Mechanism

How does Disulfiram (antabuse) prevent alcohol abuse?

Answer: People with alcohol use disorders may be prescribed Disulfiram, which is a drug that causes sickness when the person drinks alcohol.

disulfiram antabuse alcohol abuse

Alcohol abuse disorders are very common around the world. According to the World Health Organization, alcohol abuse is frequent. In the United States, it is estimated that about 5% of adult males and females older than 15 have some sort of alcohol use disorder. Alcohol addiction is very common in Russia and South America, where more than 7% of adult males older than 15 have some degree of alcohol abuse.

In previous iterations of the Diagnostic and Statistical Manual of Mental Disorders, the DSM-IV, alcohol use was divided into two categories, alcohol dependence versus alcohol abuse. The most recent update of the DSM, the 2013 DSM-V, combines these and other addiction related behaviors into one single diagnosis, the use disorders.

Treatments

Alcohol use disorders have a range of pharmacological treatments that are being tested for efficacy. These approaches are sometimes combined into the group of drug-based cessation techniques.

One pharmacological intervention that functions as an alcohol cessation strategy is the treatment with disulfiram. Disulfiram is sometimes also called Antabuse. Disulfiram is largely metabolized by the liver into diethylthiocarbamate. It is generally considered to be a second line of treatment in the event that other pharmacological alcohol cessation therapies are ineffective, such as naltrexone.

Disulfiram acts at the enzymes that are responsible for the degradation of alcohol in the liver. Without disulfiram present, a person has a series of enzymes that degrade molecules of ethyl alcohol (ethanol). This process has two steps and generally proceeds unimpeded. First, ethanol is converted into acetaldehyde by the enzyme alcohol dehydrogenase (ADH). In the second step of metabolism, this acetaldehyde is further degraded into acetic acid by the action. Of the enzyme acetaldehyde dehydrogenase. In this metabolic pathway, acetaldehyde is a toxic substance that the body reacts to very negatively. For example, the build up of acetaldehyde can cause a person to feel nausea, disorientation, and headaches. On the other hand, acetic acid is an inert substance that the body naturally uses.

Disulfiram, when present in the bloodstream, acts directly at the acetaldehyde dehydrogenase enzyme. Disulfiram inhibits the action of the enzyme, which results in the dramatic increase of toxic acetaldehyde in the body. When a person takes disulfiram then drinks alcohol, the body has a very strong adverse reaction again the accumulating acetaldehyde. The longer a person takes the disulfiram, the more effective it is at blocking the acetaldehyde dehydrogenase enzyme, so the person does not develop a tolerance to the drug.

The body has an immediate and very strong reaction against the acetaldehyde. Some of the symptoms that the person experiences include shortness of breath, accelerated heartbeat, nausea, vomiting, headache, confusion, disorientation, and visual distortions. Usually, the effects of the alcohol occur within 10 minutes, but they can persist for hours.

The main theory behind the treatment of alcohol use disorders with disulfiram has it’s roots in conditioning. If a patient taking antabuse continues to drink more alcohol, the strong adverse reaction will cause the person to develop a hatred for the feelings associated with drinking alcohol. In psychology parlance, this phenomenon is sometimes called conditioned taste aversion.

Successful treatment with antabuse requires high rates of compliance, something that is very difficult. Many patients who take antabuse may choose to stop taking the drug, which allows them to consume alcohol without feeling the adverse results. To get around this difficulty, antabuse can be implanted subdermally (under the skin). In these preparations, the drug is contained within a semipermeable capsule under the skin, and the drug is slowly released over the span of a week. This makes it so the person cannot simply stop taking the pills, possibly increasing patient compliance.

Additionally, disulfiram often has no effect on a person’s craving of alcohol. Even while taking the antabuse, people often report having no decrease in their desire to take the drug.

The standard dosing regime is a 500 mg pill once daily, for two weeks. After this time the dosage is decreased to 250 or 125 afterwards.

Disulfiram should never be given while a person already has alcohol in their system. They must be sober before beginning treatment. Also, the way the body processes other drugs can be affected by antabuse in the body. Acetaminophen and caffeine are two of the most common drugs that may interact with antabuse.

Disulfiram itself has several negative side effects, even in the absence of alcohol. For example, a person on antabuse might experience headaches, an unusual metallic taste in the mouth, a decrease in sex drive, increased sleepiness, nerve injury, and liver damage. Rarely, extrapyramidal symptoms can occur in people. In some cases, a person may have damage to their axons.

The original compound disulfiram, also called tetraethylthiuram disulfide, was originally used in the process of rubber vulcanization. When factory workers reported that they had a strange negative reaction to alcohol, the results were published in 1937.

The “disulfiram effect” in pharmacology is when a drug causes a person to have a hypersensitivity to alcohol. A handful of other drugs may cause disulfiram-like effects, including some cephalosporin drugs and certain antibiotics.

Combination treatments

Antabuse, as well as all other pharmacological interventions for alcohol use disorders, is best when paired with counseling. Having multiple approaches is essential for maximizing one’s success with any attempts to quit. The most well known non-pharmacological alcohol cessation technique is Alcoholics Anonymous, and their twelve step program. The twelve step program was first outline in 1939 in the book Alcoholics Anonymous: The Story of How More Than One Hundred Men Have Recovered from Alcoholism.

Under the philosophy of the twelve step program, a person starts by admitting that they are no longer in control of their lives. The twelve step program is founded heavily in religion, and that by giving individual power over to the control of God, an addict has the best chances of recovery. Another major step is to acknowledge that a person’s alcohol use has harmed several others, and that by making amends to all of those people, they can start on their path to self improvement.

Alcoholics Anonymous (AA) is more effective in conjunction with a pharmacological strategy like treatment with disulfiram. In the AA philosophy, a person is an alcoholic for their entire life. Their attendance at meetings is a crucial part of their success.