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Drug Overdoses during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Unpublished animal studies suggest deferoxamine may cause significant fetal effects; human clinical experience does NOT parallel these findings. The cause of adverse fetal outcomes in humans are associated with maternal iron overdose-associated pathophysiological effects, and not the direct result of iron overdose or antidote. No congenital anomalies were noted among infants whose mothers consumed high doses of iron during pregnancy (Lacoste et al., 1992; Tenenbein, 1989). It appears as though the placenta acts as a partial barrier to iron (Olenmark et al., 1987; Rayburn et al., 1983; Richards and Brooks, 1966). Chemical properties of the deferoxamine molecule strongly suggest it may not cross the placenta in large amounts because it is a large molecule (molecular weight, 657) and is highly polarized. Deferoxamine’s molecular weight is within the range for placental transfer (i.e., <1,000 m.w.), but high polarity moieties generally are impeded from transfer.
Reactive Oxygen Metabolites and Iron in Toxic Acute Renal Failure
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Karl A. Nath, Norishi Ueda, Patrick D. Walker, Sudhir V. Shah
We examined the effect of hydroxyl radical scavengers and iron chelators in gentamicin-induced acute renal failure in rats.19 We first examined the effect of a hydroxyl radical scavenger, DMTU and of an iron chelator, deferoxamine, on gentamicin-induced acute renal failure. Rats treated with gentamicin for 8 d (100 mg/kg, s.c.) had a marked increase in BUN (215 ± 30 mg/dl n = 8) compared to saline-treated controls (BUN: 16 ± 1 mg/dl, n = 8). In contrast, DMTU-treated rats had significantly lower BUNs (BUN: 48 ± 17 mg/dl, n = 8,p < 0.0001). Similarly, deferoxamine afforded a marked protective effect (BUN: 30 ± 7 mg/dl, n = 8 p < 0.0001) against gentamicin-induced acute renal failure. In additional experiments, we determined that the protective effect of DMTU and deferoxamine was not due to their effect either on the uptake of gentamicin by renal cortical tissue or to their effects on the generation of ROM by renal cortical mitochondria.
Metals
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Anirudh J. Chintalapati, Frank A. Barile
Deferoxamine is an aluminum (Al) and iron (Fe(II)) chelator that is beneficial in the treatment of acute and chronic Fe poisoning and for Al overload. The compound is isolated from bacteria (Streptomyces pilosus) and is one of the few chelators recommended for the alleviation of secondary Fe overload. It is not effective orally and requires continuous subcutaneous administration to achieve efficient Fe elimination. Figure 26.4 illustrates the structure of deferoxamine with a chelated Fe moiety. It preferentially binds both free and bound Fe from hemosiderin and ferritin but not Fe contained in hemoglobin, transferrin, or cytochromes. Chemical structure of deferoxamine with Fe in the reduced form.
Luspatercept for β-thalassemia: beyond red blood cell transfusions
Published in Expert Opinion on Biological Therapy, 2021
Ali T. Taher, Maria Domenica Cappellini
The benefits of ICT in patients with β-thalassemia are well established. RBC transfusions plus ICT have been associated with improved long-term survival among TD patients [12]. Three iron chelators are approved for the treatment of iron overload. Deferoxamine, the first commercially available iron chelator, has been the standard treatment for years; however, adherence is generally poor due to the inconvenient treatment regimen. Adverse events (AEs) associated with deferoxamine include reaction at the infusion site, allergic reaction, hearing loss, damage to the retina, and growth failure [30]. The oral iron chelators, deferiprone and deferasirox, have become available within the past decade and provide improved compliance and QoL compared with parenteral deferoxamine [31,32]. The most common side effects associated with oral ICT are gastrointestinal events, arthralgia, neutropenia, proteinuria, skin rash, and increased liver enzymes, glomerular filtration rate (GFR), and serum creatinine [30].
The combination of deferoxamine and minocycline strengthens neuroprotective effect on acute intracerebral hemorrhage in rats
Published in Neurological Research, 2021
Zhe Li, Yang Liu, Ruixue Wei, Suliman Khan, Mengzhou Xue, V. Wee Yong
After ICH, a large amount of iron is released from the destruction of erythrocytes. As one of the main degradation products of hemoglobin, iron ions cause brain edema and cell death after ICH through the activation of a series of oxygen-free radicals and inflammatory reactions [32,33]. The Iron overload around the hematoma will lead to large amounts of reactive oxygen species and lipid peroxidation, thereby aggravating secondary brain damage [34]. Deferoxamine, as a kind of iron chelator, has a strong affinity for Fe3+, which can quickly excreted from the body and reduce the pathological deposition of iron in the body [35]. After systemic administration, deferoxamine can rapidly penetrate the blood-brain barrier, accumulate in high concentration in local brain tissue [36], and reduce the content of iron ion in hematoma, thereby reducing the secondary neuronal damage after ICH. Several studies have shown that deferoxamine can attenuate hemoglobin-related edema [17], neuronal death, neurological deficits and brain atrophy in animal ICH models [15,16,37]. Our study demonstrated that DFX treatment reduced the accumulation of iron, neuronal death, and the improvement in forelimb placement and corner tests compare with the vehicle group. Most worthy of mention is that our study found the combination treatment has a better therapeutic effect, which may be related to the iron chelation effect of minocycline.
Drug safety in thalassemia: lessons from the present and directions for the future
Published in Expert Opinion on Drug Safety, 2021
Laura Grech, Janet Sultana, Karen Borg, Joseph Borg
Deferoxamine (Desferal® or desferrioxamine) is produced by bacterium Streptomyces pilosus [20]. It was the first clinically approved iron chelator for treatment of β-thalassemia and has been in use from 1980s [21]. Deferoxamine is a hexadentate iron chelator that treats iron toxicity by binding trivalent ferric iron to form a stable complex known as ferrioxamine [22] (Table 1). Deferoxamine adverse drug reactions (ADRs) include irritation at the infusion site, skeletal changes, growth retardation, and ocular or auditory disturbances, while respiratory distress was reported with high intravenous doses [23–25]. In rare cases, it was also shown that deferoxamine is a risk factor for Yersina adenomesenteritis infections, including sepsis, as this drug may increase host iron bioavailability [26,27].