Alcoholism, Ethanol Metabolism & Methanol Poisoning

Understanding alcohol metabolism is important to understanding the health effects of alcohol consumption. In the pharmacokinetics section we will discuss how alcohol dehydrogenase is an example of zero-order elimination. This means that a constant amount of alcohol is metabolized per unit time and that it can take a very long time for large amounts of alcohol to be metabolized (Or a long time to “Sober Up” after getting hammered).

Ethanol is relatively harmless when consumed in small amounts, but problems can arise when alcohol is consumed in excess. When alcohol is consumed in large quantities Acetaldehyde, an intermediate of alcohol metabolism, builds up faster than it can be metabolized. This excess Acetaldehyde contributes to hangover symptoms.

Alcohol Metabolism, Acetaldehyde, Disulfiram, USMLE

When alcohol is consumed in excess the NADH generated from alcohol metabolism can also cause many health effects. This buildup of NADH can be exacerbated when large quantities of alcohol are consumed without food being consumed. NADH is an electron transporter. Its presence signals liver cells that there is ample energy present. The presence of this signal leads to increased breakdown of glucose (Glycolysis), decreased creation of glucose (Gluconeogenesis), and decreased fat breakdown (Fat Oxidation). NADH is also used to convert Pyruvate to Lactate, which means high levels of NADH leads to increased Anaerobic Glycolysis and Lactic Acidosis.

NADH in alcoholism, Alcoholic Hypoglycemia, Lactic Acidosis

 

Here is my mnemonic for memorizing these three main effects of acute alcohol consumption. First I think about a beer bottle that is HALF full (or half empty if med school has turned you into a pessimist). Then I use each letter of HALF to remind me of the effects.

Here is my mnemonic for memorizing these three main effects of acute alcohol consumption. First I think about a beer bottle that is HALF full (or half empty if med school has turned you into a pessimist). Then I use each letter of HALF to remind me of the effects.

Alcoholism can also cause Traumatic Injuries Due to Falls or Esophageal Tears due to frequent vomiting. Alcoholism is also associated with many health outcomes which I will cover in other sections. Wernicke-Korsakoff, thiamine deficiency, is common among alcoholics, because alcoholics sometimes get a majority of their calories from alcohol. Excessive alcohol intake is also associated with Pancreatitis. Chronic steatosis can lead to liver inflammation (“non-viral” Hepatitis) and eventually Liver Cirrhosis. Unlike viral hepatitis, inflammation due to alcohol usually presents with an AST Elevated More than ALT (I remember this by thinking Alcohol –> Steatosis –> Higher AST). Excessive alcohol consumption by pregnant woman can also lead to Fetal Alcohol Syndrome and mental retardation.

Alcohol Withdrawal must be watched carefully in any hospitalized patients with a history of alcoholism as it can be life threatening. It usually occurs a couple days after abrupt cessation of alcohol (usually in the hospital where alcohol is not accessible). Mild withdrawal may present as Agitation or aggression a couple days after being brought into the hospital. Severe withdrawal can include Tremors, Seizures, confusion, and psychosis. This collection of symptoms is referred to as Delirium Tremens (DTs). Treatment for DTs is Benzos.

The best type of treatment for alcoholism is a 12 step program like Alcoholics Anonymous (AA). In some patients, Disulfiram is also used. This drug Inhibits Acetaldehyde Dehydrogenase and makes patients very sick if they drink any alcohol as Acetaldehyde builds up much faster. You are essentially giving them a really bad hangover on purpose to dissuade them from drinking. However, this it is not always effective as there is relatively low compliance for this drug. Patients considering drinking can think ahead and easily not take their medication to avoid the consequences. Disulfiram intentionally causes these hangover like symptoms after alcohol consumption, but other drugs (such as Metronidazole) inadvertently have this same effect. Drugs with this type of side effect are often described as having a Disulfiram-Like effect.

Methanol Poisoning & Metabolism

Methanol  is in antifreeze, paint thinner and improperly prepared moonshine (illegally produced spirits). It can accidentally be consumed by children or adults mistaking the liquid for ethanol. Methanol itself does not cause problems, but after being metabolized by Alcohol Dehydrogenase Formaldehyde is formed. Formaldehyde can cause blindness and death so treatment focuses on preventing aldehyde formation. Fomepizole Inhibits Alcohol Dehydrogenase decreasing the amount of methanol that is metabolized into Formaldehyde. Alcohol can also be given as it utilizes the same enzyme and will compete for alcohol dehydrogenase.

 

Now that you are finished with this video you should check out the next video in the Biochemistry section which covers Chediak-Higashi, I-Cell Disease & Kartagner’s Disease.

 

Pictures Used (In order of Appearance)
• This work is a derivative of “Bottle Beer Bottle Alcohol Drinking” available at http://pixabay.com/en/bottle-beer-bottle-alcohol-drinking-157844/ under Creative Commons 1.0 Public Domain Dedication
• This work is a derivative of “Liver steatosis fatty change” available at http://en.wikipedia.org/wiki/File:Liver_steatosis_fatty_change.jpg under Public Domain

3 thoughts on “Alcoholism, Ethanol Metabolism & Methanol Poisoning”

  1. Thank you for very clear lecture. Do we need to learn effcet of alcholo on cytochrome p450 enzyme system for step 1??

    1. Thanks for the Comment Mustafa. I don’t believe the effects of alcohol on p450 are high yield. I just looked through my gigantic collection of retired Step 1 questions and commercially available practice questions and I couldn’t find a single one on that specific topic.

  2. Thanks a Lot for these prep videos.
    I’ve one question under biochem section of ethanol
    Q: Why is that during increase in NADH leads to Increase in Gluconeogenesis but there is also change in fatty liver but instead of decreasing the levels of fat (due to Gluconeogenesis) there is increase in fat production?
    please clear this concept.

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