Antitubulin Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Neurotoxicity, usually manifesting as peripheral or autonomic neuropathy, occurs with all Vinca alkaloids and is a dose-limiting side effect of vincristine. It occurs less often with vinblastine, vindesine, vinorelbine, and vinflunine. Patients with neurotoxicity commonly experience peripheral paresthesia, loss of deep tendon reflexes, abdominal pain and constipation, and sometimes ototoxicity. If the symptoms of neurotoxicity are severe, then doses of the agents can be reduced. Motor weakness can also occur, and if this happens then dose reduction or discontinuation should be considered. Recovery from the neurotoxic effects of the Vinca agents is normally slow but complete. Myelosuppression is a dose-limiting side effect of vinblastine, vindesine, vinorelbine, and vinflunine, although vincristine is almost devoid of this effect, which is interesting from a structure activity relationship (SAR) standpoint given the similarity of chemical structures. Reversible alopecia is a common side effect of all members of the anticancer alkaloids and analogues of the Vinca family, and severe bronchospasm has also been reported following administration, especially when used in combination with mitomycin-C.
Antimicrobial Agents and Neurotoxicity
Firza Alexander Gronthoud in Practical Clinical Microbiology and Infectious Diseases, 2020
Evidence for neurotoxic effects of antibacterials, such as seizures and encephalopathy, is based on low-quality evidence (i.e. case reports), with adverse events occurring at a low frequency. Increased CNS drug concentration has been suggested to contribute to development of seizures and can result from impaired renal function and/or a disrupted blood–brain barrier (i.e. due to brain lesions). Peripheral neuropathy and optic neuritis are other adverse antimicrobial drug events directly caused by antimicrobials. Pre-existing neurological diseases also increase the risk of neurotoxicity. For instance, there are reports of epileptic insults elicited by quinolones, and aminoglycosides should be avoided in patients with myasthenia gravis. Drug-drug interactions also play a role as demonstrated by carbapenems which decrease the concentration of valproic acid which is an antiepileptic drug, and linezolid should be used with caution in individuals on certain antidepressants as it increases the risk of serotonin syndrome.
Environment, pregnancy complications, and omics
Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos in New Technologies and Perinatal Medicine, 2019
During its development, the central nervous system is highly susceptible to external stimuli that may exert a deleterious impact. Several industrial chemicals, such as lead, arsenic, and pesticides, have been associated with causing neurotoxicity (29). Maternal exposure during pregnancy to indoor environmental pollutants, such as mold and pesticides, has also been suggested to impair fetal neurologic development and cognitive function (30). Data from six European birth cohorts, including 9,482 children, demonstrated an association of exposure during pregnancy to air pollutants, particularly NO2, with reduced psychomotor development (global psychomotor development score decreased by 0.68 points [95% CI = −1.25 to −0.11] per increase of 10 μg/m3 in NO2) (31). A prospective Polish study showed an association of exposure to polycyclic aromatic hydrocarbons, which are indoor and outdoor air pollutants that result from industrial combustion, home cooking, and cigarette smoking, with impaired cognitive development in children, 5 years of age, following in utero exposure (32).
Neurological adverse effects of chimeric antigen receptor T-cell therapy
Published in Expert Review of Clinical Immunology, 2023
Kiarash Saleki, Mohamad Hosein Mohamadi, Parsa Alijanizadeh, Nima Rezaei
A possible optimal approach is the development of methods to avoid neurotoxicity. In light of the efficacy of IL-1 suppression in improving neurotoxicity in CAR T-cell administered cases, multiple clinical experiments employed anakinra for attenuation of neurotoxicity (NCT04205838, NCT04359784, NCT04148430). Such efforts need to be pursued rigorously. In xenograft studies of acute leukemia, the utilization of lenzilumab has exhibited that blockade of GM-CSF could diminish the prevalence of CRS and neurotoxicity without influencing CAR T-cell efficiency [42]. The ZUMA-19 trial has investigated this, that utilizes both lenzilumab and axi-cel for cases with R/R LBCL (NCT04314843). Also, appropriate usage of steroids could attenuate the incidence of CRS and neurotoxicity. Steroids may be considered as the treatment of choice for critical patients with ICANS [33,127]. An interesting perspective discusses that the situation with ICANS is similar to COVID-19 infection. From a practical standpoint, steroids were still the best treatment for COVID complications despite various trials of many costly therapeutics. The same may apply to ICANS management, if attention is paid to timely diagnosis and earlier institution of intervention. In this regard, two research groups found overlapping features of COVID-19 cases with encephalopathy and critical neurotoxicity related to CAR-T therapy. The authors suggested a shared cytokine-regulated neuropathophysiology, assisting the development of next-generation therapeutics [149].
