Neurotoxic effects of inhalants.

Inhalants are a group of substances that have mind-altering or psychoactive effects when inhaled. The intoxicating effect makes them liable to abuse. Volatility is the common physical characteristic shared by all inhalants. Inhalant abuse is a worldwide problem. The substances abused are numerous, cheap, legal and easily available (Table 1). They are usually emptied into a plastic bag or a used drinks can and then inhaled through the mouth or nose to produce a high. Glue sniffing, solvent and volatile abuse are synonymous terms. The lifetime prevalence in the US is approximately 2%-4%. At our hospital, inhalant abuse was estimated to rank second to alcohol abuse among inpatients. The reason for this scale of inhalant abuse is not certain. The problem is best exemplified by the abuse of inhalers beyond medication by asthma sufferers. Current understanding of the toxic effects of substance inhalation has come from documented cases of massive exposure to substances. The lipid-rich organs are particularly vulnerable (Table 2), and the nervous system is affected at many levels (Table 3). Clinical manifestations may be diffuse. As a rule, acute high-level exposure produces reversible changes, while chronic exposure results in permanent impairment. This is substantiated by MRI, autopsy and neurophysiological studies. Toxicity is determined by the metabolic processes. Inhalants are rendered harmless by detoxication. Bioactivation can result in the production of toxic metabolites, but this process is normally limited by the concentration of P450 cytochrome enzymes present in the body. Massive exposure causes enzyme induction or saturation of detoxication processes with spillover in the bioactivation pathways. This results in increased toxic metabolite production and cell damage. Harmful free radicals are also generated during metabolism that bind cellular macromolecules in a manner different from toxic metabolites. Other determinants are hypoxia, acidosis, amino acids (excessive glutamate), competitive inhibition, hepatic and respiratory perfusion and antioxidant levels in the body.