Paracetamol

History

The first Antipyrétique S exist for a long time. Since the Antiquity, the decoctions of sheets of Saule are famous for their virtues against the Fièvre and the pains, in particular at the Égyptiens. Later, towards 400 before J.C., Hippocrates, the founding father of the medicine and according to which “nature is the doctor of the patients”, recommended a Tisane sheets of willow to relieve the labor pains and cause a drop in the fever. The Romains knew also its properties (- the Latin name of the willow is salix ). This use continued in an empirical way until.

The antipyrétiques ones used at that time were natural preparations starting from compounds of barks of Cinchona from which quinine derives, or starting from salicylate contained in the bark of Saule. The bark of cinchona became rare and expensive and the need to find substituents appeared. Harmon Northrop Morse synthesizes as of 1878 a baptized substance acétylaminophénol, but they is only fifty years later that it will be marketed like drug under the name of paracetamol . At that time, other products are used as remedy against the pain and the fever: in 1897, the Aspirine is synthesized by Felix Hoffmann and is a great success. The Acetanilide (1886) and the Phénacétine (1887) are also used until proving to be products equipped with serious side effects and that the disadvantages of aspirine start to be known. Paracetamol reappears then and the first studies on the antipyretic and antalgic properties of paracetamol are led to the end of.

In 1886, the Cahn doctors and Hepp study the effect Antiparasitaire Naphtalène. With course of product for the Experiment S, they decide to be supplied but the pharmacist of Strasbourg makes an error and to them provided another chemicals: the Acetanilide. By resuming their study, the Médecin S are intrigued by the effects obtained by this new product and they discover antipyretic properties to him. The Acetanilide, whose antalgic properties will be discovered a little later were born from a providential error and are the ancestor of paracetamol and phenacetin. Doctor Hepp has a brother who works for a small company (Kalle Co) which manufactures acetanilide. He proposes to him to use his discovery and of launching on the market acetanilide like Antipyrétique S and thus competing with antipyrin and the salicylic acid. Acetanilide becomes a Médicament marketed under the name of Antifébrine. At that time, the Industrie of the dye S had a waste, the paranitrophénol, with a chemical structure rather similar to the Acétanilide and available at low prices. A few weeks later, Oskar Hindsberg presents another product: the acétophénitidine. The step of creation of this substance was purely commercial and by chance, of the tests show that it seems more powerful than Antifébrine and causes less undesirable effects. Duisberg, person in charge of research and the Patent S at Bayer AG, decides to put the new molecule in production and calls it “Phenacetin”.

However, acetanilide is very toxic and of many research devote themselves on the development of derived tolerated better. Paracetamol was found in the Urine S of the people having consumed phenacetin. In 1889, the German scientist Karl Morner discovers that the cut of phenacetin gives acetaminophene, an effective product against the pain and the fever. A metabolic study of this drug shows that it is about a metabolite déséthylé of phenacetin. This assumption was formulated as of 1894 but it was necessary to await work To ballast and Greenberg of the university of Yale and those of Flinn and Brodie of the university of New York to obtain the confirmation of this assumption. In 1893, a German doctor, J. von Mering, compares the antalgic and antipyretic properties paracetamol and phenacetin like their respective toxicities. However, it draws from this study the conclusion which paracetamol is néphrotoxique than phenacetin. Paracetamol is then forsaken during one half-century following this error. The toxicity of phenacetin for the Rein will be shown thereafter, involving its withdrawal of the market.

In 1946, the Institute for the Study off Analgesic and Sedative Drugs proposes a purse with the New York City Department off Health in order to studied the problems associated with the agents analgesics. Bernard Brodie and Julius Axelrod are indicated to study the bond supposed between the agents nonderived from aspirine and the development of the Méthémoglobinémie. In 1948 they publish their study which shows that acetanilide is degraded in the organization in N-acetyl p-aminophenol, and that only this metabolite is active against the pain. They also show that the acetanilide administration is responsible for the formation of méthémoglobine, but they add that it east can be the phenylhydroxylamine the responsible agent, and not paracetamol as one believed it before. They thus suggest with the industrialists replacing acetanilide, person in charge of the methemoglobinemy, by acetaminophene. There is then an renewed interest for paracetamol, because of its properties Antalgique S and Antipyrétique S, and of its apparent good tolerance.

