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)

Glatiramer acetate (GA, Copaxone), a standardized mixture of synthetic polypeptides, has now been approved also in Germany for the treatment of relapsing-remitting multiple sclerosis (RR-MS). After it had been shown effective in suppression of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), it was evaluated in several clinical studies. In these studies, GA could alter the natural history of MS by both reducing the relapse rate and affecting disability. The clinical therapeutic effect of GA was consistent with the effect on magnetic resonance imaging-defined disease activity and burden in a recent multicenter study. As a daily standard dose, 20 mg of GA is injected subcutaneously. The induction of GA-reactive T-helper 2-like regulatory suppressor cells is thought to be the main mechanism of action. The most common adverse effects are mild injection site reactions. A remarkable but rare adverse effect is the only transient immediate post-injection systemic reaction manifested by flushing, chest tightness, palpitations, and dyspnea. Antibodies to GA which are induced during GA treatment do not interfere with its clinical effects.
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PMID:[Treatment of multiple sclerosis with glatiramer acetate. Current aspects of mechanisms of action, pharmacokinetics, adverse effect profile and clinical studies]. 1204 Sep 79

Paclitaxel (Taxol) a taxane antineoplastic agent causing irreversible microtubule aggregation with activity against breast, ovarian, lung, head and neck, bladder, testicular, esophageal, endometrial and other less common tumors was derived from the bark of the Pacific yew (Taxus brevifolia). Phase I trials conducted in the late 1980s were almost halted because of the high frequency of hypersensitivity-like reactions. Respiratory distress (dyspnea and/or bronchospasm), hypotension, and angioedema were the major manifestations, but flushing, urticaria, chest, abdomen, and extremity pains were described also. Reactions occurred on first exposure in the majority of cases raising etiologic questions. The vehicle for paclitaxel Cremophor EL (polyoxyethylated castor oil in 50% ethanol) was strongly suspect as a direct (non-immunoglobulin E dependent) histamine releaser. Premedication regimens and longer infusion times lowered the incidence of reactivity allowing phase II and III trials to progress through the early 1990s. The mechanism(s) underlying paclitaxel hypersensitivity-like reactions is still unknown, and clinical data on probable complement and mast cell activation are lacking. The original clinical trial protocols for paclitaxel required discontinuation of therapy for patients who experienced hypersensitivity-like reactions. Here, we review the current etiologic knowledge of these reactions and describe our clinical approach to allow completion of chemotherapy with this powerful plant-derived agent.
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PMID:Taxol reactions. 1212 9

To evaluate the efficacy and safety of PGF2a (prostaglandin) and 15(S) 15-methyl-PGF2a as abortifacient agents, the Indian Council of Medical Research studied 124 cases of medical termination of pregnancy between 10-20 weeks. 30 cases were given intraamniotic and 94 cases were given extraamniotic prostaglandin injections. All patients were constantly and carefully monitored in the postoperative ward. The age group 15-20 years had the highest % cases of intraamniotic injection while the age group 21-25 years had the highest % cases of extraamniotic injections. Highest % cases given intraamniotic injections were those with gestation period of 18-20 weeks; highest % of cases given extraamniotic route were those with gestation between 12-14 weeks. Success rate for the intraamniotic injection was 93.33% (28 aborted within 28 hours). Of the 94 given extraamniotic injection, 64 had induction-abortion interval less than 36 hours. Side effects and complications experienced included vomiting in 60% cases; diarrhea in 56.7% cases given intraamniotic injection (6% in those given extraamniotic injection); rise of temperature up to 100 degrees F after expulsion of fetus in 3.33%; cervical tear requiring suturing in 2 cases; flushing of faces after injection in 3 cases; dyspnoea following injection in 1 case; anaphylatic shock in 1, and; death in 1 (mortality rate, 0.8%) due to uncontrollable hemorrhage. It was concluded that prostaglandins are not without hazards when used for medical termination of pregnancy.
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PMID:A trial of intra-amniotic and extra-amniotic prostaglandin for medical termination of pregnancy. 1232 33

There is an ever-increasing number of therapeutics used to treat cancer. A recent publication listed 86 currently available antineoplastic medications. Despite this large number, hypersensitivity reactions are not common except with platinum compounds (cisplatin, carboplatin), epipodophyllotoxins (teniposide, etoposide), asparaginase, taxanes (paclitaxel), and procarbazine. Doxorubicin and 6-mercaptopurine are occasionally associated with hypersensitivity reaction. Comparable reactions with other chemotherapeutic agents are. uncommon; many are only anecdotal reports. Reactions associated with individual drugs are discussed in detail. The mechanisms responsible for most of these reactions are not known, as they have generally not been evaluated. The term "hypersensitivity" is widely used in the chemotherapy literature without a common definition. Hypersensitivity is defined here as an unexpected reaction with signs and symptoms not consistent with known toxicity of the drug. Most reactions are coincident with or within hours of drug administration. Almost all are associated with parenteral administration. Symptoms include flushing, alterations in heart rate and blood pressure, dyspnea and bronchospasm, back pain, fever, pruritus, nausea and all types of rashes. Some cases may be due to non-immune mediated release of histamine or cytokines, as many patients can subsequently tolerate re-exposure after pretreatment with steroids and antihistamine, and slow readministration of the drug. This is more compatible with a graded challenge, than desensitization and is generally successful for taxanes, less so for platinum compounds. In most cases hypersensitivity reactions are associated with the specific chemotherapeutic drug. Reaction rates may vary with different forms of the drugs, e.g. pegylated. Occasionally excipients such as Cremaphor EL may induce hypersensitivity reactions.
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PMID:Hypersensitivity reactions to chemotherapeutic drugs. 1272 96

