Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desferrioxamine (DFX) remains the most effective and safe iron chelator for treatment of patients with transfusional iron overload. It is usually given by intermittent subcutaneous infusions for 8-12 h on 4-6 days weekly using a battery-driven pump. Disposable balloon infusers provide a suitable method of giving continuous subcutaneous infusions with improved patient compliance. For patients with cardiac abnormalities due to iron overload, continuous intravenous desferrioxamine is essential to eliminate toxic plasma non-transferrin bound iron and to reduce body iron stores. Deferiprone (L1, l-2 dimethyl-3hydroxy-pyrid-4-one) is a less effective iron chelator but has the advantage of being orally active. Long-term trials in which patients have taken 75 mg/kg/day have shown that deferiprone is capable of maintaining body iron stores at safe levels in a proportion of thalassaemia major patients but body iron stores, assessed by liver biopsy remain at high levels (> 15.0 mg/g dry weight) in a substantial number of patients. These concentrations have been associated with tissue damage. Trials of increased doses of deferiprone (up to 100 mg/kg/day) or of combined therapy with daily deferiprone and DFX or 1 or 2 days each week are being carried out in an attempt to achieve lower body iron burden in these patients. Preliminary results show that the drugs can be given safely together and urine iron excretion produced is additive, implying that the drugs chelate different body iron pools. Patients previously well chelated with serum ferritin levels less than 2500 micrograms/L have the fewest side-effects from deferiprone and usually may be kept at the same level of body iron for periods of at least 4 years, assessed by serum ferritin and urine iron excretion. The side-effects of deferiprone result in some patients discontinuing therapy. These side-effects, especially arthropathy, mainly occur in previously poorly chelated and so the most heavily iron-loaded patients. Nausea and other gastrointestinal symptoms, agranulocytosis or milder degrees of neutropenia account with arthropathy for nearly all the withdrawals from deferiprone therapy. Patients with cardiomyopathy due to iron overload should be given intravenous DFX rather than deferiprone. Deferiprone, licensed for pharmaceutical use in India, awaits official approval for widespread clinical use in Western Europe and North America. Meanwhile, attempts to find new orally active iron chelators and improved methods of administration of desferrioxamine are in progress.
 ...
PMID:Iron chelation therapy. 935 Jan 80

Iron overload caused by lifelong transfusion-dependent anaemias, such as beta-thalassaemia major, usually results in lethal cardiac toxicity in the second decade of life if not treated by iron chelation. There is no physiological mechanism for excreting the excess iron accumulated from blood transfusions and, unlike hereditary haemochromatosis, venesection is not an option. Therefore, chelation therapy is the only way to remove excess iron. This must be removed while not depriving cells of the essential iron needed for normal metabolism. Additionally, the iron chelator must prevent iron from participating in the generation of harmful free radicals. Parenteral chelation therapy with deferoxamine (desferrioxamine) is well established as promoting negative iron balance, reversing cardiac toxicity, and prolonging life expectancy well into the fourth decade of life and, most likely, beyond. Unfortunately, poor compliance with the rigours of parenteral treatment in a minority of patients limits its regular use, resulting in reduced life expectancy in these patients. Use of deferoxamine in excessive dosages may result in growth retardation, sensorineural ototoxicity and ocular toxicity, as well as bone deformities. These effects can be largely avoided if the dosage is adjusted to take account of the degree of iron overload (using the therapeutic index) and if the mean daily dose does not exceed 40 mg/kg. Nevertheless, it is recommended that patients be regularly monitored for such adverse effects. Deferiprone (L1; CP20) is an orally absorbed bidentate hydroxypyridinone iron chelator that can induce urinary iron excretion, promote negative iron balance and reduce hepatic iron levels in some transfusion-dependent patients, particularly in those who are markedly iron overloaded and have not received regular deferoxamine therapy. The long term efficacy and toxicity of deferiprone are the subjects of some controversy, and the published results of randomised controlled trials are awaited. Preliminary results suggest that when currently recommended dosages of deferiprone (75 mg/kg/day) are used, hepatic iron settles at levels that still put most patients at an increased risk from iron overload. A number of adverse effects may occur, and require cessation of therapy in up to 30% of patients. These effects include arthritis, nausea and (most seriously) agranulocytosis in 0.6 to 4% of patients. The risk of the latter complication means that frequent white blood cell counts are mandatory for patients taking this drug. There remains an urgent need to identify an orally active chelator regimen that is as effective as deferoxamine and has an acceptable degree of tolerability.
 ...
PMID:A risk-benefit assessment of iron-chelation therapy. 942 39

