Health - Acetaminophen (USA)/Paracetomol (UK) Poisoning:

[Fantasian]

Here's some information i scrapped together on acetaminophen and overdoses related to this. If this isnt in the right sub-forum feel free to move it. I felt it helped alot when sometimes people consume drugs with acetaminophen in. Although i dont reccommend it.

As little as 10-15 g (10-30 tablets) or 150mg/kg of acetaminophen taken within 24 hours may cause severe hepatocellular necrosis and much less frequently renal tubular necrosis.Nausea and vomiting, the only early features of poisoning, usually settle within 24 hours. Persistence beyond this time, often associated with the onset of right subcostal pain and tenderness, usually indicates development of hepatic necrosis. Liver damage is maximal 3–4 days after ingestion and may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death.

Therefore, despite a lack of significant early symptoms, patients who have taken an overdose of paracetamol should be transferred to hospital urgently.

Administration of activated charcoal should be considered if paracetamol in excess of 150 mg/kg or 12 g whichever is the smaller, is thought to have been ingested within the previous hour.

Acetylcysteine protects the liver if infused within 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion after which effectiveness declines sharply and if more than 24 hours have elapsed advice should be sought from a poisons information centre or from a liver unit on the management of serious liver damage. In remote areas methionine (2.5 g) by mouth is an alternative if acetylcysteine cannot be given promptly. Once the patient reaches hospital the need to continue treatment with the antidote will be assessed from the plasma-paracetamol concentration (related to the time from ingestion).

Patients at risk of liver damage and therefore requiring treatment can be identified from a single measurement of the plasma-paracetamol concentration, related to the time from ingestion, provided this time interval is not less than 4 hours; earlier samples may be misleading. The concentration is plotted on a paracetamol treatment graph of a reference line (‘normal treatment line') joining plots of 200 mg/litre (1.32 mmol/litre) at 4 hours and 6.25 mg/litre (0.04 mmol/litre) at 24 hours (see Paracetamol poisoning treatment graph). Those whose plasma-paracetamol concentration is above the normal treatment line are treated with acetylcysteine by intravenous infusion (or, if acetylcysteine is not available, with methionine by mouth, provided the overdose has been taken within 10–12 hours and the patient is not vomiting).

Patients on enzyme-inducing drugs (e.g. carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, alcohol, and St John’s wort) or who are malnourished (e.g. in anorexia, in alcoholism, or those who are HIV-positive) may develop toxicity at lower plasma-paracetamol concentration and should be treated if the concentration is above the high-risk treatment line (which joins plots that are at 50% of the plasma-paracetamol concentrations of the normal treatment line).

The prognostic accuracy of plasma-paracetamol concentration taken after 15 hours is uncertain but a concentration above the relevant treatment line should be regarded as carrying a serious risk of liver damage.

Plasma-paracetamol concentration may be difficult to interpret when paracetamol has been ingested over several hours. If there is doubt about timing or the need for treatment then the patient should be treated with an antidote.

(information from BNF 51, a uk book for medical professionals)

Reputation Comments on this post:

	Interesting and good info!
	Great post

[themidnite1]

As SWIM used to have a very big Lortab 10/500 habit. At it's height, SWIMS habit was over 30 tablets a day, reaching up to 50+. SWIM did this for well over a year, on and off for 3. SWIM had a tolerance that required ingesting 12 of these pills at one time for bees to buzz. SWIM would usually repeat this several times a day, or just pop a few here and there to keep it going. SWIM has their liver tested still, regularly, and always thanks G-D and knocks on wood!
As a matter of fact, SWIM just obtained a script and p/u today for 20 of the Lortab 7.5/500 and took 12 at once. Bees were buzzing. Sorry, SWIM thinks they may have posted this information before, but SWIM is getting used to the forum and tends to be buzzzing a lot. Also SWIM has fibro, which can mess with the brain and memory and it does.

[Fantasian]

Damage caused it not Solely to the liver, nor can it always be picked up in tests. The way i understand it the liver tests only pick up necrosis of cells not deposits.