The Food and Drug Administration grants in 1955 the authorization of sale of paracetamol to the United States. It is marketed for the first time the same year by McNeil Laboratories under the name of Tylenol® Children' S Elixir; it is a syrup for child against the Fièvre and the Douleur, presented in one limps red in the shape of truck of fireman. This small company of Pennsylvania was interested in this product because it does not cause pains with the Estomac. The product then became popular at the Adulte S for the same reason. In 1956, paracetamol is sold with the the United Kingdom under the name of Panadol® in amount of 500 Mg, produced by Frederick Stearns & Co, a subsidiary company of Sterling Drug Inc. In 1958, appears Panadol Elixir®, a version intended for the use of the children. The suffix - fraud at the end of the name of the drug comes from Latin dolor , who means “pain”. In France, paracetamol appears in 1957 within a drug of pediatric use, Algotropyl®, marketed by the Theraplix Laboratories. Then the same pharmaceutical firm puts on the market Doliprane® as of 1961. Nowadays, of many drugs containing of paracetamol were developed and marketed in much country.

Chemistry

Structure and reactivity

Under the ordinary conditions, paracetamol is a powder white with a light taste, soluble in 70 volumes of Eau, 7 volumes of alcohol to 95%,13 volumes of Acétone, 40 volumes of Glycérol or 50 volumes of Chloroforme. However, it is insoluble

The molecule consists of a benzene cycle, substituted by a grouping Hydroxyle and a grouping Amide in para position. Paracetamol does not comprise a asymmetrical Carbone and has only a Stéréoisomère. The amide group, the free pair of the grouping hydroxyl, the orbital p of carbonyl and the free pair of the oxygen of carbonyl form a Système combined with the cycle. This conjugation reduces the alkalinity of oxygens and nitrogen and makes the grouping hydroxyl more acid because the delocalization of the loads is carried out on an ion phenolate.

The presence of two groupings activators makes the cycle highly reactive for a aromatic Substitution électrophile, the substituents being Ortho and directing Para. All the positions of the cycle are more or less activated same manner and thus does not have there a site privileged in the case of a substitution électrophile. Paracetamol is the active Métabolite of the Acétanilide and the Phénacétine: paracetamol is produced by the Décomposition of these two products in the organization. These products are same chemical family and have a chemical structure very near.

Synthesis

Paracetamol not including/understanding a chiral center exists in the form of only one stéréoisomère, the Synthèse does not need to be stéréocontrolée, and it is simpler compared to the asymmetrical syntheses of other pharmaceutical substances

Paracetamol was synthesized for the first time in 1878 by Harmon Northrop Morse by reduction of p-nitrophenol in the presence of tin in acetic Acid icy. The p-aminophénol obtained is then acylé by the acetic acid to obtain paracetamol. Vignolo simplified this synthesis by using the p-aminophénol as starting product. However, it was shown that it acts mainly on the level of the central Nervous system. Studies showed that paracetamol acts by reducing the production of Prostaglandine S, implied in the processes of the Douleur and of the Fièvre by inhibition of the Enzyme S Cyclo-oxygénase S (COX). Other studies showed that paracetamol does not have an action on the COX-1 and the COX-2. The existence of two forms of COX (COX-1 and COX2) on which act the AINS like the Aspirine or the Ibuprofène was clearly established. Indeed, the action blocking on the COX-1 results in to cause the gastro-intestinal undesirable effects of aspirine and ibuprofene. One suspects the existence of a news Isoenzyme COX-3 on which paracetamol would act specifically, which would explain why paracetamol reduces the fever and the pain without gastro-intestinal undesirable effects. For the moment, this assumption was not proven at the man, who end to the formation of a intermediate toxic reagent, N-acétyl benzoquinone imine or NAPQI. It is normally quickly eliminated by reaction with the reduced glutathion then evacuated in the urines after conjugation with mercaptopuric cystein and the acid.

