Alcohol and Acetaminophen

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Alcohol and Acetaminophen

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DrVirgo
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08/07/07 - 07:12 AM

What is the difference in OD of Acetaminophen along with
1. Acute Alcohol intake
2. Chronic Alcohol intake

(has to do with P450)

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new_n_lost
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08/07/07 - 07:43 AM

Acute Alcohol Intake= Saves u from the Toxic Effects of Acteominophen Toxic Metabolite cos the Alcohol and Acetominophen share the Same Cytochrome P450 CYP2E1.

When large Amounts of Acetominophen r ingested the normal Conjugation pathway Becomes concerntrated resulting in the shunting of the excess concerntrations of APAP( acetominophen) to Cyt P450. Normally the CYP2E1 takes in APAP oxidizes it to NAPQI (the TOXIC METABOLITE OF APAP), then NAPQI gets Buffered by Glutathione.

Alcohol Competes with APAP for CYP2EI thus in Acute Ingestion of Alcohol ( first timers) the APAP doesnt Form the NAPQI hence saving from the Acuite Liver Injury.

But with Chronic Alcohol Ingestion there is an Increased Up regulation of the CYP2E1 thus the APAP gets Metabolized and the Excess NAPQI is not buffered by Glutathione cos Alcohol has Already depleted the Glutathione stores.

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DrVirgo
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08/07/07 - 07:48 AM

Thanks,
I'm tryint to simplify it...
Would it be right to say:

Acute alcohol inhibits P450 --> less to break down Acetaminphen --> less toxic metab.
--> less hepatic injury

Chronic alcohol reves up P450--> more break down of Acetaminophen -->more toxic metab. --> more hepatic injury

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new_n_lost
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08/07/07 - 07:50 AM

Add Glutathione Reserves Depletion to the Chronic Part.

sorry if i made it more confusing

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DrVirgo
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08/07/07 - 08:30 AM

new_n_lost wrote:
Add Glutathione Reserves Depletion to the Chronic Part.

sorry if i made it more confusing

What does "Add Glutathione Reserves Depletion to the Chronic Part." mean?

You didn't make it more confusing; you cleared up my doubts. Thanks smiling face

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new_n_lost
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08/07/07 - 08:42 AM

NAPQI is Detoxified by Glutathione. Alcohol Depletes the Glutathione Reserves thus the Toxicity of the NAPQI is More than Normal cos there is nothing to Detoxify it therefore requiring more of NAC to provide Glutathione.

The Down Regulation of the Enzyme takes more than 5 days and during this time its advised to Alcoholics to refrain from even normal dosages of Acetominophen cos in them the Normal Dosages will lead to Acute Liver Failure. therefore named as Alcohol Acetominophen Syndrome.

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