From: On@aday.com (Iron) Newsgroups: alt.drugs,sci.med.pharmacy Subject: Re: Codeine in USA? Date: Thu, 13 May 1999 16:57:40 GMT [...] Acetaminophen, 4'-hydroxyacetanilide, is a non-opiate, non-salicylate analgesic and antipyretic which occurs as a white, odorless, crystalline powder, possessing a slightly bitter taste. It has the following structural formula: C8H9NO2, with a molecular meight of 151.16 [...] [Overdose] Signs and Symptoms: In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur. In adults, hepatic toxicity has rarely been reported with acute overdoses of less than 10 g and fatalities with less than 15 g. Importantly, young children seem to be more resistant than adults to the hepatotoxic effect of an acetaminophen overdose. Despite this, the measures outlined below should be initiated in any adult or child suspected of having ingested an acetaminophen overdose. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours postingestion. Treatment: The stomach should be emptied promptly by lavage or by induction of emesis with syrup of ipecac. Patients' estimates of the quantity of a drug ingested are notoriously unreliable. Therefore, if an acetaminophen overdose is suspected, a serum acetaminophen assay should be obtained as early as possible, but no sooner than four hours following ingestion. Liver function studies should be obtained initially and repeated at 24-hour intervals. The antidote, N-acetylcysteine, should be administered as early as possible, preferably within 16 hours of the overdose ingestion for optimal results, but in any case, within 24 hours. Following recovery, there are no residual, structural or functional hepatic abnormalities. ==================================================================== From: Samson Subject: Re: Acetaminophen Date: 28 May 2000 Newsgroups: alt.drugs.hard In article , "Reverend Jamie P. Cecil" wrote: > Hey I know that the Acetaminophen in Vicoden can fuck you up, but does > someone know what happens? I mean do you just up and croak in the middle on > the night? Do you slowly deteriorate and wind up a puddle of mucous and > blood on the floor in front of your computer? Do you spontaneously combust? There are three phases of acetaminophen toxicity: 1. 2-24hr: Loss of appetite, nausea, vomiting and runny nose. General malaise. CNS depression. Symptoms are mild, however, and may be mistaken for a false alarm. 2. 24hr+: Phase 1 symptoms become less pronounced. Pain in right side of torso may be present, indicating early stages of hepatic damage. Liver enzymes are elevated. Kidney function begins to deteriorate, but may not be noticed due to decreased hepatic urea formation. 3. 3-5days: Blood coagulation failure, jaundice, renal failure (secondary to hepatic necrosis), heart problems. Death ensues following anuria (piss backing up in your bloodstream) and coma. There is some dispute as to what a "typical" lethal dose is in humans. There is compelling evidence that for the vast majority of people, doses well in excess of the oft-cited figure of 15g (~140 mg/kg) are tolerated without ill-effect. APAP is converted to the toxic metabolite NABQI by the P450 enzyme cyp2E1, and small amounts of NABQI are cleared by reduced glutathione (another enzyme). It may be that a minority of people have a "hyperactive" cyp2E1 system that makes them susceptible to NABQI overload, glutathione depletion and death. (But you never know if you're one of the gang, and it is most definitely the case that alcohol both increases 2E1 activity *and* depletes glutathione). If, for some reason, you happen to take 10g or more acetaminophen, and you don't want to test your luck, get ye to the ER within 12 hours of the dose. It is (virtually) 100% treatable with N-acetylcysteine (Mucomyst): a loading dose of 140mg/kg followed by 70mg/kg doses at 4-hour intervals for a 72-hour period. (With lots of blood drawn while you lay in the ward, feeling like a complete moron). NAC efficiently replaces glutathione, allowing for damage- free excretion of NABQI. (You can get NAC at any health-food store in 600 mg capsules -- but I don't recommend self-resucitation in situations such as these. Ever try to give yourself CPR?) ==================================================================== From: (Samson) Subject: Re: Loratab Date: 28 Jun 1999 00:00:00 GMT Newsgroups: alt.drugs.hard "Robert F. Golaszewski" wrote: > > > > well texts like PDR arent written by idiots - > > > if they say 10g is potentially toxic, it probably is. > Samson wrote > > Idiots, no. However, it is essentially written by lawyers, not > > doctors, so it is not always a reliable source of medical > > information. (Nor are many texts written by doctors, for that > > matter.) > > > I've posted this earlier in the thread. The 10-15g range for a > > 'minimum toxic dose' is extrapolated in part from clinical > > research (less than 1 in 1000 cases of toxicity involved doses > > less than 10mg -- definition of "rarely" in PDRese), and in > > part from the fact that 50 out 100 mice and/or rabbits show > > signs of toxicity at about 180mg/kg (12.6g/70kg). However, > > _in vitro_ studies of isolated hepatocytes show that humans > > are closer to rats (ED50 = 1200mg/kg) in their susceptibility > > to APAP-induced toxicity -- with the average dose likely to > > cause hepatotoxicity in a healthy human closer to 1000mg/kg > > (70g/70kg). This value varies widely depending on genetic > > differences in enzyme production, alcohol intake, use of > > certain other drugs, etc. [I may have the species wrong, but > > the numbers are right. I can't find the article...] [Found it: substitute 'hamsters' for 'rabbits'] > > None of this is an invitation to take 70g of APAP, but the > > PDR can be off by several orders of magnitude, and most > > certainly will be if it means that many fewer lawsuits. > > (There is absolutely no clinical benefit to be had from > > a dose of more than 1.5g of APAP*. They are not going to > > recommend one microgram more.) > > > > > Liver damage from APAP is a binary phenomenon: either > > > >you're fine, or you're dead. > > > > are you sure? is this your own opinion or medical > > > fact? i'm genuinely curious. > > > This is a medical fact. (Well, if there's some hepatic injury, > > while it should "mend" if you leave your liver alone for a > > while, it may accumulate if you keep pills a-popping. But it > > will not be without symptoms.) > > Be careful with these statistics. These clearly > are referring to measurable damage from a *one-time* dose. > While it may well be that it typically takes a one time dose > of 12 grams in a normal adult to get detectable liver damage, > this doesn't necessarily mean that much lower doses don't > cause some minor damage. This has been explained before. Until GSH stores are significantly depleted -- which requires large doses of APAP to sufficiently engage oxidative metabolism -- there is no damage, not even any potential for damage, hence there is no cumulative damage. Now, these statistics say that in the "typical" healthy adult human, doses far in excess of 12g are required to reach that threshold. You should be careful with your use of the word "typically" -- "typically", patients who present with APAP- induced hepatotoxicity have consumed no less than 10-15g of APAP. That is not the same as saying that 10-15g APAP "typically" causes damage. In fact, this is thought to be quite atypical: "...the average susceptibility of man to paracetamol hepatoxicity appears to resemble more nearly that of the rat than the mouse or hamster. This would put the ED50 dose [for impaired detoxification] at 1500mg/kg rather than the 200mg/kg suggested in some clinical papers. Comparison of the rates of oxidation in a number of subjects, both in vivo and in vitro, revealed a fivefold range in activity [of oxidative metabolism of APAP to the toxic metabolite], with most subjects at the lower end of the range. This would suggest that the few subjects at the upper end of the range were almost as sensitive as the mouse to the toxic effects of paracetamol." (Fed. Chem. Toxicol, 24, p735) "Few" is not defined. But it is contrasted with "most", and clearly represents something not "typical". > To me the deciding factor is that there is just no > *need* to ever take the chance. Extraction (even crude > ones get the APAP dose down into safe ranges) is easy. > Having a liver go bad sucks big time. No rational person > should take the risk. I agree with that.