The elimination of paracetamol is primarily urinary: 90% of the introduced amount are eliminated by the kidney of 24 hours, mainly in form glycuroconjuguée (60 to 80%) and sulfoconjuguée (20 to 30%) and less than 5% is eliminated in the form of paracetamol. The Demi-vie of elimination is of approximately 2 hours.

physiopathological Variations: In the event of severe impaired renal function, with a Clearance of the Creatinin lower than 10 ml/min, the elimination of paracetamol and its metabolites is delayed. The glycuroconjugaison is immature in the infant and the child, paracetamol is thus primarily sulfoconjugué. The passage to a metabolic way identical to that of the adult intervenes towards 9-12 years.

Galéniques, association and trade descriptions

galenic Forms:

Paracetamol uses the composition of an about sixty proprietary medical products and can be presented in various forms or conditionings. Paracetamol alone is sold under many galenic forms.

Paracetamol is used in association with other active substances to benefit from its antalgic and antipyretic properties. One of the problems of associations is the accumulation of the side effects, however, paracetamol being very well tolerated, it is particularly interesting within the framework of associations, and this is why the pharmaceutical laboratories developed very many formulas including/understanding of paracetamol.

trade Descriptions :

Nonassociated paracetamol is sold in generic name or under many marks of which some very known:

Doliprane (Sanofi Aventis, drug more prescribed in France), Dafalgan (Bristol-board-Myers-Squibb) or Efferalgan (Laboratory UPSA) in France;
Tylenol or Panadol with the Canada and the the United States.

It is found associated with other active substances in certain remedies against the grippaux states (Actifed, Dolirhume, Humex Rhume, Rhinofébral), where it is effective at the same time on the fever and the pain. It is sometimes mixed with Caféine (Claradol cafeine, Exidol, Theinol), substance which could increase its analgesic effect, but this concept remains very discussed. It can also be associated with other analgesics the such Aspirine (Novacétol) It is found often associated with a weak Opiacé like the Codéine (Efferalgan codeine, Codoliprane) or the Dextropropoxyphène (Dialgirex, Di-antalvic) what makes it possible to increase its antalgic action and to treat the average or strong pains. The antalgic clinical effectiveness (in term of synergy of analgesia) of association paracetamol + dextropropoxyphene remains badly evaluated (with the difference of that using the Codéïne). For the moment, it was not shown that association paracetamol + dextropropoxyphene is higher than paracetamol alone. Association with the Tramadol is also used (Ixprim, Zaldiar), with 37.5 Mg from tramadol and 325 paracetamol Mg by tablet, which would make it possible to obtain an antalgic effectiveness equivalent to 50mg of tramadol but with a better tolerance. The association of paracetamol with an opiate can pose problems of dependence and diversion of use.

Indications, posology and practical informations

Indications

Paracetamol is used for. It is about a analgesics of stage 1 according to the classification of WHO. It can be used only, or in partnership with other analgesics (codeine, dextropropoxyphene, tramadol), it returns then in the classification of the analgesics of stage 2 indicated in the pains of intensity moderated to intense and/or not answering the use of peripheral analgesics only.

symptomatic treatment of the Fever, in particular in the child in whom it constitutes the antipyrétique one of first intention. In this case, a monitoring of the INR would be recommended.

