Current and Emerging Detoxification Therapies for Critical Care

Abstract

Toxicity resulting from prescription drugs such as tricyclic antidepressants and cardioactive steroids, as well as drugs of abuse and exposure to environmental chemicals, represents a major need for detoxification treatments. Particles and colloids, antibody fragments (Fab), and indirect treatment methods such as macroemulsions, are currently being developed or employed as detoxification therapies. Colloids, particles, and protein fragments typically mitigate toxicity by binding to the toxin and reducing its concentration in vital organs. Indirect methods such as macroemulsions and sodium bicarbonate act directly on the affected organs, rather than the toxin. In this review, key design parameters (i.e. binding affinity, biocompatibility, pharmacokinetics) are discussed for each type of detoxification treatment. In addition, some of the latest research in each area is reviewed.

The Mechanisms Underlying α-Amanitin Resistance in Drosophila melanogaster: A Microarray Analysis

“…In yeast cells, lipid particles detoxify excessive amounts of lipophilic substances [51] . Even in humans, liposomes are used for detoxifying patients with overdoses of drugs, such as heroin, opioids, and cocaine [52] . The fact that the Ama-KTT/M/2 stock responds to α-amanitin with a several thousand-fold induction of lipid particle genes suggests that cytoplasmic lipid particles contribute to the resistance to α-amanitin in the Ama-KTT/M/2 stock.…”

Metal–Organic Frameworks as Efficient Oral Detoxifying Agents

“…However, some toxins present poor affinity for charcoal (e.g., alcohols, hydrocarbons, nicotinic acid, and some metals such as iron or lithium), , reducing the efficacy of activated charcoal. Although the ability of various nanomaterials (e.g., liposomes, antibody fragments, microemulsions) to capture drugs and other toxins has been reviewed, , to date only an injectable γ-cyclodextrin (Sugammadex) has reached the clinical stage for the reversal of neuromuscular blockade induced by specific anesthetics . Consequently, there is great interest in the development of safe and effective detoxification treatments.…”

Monitoring for overdoses

“…The most common TCAs reported in overdose are amitriptyline, dosulepin, and imipramine (Howell and Chauhan, 2010). Poison Control Centers in the United States report TCAs as the third most reported type of poisoning.…”

“…There have been cases of small human studies with mild TCA overdose that have shown success using this therapy but it is not yet approved for use in the United States and studies are continuing (Howell and Chauhan, 2010). Fab therapies have a high binding capacity for the toxin and work like Digibind in digoxin overdose.…”