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CE ARTICLE Pathophysiology of Alcohol Use Disorder and Withdrawal Alcohol is a central nervous system depressant, stimulating gamma-amino- butyric acid (GABA) receptors and as an antagonist at N-methyl-D-aspartate (NMDA) receptors. It also interacts with other neurotransmitter systems in the brain, such as the endogenous opioid, serotonin and dopamine systems, but its interactions with NMDA and GABA recep- tors have the most profound effects. GABA is the chief inhibitory neurotransmitter in the brain, and binding sites specific for ethanol are located on the GABA receptor complex. GABA plays an active and important role in regulating neuronal excitability in the brain, and in humans it is also responsible for the regulation of muscle tone. Ethanol acts as an indirect GABA agonist. With chronic ethanol use, the human brain becomes increasingly insensitive to GABA, so that more ethanol is required to maintain a consistent inhibitory tone and prevent neuronal excitability. NMDA receptors in the brain are activated when bound to glutamate, one of the more prominent excitatory amino acids. Ethanol inhibits glutamate- inducted central nervous system excita- tion and results in lethargy. Adaptation to ethanol occurs when the brain increases sensitivity to glutamate in an attempt to maintain a normal state of arousal. As the chronic alcoholic continues to expose his or her body (and in turn its GABA and NMDA receptors) to ethanol, those receptors begin to upregulate, or increase in number. This upregula- tion is the basis of tolerance: When the body has a greater number of recep- tors, a greater amount of stimulation (or suppression) is required to cause the end effect. GABA is inhibitory, so once the chronic alcoholic has a much greater number of GABA receptors and stops drinking, many of the receptors are not stimulated, and the overall neurologic suppression effect cannot be achieved. As a result, the patient becomes hyperac - tive, agitated and hallucinogenic. The NMDA is excitatory and leads Value Life Because Higher FiO 2 Matters ... Boussignac CPAP delivers the FiO 2 your transport patients need Contact Vygon today to learn more by calling toll-free at 800-473-5414 or email us at marketing@vygonusa.com 10 20 30 40 50 60 70 80 90 100 Boussignac Competitor A Competitor B Competitor C 71.5 94.3 29.7 43.8 42.2 32 57.8 52.7 %FiO 2 CPAP 5cm H20 CPAP 10cm H20 Visit: www.vygonCPAP.com Supporting data on fle, available on request from Vygon USA. For More Information Circle 49 on Reader Service Card Inhibitory Excitatory Clinical Receptors Receptors Symptoms Alcohol Withdraw GABA NMDA Sympathetic Activity Hallucinations Delirium Tremems Seizures Figure 1: Relationship between inhibitory receptors, excitatory receptors and clinical symptoms in alcohol withdrawal 46 APRIL 2014 | EMSWORLD.com EMS_44-51_CEArticle,Index0414.indd 46 3/14/14 8:55 AM