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A LCOHOL A DDICTION AND T HE T REATMENT OF A LCOHOL A BUSE WITH D ISULFIRAM By: Chvez, Jessica Coffey, Alisha Folkes, Lennora

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A LCOHOL

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E THANOL M ETABOLISM Lieber, C. 2004 CH 3 CHOCH 3 COOHCH 3 CO-S-CoA Acetaldehyde DHAcetyl-CoA Synthase

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A LCOHOL A DDICTION What is it? Compulsive need for an intoxicating liquid. Beer, wine, liquor, etc. Cannot limit or contain his or her drinking. Desire to drink great amount of alcohol in order to feel a high Suppresses the ability to stop drinking Feeling of wanting to drink in order to relax or feel better Relying on alcohol to function and physically compelled to drink.

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A DDICTION When Alcohol is consumed endorphins, the bodys natural opiates, are released. Endorphins bind to the receptor sites in the brain and result in the feeling of pleasure when consuming alcohol. Alcoholics and their family members have reduced plasma levels of -Endorphins which means they are more prone to becoming alcoholics because of the pleasure caused by consuming alcohol. o The dopaminergic pathway from the ventral tegmental area (VTA) to the nucleus accumbens mediates stimulatory and positive reinforcing properties of alcohol. Clapp, et. al. 2008

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D IFFERENT L OOK I NSIDE A LCOHOL E FFECTS IN N EURONS Clapp, et. al. 2008

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A LCOHOL E FFECTS IN THE L IVER Fatty liver -Steatosis- is the collection of excessive amounts of fats and triglycerides. Fat metabolism or the production of energy is disturbed by alcohol causing fat to not break down properly. Fat vacuoles form growing larger as drinking increases, soon fat vacuoles coalesce to form cysts Once cysts form, liver cells are damaged for good.

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L IVER D AMAGE FROM A LCOHOL A BUSE

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D ISULFIRAM

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DISULFIRAM : W HAT IS IT ? Chemical name: tetraethylthiuram disulfide [TETD] Brand name: Antabuse Drug used to treat chronic Alcoholism. Causes unpleasant side effects when small amounts of alcohol is consumed. The rationale behind the use of the drug is to induce fear in the patient of the consequences of ingesting alcohol and to reinforce abstinence. The punishment for drinking alcohol while taking the medication results in the disulfiram-ethanol reaction (DER). The drug should not be taken if allergic to thiuram or thiuram-related chemicals.

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S YMPTOMS OF D ISULFIRAM Less Serious Side Effects: Face/body flushing Skin rash Drowsiness Throbbing Headache Metallic or garlic-like taste in the mouth Impotence Swollen or sore tongue Nausea/vomiting Side Effects That Require Medical Attention Immediately: Dark urine Extreme Fatigue Loss of appetite Upset stomach Yellowness of the skin or eyes Severe Diarrhea and Vomiting Seizures Shortness of Breath Allergic Reaction (Swelling of lips, tongue, or face) The Side Effects the Medication Causes:

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R OLE OF D ISULFIRAM IN E THANOL M ETABOLISM Ethanol Acetaldehyde Acetate Acetyl CoA Disulfiram Disulfiram: Irreversively inhibit ALDH Reduces Oxidation of acetaldehyde Accumulation of acetaldehyde causes unpleasant side effects. Alcohol DH Acetaldehyde DH Acetyl CoA Synthase

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D ISULFIRAM -E THANOL R EACTION (DER) Disulfiram blocks the enzyme Acetaldehyde Dehydrogenase (ALDH). The symptoms are due to an increase of serum acetaldehyde concentrations. Discomforts associated with the syndrome are intended to serve as a negative stimulus; however, the reaction may be severe enough to cause hypotension and death if a high dose is taken.

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Gaval cruz et. al. 2009

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Vicari, Katie et al 2010

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C ONCLUSION o Ethanol is broken down by the body in several different ways that all end with acetaldehyde o Alcohol can cause fatty acids and triglycerides to accumulate in the liver and if left untreated can cause Fatty Liver, Hepatitis, and eventually Cirrhosis o Alcohol abuse effects not only the liver, but the sympathetic nervous system as well o Disulfiram is a treatment for people who abuse alcohol by using negative reinforcement

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REFERENCES Clapp, Peter, Bhave, Sanjiv V., Hoffman, Paula L. (2008) How Adaptations of the Brain to Alcohol Leads to Dependence. National Institute on Alcohol Abuse and Alcoholism. http://pubs.niaaa.nih.gov/publications/arh314/310-339.htm Gaval-Cruz, M. and Weinshenker, D. (2009). Mechanisms of Disulfarim-Induced Cocaine Abstinence Antabuse and Cocaine Relapse. Molecular Intervention. 9(4), 135-187. Fairbanks, Krysten D. Alcoholic Liver Disease. The Cleveland Clinic Foundation. Retrieved by http://www.clevelandclinicmeded.com/medicalpubs/diseasema nagement/hepatology/alcoholic-liver-disease/ Fatty Liver. The Free Dictionary by Farlex. Retrieved by http://medical- dictionary.thefreedictionary.com/Hepatic+steatosis Kitson, Trevor, M. (1977) The Disulfiram-Ethanol Reaction. Journal of Studies on Alcohol, 38 (1) 96-112. Lieber, Charles S. (20 July, 2004) Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol, 34, 9-19.