RA patients who had failed either methotrexate or 2 other disease modifying antirheumatic drugs (DMARD) and who had predefined active disease. All disease-modifying agents were discontinued at least 30 days prior to entry. Patients received 12 weekly procedures after being randomized to the active treatment arm or to the sham treatment arm (apheresis only). Evaluations were double-blinded and occurred at baseline and periodically for 24 weeks thereafter. Primary efficacy was assessed at 7 and 8 weeks after the completion of 12 treatments (at trial Weeks 19 and 20) using the American College of Rheumatology (ACR) definition of improvement (1,2), and results from the assessments at Weeks 19 and 20 were averaged. Ninety-nine randomized patients had a mean disease duration of 15.4 years and received an average of greater than 5 DMARD regimens prior to entry. Analysis of patients who completed all treatments and follow-up indicated that 15 of 36 (41.7%) column-treated patients responded compared to 5 of 32 (15.6%) sham-treated patients (p < or = 0.003). Intent to treat analysis of all patients who were randomized in the study indicated 15 of 52 (28.9%) column-treated patients responded compared to only 5 of 47 (10.6%) patients who received sham treatments (p = .005). Common adverse events (AEs) included joint pain, fatigue, joint swelling, and hypotension. Central line usage was clearly associated with significant AEs during this trial and is not recommended. Hemoglobin, hematocrit, and mean corpuscular volume values decreased similarly in both treatment arms, attributed to phlebotomy for laboratory and scientific studies and to small, repetitive (normal) apheresis losses. Other AEs such as nausea, rash, pruritus, flushing, and fever occurred in 1 to 6% of treatments in each arm (NS). There was no significant increase in AEs in column-treated patients compared to sham-treated patients. Protein A immunoadsorption was proven to be a new therapeutic alternative in patients with severe, refractory disease.
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PMID:Immunoadsorption for the treatment of rheumatoid arthritis: final results of a randomized trial. Prosorba Trial Investigators. 1111 18

Clinical studies have traditionally identified treatment-specific side effects by comparison of voiced side effects in treatment and placebo arms of a study. Highly motivated women in a clinical trial may underreport drug-induced symptoms for medications which may be considered lifesaving. Affective symptoms during treatment of early breast cancer with tamoxifen (an estradiol receptor antagonist) were reported as infrequent by the manufacturer. However, reports suggest a higher rate of depression during general use. The objective of the present study was to examine the frequency of symptoms that might be side effects of tamoxifen and to relate them to the way the women attributed such symptoms. The exploratory study involved semistructured telephone interviews of 25 women who were taking tamoxifen. Textual analysis of the information was used to examine the symptoms described by the women. They were also asked whether any symptoms were related to the medication. The symptoms and their attribution were evaluated against a background of self-perceived stress. The principal finding was a pattern of ambivalence in attributing symptoms to the drug. Of all the symptomatic changes noted, the women only attributed 51% to tamoxifen. Flushes, fatigue, and depression were reported most frequently during treatment; flushes were readily attributed to tamoxifen but depression and fatigue were attributed to another factor by half of the symptomatic women. Women who reported moderate to high levels of life stress were less likely to attribute symptoms to drug therapy. The results suggest that women taking tamoxifen may not attribute known drug side effects to use of the medication.
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PMID:Tamoxifen in breast cancer: symptom reporting. 1132 15

Hypericum Perforatum Extract is an extract of the capsules, flowers, leaves, and stem heads of Hypericum perforatum, commonly called St. John's Wort. Hypericum Perforatum Oil is the fixed oil from H. perforatum. Techniques for preparing Hypericum Perforatum Extract include crushing in stabilized olive oil, gentle maceration over a period of weeks, followed by dehydration and filtration. Propylene Glycol and Butylene Glycol extractions were also reported. The following components have variously been reported to be found in H. perforatum: hypericin, naphtodianthrones, flavonoids, terpene and sesquiterpene oils, phenylpropanes, biflavones, tannins, xanthones, phloroglucinols, and essential oils. Hypericum Perforatum Extract is used in over 50 cosmetic formulations and Hypericum Perforatum Oil in just over 10, both across a wide range of product types. Acute toxicity studies using rats, guinea pigs, and mice indicate that the extract is relatively nontoxic. Animals fed H. perforatum flowers for 2 weeks showed significant signs of toxicity, including erythema, edema of the portion of the body exposed to light, alopecia, and changes in blood chemistry. In a chronic study, rats fed H. perforatum gained less weight than control animals. Mixtures containing the extract and the oil were not irritants or sensitizers in animals. Because of the presence of hypericin, H. perforatum is a primary photosensitizer. In clinical tests, a single oral administration of Hypericum extract resulted in hypericin appearing in the blood. With long-term dosing, a steady-state level in blood was reached after 14 days. The polyphenol fraction of H. perforatum had immunostimulating activity, whereas the lipophilic portion had immunosuppressing properties. Mixtures of the extract and the oil produced minimal or no ocular irritation in rabbit eyes. Mutagenic activity in an Ames test was attributed to flavonols in one study and to quercitin in another, but other genotoxicity assays were negative. No carcinogenicity or reproductive and developmental toxicity data were available. A mixture of the extract and the oil was not irritating in clinical studies. Adverse reactions to Hypericum extract in the clinical treatment of depression include skin reddening and itching, dizziness, constipation, fatigue, anxiety, and tiredness. Absent any basis for concluding that data on one member of a botanical ingredient group can be extrapolated to another in a group, or to the same ingredient extracted differently, these data were not considered sufficient to assess the safety of these ingredients. Additional data needs include current concentration of use data; function in cosmetics; photosensitization and phototoxicity data using visible light; gross pathology and histopathology in skin and other major organ systems associated with repeated dermal exposures; dermal reproductive/developmental toxicity data; human skin irritation and sensitization data using the oil; and ocular irritation data, if available. Until these data are available, it is concluded that the available data are insufficient to support the safety of these ingredients in cosmetic formulations.
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PMID:Final report on the safety assessment of Hypericum perforatum extract and Hypericum perforatum oil. 1155 39


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