Utilizing network pharmacological analysis to investigate the key targets and mechanisms of kaempferol against oxaliplatin-induced neurotoxicity
Published in Toxicology Mechanisms and Methods, 2023
Hongxing Wang, Jing Quan, Youming Deng, Jie Chen, Ke Zhang, Zhan Qu
Chemotherapy-induced peripheral neuropathic pain is a serious adverse observed in up to 80% of patients during anti-cancer drug therapy (Sisignano et al. 2014). Colorectal carcinoma is common cancer in the world. Oxaliplatin is a third-generation platinum-based anti-cancer drug, which was widely applied to treat colorectal carcinoma. Although oxaliplatin is well known for its efficacy in the treatment of colorectal cancer, it can induce severe peripheral neurotoxicity (Graham et al. 2004). This neurotoxicity can be hazardous because it could disrupt treatment plans by decreasing doses or interrupting treatment (Han et al. 2016). Neuroinflammation, glial activation, oxidative stress, mitochondrial injury, and nuclear DNA injury were considered the major mechanisms of chronic peripheral neuropathy (Xu et al. 2018; Gui et al. 2020; Kang et al. 2021). Growing evidence indicated that the activation of astrocytes plays a pro-inflammatory effect in the pathological process of neurotoxicity (Ji et al. 2014). It has been reported that the pro-inflammatory cytokine and PI3K-mTOR signal pathways lead to oxaliplatin-induced neurotoxicity (Duan et al. 2018). Besides, curcumin could improve oxaliplatin-induced neurotoxicity by mitigating neuroinflammation (Zhang et al. 2020). Astragaloside IV alleviated oxaliplatin-induced neuropathic pain via the regulation of oxidative stress and neuroinflammation (Xu et al. 2021). Therefore, suppression of neuroinflammation may be a novel treatment strategy for oxaliplatin-induced neurotoxicity.
Vincristine-induced neurotoxicity in pediatric patients with rhabdomyosarcoma: A retrospective analysis of clinical features and outcome
Published in Pediatric Hematology and Oncology, 2022
Lama Dakik, Maya Basbous, Hani Tamim, Yacoub Moubarak, Nidale Tarek, Dima Hamideh, Samar Muwakkit, Miguel Abboud, Raya Saab
In contrast to other reports, we were able through this single institution review, to investigate the duration of neuropathy, feasibility of dose re-escalation, and the potential association of the dose reductions with overall patient outcome. We found that 47% of patients had improvement of their symptoms while on-therapy, allowing re-escalation of subsequent dosing. Neurotoxicity persisted in 4 patients throughout their treatment despite early dose reduction, and symptoms persisted for months to years in some patients. A previous study in a different patient population also showed neuropathy to persist beyond 6 months after treatment especially in solid tumor patients,14 while other studies have shown nerve conduction velocity abnormalities to persist for 6 months to several years post treatment.1,15 Importantly, most of our patients who had long-term follow-up data captured (73%) had complete eventual resolution of motor neuropathy, as documented by physical examination. Within the limitation of the small sample size, disease and survival outcome analyses in our series showed no apparent impact of vincristine dose reduction on disease control.
Related Knowledge Centers
- Central Nervous System
- Nervous Tissue
- Neurotoxin
- Neurotransmission
- Peripheral Nervous System
- Toxicity
- Neuron
- Organ Transplantation
- Radiation Therapy
- Pharmacotherapy