Disturbance of test of laboratory:

The paracetamol catch can distort. Undesirable effects nevertheless were reported without the imputability (the fact that the undesirable effect is well caused by the drug) being established most of the time. The principal undesirable effects found in the literature are:

Very seldom: Cutaneous eruption with rash or probably allergic eruption urticarienne of origin, Thrombopénie and Asthma.
Discussed: cytolytic Hepatitis acute, and chronic Impaired renal function.
In a specific way: anaphylactic Hypotension, Shock, will purpura vascular, Syndrome of Lyell and Syndrome of Stevens-Johnson, ulceration rectal, Agranulocytose, Pancréatite acute generally in partnership with other drugs like codeine, active Hépatite chronic, granulomateuse Hépatite and Rhabdomyolyse.

In front of the appearance of an undesirable effect, it is necessary to stop the accused drug and to consult its doctor.

Overdose

Paracetamol is a Médicament used very usually and available in the Pharmacie S without ordinance. The cases of overdose are current and have sometimes very serious consequences.

Proportion toxic

The toxic amount of paracetamol is highly variable according to the individuals. In a single catch, it is about 10 G or 125 mg/kg in the adult and from 100 to 150 mg/kg in the child.

Paracetamol could be toxic for the Foie, even with therapeutic amounts, that is to say 4g/24h, at patients presenting a chronic Alcoolisme, a Dénutrition, a Hépatite C, a Cirrhose or the AIDS; all these affections cause a drop in the rate of Glutathion. Thus, of the deaths took place after an ingestion of therapeutic paracetamol amounts among patients presenting a sick Foie beforehand. Since paracetamol is mixed with others Médicament S, it is important to take into account this additional paracetamol contribution well in the calculation of the toxic amount. The paracetamol catches must always be separated by 4 a.m. at least. To avoid the overdose, it is useful to discuss with a Pharmacien to know the drugs containing of paracetamol or to look at the composition of the drugs to detect the presence of paracetamol.

Risks

One of the stages of the transformation of paracetamol produces a toxic Molécule which can cause the death of the hepatic cell S. However, in the amounts recommended for the organization the toxic product can be eliminated and there is no danger. On the other hand, when the paracetamol amount is too important, the quantity of toxic product is too important and the Foie will not manage to eliminate sufficiently quickly; it will suffer more or less important damage according to the quantity of paracetamol absorptive. Paracetamol is eliminated from the organization mainly by reaction with the Glucuronic acid on the level of the liver. A weak part is transformed by the Cytochrome S P450 (CYP2E1, CYP1A2, CYP3A4) into a reactive Métabolite (N-acétyl-p-benzoquinone imine, NAPQI) which constitutes the principal toxic element of paracetamol. This one is eliminated, in the liver, by a reaction with the Glutathion (donor of HS) which collects the radicals. If the Glutathion is not available in sufficient quantity or that the reserve in the liver is exhausted, the NAPQI causes lesions of the liver. An increased risk of toxicity is caused by a lack of glutathion (Malnutrition, Anorexie, possibly diseases of the liver) and/or an increased formation of the toxic Métabolite.

The overdose can involve, because of the formation of a reactive Métabolite, a Hépatite with low registers lesion S of the liver (hepatic Cytolyse), leading to a Nécrose in the extreme cases. The consequences of an overdose are serious, sometimes mortals. The damage caused with the liver is irreversible, a Clerc's Office of liver proving to be necessary when the damage is very important. The NAPQI involves the creation of adduits fixed at hepatic proteins, degradation of the membrane Lipide S, disturbances of the calcic Homéostasie, causing one necroses and cytolytic hepatitis. The Rein is touched by the same mechanism.

The Toxicité on the Foie is prédictible using two parameters: the introduced amount and the rate plasma tick of paracetamol. The intentionally abusive paracetamol catches can be detected quickly and the damage can be limited by the administration of N-acétylcystéine. It is not the case of overdoses nonintentional and chronicles which are detected more tardily whereas important damage already could occur.

Moreover, it is possible to calculate the Demi-vie elimination of paracetamol. In the cases of Intoxication, the hepatic Nécrose prevents elimination and the half-life increases. A half-life higher than four hours testifies to a Hépatite. A half-life higher than twelve hours indicates a hépatocellulaire insufficiency.

