Paracetamol

PARACETAMOL ANTIARRHYTHMICS Disopyramide and propafenone may slow the onset of action of intermittent-dose paracetamol Anticholinergic effects delay gastric emptying and absorption Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly 

PARACETAMOL ISONIAZID Risk of paracetamol toxicity at regular, therapeutic doses when co administered with isoniazid Uncertain it seems that formation of toxic metabolites is t in fast acetylators when isoniazid levels i (i.e. at the end of a dosing period) There have been cases of hepatic pathology regular paracetamol should be avoided in patients taking isoniazid 

PARACETAMOL RIFAMPICIN Rifampicin i paracetamol levels Rifampicin t glucuronidation of paracetamol Warn patients that paracetamol may be less effective 

PARACETAMOL ANTICANCER AND IMMUNOMODULATING DRUGS-BUSULFAN Busulfan levels may be t by coadministration of paracetamol Uncertain paracetamol probably inhibits metabolism of busulfan Manufacturers recommend that paracetamol should be avoided for 3 days before administering parenteral busulfan 

PARACETAMOL ANTICOAGULANTS - ORAL Possible t anticoagulant effect when paracetamol is taken regularly (but not occasionally) Uncertain possibly due to competitive inhibition of CYP-mediated metabolism of warfarin Monitor INR closely for the first 1-2 weeks of starting or stopping regular paracetamol 

Paracetamol causes skin rashes, blood dyscrasia, and liver damage and nephrotoxicity in overdose. Large doses of paracetamol cause nephritis and 

Whereas the mode of action of acetylsalicylic acid is now weU understood, that ofparacetamol (also known as acetaminophen , especially in the USA, Canada, Japan, Hong Kong, Iran and Colombia), stiU remains a mystery, in spite of being equally powerful in terms of both, its breadth of use and its market presence. 

Paracetamol was first prepared in 1878 by Harmon Northrop Morse (1848-1920) at the Johns Hopkins University by reduction ofp-nitrophenol with tin in acetic acid. [172, 173] In 1887, Josef von Mehring (1849-1908) used the compound for the first time as a drug, which did however not achieve any great therapeutic significance. 

A much wider use was found for two molecules closely related to paracetamol, namely acetanilide and phenacetin. The serendipitous discovery of acetanilide 

In 1893, paracetamol was discovered for the first time in human urine from a man who had been treated with phenacetin. Shortly before the turn of the century, it became clear that paracetamol is a metabolite of acetanilide. This information however attracted no attention for almost 50 years. 

Traditionally, the drug counts as a non-steroidal inflammation inhibitor, although its anti-inflammatory effect is comparatively low, while its antipyretic and analgesic action predominate. There has been a series of studies so far to determine the molecular mode of action. [174] 

2 Synonyms. Acetaminophen N-Acetyl-p-aminophenol N-(4-Hydrox3 )henyl) acetamide Calpol Tylenol Panadol Disprol Parmol Valdol Pacemol Naprinol. 

Many preparative methods have since been described for the synthesis of paracetamol, mostly emplo3ring the acetylation ofpara-aminophenol with acetic anhydride as indicated above. However, a number of other routes of synthesis have also been discovered and used commercially, namely  

4 Chemicals Required. para-Aminophenol 6 g Acetic anhydride 6.5 ml Concentrated Sulphuric acid 4 drops. 

7 Recrystallisation. Dissolve the crude product in 70% ivlv) ethanol and warm it to 60°C add 2 g of powdered animal charcoal (decolourizing carbon). Filter and concentrate the filtrate over a water-bath. Allow it to cool and large monoclinic crystals will separate out. The yield of the pure paracetamol (mp 169-170.5°C) is 6.5 g. 

6 g of p-Aminophenol shall yield Paracetamol Hence, Theoretical yield of Paracetamol 

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Figure Bl.11.3. 400 MHz H NMR spectrum of paracetamol (structure shown) with added integrals for each singlet or multiplet arising from the paracetamol molecule.