Deferiprone, also known as L1, is an orally active iron chelator that has been studied extensively in clinical trials. The sporadic occurrence of agranulocytosis in association with deferiprone and the highly variable frequency of other possible side effects such as arthralgia have created uncertainty about the true incidence of deferiprone-related complications. A multi-center, 1-year trial was initiated to determine the safety profile of deferiprone. Using the Apotex formulation of deferiprone, 187 patients with thalassemia who were unable or unwilling to use deferoxamine were enrolled in four centers; 162 patients completed one year of therapy. Agranulocytosis (ANC < 500/mm3) occurred in one patient after 15 weeks of treatment, was not accompanied by infection and resolved following treatment with G-CSF. Nine other subjects developed less severe neutropenia (ANC 500-1500/mm3) with the lowest absolute neutrophil count reaching 500-1250/mm3. The neutropenia in these patients developed after 1-50 weeks of therapy, frequently accompanied febrile illnesses, and occurred predominantly in non-splenectomized patients. Reasons other than neutropenia for discontinuing use of deferiprone included nausea (4), voluntary withdrawal (3), high ALT (2), platelet count < 100,000/mm3 (2), low but unconfirmed ANC (1), protocol violation (1) fatigue (1), and depression (1). Mean ALT levels rose within three months of therapy and stabilized thereafter. Arthralgia and nausea and/or vomiting occurred in 6% and 24% of subjects, respectively. In this multi-center trial with weekly monitoring of blood counts, the incidence of agranulocytosis was 0.58 per 100 patient-years, and the frequency of agranulocytosis after one year was 0.5%. These findings support the safety of this formulation of deferiprone, using the careful monitoring system employed in this trial.
 ...
PMID:A multi-center safety trial of the oral iron chelator deferiprone. 966 43

Provision of zinc supplements to children should be considered when their usual diet is low in absorbable zinc; severe stunting, low plasma zinc, or both; or persistent diarrhea. Inadequate zinc intakes are highly prevalent in developing countries, especially during the period of complementary feeding when zinc requirements are high and breast milk contributes little. To date, systematic evaluation of the acceptability of different zinc salts used as supplements is lacking. Some zinc salts are unpalatable and cause problems, such as nausea, at higher doses. Zinc carbonate and oxide are insoluble and poorly absorbed. Little information on the bioavailability of different zinc supplements in the presence of dietary inhibitors of zinc absorption exists. More information is needed on the quantity and frequency of dosing. Consideration should be given to the routine inclusion of zinc in iron supplements provided to children and to the simultaneous inclusion of other micronutrients in zinc supplements.
 ...
PMID:Zinc and micronutrient supplements for children. 970 Nov 67

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.
 ...
PMID:Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial. 1067 41

We report our experience with deferiprone (L1) (DFP) in 17 thalassemic patients, followed up in one center in Lebanon, who were initially on desferrioxamine and then shifted to DFP at a dose of 50-75 mg/kg/day as the sole chelator during 1-year follow-up. All 17 patients were compliant with therapy and there was no change in physical examination over the study period. Eight patients (47.1%) were positive for hepatitis C virus (HCV) antibodies. Urinary iron excretion was 21.8 +/- 14 mg/24 h (mean +/- SD) 1 week after starting DFP and dropped 12 months later to 13 +/- 7.4 mg/24 h (p = 0.009, paired t test). The initial serum ferritin level was 3,863 +/- 2,344 microg/l which dropped to 3,179 +/- 2,075 at 12 months after starting therapy (p = 0.07). HCV-negative patients as a group exhibited a significant decrease in serum ferritin after 6 and 12 months of DFP therapy (3,942 +/- 2,739 vs. 2,341 +/- 1,179 and 2,681 +/- 1,519 microg/l; p < 0.03 and p < 0.05, respectively). The most frequent side effects were joint pain, stiffness or swelling in 6 patients (35.3%), and nausea in 7 patients (41.2%), but these were well tolerated and did not require stopping treatment.
 ...
PMID:Efficacy and side effects of deferiprone (L1) in thalassemia patients not compliant with desferrioxamine. 1043 97