We investigated the clinical characteristics and treatment of patients with a distinctive triad of acute infusion-related reactions (AIRRs) to liposomal amphotericin B (L-AMB) via single-center and multicenter analyses. AIRRs occurred alone or in combination within 1 of 3 symptom complexes: (1) chest pain, dyspnea, and hypoxia; (2) severe abdomen, flank, or leg pain; and (3) flushing and urticaria. The frequency of AIRRs in the single-center analysis increased over time. Most AIRRs (86%) occurred within the first 5 min of infusion. All patients experienced rapid resolution of symptoms after intravenous diphenhydramine was administered. The multicenter analysis demonstrated a mean overall frequency of 20% (range, 0%-100%) of AIRRs among 64 centers. A triad of severe AIRRs to L-AMB may occur in some centers; most of these reactions may be effectively managed by diphenhydramine administration and interruption of L-AMB infusion.
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PMID:Triad of acute infusion-related reactions associated with liposomal amphotericin B: analysis of clinical and epidemiological characteristics. 1274 64

Patients treated with platinum compounds are subject to hypersensitivity reactions. Our study has highlighted the reactions related to oxaliplatin (OHP) infusion. One hundred and twenty-four patients affected by advanced colorectal cancer were treated with different schedules containing OHP, at the Institute of Haematology and Medical Oncology 'L. and A. Seragnoli' of Bologna and at the Medical Oncology Division of Livorno Hospital. Seventeen patients (13%) showed hypersensitivity reactions after a few minutes from the start of the OHP infusion. Usually, these reactions were seen after 2-17 exposures to OHP (Mean+/-s.e.: 9.4+/-1.07). No patient experienced allergic reactions at his/her first OHP infusion. Eight patients developed a mild reaction consisting of flushing and swelling of the face and hands, itching, sweating and lachrymation. The remaining nine patients showed a moderate-severe reaction with dyspnoea, wheezing, laryngospasm, psycho-motor agitation, tachycardia, precordial pain, diffuse erythema, itching and sweating. Six patients out of 17 were re-exposed to the drug with premedication of steroids and all except one developed the hypersensitivity reaction again. The cumulative dose, the time of exposure to OHP and the clinical features are variable and unpredictable. The risk of developing hypersensitivity reactions in patients treated with a short infusion of OHP cannot be underestimated.
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PMID:Hypersensitivity reactions related to oxaliplatin (OHP). 1288 15

A 32-year-old woman, gravida 4, para 2, visited Teikyo University Hospital with complaints of abnormal uterine bleeding and lower abdominal pain. Urine hCG level was 1,024 x 10(3) IU/l. MRI examination showed a vascular, rich solid mass 10 cm in diameter at the posterior region of the uterus. Under the clinical diagnosis of choriocarcinoma, she underwent total hysterectomy with right salpingooophorectomy. The ovarian choriocarcinoma was confirmed by pathologic examination. Additional chemotherapy was planned using the combined regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovin. After 2 min of etoposide administration (100 mg/m2), the patient complained of acute dyspnea, which was caused by bronchospasms and cutaneous flushing. Etoposide infusion was immediately stopped, and anti-anaphylaxic treatment was done by administering hydroxyzine hydrochloride. Five min after the episode had occurred, the patient recovered. This episode was thought to have been induced by etoposide, but etoposide was a key agent for choriocarcinoma. Thus, we devised a modified chemotherapy using etoposide as follows. The regimen was hydrocortisone 100 mg i.v. q6 h and promethazine hydrochloride 50 mg i.m. q6 h for 24 h before infusion of etoposide. The etoposide concentration was diluted to 50%, and the drug administration rate reduced by half. With the modified regimen, the patient showed no anaphylaxic symptoms. The few reports on anaphylaxic reactions to chemotherapeutic agents induced by side effects must be taken into account when we use these drugs.
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PMID:[Anaphylaxia induced by etoposide--a case report]. 1293 79

