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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by Nikita on November 15, 2002, at 14:48:17
O.k., so most of these meds say don't drink alcohol. I'm a casual drinker, a few glasses of wine a few nights a week at most. I'm taking Risperdal, Topomax, and Wellbutrin now. When I have had a few drinks, I don't feel any worse for wear in the morning, but while I'm drinking, I feel absolutely zip, no buzz, no nada. I'm a lightweight so it's usually one glass of wine and a little buzz at least. Of course I'd rather be mentally healthy than buzzed, just curious what anyone else has experienced, if that is normal, what effects alcohol has with these drugs and if it is really unsafe. I need to ask my pdoc about it but in the meantime...
Posted by cybercafe on November 15, 2002, at 19:06:24
In reply to Can you really not drink alcohol or what?, posted by Nikita on November 15, 2002, at 14:48:17
> O.k., so most of these meds say don't drink alcohol. I'm a casual drinker, a few glasses of wine a few nights a week at most. I'm taking Risperdal, Topomax, and Wellbutrin now. When I have had a few drinks, I don't feel any worse for wear in the morning, but while I'm drinking, I feel absolutely zip, no buzz, no nada. I'm a lightweight so it's usually one glass of wine and a little buzz at least. Of course I'd rather be mentally healthy than buzzed, just curious what anyone else has experienced, if that is normal, what effects alcohol has with these drugs and if it is really unsafe. I need to ask my pdoc about it but in the meantime...
i was told that alcohol takes at least 2.5 days to be processed by your liver, during which time any meds you take get ... uh... urinated out unmetabolized... so you may as well just not take any meds and save yourself the cash(you should probably verify this though :) )
Posted by Larry Hoover on November 15, 2002, at 19:54:05
In reply to Re: Can you really not drink alcohol or what?, posted by cybercafe on November 15, 2002, at 19:06:24
> i was told that alcohol takes at least 2.5 days to be processed by your liver, during which time any meds you take get ... uh... urinated out unmetabolized... so you may as well just not take any meds and save yourself the cash
>
> (you should probably verify this though :) )
>That's not true....
Alcohol takes much less than 2 1/2 days to be metabolized. Most people can process about 1 oz. of alcohol per hour, give or take.
Alcohol competes with other substances for the liver enzyme CYP2E1 (which is also found in the gut). Any drug metabolized by 2E1 will *not* be eliminated, but instead, will remain at a high level in the blood. Some tricyclics, or acetominophen (paracetemol in U.K.) are examples of drugs using the 2E1 enzyme. The effect will be similar to overdosing.
Now, that's the simple case. Chronic alcohol consumption, however, causes the body to produce a larger amount of the 2E1 enzyme (the enzyme is said to be induced). Heavy drinkers will process drugs using the 2E1 enzyme faster than normal. The result will be similar to underdosing on the med.
This isn't to be taken literally (because there are exceptions to everything), but when the liver processes a drug, it changes the structure a little bit so that the kidneys can recognize that the substance should be excreted. Think of it like placing a bar code on the molecule. When the kidney scans the bar-coded substance, out it goes in the urine. So, if the liver's work is inhibited, the substance just stays in circulation in the blood.
Posted by cybercafe on November 15, 2002, at 20:44:58
In reply to Re: Can you really not drink alcohol or what?, posted by Larry Hoover on November 15, 2002, at 19:54:05
> > i was told that alcohol takes at least 2.5 days to be processed by your liver, during which time any meds you take get ... uh... urinated out unmetabolized... so you may as well just not take any meds and save yourself the cash
> >
> > (you should probably verify this though :) )
> >
>
> That's not true....
>
> Alcohol takes much less than 2 1/2 days to be metabolized. Most people can process about 1 oz. of alcohol per hour, give or take.
>
> Alcohol competes with other substances for the liver enzyme CYP2E1 (which is also found in the gut). Any drug metabolized by 2E1 will *not* be eliminated, but instead, will remain at a high level in the blood. Some tricyclics, or acetominophen (paracetemol in U.K.) are examples of drugs using the 2E1 enzyme. The effect will be similar to overdosing.
>
> Now, that's the simple case. Chronic alcohol consumption, however, causes the body to produce a larger amount of the 2E1 enzyme (the enzyme is said to be induced). Heavy drinkers will process drugs using the 2E1 enzyme faster than normal. The result will be similar to underdosing on the med.
>
> This isn't to be taken literally (because there are exceptions to everything), but when the liver processes a drug, it changes the structure a little bit so that the kidneys can recognize that the substance should be excreted. Think of it like placing a bar code on the molecule. When the kidney scans the bar-coded substance, out it goes in the urine. So, if the liver's work is inhibited, the substance just stays in circulation in the blood.hmmm.. fascinating! .. but i thought there were enzymes that were shared between all substances, like ALT, AST alkaline phosphatase etc etc
Posted by Jumpy on November 15, 2002, at 21:09:13
In reply to Re: Can you really not drink alcohol or what?, posted by cybercafe on November 15, 2002, at 20:44:58
Well, the liver usually adds another methyl group to the drug so it can be filter and excreted by the gallbladder or kidneys. I think the problem with alcohol is it affects the neurotransmitter systems so much ... depleted serotonin, dopamine, etc. so that ad and ms can not work adequately.
Paul
Posted by cybercafe on November 15, 2002, at 23:13:02
In reply to Re: Can you really not drink alcohol or what? » cybercafe, posted by Jumpy on November 15, 2002, at 21:09:13
> Well, the liver usually adds another methyl group to the drug so it can be filter and excreted by the gallbladder or kidneys. I think the problem with alcohol is it affects the neurotransmitter systems so much ... depleted serotonin, dopamine, etc. so that ad and ms can not work adequately.