The other peaks demonstrate the power of NMR to identify and quantitate all the components of a sample. This is very important for die phannaceutical industry. Most of the peaks, including a small one accidentally underlying the methyl resonance of paracetamol, arise from stearic acid, which is connnonly added to paracetamol tablets to aid absorption. The integrals show diat it is present in a molar proportion of about 2%. The broader peak at 3.4 ppm is from water, present because no attempt was made to dry the sample. Such peaks may be identified either by adding fiirther amounts of the suspected substance, or by the more fiindamental methods to be outlined below. If the sample were less concentrated, then it would also be... 

Their effects are illustrated in figure B1.11.4 which is a H-decoupled C NMR spectrum of the same sample of paracetamol, obtained without such precautions. The main peak integrals are displayed both as steps and... 

Figure Bl.11.4. Hydrogen-decoupled 100.6 MHz C NMR spectrum of paracetamol. Both graphical and numerical peak integrals are shown.

The analysis of APC tablets (a mixture of aspirin, phenacetin, and caffeine) has been a common undergraduate laboratory experiment. This experiment describes modifications to the standard analysis for APC tablets in which paracetamol (also known as acetaminophen) replaces phenacetin. 

This experiment focuses on developing an HPLG separation capable of distinguishing acetylsalicylic acid, paracetamol, salicylamide, caffeine, and phenacetin. A Gjg column and UV detection are used to obtain chromatograms. Solvent parameters used to optimize the separation include the pH of the buffered aqueous mobile phase, the %v/v methanol added to the aqueous mobile phase, and the use of tetrabutylammonium phosphate as an ion-pairing reagent. 

Hydroxyacetanilide. This derivative (21), also known as 4-acetamidophenol, acetaminophen, or paracetamol, forms large white monoclinic prisms from water. The compound is odorless and has a bitter taste. 4-Hydroxyacetani1 ide is insoluble in petroleum ether, pentane, and ben2ene slightly soluble in diethyl ether and cold water and soluble in hot water, alcohols, dimethylformamide, 1,2-dichloroethane, acetone, and ethyl acetate. The dissociation constant, pfC, is 9.5 (25°C). 

HPLC method with amperometric detection was applied for detenuination of phenols in sea sediment and some dmg preparation. Peaks of phenol, guaiacol, cresols, hydroquinon and resorcinol were identified on chromatogram of birch tai. The HPLC method with electrochemical detectors was used for detenuination of some drug prepai ation of aminophenol derivate. So p-acetaminophenol (paracetamol) was determined in some drug. 

A medical journal reported that patients suffering from paracetamol poisoning should be nursed at 30° 0°. In the next issue, it said that this refened to the angle in bed, not the temperature [7]. 

Therapeutic Function Analgesic, antipyretic Chemical Name N-(4-hydroxyphenyl)acetamlde Common Name Paracetamol, Acetylfl-Aminophenol, APAP Structural Formula ... 

Antipyretic agents are used for the treatment of fever. The most commonly used antipyretics are acetylsa-licylic acid and paracetamol (synonym acetaminophen). 

The second group of non-opioid analgesics, which are not classified as NSAIDs, consists of substances that lack anti-inflammatory properties, such as phenazones, metamizole (dipyrone) and paracetamol. Their molecules are neutral or weakly basic, have no hydrophilic... 

Tylenol paracetamol N-acetyl-para-aminophenol para-acetyl-amino-phenol... 

The permeability of the films to paracetamol as a model compound was dependent on film composition and was markedly increased after exposure to pectinolytic enzymes, used to mimic conditions in the colon. Similar formulations, apphed as a film coat to tablets, were used with colonic conditions for an increased release rate [242],... 

Winthrop) wfm Muskel Trancopal comp. (Winthrop)-comb. with paracetamol wfm... 

Ben-u-ron (bene- Paracetamol SmithKline Fluental (Camillo Corvi)-... 

Paracetamol (Hexal further combination Omniadol (Montefarmaco)-... 

Paracetamol-ratiopharm I Acetamol (Abiogen Panadol (Maggioni)... 

Formulation(s) drg. 1 mg syrup 0.5 mg in comb, with paracetamol, ethenzamide... 

C( H, 02 99-93-4) see Bamethan Bufexamac Paracetamol Pifoxime Salbutamol 4-hydroxy-L-allothreonine monosodium salt (C4H,NNa04 117095-55-3) see Carumonam 4 -hydroxy-2-aminoacetophenone (CSH9NO2 77369-38-1) see Octopamine... 

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