Deferoxamine indications

The fitted means and standard errors for log-transformed comet tail moments, as well as the percentage of cells exhibiting extensive DNA damage (e.g., cells labeled 3 and 4) are reported in Table 2 [see p. 137]. An adjusted p value indicated no differences existed between cells treated with extracts from exposed filters or with hydrogen peroxide. Cellular responses were significantly different (P < 0.05) between unloaded PMj 5 filter extracts and loaded PM2 5 extracts as well as extracts containing deferoxamine. 

Deferoxamine derives from Streptomyces pilosus. The substance possesses a very high iron-binding capacity but does not withdraw iron from hemoglobin or cytochromes. It is poorly absorbed enterally and must be given parenterally to cause increased excretion of iron. Oral administration is indicated only if enteral absorption of iron is to be curtailed. Unwanted effects include allergic reactions. 

As a result of the crises entailing destruction of the red blood cells and the frequently required blood transfusions, liver siderosis develops. This may subsequently lead to fibrosis in some cases. Episodic cholestasis can be witnessed. In progressive siderosis, treatment with deferoxamine is indicated. Pigment gallstones (s. figs. 

Intravenous deferoxamine can be indicated in gross iron overload, serious cardiomyopathy, or intolerance of or non-adherence to subcutaneous administration. The results of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in 17 patients (25 intravenous lines) have been presented (154). The doses of deferoxamine were calculated with reference to the serum ferritin concentration, with a view to maintaining the therapeutic index (mean daily dose in mg/kg divided by the serum ferritin concentration in ng/ml) below... 

The vitamin is indicated fur the treatment and prevention of ascorbic acid deficiency. Although scurvy occurs infrequently. it is. seen in the elderly, infants, alcoholic.s. and drug users. Ascorbic acid (but not the sodium. salt) frequently is administered with methcnaminc to improve the effectiveness of this antibacterial agent. Because a.scorbic acid increases imn chelation by deferoxamine, it is u.scd in the treatment of chronic iron toxicity. It is also a useful adjunct in the ireatment of methemoglobinemia. 

Rapid infusion of deferoxamine over 15 min results in hypotension and tachycardia. An infusion rates of 15mgkg h or longer is recommended. Intravenous deferoxamine administration has been reported to cause renal insufficiency indicated by a progressive increase in serum creatinine and decrease in creatinine clearance. 

Deferoxamine is an effective chelator of iron. Deferoxamine chelates iron and converts it to a water-soluble complex, ferrioxamine, which is eliminated readily via the urine. Indications for deferoxamine infusion include significant clinical signs of iron toxicity, metabolic acidosis, shock, serum iron levels >500pgdl , and/or an X-ray positive for multiple pills. Deferoxamine should be infused intravenously at a starting rate of 15mgkg h , not to exceed lgh , over a total of 6h and then reevaluated. Deferoxamine-induced hypotension may occur at fast rates, and adequate hydration should be assured before infusion initiation. As iron is chelated and excreted, urine may develop a characteristic rusty-red ( vin rose ) appearance. 

Patients with systemic symptoms (e.g., shock, coma, or gross gastrointestinal bleeding or metabolic acidosis) should receive deferoxamine as soon as possible. If the serum iron concentration exceeds 500 mcg/dL, deferoxamine is also indicated because serious systemic toxicity is hkely. Its use is less clear in patients with serum iron concentrations in the range of350-500 mcg/dL because many of these patients do not develop systemic symptoms. ... 

Deferoxamine is a highly selective chelator of iron that theoretically binds ferric (Fe +) iron in a 1 1 molar ratio (100 mg deferoxamine to 8.5 mg ferric iron) that is more stable than the binding of iron to transferrin. Deferoxamine removes excess iron from the circulation and some iron from transferrin by chelating ferric complexes in equilibrium with transferrin. The resulting iron-deferoxamine complex, ferrioxamine, is then excreted in the urine. Its action on intracellular iron is unclear, but it may have a protective intracellular effect or may chelate extramitochondrial iron. The parenteral administration of deferoxamine produces an orange-red-colored urine within 3 to 6 hours because of the presence of ferrioxamine in the urine. For mild to moderate cases of iron poisoning, where its use is unclear, the presence of discolored urine indicates the persistent presence of chelatable iron and the need to continue deferoxamine. The reliance on discolored urine as a therapeutic end point has been challenged because it is not sensitive and is difficult to detect. ... 

The desired end point for deferoxamine therapy is not clear. Some have suggested that deferoxamine therapy should cease when the serum iron concentration falls below 150 mcg/dL. The decline of serum iron concentrations, however, may not account for the potential cellular action of deferoxamine irrespective of its effect on iron elimination. The cessation of orange-red urine production that is indicative of ferrioxamine excretion is also notrehable because many individuals cannot distinguish its presence in the urine. Considering these shortcomings, deferoxamine therapy should be continued for 12 hours after the patient is asymptomatic and the urine returns to normal color or until the serum iron concentration falls below 350 mcg/dL and approaches 150 mcg/dL. 

Answer D. Deferoxamine chelates iron and is the antidote in iron poisoning. Gastric lavage should be attempted with care regarding aspiration, but changes in urine pH have no effect on the elimination of iron. laboratory results will reveal an increased anion gap indicative of acidosis. The systemic absorption of many drugs taken orally can be reduced by activated charcoal unfortunately, iron is not one of them. 

B. Deferoxamine is sometimes used as a lest dose to determine the presence of free iron by observing for the characteristic vin rose color in the urine however, a change in urine color is not a reliable indicator. 

Sensory systems Eyes Vitelliform or egg yolk-like cysts in the retinal macula are typical of Best s disease, an autosomal inherited retinopathy and can also occur in deferoxamine-related retinopathy. This has again been reported in a woman with (unspecified) thalassemia who had been treated with regular blood transfusions and intramuscular and subcutaneous deferoxamine for about 20 years [20 ]. She had bilaterally reduced visual acuity of sudden onset and there were no indicators of a genetic disposition. 

Vanadium(IV) caused molecular oxygen-dependent 2 -deoxyguanosine hydroxylation and DNA strand breaks (Shi et al. 1996). ESR spin trapping measurements demonstrated that the reaction of vana-dium(IV) with HjOj generated HO radicals, which were inhibited by the metal ion chelators, diethyle-netriaminepentaacetic acid (DTPA) and deferoxamine. UV-visible measurements indicated that 2 -... 

The use of a combination of scanning electron microscopy to examine sur-faee adhesion and light mieroscopy to examine uptake, indicated that deferoxamine treatment decreased both the number of adherent fibers and the amount of fiber uptake, whereas catalase treatment deereased uptake with little effeet on adhesion (Churg A, unpublished data), and reagent hydrogen peroxide inereased... 

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