Carbamazepine-Induced Hemolytic Anemia

Stroink, Ann R.; Skillrud, David M.; Kiely, Joseph M.; Sundt, Thoralf M.

doi:10.1159/000206413

Cited by 7 publications

(2 citation statements)

References 2 publications

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“…Despite hemolysis caused by cationic and anionic dendrimers is reported to be generation-and concentrationdependent, non-hemolysis is found at low dendrimer concentration (<1 mg/mL) (Asthana et al, 2005;Bhadra et al, 2003;Malik et al, 2000;María Jimena Prieto et al, 2011). However, it is of importance to test the hemolytic effect of the complexes as it has been reported that CBZ can induce hemolytic anemia (Sobotka et al, 1990;Stroink et al, 1984;Yamamoto et al, 2007). In this work, we evaluated the hemolytic effects ( Figure 5) and possible morphological changes ( Figure S5) after 4-and 24-h human red blood cells incubation with free CBZ, dendrimers and D-CBZ complexes.…”

Section: Ex Vivo Toxicity: Hemolysis Assay and Human Red Blood Cells mentioning

confidence: 99%

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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Carbamazepine (CBZ) is an antiepileptic drug, which also could be used in the treatment of neurodegenerative diseases, such as the Alzheimer's disease. However, its use has been limited due to its low solubility, inefficient pharmacokinetic profiles, and multiple side effects. PAMAM dendrimers, ethylenediamine core, generation 4.0 (amine terminal groups) and 4.5 (carboxylate terminal groups) (DG4.0 and DG4.5 respectively) are polymers that can increase drug solubility through complexation. Thus, the aim of this work was to obtain and characterize complexes between CBZ and dendrimers. Both DG4.0 and DG4.5 allowed the incorporation of ∼20 molecules of CBZ per dendrimer, into their hydrophobic pockets. DG4.0-CBZ and DG4.5-CBZ complexes were found to be stable for 90 days at 37 °C and resistant to a lyophilization process, presenting controlled drug release. Also, the complexes nanotoxicity was tested ex vivo (human red blood cells), in vitro (N2a cell line), and in vivo (zebrafish). No hemolytic effect was observed in the ex vivo model. As regards in vitro toxicity, the DG4.5-CBZ complexes significantly reduced the toxicity caused by the free drug. Moreover, the DG4.5-CBZ did not cause neurotoxicity or cardiotoxicity in zebrafish larvae. In conclusion, a stable and biocompatible drug delivery system based on the DG4.5 capable of complex the CBZ has been developed. This achievement highlights the advantages of using negatively charged dendrimers for nanomedicine.

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Section: Ex Vivo Toxicity: Hemolysis Assay and Human Red Blood Cells mentioning

confidence: 99%

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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“…In some cases, specific autoantibodies can be demonstrated. Both haemolytic and aplastic anaemia have been reported during anticonvulsant administration (Gerson et al 1983;Stroink et al 1984). Bone marrow depression is a rare adverse reaction to anticonvulsants, but is obviously important for the potentially fatal consequences.…”

Section: Autoimmune Diseasesmentioning

confidence: 99%

Immunological Adverse Effects of Anticonvulsants

et al. 1993

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Long term administration of anticonvulsants is sometimes associated with impairment of the humoral and/or cellular immune response. Furthermore, certain well known adverse reactions to antiepileptics may have an immunotoxicological origin e.g. lymphadenopathy, pseudolymphoma and systemic lupus erythematosus. However, two important questions remain unresolved. First, the possibility that epilepsy per se might be primarily associated with immune alterations makes it difficult to assess the pathogenetic role of a specific drug, especially in a patient population usually on multiple drug therapy. Secondly, the clinical relevance of some of the observed immunological abnormalities is still highly controversial. This review is intended to give an outline of the present state of knowledge on the effects of anticonvulsants on humoral, cellular and nonspecific immunity, with particular regard to some of the major clinical conditions that have been ascribed to drug-induced immune dysregulation, such as pseudolymphoma and systemic autoimmune diseases. The immunotoxic potential of anticonvulsants appears to be low, and immunological monitoring is not usually required except in patients with known immune defects.

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