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)

Taxol inhibits cell division by promoting the assembly and stabilization of microtubules. This report describes the results of a phase I trial of taxol administered as a short iv infusion daily for 5 days every 4 weeks. Sixteen patients with refractory malignancy received 21 courses of taxol at five doses between 5 and 40 mg/m2/day X 5. The first nine patients received taxol as a 60-minute infusion. Two patients experienced anaphylactoid reactions, one at the 5-mg/m2/day and the second at the 15-mg/m2/day X 5 dose levels. These reactions were characterized by facial flushing, tachypnea, and hypotension within several minutes of drug administration. These anaphylactoid reactions occurred on the first day of treatment in the first patient and on the first day of the second course in the second patient. These reactions may be related to the rapid administration of the polyoxyethylated castor oil (Cremophor EL) vehicle in which taxol is formulated. No anaphylactoid reactions were observed in the seven patients who received taxol as a 6-hour infusion with antihistamine and prednisone premedication. Dose-related myelosuppression was seen; leukopenia (wbc count less than 1000/mm3) and granulocytopenia (granulocytes less than or equal to 200/mm3) occurred on Days 8 and 9 in two of two patients treated at the 40 mg/m2/day X 5 level. Thrombocytopenia was mild, with a platelet nadir of 87,000-95,000/mm3 at the highest dose level. Premedication with glucocorticoids and antihistamines coupled with a prolonged 6-hour infusion permitted taxol to be administered at 30 mg/m2/day X 5 safely without immediate life-threatening reactions.
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PMID:Phase I study of taxol administered as a short i.v. infusion daily for 5 days. 289 42

Acute anaphylactoid reactions occurred immediately after initiation of intravenous infusions of cyclosporine in three patients post-organ transplantation. Shortness of breath, flushing, tachypnea, chest pain, pruritus, or urticaria were noted; rapid recovery followed cessation of drug infusion. Subsequently, oral cyclosporine has been used in each patient without recurrence of the observed reaction. The presence of Cremophor EL as an emulsifying agent in the parenteral dosage formulation of cyclosporine is a likely etiology for this acute adverse reaction. Slowed rates of drug infusion and antihistamine premedication may permit continued intravenous cyclosporine use in affected patients.
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PMID:Anaphylactoid reactions associated with parenteral cyclosporine use: possible role of Cremophor EL. 400 35

Adverse effects of intravenous anaesthetic drugs may be divided into local and general effects. The former include venous sequelae ranging from soreness on palpation on the day after the injection to thrombosis of the whole venous system of the arm. Frequency of venous sequelae for water-soluble anaesthetics 5 to 10%; drugs sparingly soluble in water are similar in this regard when solubilised in 'Cremophor EL'. Diazepam or etomidate dissolved in propylene glycol can produce venous reactions in about 25% of patients on the 3rd day and more by the 15th day if given directly into the vein, and are really only acceptable when injected in an infusion. The general adverse effects of anaesthetic agents include excitatory effects, as well as those on the cardiovascular and respiratory systems which are almost unavoidable. Excitatory effects are diminished by suitable premedication, and the cardiovascular and respiratory effects can be minimised by low dosage and slow administration. Cardiovascular effects of the muscle relaxants are also unavoidable with the drugs presently available, but further research should provide drugs with greater selectivity. More troublesome are the hypersensitivity reactions which occur with both the induction agents and the neuromuscular blocking drugs. These range in frequency from about 1 in 30,000 with the barbiturates to about 1 in 1000 with the 'Cremophor'-containing solutions of propanidid and alphaxalone/alphadolone. However, it appears that the barbiturate reactions are more severe and prolonged. The frequency of hypersensitivity reactions following muscle relaxants is difficult to assess because marked flushing is very common following tubocurarine and bronchospasm can frequently be due to passage of an endotracheal tube. In spite of the alarm created by these reactions, provided the patient is treated in the standard manner, the mortality should be low.
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PMID:Adverse effects of intravenously administered drugs used in anaesthetic practice. 702 Nov 21

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

Intravenous injection of some liposomal drugs, diagnostic agents, micelles and other lipid-based nanoparticles can cause acute hypersensitivity reactions (HSRs) in a high percentage (up to 45%) of patients, with hemodynamic, respiratory and cutaneous manifestations. The phenomenon can be explained with activation of the complement (C) system on the surface of lipid particles, leading to anaphylatoxin (C5a and C3a) liberation and subsequent release reactions of mast cells, basophils and possibly other inflammatory cells in blood. These reactions can be reproduced and studied in pigs, dogs and rats, animal models which differ from each other in sensitivity and spectrum of symptoms. In the most sensitive pig model, a few miligrams of liposome (phospholipid) can cause anaphylactoid shock, characterized by pulmonary hypertension, systemic hypotension, decreased cardiac output and major cardiac arrhythmias. Pigs also display cutaneous symptoms, such as flushing and rash. The sensitivity of dogs to hemodynamic changes is close to that of pigs, but unlike pigs, dogs also react to micellar lipids (such as Cremophor EL) and their response includes pronounced blood cell and vegetative neural changes (e.g., leukopenia followed by leukocytosis, thrombocytopenia, fluid excretions). Rats are relatively insensitive inasmuch as hypotension, their most prominent response to liposomes, is induced only by one or two orders of magnitude higher phospholipid doses (based on body weight) compared to the reactogenic dose in pigs and dogs. It is suggested that the porcine and dog models are applicable for measuring and predicting the (pseudo)allergic activity of particulate "nanodrugs".
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PMID:Animal models of complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanoparticles. 1761