Elevated blood pressure is a risk factor for a variety of cardiovascular disorders, including coronary heart disease, peripheral vascular disease, cardiac failure and cerebrovascular disease. The prevailing view is that an elevated systolic rather than diastolic blood pressure is the major contributor in mortality and morbidity attributed to cardiovascular disorders. Isolated high systolic blood pressure, especially in the elderly, is a major risk factor and should undoubtedly be a target for drug treatment. In the general population, systolic and diastolic blood pressure are highly correlated, and thus it is difficult to dissociate the effects of these two components of the blood pressure and specifically ascribe cardiovascular risk factors to just elevated systolic blood pressure. Therefore, the goal in therapy of an individual with hypertension must be to reduce elevated systolic and diastolic blood pressure in order to reduce mortality and morbidity. ACE and neutral peptidase inhibitors are a new class of drugs that may be beneficial in the treatment of patients with hypertension and heart failure. They may also be useful in the treatment of diabetic patients with hypertension and/or heart failure. Drugs of this class are dual inhibitors of ACE and neutral endopeptidase, and are capable of affecting vascular tone and fluid balance. They are capable of producing vasodilatation by virtue of inhibiting the production of angiotensin II, degradation of natriuretic peptides and bradykinin. They also appear to promote natriuresis and diuresis by amplifying the actions of natriuretic peptidase and reducing aldosterone effects. In addition, they should also attenuate trophogenic actions of the renin angiotensin system and the sympathetic nervous system. Omapatrilat is one drug that appears to be at the advanced stages of clinical development. This drug has been shown to be quite effective in the treatment of hypertension. Evidence also seems to indicate that treatment with omapatrilat results in a higher tendency towards preventing death and worsening heart failure when compared with treatment with a pure ACE inhibitor in patients with advanced heart failure. Overall safety with omapatrilat appears to be good, but like other ACE inhibitors the incidence of cough is higher when compared with placebo. Other common adverse effects noted are headaches, facial flushing/warm sensation, dizziness, nausea and dyspnoea. Of greater concern is the occurrence of angio-oedema, the true incidence of which remains to be fully established as part of the published medical literature.
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PMID:Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders. 1501 94

Dexamethasone-cyclophosphamide pulse (DCP) is the prefered mode of therapy in pemphigus in India because it is relatively free from the side effects seen with heavy doses of daily oral steroids. One hundred forty-six pemphigus patients treated with DCP were observed for side effects of this regimen. One hundred forty mg of dexamethasone was administered IV in 200 ml of 5% dextrose over a period of 60-90 minutes on 3 consecutive days. Five hundred mg of cyclophosphamide was added on first day of the pulse and 50 mg given orally daily in the intervening period. DCP was repeated every 4 weeks and continued for 6 months after subsidence of the disease (no new lesions). Flushing over the face was the most common event recorded during the adiministration in 78 subjects followed by palpitations in 11, hiccups in 9, and numbness of feet in 6. Fourteen patients had polyurea, and 3 developed skin rash. Shivering, shooting pains along thighs, breathlessness, seizure and unilateral limb edema were observed in one patient each. Generalized weakness/malaise was the most troublesome delayed side effect in 81 (55.4%) patients; it lasted for 8-15 days after the pulse. Thirty-six (24.6%) had inadequate sleep syndrome, 23 (15.7%) had headache, 21 (14.3%) complained of arthralgias, 19 (13%) experienced alteration in taste, and 13 (9%) had diffuse hair loss. 28 females developed menstrual disturbances, and 14 (9.5%) had blurring of vision (glaucoma in 3 and posterior subcapsular cataract in 1). Thirteen of eighteen diabetics had an increase in blood sugar requiring higher doses of insulin. Five NIDDM patients needed insulin. Four (2.7%) developed hypertension. Pulse therapy is not absolutely free from side effects. Hypertension and diabetes occur less frequently as compared to conventional steroid therapy. Generalized weakness, flushing, headache and taste alteration occur exclusively with pulse therapy.
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PMID:Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy. 1468 52

Bosentan is a nonpeptide, specific, competitive, dual antagonist at both endothelin receptor subtypes (ET(A) and ET(B)). Orally administered bosentan effectively prevents endothelin 1-induced vasoconstriction in pulmonary vessels in patients with pulmonary arterial hypertension. Improvement in exercise capacity from baseline was significantly greater with bosentan than with placebo in two phase III trials in patients with WHO functional class III or IV pulmonary arterial hypertension (primary or associated with connective tissue disease) despite treatment with vasodilators, diuretics, anticoagulants, cardiac glycosides, or supplemental oxygen. The beneficial effects of bosentan on exercise capacity were maintained for at least 20 weeks. Compared with placebo, bosentan led to a significantly greater improvement from pretreatment values in secondary efficacy endpoints such as the Borg dyspnea index, WHO functional class, and cardiopulmonary hemodynamic parameters (cardiac index, pulmonary vascular resistance, pulmonary artery pressure, pulmonary capillary wedge pressure, mean right atrial pressure). Bosentan significantly reduced the incidence, and delayed the onset, of clinical worsening of pulmonary arterial hypertension compared with placebo. In published clinical trials, adverse events that occurred with similar or greater frequency with bosentan 125 mg twice daily than with placebo included headache, syncope, flushing and abnormal hepatic function. Those that occurred less frequently with bosentan 125 mg twice daily than with placebo included dizziness, worsening of symptoms of pulmonary arterial hypertension, cough and dyspnea.
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PMID:Bosentan. 1472 63


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