The individuals who took too much paracetamol generally do not have a Symptôme S during the first 24 hours . Although nausea S or Vomissement S appear in first, these symptoms disappear after a few hours. The subjects feel better and believe that the worst passed. If the absorptive amount is toxic, after this period of wellbeing, the subject has a hepatic failure. In the extreme cases, the subject falls into the Coma before having a failure of the liver. The half-life will be more important in the child who has capacities of glucuronoconjugaison lower than those of the adult.

The Activated carbon makes it possible to fight against many Empoisonnement S including by paracetamol, it reduces the digestive absorption of this one and presents less risks than gastro-intestinal decontamination. Previously, the Médecin S were reticent to manage activated carbon since in the event of overdose, this one can also absorb the Antidote and thus decrease its effectiveness. Studies since showed that only 39% of N-acétycystéine are absorbed when they are managed together. If not, the use of acétylcystéine per way Intraveineuse is effective in combination with activated carbon. If it is envisaged to give N-acétylcystéine by oral way, it is recommended to differ the treatment from 1 with 2:00 after the administration of Activated carbon. The syrup of ipéca must in particular be regarded as obsolete.

N-Acétylcystéine

In the overdoses, the N-Acétylcystéine is used to reinforce defenses of the organization with respect to the toxic metabolites and is a precursor of the glutathion. The N-acétylcystéine is a product which reduces the toxicity of paracetamol in substituent of the reducing Glutathion like of the radical ; The grouping Thiol makes it possible to reduce the toxic Métabolite and reacts to detoxify paracetamol, i.e. to eliminate the toxic Métabolite. It makes it possible to mitigate the insufficiency of the glutathion and to reduce the risk of toxicity on the Foie if it is absorbed less than eight hours after the ingestion of paracetamol. It does not damage the cell S and can be excreted without danger.

N-acétylcystéine is managed as Antidote either by oral way (granulated FLUIMUCIL® or MUCOMYST® aqueous solution), or in Perfusion Intraveineuse (FLUIMUCIL®). These products are available in Pharmacie. With the the United States, the oral and intravenous administration are considered of identical effectiveness. However in Australia and Europe, the introduction by intravenous way is preferred. The acétylcystéine by oral way is not well tolerated because of sound Goût, of sound sulfur Odeur and its tendency to cause Vomissement S and nausea S. It can be diluted in solutions at 5% starting from the commercial solutions with 10% or 20%. In certain country, the antidote by way Intraveineuse is not available.

Comparison with anti-inflammatory drugs not stéroïdiens and aspirine

Paracetamol, contrary to the Aspirine and the Ibuprofène is deprived of properties Anti-inflammatoire S. It does not form part of the class of the anti-inflammatory drugs not stéroïdiens (AINS), not being a good inhibiter of the COX and in particular of the COX-2. The AINS them, have jointly the property to be able to decrease the production of the prostanoïdes by inhibiting the activity of both isoformes the cycloone (COX-1 and COX-2).

With regard to the treatment of the pain, the antalgic activity of paracetamol is comparable with that of aspirine, for posologies identical from 1 to 3 g/j and for pains of various causes according to evaluations carried out relative with harmlessness, the effectiveness and the cost.

Paracetamol does not present counter-indications for the expectant mothers and does not affect the development of the Fetus as the AINS do it (treatment of the persistence of the arterial channel). The use of the AINS by the expectant mothers is associated, in an important way, with the persistent Hypertension pulmonary at the new-born babies. Paracetamol currently is very much used, in particular in pediatry. It can be managed to the children because it is not associated with the risk of the Syndrome of Reye for the children having an immunizing deficiency. The clinical studies show that a standard amount of ibuprofene (400 Mg) causes a greater relief of the pain than a standard paracetamol amount. (1000 Mg). Like the AINS and contrary with the Opiated S, paracetamol was not recognized as the cause of Euphorie S or modification of Humeur but contrary with opiates, it can damage the liver. However, this effect is neglected in comparison of the risk of addiction. Paracetamol and the AINS profit from a weak risk of Addiction.

