Month 1, Day 12

Missed my pill again last night, so took it this morning at 6.  I figure that 14 hours between now and my next pill should be enough time, given that INH peaks in the system 90 minutes after taking it.

I was thinking about the beer I wanted to have yesterday.  My partner brought up a good point.  One beer, or one glass of wine every week won't hurt, right?

Well, in fact, the lady at the public health office told me the same thing.  "It's OK to have a few drinks every now and then, it's the continued drinking that's bad."

Well, now...I'll admit, when I was pregnant I drank a glass of wine about every other week, sometimes every week, and my son is healthy, energetic and smart.  No harm to him!  Just how dangerous is a glass of wine or a bottle of beer once a week?

Hmmmm...Research time!  Now, if some of this is wrong, please don't hesitate to tell me!  I'm just trying to piece it together as best as I can.

Background:
Only a small amount of alcohol is metabolized in the stomach.  The rest is pretty much absorbed through the stomach and intestines into the bloodstream and then transported to the liver ("first pass metabolism").  The liver is the primary site of alcohol metabolism. In general, only about 10 percent of a low dose of alcohol is eliminated by first pass metabolism, and as alcohol ingestion increases, the amount metabolized decreases (due to decreased glutathione).  Alcohol that has not been eliminated is recirculated through the body water (blood and water surrounding the cells).  It comes back to the liver through this circulation where it ideally is broken down by several different enzymes (ADH and cytocrome P450 are the two most important).  (Source)

P450 converts alcohol to acetaldehyde (more toxic than alcohol itself), and is popularly thought to be the cause of hangovers. The acetaldehyde is then attacked by another enzyme, acetaldehyde dehydrogenase, and another substance called glutathione, which contains high quantities of cysteine (a substance that is attracted to acetaldehyde). Together, the acetaldehyde dehydrogenase and the glutathione form the nontoxic acetate (a substance similar to vinegar).  Drinking a lot of alcohol will decrease glutathione levels and make it very difficult to metabolize the alcohol quickly. (Source)

INH Role:
INH induces the P450 enzyme.  This causes oxidation to occur, creating acetaldehyde. INH also depletes glutathione. (Source) This causes excess acetaldehyde to remain in the body.  Acetaldehyde toxicity can result in really terrible headaches and vomiting, although I couldn't find anything on pure INH association.

Here's a quote I like:
Although probably best recognized as an inhibitor of drug metabolism, isoniazid has a biphasic effect of inhibition-induction on one cytochrome P450 isozyme, CYP2E1, which partially explains the interaction with acetaminophen and increased risk of hepatotoxicity. (Source)

Additionally, INH reduces Histamine metabolism. (Source).  Guess what many alcohols are high in?  Right, Histamines!

INH and Hepatitis:
INH increases the chance for Hepatitis. (Source) Risk factors associated with this are:

• Age (older means increased risk)
• Gender (we females have it rough)
• Genetic predisposition (undefined as yet)
• Drug interactions (with drugs that induce P450)
• Phenobarbital
• Rifampin
• Alcohol- Slow acetylators of INH may be at greater risk for adverse drug interactions, as the degree of inhibition is concentration dependent. (Source)

Conclusion: 
Hey, I might try a glass of wine every now and then...but for the most part, I plan on STAYING AWAY!  The risk factor is high, and in an unknown quantity.  Since I am older (will turn 40 while on this drug), female and don't know my genetic predisposition, the risks weigh against me.  Additionally, with decreased histamine metabolism I could have an allergic response.  Hmmm...If I do drink, I plan on taking additional antioxidants and drinking tons of water with it!!!  Of course, that will be a different post!

One last thing - If you really have to drink (and I would say limited quantities is very, very important) you may want to try supplementing your diet with things that will increase your antioxidant levels.  Here's a page I found that offers suggestions:

Typical doses of cysteine that are sufficient to block a major portion of the toxic effect of alcohol/acetaldehyde are about 200 mg per ounce of alcohol consumed. However, the rapid assimilation and metabolism of alcohol requires both prior and concurrent dosing of cysteine to maintain protection. Furthermore, a multifold excess of vitamin C is required to keep the cysteine in it’s reduced state and “on the job” against acetaldehyde. I use capsules (because they dissolve fast) containing 200 mg cysteine plus 600 mg of vitamin C (with or without extra B-1). I take one before I start drinking, one with each additional drink and one when I’m finished. It works remarkably well.

I know there are some holes in my research, so I welcome any additional comments you may have!