Iron deficiency anemia is a significant health problem for women. An intervention utilizing home visits by a nurse and the intake of alternate iron supplements was examined. Outcome measures of hematocrit levels and side effects are reported in this manuscript. Ten African-American inner city homeless women in transitional housing agreed to participate in this longitudinal study. Each participant was encouraged to take the alternate iron supplements for a three month period. Hematocrit values increased from recruitment through the third month. A paired t-test was significant (t value -5.39; df, 9; p < .0001). In addition, the side effect of fatigue decreased from recruitment through the third month. A paired t-test was significant (t value 3.18: df, 7: p = .015). During the weekly and monthly visits, when the subjects were asked if the supplements had any effect on their feelings of well-being, two women stated they had "little effects." In terms of side effects there were no complaints of nausea, stomach ache, or black tarry stools. Of the approximately 12 visits to each subject, constipation was reported only two times by two subjects. While the women did not report black stools they did offer that the vitamins seemed to color their stools green (three reported it one time and two subjects reported it three times). The benefits and the lack of side effects may have far-reaching implications for client populations such as the elderly and pregnant women who typically have difficulty with anemia and constipation alike. The weekly visits by the nurse may have added to the compliance and success of this program.
 ...
PMID:Side effects of alternative iron supplementation: a pilot study. 1061 42

In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.
 ...
PMID:Safety profile of the oral iron chelator deferiprone: a multicentre study. 1069 60

BACKGROUND: Major complications of modern bariatric operations are infrequent but can be quite disabling to the patient and pose therapeutic challenges to the surgeon. We present our experience with five patients who underwent gastrectomy for complications following gastric reduction procedures. PATIENTS AND METHODS: Between 1991 and 1995, four women and one man, average age 46.8 years (34-66), underwent total gastrectomy and Roux-en-Y end-to-side esophagojejunostomy (4), or near-total gastrectomy with esophagogastrostomy (1). The decision to perform total gastrectomy was based on the poor quality of the remaining gastric pouch and the surgeon's judgement. Preoperative diagnoses included gastric outlet obstruction secondary to anastomotic ulcer or stricture, gastroesophageal reflux with esophagitis, chronic gastrocutaneous fistula, and iatrogenic linitis secondary to gastric wrap with mesh. Preoperatively, the patients complained of intolerable nausea, vomiting, abdominal pain, and dysphagia. RESULTS: in the five patients who underwent total or near-total gastrectomy, there was no operative mortality or morbidity; however, one patient (near-total gastrectomy) has required a second operation for pyloroplasty. Although one patient was lost to follow-up 6 months after surgery, the average follow-up for the remaining four patients is 2 years. These four patients were interviewed and all report complete satisfaction with their surgery and much improvement in their symptoms. Presently, they consume an average of three meals per day (range 2-6), with each meal measuring about 2 cups in size. All report the sensation of satiety after meals. All patients receive supplemental iron, B12, and multivitamins. From a nutritional standpoint, there has not been a significant change in the levels of albumin, total protein, hematocrit, weight and BMI since total gastrectomy. CONCLUSIONS: In our experience, total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy is an appropriate therapy with low morbidity and mortality in highly selected patients with complications resulting from gastric reduction procedures.
 ...
PMID:Gastrectomy for Complications of Bariatric Procedures. 1072 78

In the last 10 years, the use of intravenous contrast media in magnetic resonance (MR) has become well-established clinical practice. Contrast media provide critical additional diagnostic information in many instances. The gadolinium chelates constitute the largest group of MR contrast media and are considered to be very safe. These agents are thought to be safer than nonionic iodinated contrast agents. Unlike x-ray agents, the gadolinium chelates are not nephrotoxic. Minor adverse reactions, including nausea (1%-2% for all agents) and hives (<1% for all agents), occur in a very low percent of cases. Health care personnel should be aware of the (extremely uncommon) potential for severe anaphylactoid reactions in association with the use of MR contrast media and be prepared should complications arise. The four gadolinium chelates currently available worldwide, gadopentetate dimeglumine, gadoteridol, gadodiamide, and gadoterate meglumine, cannot be differentiated on the basis of adverse reactions. Far fewer patients have been examined to date with the two other agents that have widespread approval, mangafodipir trisodium and ferumoxides. These latter two agents are considered to be very safe but have a higher percentage of associated adverse reactions (7%-17% with mangafodipir trisodium and 15% with ferumoxides). This review discusses the safety issues involved with administration of intravenous contrast media in MR imaging, focusing on the six agents (four gadolinium chelates, one manganese chelate, and the last a large iron particle) with widespread use world-wide.
 ...
PMID:Safety of approved MR contrast media for intravenous injection. 1093 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>