[jesusfreak666er]

(swims post was directed toward the midnite1 but is applicable to any not cwe practicing RX pill head)

Well instead of hoping and praying to god swiy isn't fucking swiy's self over, why doesn't swiy actually take measures to prevent further harm. Preform CWE always before doing.... it is such a quick and easy process that if one is really so arrogant and ignorant to ignore it liver poision might be deserved. Now you know there is an option (search CWE) plz do swiy's body a favor, along with proventing one of our forum members from dying... CWE.

Heres an intresting note... Tylonal poisioning can cause nice Anal Bleeding.. or is that asprin posioning... it doesnt matter since now swiy has the knowledge needed to never fear posioning again...

Reputation Comments on this post:

Nice post

[Fantasian]

Just to add while the above refers to more acute dosages, long term use of lower dosages also does put considerable stress on the liver.

[0utrider]

Dosages:
Paracetamol / Acetominaphen

Melt. point 169 °C (336 °F)
Boiling point:
Solubility in water 0.1-0.5 g/100 mL at 22 C mg/mL (20 °C)
CWE: Filtration possible by using CWE (cold water!!). Doesn't stay in the water, if done properly.Very slightly soluble in cold water, considerably more soluble in hot water . Soluble in methanol, ethanol, dimethylformamide, ethylene dichloride, acetone, ethyl acetate. Slightly soluble in ether. Practically insol in petr ether, pentane, benzene. CWE FAQ: Links, Lists & Manuals
Dosage: It seems, even though there is an individual lvl, that one can take quite a large dose once, way less if on a regular basis. It seems to be safe (meaning not necessarily irreversible harming! Its still dangerous!!!) to take up to 4000mg once, one is on the safer side if (s)he goes by Quote:
Optimal adult dosing appears to be somewhere in the 20 to 30 mg/kg Source
and doesnt OD on this. If taken regulary/daily, its a lot less and it should not be taken regular!
Side-effects: Because of the wide availability of paracetamol, there is a large potential for overdose and toxicity. Without timely treatment, overdose can lead to liver failure and death within days; paracetamol toxicity is, by far, the most common cause of acute liver failure in both the United States and the United Kingdom. It is sometimes used in suicide attempts by those unaware of the prolonged timecourse and high morbidity (likelihood of significant illness) associated with paracetamol-induced toxicity in survivors.
http://en.wikipedia.org/wiki/Acetaminophen

Grapefruit juice and APAP. GPJ is an inhibitor of CYP3A4, which is a minor
metabolizer of hydrocodone and a major
metabolizer of acetaminophen. What this means is that degree to
which plasma concentrations of acetaminophen increase would be much
greater than the degree to which plasma levels of hydrocodone would
increase; thus the risk of liver toxicity is actually higher.

Aspirin (Acetylsalicylic acid)

Melting point: 138–140 °C (280–284 °F)
Boiling point: 140C (284F) *decomposes into swiM believes Acetic acid and Salicylic acid (the chemicals list)
Soluble in: Water 10 mg/mL
Insoluble in: ?
CWE: Filtration possible by using CWE. Doesn't stay in the water, if done properly. One gram dissolves in 300 ml water at 25°, in 100 ml water at 37°, in 5 ml alcohol, 17 ml chloroform, 10-15 ml ether. Less soluble in anhydrous ether. Decomposes by boiling water or when dissolved in solutions of alkali hydroxides and carbonates. Inorganic salts of acetylsalicylic acid are soluble in water (esp the Ca salt, q.v.), but are decomposed quickly. CWE FAQ: Links, Lists & Manuals
Dosage: The toxic dose of aspirin is generally considered greater than 150 mg per kg of body mass. Moderate toxicity occurs at doses up to 300 mg/kg, severe toxicity occurs between 300 to 500 mg/kg, and a potentially lethal dose is greater than 500 mg/kg. This is the equivalent of many dozens of the common 325 mg tablets, depending on body weight. However children cannot tolerate as much aspirin per unit body weight as adults can.
Side-effects: Aspirin overdose has potentially serious consequences, sometimes leading to significant morbidity and mortality. Patients with mild intoxication frequently have nausea and vomiting, abdominal pain, lethargy, tinnitus, and dizziness. More significant symptoms occur in more severe poisonings and include hyperthermia, tachypnea, respiratory alkalosis, metabolic acidosis, hyperkalemia, hypoglycemia, hallucinations, confusion, seizure, cerebral edema, and coma. The most common cause of death following an aspirin overdose is cardiopulmonary arrest usually due to pulmonary edema.
http://en.wikipedia.org/wiki/Aspirin

Ibuprofen

Melt. Point: 76°C (169 °F)
Boiling Point:
CWE: Seems to be possible to filter out, but not as easy & efficient as PCM & Aspirine. Relatively insoluble in water. Readily soluble in most organic solvents. CWE FAQ: Links, Lists & Manuals
Dosage: 1200mg of ibuprofen is the maximum standard dose for a day. In medical practice, doses of 3200mg can be used reportedly. High doses involve a whole plethora of nasty side effects ranging from gastrointestinal ulceration to diarrhea.
Side-effects: Human response in cases of overdose ranges from absence of symptoms to fatal outcome in spite of intensive care treatment. Most symptoms are an excess of the pharmacological action of ibuprofen and include abdominal pain, nausea, vomiting, drowsiness, dizziness, headache, tinnitus, and nystagmus. Rarely more severe symptoms such as gastrointestinal bleeding, seizures, metabolic acidosis, hyperkalaemia, hypotension, bradycardia, tachycardia, atrial fibrillation, coma, hepatic dysfunction, acute renal failure, cyanosis, respiratory depression, and cardiac arrest have been reported.
http://en.wikipedia.org/wiki/Ibuprofen

PCM Poisoning: Acetylcysteine

PCM Poisoning Experiences, Infos & Discussion Thread
Acetylcysteine as antidote: overdosed toxic itself, drinking lots of water always recommended due to possible harm to kidneys)

"Administration of activated charcoal should be considered if paracetamol in excess of 150 mg/kg or 12 g whichever is the smaller, is thought to have been ingested within the previous hour.

Acetylcysteine protects the liver if infused within 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion after which effectiveness declines sharply; if more than 24 hours have elapsed advice should be sought from a poisons information centre or from a liver unit on the management of serious liver damage. In remote areas methionine (2.5 g) by mouth is an alternative if acetylcysteine cannot be given promptly. Once the patient reaches hospital the need to continue treatment with the antidote will be assessed from the plasma-paracetamol concentration (related to the time from ingestion).

Patients at risk of liver damage and therefore requiring treatment can be identified from a single measurement of the plasma-paracetamol concentration, related to the time from ingestion, provided this time interval is not less than 4 hours; earlier samples may be misleading. The concentration is plotted on a paracetamol treatment graph of a reference line (‘normal treatment line') joining plots of 200 mg/litre (1.32 mmol/litre) at 4 hours and 6.25 mg/litre (0.04 mmol/litre) at 24 hours. Those whose plasma-paracetamol concentration is above the normal treatment line are treated with acetylcysteine by intravenous infusion (or, if acetylcysteine is not available, with methionine by mouth, provided the overdose has been taken within 10–12 hours and the patient is not vomiting).

Patients on enzyme-inducing drugs (e.g. carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, alcohol, and St John’s wort) or who are malnourished (e.g. in anorexia, in alcoholism, or those who are HIV-positive) may develop toxicity at lower plasma-paracetamol concentration and should be treated if the concentration is above the high-risk treatment line (which joins plots that are at 50% of the plasma-paracetamol concentrations of the normal treatment line).

The prognostic accuracy of plasma-paracetamol concentration taken after 15 hours is uncertain but a concentration above the relevant treatment line should be regarded as carrying a serious risk of liver damage.
Plasma-paracetamol concentration may be difficult to interpret when paracetamol has been ingested over several hours. If there is doubt about timing or the need for treatment then the patient should be treated with an antidote." thanks to Jatelka.

Aspirine Poisoning

Grapefruit juice and APAP. GPJ is an inhibitor of CYP3A4, which is a minor
metabolizer of hydrocodone and a major
metabolizer of acetaminophen. What this means is that degree to
which plasma concentrations of acetaminophen increase would be much
greater than the degree to which plasma levels of hydrocodone would
increase; thus the risk of liver toxicity is actually higher.
Aspirine Poisoning: Infos, Basics & Discussion Thread
There is no antidote to salicylate poisoning. Frequent blood work is performed to check metabolic, salicylate, and blood sugar levels; arterial blood gas assessments are performed to test for respiratory alkalosis and metabolic acidosis. Patients are monitored and often treated according to their individual symptoms, patients may be given intravenous potassium chloride to counteract hypokalemia, glucose to restore blood sugar levels, benzodiazepines for any seizure activity, fluids for dehydration, and importantly sodium bicarbonate to restore the blood's sensitive pH balance. Sodium bicarbonate also has the effect of increasing the pH of urine, which in turn increases the elimination of salicylate. Additionally, hemodialysis can be implemented to enhance the removal of salicylate from the blood. Hemodialysis is usually used in severely poisoned patients; for example, patients with significantly high salicylate blood levels, significant neurotoxicity (agitation, coma, convulsions), renal failure, pulmonary edema, or cardiovascular instability are hemodialyzed. Hemodialysis also has the advantage of restoring electrolyte and acid-base abnormalities; hemodialysis is often life-saving in severely ill patients.

All overdose patients should be conveyed to hospital for assessment immediately. Initial treatment of an acute overdose includes gastric decontamination. This is achieved by administering activated charcoal which adsorbs the aspirin in the gastrointestinal tract. Stomach pumps are no longer routinely used in the treatment of poisonings but are sometimes considered if the patient has ingested a potentially lethal amount less than 1 hour previously. Repeated doses of charcoal have been proposed to be beneficial in aspirin overdose. A study performed found that repeat dose charcoal might not be of significant value. However, most toxicologists will administer additional charcoal if serum salicylate levels are increasing.

Edit: apparently Capsaicin (in chili plants) is supposed to be a mild antibiotic but also having properties of lowerin side-effekts of asprine.. Thats what SWIM heard, no source about that, further info would be nice.

Ibuprofen Poisoning

Basics, Infos & Experiences on Ibuprofen Poisoning Thread

Therapy is largely symptomatic. In cases presenting early, gastric decontamination is recommended. This is achieved using activated charcoal; charcoal absorbs the drug before it can enter the systemic circulation. Gastric lavage is now rarely used, but can be considered if the amount ingested is potentially life threatening and it can be performed within 60 minutes of ingestion. Emesis is not recommended. The majority of ibuprofen ingestions produce only mild effects and the management of overdose is straightforward. Standard measures to maintain normal urine output should be instituted and renal function monitored. Since ibuprofen has acidic properties and is also excreted in the urine, forced alkaline diuresis is theoretically beneficial. However, due to the fact ibuprofen is highly protein bound in the blood, there is minimal renal excretion of unchanged drug. Forced alkaline diuresis is therefore of limited benefit. Symptomatic therapy for hypotension, GI bleeding, acidosis, and renal toxicity may be indicated. Occasionally, close monitoring in an intensive care unit for several days is necessary. If a patient survives the acute intoxication, he/she will usually experience no late sequelae.

Reputation Comments on this post:

Good info

[BEEKSc1]

Median lethal dose (LD50)

median lethal dose, LD50 (abbreviation for “Lethal Dose, 50%”), or LCt50 (Lethal Concentration & Time) of a toxic substance or radiation is the dose required to kill half the members of a tested population. LD50 figures are frequently used as a general indicator of a substance's acute toxicity.

http://en.wikipedia.org/wiki/LD50

+++

LD50 of acetaminophen (Abernethy et. al, 1983)

In an animal model used to assess the effect of cimetidine on acetaminophen toxicity, the LD50 of acetaminophen alone in Charles River CD-1 mice was 480 mg/kg (95% confidence interval: 436-528 mg/kg).

Differential effect of cimetidine on drug oxidation (antipyrine and diazepam) vs. conjugation (acetaminophen and lorazepam): prevention of acetaminophen toxicity by cimetidine
http://jpet.aspetjournals.org/cgi/co...ract/224/3/508

+++

Toxicity of acetaminophen (DrugLib.com)
[QUOTE]
Oral, mouse: LD50 = 338 mg/kg; Oral, rat: LD50 = 1944 mg/kg
[/QUOTE}
http://www.druglib.com/activeingredient/acetaminophen/

+++

Alcohol and acetaminophen (Banda and Quart, 1984)

This study suggested that alcohol may be of value as an antidote in cases of acetaminophen overdose, by inhibiting the oxidative metabolism of acetaminophen. ... We have observed that 0.2 ml per animal of 19% alcohol, given at 3 - 4 hours after an LD50 dose of acetaminophen, produced a 24 hour survival of 92%. N Acetyl-cysteine produced 100% survival. Changes in either the dose or timing of the alcohol produced smaller increases in survival (75%), and in no case of alcohol treatment was survival less than control levels (50%). Alcohol thus appears to be an effective antidote for acetaminophen overdose in the mouse model, when given at an appropriate time and dose. It remains to be determined whether these results are applicable to human subjects.

The effect of alcohol on the toxicity of acetaminophen in mice
http://www.ncbi.nlm.nih.gov/pubmed/6701398

+++

Alcohol and acetaminophen (McClain et. al, 1980)

These findings suggest that alcohol enhances acetaminophen hepatotoxicity in mice and provides supportive evidence that these three alcoholic patients probably had a similar pathophysiological basis for their liver disease.

Potentiation of acetaminophen hepatotoxicity by alcohol
http://jama.ama-assn.org/cgi/content/abstract/244/3/251

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Alcohol and acetaminophen (Thummel et. al, 1989)

It was shown that ethanol must be administered early relative to APAP for hepatoprotection to be maximized. ... This result suggests that direct inhibition of cytochrome P450 by ethanol plays a role in the protection against acetaminophen-induced hepatotoxicity in mice. In human liver microsomes the inhibition of APAP oxidation to the hepatotoxic intermediate by 48 mM ethanol is less than half of the apparent inhibition of APAP oxidation reported in clinical studies in which the maximum ethanol concentration would have been 15-20 mM. Thus, in contrast to the mouse, inhibition of APAP oxidation to NAPQI in humans appears to be largely indirect, as has been reported previously in the rat.

Effect of ethanol on hepatotoxicity of acetaminophen in mice and on reactive metabolite formation by mouse and human liver microsomes.
http://www.ncbi.nlm.nih.gov/pubmed/2...ubmed_RVDocSum

So it sounds like it depends when the alcohol is entered into the system?

Before OR after:
the acetaminophen is introduced?

Reputation Comments on this post:

good info

[Fantasian]

the point is moot, acetaminophen/paracetamol should not be taken in toxic doses alcohol or not. There is no reason to it whatever circumstance. Also can i make it clear that the doses that are the LD50 for mice and rats are significantly higher than that of a human being in terms of mg per kg.

Reputation Comments on this post:

Great information in this thread :)

[madmatt3d]

Great information man. People need to know this stuff... it's critical.

madmatt3d added 0 Minutes and 40 Seconds later...

Added rep for this thread.

[<>-Lock.&.Load-<>]

I once had a friend who was absolutely convinced that she could get high from taking Tylenol (acetaminophen). Mind you, we're talking about straight Tylenol here, not Tylenol PM, which has some diphenhydramine in it. I tried to tell her that there was no way she was getting high from it, seeing as Tylenol has no psychotropic effects whatsoever. I also warned her about the possible damage to her liver that could result from an overdose on acetaminophen. She didn't listen, but it was quite a demonstration of the power of the placebo effect. I wonder if sugar pills would be able to get her high as well...?