Paracetamol acetaminophen

Cross-reactions with aspirin and NSAIDs are of practical importance. Typically, AIA patients are sensitive to all NSAIDs that preferentially inhibit COX-1 (table 2). Acetaminophen (paracetamol), a weak inhibitor of COX-1, is regarded as a relatively safe therapeutic alternative for almost all patients with AIA. High doses of the drug (>1,000 mg) have been reported to provoke mild, easily reversed bronchos-pasm in some AIA patients [13]. Some rare, well-documented cases of coexistence of aspirin and paracetamol sensitivity have been described. However, according to a recent meta-analysis, less that 2% of asthmatics are sensitive to both aspirin and paracetamol [14]. 

TABLE 28.1 An Example of a Tablet Eormulation for Acetaminophen (Paracetamol) as Generated by the Cadila System... 

Transformation of the widely used over-the-counter analgesic acetaminophen (paracetamol) during chlorination produced the toxic 1,4-benzoquinone via the A-acetylquinone-imine and minor amounts of products from chlorination of the phenolic ring (Bedner and Maccrehan 2006). 

Bindschaedler and Gurny [12] published an adaptation of the simplex technique to a TI-59 calculator and applied it successfully to a direct compression tablet of acetaminophen (paracetamol). Janeczek [13] applied the approach to a liquid system (a pharmaceutical solution) and was able to optimize physical stability. In a later article, again related to analytical techniques, Deming points out that when complete knowledge of the response is not initially available, the simplex method is probably the most appropriate type [14]. Although not presented here, there are sets of rules for the selection of the sequential vertices in the procedure, and the reader planning to carry out this type of procedure should consult appropriate references. 

Emorfazone has been launched as Pentoil, Pentoyl, Nandron. Synergistic analgesic formulations containing (3) and either acetaminophen (paracetamol), sulpyrine (dipyrone), grafinin or phenylbutazone were claimed in patents [68, 69], The combined use of emorfazone with different non-steroidal acidic antiinflammatory drugs has been reported to be beneficial [70, 71]. 

The reaction of the lipid-regulator gemfibrozil with free chlorine yielded four chlorinated derivatives of this compound [94]. Chlorination of acetaminophen (paracetamol) generated 11 discernible DBFs, including the toxic compounds 1,4-benzoquinone and A-acetyl-p-benzoquinone imine and two ring chlorination products, chloro-4-acetamidophenol and dichloro -acetamidophenol [95]. 

Acetaminophen (paracetamol) has good analgesic efficacy in toothaches and headaches, but is of little use in inflammatory and visceral pain. Its mechanism of action remains unclear. It can be administered orally or in the form of rectal suppositories (single dose,... 

Figure 7.5 Metabolism of (a) acetanilide into the toxic species (b) aniline and the safer analgesic (c) acetaminophen (paracetamol).

Acetaminophen (paracetamol) poisoning is common in Western countries and is increasing elsewhere. Single doses as low as 7.5 g in adults or 150 mg/kg in a child can cause severe toxicity. Very occasionally, lower doses cause harm. Mortality, from hepatic or occasionally renal failure, is related to blood concentration and the time between ingestion and the initiation of antidotal treatment. Even severely poisoned patients may be asymptomatic, although nausea and vomiting are fairly common. 

Acetaminophen (Paracetamol) N- (4 -Flydroxypheny 1) acetamide Partial hydrogenation of nitrobenzene, A-acetylation... 

Bioactivation is a classic toxicity mechanism where the functional group or the chemical structure of the drug molecule is altered by enzymatic reactions. For example, the enzymatic breakdown of the analgesic acetaminophen (paracetamol), where the aromatic nature and the hydroxyl functionality in paracetamol are lost, yields A -acetyl-p-benzoquinone imine, a hepatotoxic agent. Paracetamol can cause liver damage and even liver failure, especially when combined with alcohol. 

Finally, acetaminophen (paracetamol) products may provide some temporary analgesic effects in people with rheumatoid arthritis, but these products are not optimal because they lack anti-inflammatory effects. As discussed in Chapter 15, acetaminophen can be used to treat mild-to-moderate pain, but the lack of anti-inflammatory effects makes acetaminophen fall short of NSAIDs for conditions such as rheumatoid arthritis. Hence, patients with rheumatoid arthritis usually prefer the effects of NSAIDs to acetaminophen,110 and acetaminophen products are not typically used for the routine treatment of this disease. 

Bose and coworkers have performed known chemical processes in various kitchen microwave devices to explore microwave chemistry at a larger scale [33]. Representative examples for multigram-scale synthesis without optimization of reaction conditions have been presented, such as the rapid preparation of 500-800 g of acetylsalicylic acid (Aspirin). Another valuable pharmaceutical compound, Tylenol (acetaminophen, paracetamol), could be... 

Zimmerman HJ, Maddrey WC. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol analysis of instances of therapeutic misadventure. Hepatology 1995 22 762-777. 

Most ultramicrobiosensors use differential measurement to overcome the problems of interferences and electrode fouling. The practical use of these biosensors for direct measurement is limited by interferents, such as ascorbic acid, acetaminophen (paracetamol), uric acid, etc., which are present in complex matricies such as serum. The specificity of the biochemical system is compromised by the partial selectivity of the electrode. The electrode not only oxidizes the desired product (e.g., H2O2 formed in the enzymatic oxidation of glucose by glucose oxidase), but also any other species oxidizable at the working potential. This produces a larger current response and a positive error. 

Antipyretic analgesics represent p-ami-nophenol or pyrazolone derivatives with clinically useful analgesic and antipyretic efficacy. Their mechanism of action is not completely understood but thought to be mediated via inhibition of prostanoid formation by variants of COX enzymes. Acetaminophen (paracetamol), phenazone, and dipyrone belong in this group. 

Acetaminophen (paracetamol, 4-hydroxyacetanilide, APAP), a commonly used analgesic drug, causes centrilobular hepatic necrosis upon overdosage. APAP displays toxicity characteristics that demonstrate, very clearly, dependence upon GSH for protection. Hepatotoxicity, including liver failure, often occurs when APAP is... 

Fig. 5 Formation of 3 -phosphoadenosine-5 -phosphosul-fate (PAPS) and its conjugation with acetaminophen (paracetamol). Strictly, the process is one of sulfonation because the —S03 group is being transferred.

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