With regard to the treatment of the fever, it does not seem to exist of difference in effectiveness anti-pyretic between paracetamol and the AINS.

Paracetamol and company

Nonvoluntary overdose and commits suicide

The nonvoluntary overdose paracetamol is the first cause of failure of the liver in England and with the the United States. The involuntary intoxications with paracetamol represent every year in the United States more than 13.000 passages to the urgencies, more than 2000 hospitalizations and nearly 100 deaths according to the Food And Drug Administration. These important figures are explained by the fact why many products are available to the the United States on sale free without ordinance and contain paracetamol without that being indicated on limps; and by the fact that conditionings of the Antalgique S containing paracetamol often exceed the amount potentially mortal of 8 Gram S by limps. In France in the years 1980, the Agency of the drug, old name of Afssaps, the conditioning of the antidouleurs containing paracetamol had reduced so that they do not exceed this amount. Since this change of conditioning, the Décès by Intoxication did not increase whereas consumption did not cease growing. Thus in 1990,177 420 limp of paracetamol were sold in France, and 5.335 Intoxication S and 6 deaths were listed. These figures have remained stable for this year. In England, at the time where conditioning was not limited to a maximum of 8 grams, the deaths were included/understood between 200 to 600 according to the sources, which carried out the Autorité S to adopt similar measures with the France as from 1998.

Paracetamol is sometimes used at the time of Suicide S or suicide attempts. However, more half of died by overdoses are Accident S. the consecutive acute hepatic failures with a nonintentional overdose often give more severe tables and have a forecast less good than at the Patient S having an intentional overdose. Indeed, the Victime S of accidental overdoses are often taken of load later, and the risks are thus higher. However, compared with the numbers of consumed paracetamol amounts each day, the accidental overdoses touch only one minority of the users. In France, the suicides with paracetamol are much less current but also more difficult to evaluate because in France, there does not exist national register of the Intoxication S volunteers.

Although the rate of Intoxication to paracetamol is weak compared to the million shelves used each year, certain authors propose to change the mode of sale of paracetamol. Current conditionings limit fortunately the risk of accidental overdoses, the quantity of paracetamol per box was decreased and the regulations of Médicament S combining of opiates with paracetamol were restricted to reduce the accidents. The Enfant S are accidental victims of surdoses in the event of massive Absorption in the form of Sirop. On the other hand, the effervescent shapes of paracetamol limit the risk of accidental catch because they force to drink a great quantity of Liquide and have a sapid taste. The association of a substance and sound Antidote in the same drug makes it possible to decrease the risks of surdose. Paradote is a drug in the form of shelves containing 100mg Méthionine and paracetamol 500mg (c.à.d 20% of methionine). The Méthionine is used to substitute for the lack of Glutathion and makes it possible to protect the Foie in the event of surdose.

Sales figure

Paracetamol is one of the drugs most sold in the world. The report/ratio of 2005 of the National bank of health insurance finds that in France, the family of drugs the most prescribed is that of analgesics, which still progresses in an important way (+ 9,2% compared to 2004) to reach 340 million sold boxes.
One finds top of the list of the ten Médicament S the most prescribed in quantity in France in 2005 three Antalgique S containing paracetamol alone: Doliprane (1st with 73,3 million units prescribed in 2005 either +15,2% since 2004), Efferalgan (2nd with 42,5 million or +5,8%) and Dafalgan (3rd with 35,5 million or +11,2%). Their respective classification was identical in 2004. Two Antalgique S with associated paracetamol are also placed in the 10 most prescribed products: Propofan (6th, with 14.6 million units prescribed in 2005 either -5,2% since 2004) and Di-Antalvic (8th with 12,8 million or -0,6%).
What means that 5 of the 8 products most prescribed in France are Antalgique S containing of paracetamol, with very a strong progression for some like Doliprane (+15%) and Dafalgan (+11%). According to the report/ratio of the French Agency of public health of health products (AFSSAPS), the paracetamol regulations in France were multiplied by 2 in 10 years. This strong growth means that the use of these Antalgique S was standardized, which could be detrimental in the long term.