>
> Paul
hmmmm..... i thought alcohol worked on GABA-B and NMDA-glutamate receptors plus it distorted cell membranes ....... any of that right ?
Posted by Jumpy on November 16, 2002, at 0:12:44
In reply to Re: Can you really not drink alcohol or what?, posted by cybercafe on November 15, 2002, at 23:13:02
> > Well, the liver usually adds another methyl group to the drug so it can be filter and excreted by the gallbladder or kidneys. I think the problem with alcohol is it affects the neurotransmitter systems so much ... depleted serotonin, dopamine, etc. so that ad and ms can not work adequately.
> >
> > Paul
>
>
> hmmmm..... i thought alcohol worked on GABA-B and NMDA-glutamate receptors plus it distorted cell membranes ....... any of that right ?
>Oh yeah ... that to ... I think I have to retract my above statement. I really haven't done too much reading or course work on alcohol's effects on ad/ms function. Sorry about the post.
Paul
Posted by Larry Hoover on November 16, 2002, at 8:53:32
In reply to Re: Can you really not drink alcohol or what?, posted by cybercafe on November 15, 2002, at 20:44:58
> hmmm.. fascinating! .. but i thought there were enzymes that were shared between all substances, like ALT, AST alkaline phosphatase etc etc
ALT and AST are very substrate-specific.
AST (Aspartate aminotransferase)
ALT (Alanine aminotransferase)
-one of the thousands kinds of liver enzymes, and a kind of transferase.
-having the function of transfering amino group of amino acids from alpha-amino acids to alpha-keto acids, therefore, named transaminase.
L-Aspartic Acid + Ketoglutaric Acid = Oxaloacetic Acid + L-Glutaric Acid
L-Alanine + Ketoglutaric = Pyruvic Acid + Glutaric Acid
These enzymes are found in high concentration throughout the liver, so elevation in blood levels of both of these enzymes simultaneously is presumptive evidence of liver cell death.
Many of the liver enzymes are dedicated to 'workhorse' functions needed for the body's basic biochemical processes. Others seem to be dedicated to the detoxifaction and directing to excretion of ingested non-nutritive substances.
Many drugs can be acted upon by more than one liver enzyme, based on molecular structure (enzymes are always structure-specific). Therefore, multiple metabolites are produced. Each of these may have physiological activity independent of the parent drug. For example, oxazepam is a major metabolite of diazepam, which therefore adds to the physiological effect of the diazepam. In turn, temazepam is a major metabolite of oxazepam.
You can see how things quickly become exceedingly complex, making stock generalizations inappropriate.
Posted by Larry Hoover on November 16, 2002, at 9:17:51
In reply to Re: Can you really not drink alcohol or what?, posted by cybercafe on November 15, 2002, at 23:13:02
> > Well, the liver usually adds another methyl group to the drug so it can be filter and excreted by the gallbladder or kidneys. I think the problem with alcohol is it affects the neurotransmitter systems so much ... depleted serotonin, dopamine, etc. so that ad and ms can not work adequately.
> >
> > Paul
>
>
> hmmmm..... i thought alcohol worked on GABA-B and NMDA-glutamate receptors plus it distorted cell membranes ....... any of that right ?You're both right, but the picture still isn't complete. Here's a summary article:
Neurochem Int 1995 Apr;26(4):305-36; discussion 337-42
Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and alcoholism.Nevo I, Hamon M.
INSERM U.288, Faculte de Medecine Pitie-Salpetriere, Paris, France.
Acute or chronic consumption of alcohol interferes differentially with transmission processes in the CNS, affecting many--if not all--of the known neurotransmitter systems. Conversely, selective pharmacological manipulations of some of these neurotransmitter systems have been shown to reduce ethanol intake and preference as well as the severity of the ethanol withdrawal syndrome in animal models, certain compounds having even been employed successfully in the clinic. This review examines the studies which have attempted to elucidate the roles of these neurotransmitter systems in the mechanisms involved in the various aspects of alcohol abuse and alcoholism, with an emphasis on recent developments. The brain's major amino acid transmitter systems--inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate--have been widely studied over the past decade, with the general consensus that acute ethanol facilitates GABAergic transmission (by enhancing chloride conductance through the GABAA receptor) and inhibits glutamatergic function (by decreasing cationic conductance through the NMDA receptor). Conversely, the development of tolerance associated with chronic ethanol consumption leads to a reduced GABAergic and increased glutamatergic function. Interactions between ethanol and the monoaminergic transmitter systems are complex. Dopaminergic and noradrenergic mechanisms, along with the endogenous opioid systems of the brain, seem to be implicated in the rewarding effects of ethanol via activation of positive reinforcement pathways, while the serotonergic system mediates negative reinforcement. A number of ligands of the dopaminergic, serotonergic and opioidergic receptors involved in ethanol consumption-related behaviors have been recognized for their effects in reducing ethanol preference and/or alleviating symptoms of the ethanol withdrawal syndrome in various animal models. Several of these substances are being used with success clinically. Studies of the central cholinergic system in alcoholics have provided clues to the mechanisms underlying the deleterious effects of ethanol on learning and memory, and evidence of a reduced central cholinergic activity has been reported in alcohol-dependent patients. Interestingly, acetylcholine-rich grafts and cholinomimetic drugs have been found to ameliorate ethanol-induced behavioral deficits in alcoholized rats. More generally, basic studies on alcohol's effects on central neurotransmission certainly hold the key to the development of new strategies for the treatment of alcoholism.
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