Related Experiment Video
Updated: Aug 8, 2025
07:01
Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
9.1K
Ifosfamide - History, efficacy, toxicity and encephalopathy
Jeffrey R Idle1, Diren Beyoğlu1
1College of Pharmacy and Health Sciences, Western New England University, Springfield, MA 01119, USA.
Pharmacology & Therapeutics
|February 26, 2023
Summary
This review traces the history of oxazaphosphorines, crucial cancer drugs like cyclophosphamide (CP) and ifosfamide (IFO). It details ifosfamide-induced encephalopathy (IIE) and its potential treatment with methylene blue (MB).
Area of Science:
- History of Medicine
- Oncology
- Pharmacology
Background:
- Cancer research in the 20th century evolved from early observations of mustard gas toxicity.
- This led to the development of oxazaphosphorines, a significant class of chemotherapeutic agents.
- Key figures like Haddow, Gilman, Goodman, Gomori, and Brock were instrumental in this breakthrough.
Purpose of the Study:
- To review the historical development of oxazaphosphorines in cancer chemotherapy.
- To analyze the metabolic disposition of ifosfamide (IFO) and its link to ifosfamide-induced encephalopathy (IIE).
- To discuss potential treatments for IIE, including methylene blue (MB).
Main Methods:
- Historical review of scientific literature and research contributions.
- Analysis of metabolic pathways and proposed metabolites of ifosfamide.
- Evaluation of clinical data on ifosfamide-induced encephalopathy and methylene blue efficacy.
Main Results:
- Ifosfamide (IFO) causes encephalopathy in susceptible patients, unlike cyclophosphamide (CP), potentially due to a combination of five metabolites.
- Several metabolites, including 2-chloroacetaldehyde and acrolein, are candidates for causing IIE.
- Methylene blue (MB) shows promise in preventing and treating IIE, likely by modulating neurotransmitter systems.
Conclusions:
- The development of oxazaphosphorines represents a major advancement in cancer treatment.
- Ifosfamide-induced encephalopathy is a complex side effect linked to specific metabolites.
- Methylene blue offers a potential therapeutic strategy for managing ifosfamide-induced encephalopathy.
Related Concept Videos
01:20Antiepileptic Drugs: Potassium Channel Activators
235
Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
Ezogabine has gained approval as an adjunctive treatment...
235
01:12Local Anesthetics: Adverse Effects
474
While local anesthetics are generally safe and well-tolerated, they can occasionally cause adverse effects that vary in severity. Local anesthetics can induce toxicity at two distinct levels. They can either produce local effects through direct contact with the neural elements or be absorbed into the bloodstream from the injection site, leading to systemic effects.
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
474
01:25Drug Regulation
1.5K
Drug regulation encompasses the management of drug usage by evaluating its safety and efficacy through assessments conducted by regulatory authorities. Regrettably, the history of drug regulation is marred by several catastrophic events. One such incident is the Elixir Sulfanilamide tragedy, in which the toxic compound diethyl glycol was included in a sweet-tasting medication, leading to numerous fatalities. This event prompted the enactment of the Food, Drug, and Cosmetic Act in 1938. Under...
1.5K
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
228
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
228
01:26Drug Administration and Therapy Phases: Overview
606
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
606
01:30Electroconvulsive Therapy
100
Electroconvulsive therapy (ECT), or shock therapy, remains a critical biomedical intervention for severe, treatment-resistant depression. While its origins can be traced back to Hippocrates' observations that malaria-induced convulsions alleviated mental illness, modern ECT has evolved significantly from its earlier, more primitive applications. First introduced in 1938 by Ugo Cerletti and his colleagues, ECT involves inducing controlled seizures using electrical currents. In its early...
100