In term of cost, Doliprane which is the speciality most prescribed in quantity, is located only at the 15th rank of the Dépense S (96,3 million euros, in progression of 11,7% since 2004). Efferalgan is 42e, with 57,5 million and + 3,0% and Dafalgan 52e, with 47,5 million and + 7,9%. The whole of the specialities containing paracetamol alone represents 236 million euros (+12% since 2004) and the 5th rank of the expenditure analgesics preserves a constant Croissance (+4%) and at the head remains classification of the families of the most prescribed Médicament S, with 358 million prescribed and refunded boxes. They remain the Médicament S the most prescribed, with for 2006, a growth which remains higher than +5% for Doliprane and Dafalgan. The Antalgique S containing paracetamol alone or associated account for 4 of the 10 most prescribed products and the important fall of Propofan (- 45,8%) is only fictitious when one takes into account the market of the generic group corresponding.

Effects on the animals

In the case of an ingestion supposed for the Cat S or of a surdose for the Dogs, it is important to consult immediately a Vétérinaire for a Désintoxication.

Paracetamol is a substance extremely Toxique for the Chat S which should absorb some in no case. The cats not having the Enzyme glucuronyl transferase, of minor amounts can be to them fatal. Toxicity appears for amounts day laborers as weak as 10 mg/kg. The initial Symptôme S are the Vomissement, the salivation and the discoloration of the Langue and the Gencive S. At the end of two days, the physical injuries are obvious and appears a jaundice. Contrary to what occurs to the man, in fact the hepatic damage causes death but it is the production of méthémoglobine and body of Heinz in the red globules who prevents the transport of the Oxygène in the Sang, causing a death by Asphyxie. Effective treatment S are possible for low dose but they must be managed very quickly.

For the Dog S, paracetamol is a useful Antalgique with a good performance as regards effectiveness, which causes less gastric ulcers than the anti-inflammatory drugs not stéroïdiens. But it should be managed only on the councils of a Vétérinaire. Indeed, the overdose, possibly mortal, is quickly reached even with low dose. The hepatotoxicity can occur starting from 100 mg/kg and a methemoglobinemy starting from 200 mg/kg.

Effects on the environment

According to a study, paracetamol could be transformed into toxic product, when the factories of Traitement of the waste water use the process of chlorination. Paracetamol would change, under the action of the ion Hypochlorite ClO^-, in N-acétyl-p-benzoquinone imine and 1,4-benzoquinone. The first Molécule is toxic for the Foie while second is suspectée to be Génotoxique and Mutagène. Additional studies must be carried out to know which is the Concentration of these substances at the exit of waste water and to know the persistence of these products in the Environnement.

Other denominations

Acetaminophen ( name used in the Anglo-Saxon countries )
Acétyl paraminophenol, Acétyl-p-amino-phenol, Hydroxy-4' acetanilide, Para-acétamidophénol, Para-acétamino-phenol, N-Acétyl-para-aminophénol.

Anecdote

September 30th, 1982, the first victim of a macabre series dies in Chicago after having absorbed a capsule of acetaminophene (marketed under the name of Extra Strength Tylenol ). On the whole, seven people will be victims of this Empoisonnement in the United States. These capsules contained in fact of the Cyanure in sufficiently large quantity to be lethal for an adult. The Johnson-Johnson company then proposed to exchange all the capsules of Tylenol in circulation by solid shelves of Tylenol. In this business, the company had a loss of a million dollars and was condemned to pay heavy allowances with the victims. The forever stopped person in charge and this business remain a mystery.

Reference

External bonds

Vidal - List of the drugs in France containing of paracetamol
BIAM - card Paracetamol and Summarized Biam
Side effects of Paracetamol

Simple: Paracetamol

Random links: