Article from Medical Letter:
[Acetaminophen, NSAIDS and Alcohol. Med Lett Drugs Ther 1996;38(977):55-6.]

ANALGESIC EFFECTIVENESS - Mild to moderate pain usually responds to 650
mg of acetaminophen; more severe pain is more likely to respond to 1000
mg. A 200 mg dose of ibuprofen is equianalgesic to 650 mg of aspirin or
acetaminophen. A 400-mg dose of ibuprofen is superior to 660 mg of
aspirin or acetaminophen and, at least for treatment of some types of
pain, superior to 1000 mg as well. A 25 mg dose of ketoprofen or 440-mg
dose of naproxen sodium is comparable in peak analgesic effectiveness to
400 mg of ibuprofen (Medical Letter, 35:1,1993).
    
ACETAMINOPHEN (Tylenol, and others) Hepatic injury from acetaminophen is
due mainly to one toxic metabolite, N-acetyl-p-benzoquinoneimine, which
is formed by oxidation of the drug and catalyzed by cytochrome P450
enzymes tA2, 2E1 and 3A4 (GC Farrell, Drug-lnduced Liver Disease,
Edinburgh:Churchill Livingstone, 1994, page 205). With therapeutic doses
in healthy subjects, oxidation is a minor metabolic pathway and stores
of glutathione conjugate the toxic metabolite. The maximum recommended
dosage of acetaminophen is 4 grams per day. The minimum toxic single
dose is between 7.5 and 10 grams in healthy adults. Single doses of more
than t0 to 15 grams can cause hepatic necrosis, but even much larger
doses may not cause serious liver injury in some patients, probably due
to differences in metabolism of the drug. Concurrent use of some drugs,
such as isoniazid, phenobarbital, phenytoin (Dilantin, and others) and
zidovudine (Retrovir), may increase serum concentrations of the toxic
metabolite, either by inducing the enzymes that catalyze oxidation or by
inhibiting conjugation, and could increase the risk of hepatotoxicity.
    
Effect of Alcohol - Regular consumption of alcohol lowers the threshold
for acetaminophen-induced liver damage because it induces the enzymes
that catalyze oxidative metabolism of the drug. In addition, alcoholics
may have depleted stores of glutathione and an already-damaged liver.
Severe liver injury has been reported in alcoholics who took less than 4
gm of acetaminophen per day ((HJ Zimmerman and WC Maddrey, Hepatology,
22:767, 1995). The risk of regular or sporadic use of acetaminophen in
patients who regularly drink moderate amounts of alcohol is not clear;
fatal hepatic injury has been reported in such patients, sometimes
associated with fasting, but the accuracy of alcohol histories is
notoriously questionable and fasting alone can increase the risk of
hepatotoxicity from acetaminophen (DC Whitcomb and GD Block, JAMA,
272:1345, 1994).
    
NSAIDs - With chronic use, nonsteroidal anti-inflammatory drugs
(NSAIDs), including over-the-counter drugs such as aspirin, ibuprofen,
naproxen sodium and ketoprofen, can cause upper gastrointestinal
bleeding, ulceration and perforation. There is some evidence that
ibuprofen in doses of 1600 mg/day or less may cause less
gastrointestinal toxicity than aspirin or other NSAIDs, but fatal
hemorrhage has occurred with all of these drugs High doses, prolonged
use and advanced age are risk factors. Alcohol can also cause gastric
injury and is associated with development of peptic ulcers; five drinks
or more per day has been associated with an increased incidence of
gastrointestinal toxicity in patients who take NSAIDs (D Henry et al,
Gastroenterology, 106:1076, 1993).
    
CONCLUSION - Alcohol may increase the risk of hepatic injury due to
acetaminophen or gastrointestinal bleeding due to NSAIDs, but the
relative risk of OTC doses of these drugs in patients who drink small
amounts of alcohol is unknown. Regular use of any analgesic should be
discouraged in alcohol drinkers, and those who do use them should be
encouraged to use the lowest possible doses.