Drugs paracetamol

The different reactivities associated with nucleophiles and leaving groups is nicely exemplified in the synthesis of the analgesic drug paracetamol (USA acetaminophen) from 4-aminophenol. If 4-aminophenol is treated with an excess of acetic anhydride, aeetylation of both amino and phenol groups is observed, and the product is the diacetate. Paracetamol is the A-acetate of 4-aminophenol, so how might mono-acetylation be achieved There are two approaches. 

In contrast to local irritants and corrosive acids and alkalis, other chemicals, such as the drug paracetamol (see chap. 7), cause systemic toxicity, damaging the liver, possibly irreversibly and with some delay after an oral overdose. Penicillin can also cause systemic toxicity as a result of an immune reaction, which may be immediate and serious, if it is anaphylaxis (see chap. 7). However, this effect, if not fatal, is reversible. 

The analgesic drugs paracetamol and acetylsalicylic acid at normal clinical doses had no acute effect on toxicokinetics of toluene inhaled at 300 mg/m (Lbf el al., 1990b) similarly, neither carbohydrate diets nor the consumption of 47 g ethanol as wine on the evening before exposure to 200 mg/m- toluene for 2 h had any effect on toluene kinetics (Hjelm et al., 1994). 

Some of us intentionally expose ourselves to substances like alcohol and tobacco. Both of these are capable of changing the metabolism and toxic effects of other substances. For example, the drug paracetamol is more poisonous in individuals who are habitual and heavy drinkers, while tobacco smoke and charcoal-grilled meat contain substances called polycyclic aromatic hydrocarbons which can increase the metabolism of some drugs. 

A particular animal species may have a deficiency and be unable to metabolize and so eliminate a chemical. For example, the domestic cat has a particular deficiency which affects the handling of the drug paracetamol. If pet owners give doses of paracetamol to their cats, it may kill them. Understanding such differences is crucial for the use of veterinary drugs. 

Table 2 An example of a tablet formulation for the analgesic drug paracetamol as generated by the Cadila system...

Because aldesleukin stimulates T cells, it has been suggested to have favored the development of successive episodes of multifocal fixed drug eruption in response to chemically unrelated drugs (paracetamol, ondansetron, and tropisetron) in a 43-year-old patient (107). 

The remaining drug, paracetamol, may be isolated by simple evaporation of the toluene or extracted into aqueous solvent by addition of a strong base such as sodium hydroxide solution. 

Other elements besides carbon, nitrogen, and sulfur can undergo metabolic redox reactions. The direct oxidation of oxygen atoms in phenols and alcohols is well documented for some substrates. Thus, the oxidation of secondary alcohols by some peroxidases can yield a hydroperoxyde and ultimately a ketone. Some phenols are known to be oxidized by cytochrome P450 to a semiquinone and ultimately to a quinone. A classical example is that of the anti-inflammatory drug paracetamol (8)(Fig. 13.10 acetaminophen), a minor fraction of which is oxidized by CYP2E1 to the highly reactive and toxic quinoneimine 9. 

The drug paracetamol decays by first-order kinetics in the body with a half-life of 4.0 h. A person s blood is found to contain 50 mg dm 3 of paracetamol 8.0 h after ingestion of the drug. 

Photodegradation of the analgesic and antipyretic drug paracetamol under UV exposure at 254 nm leads to photo Fries rearrangement, affording 2-amino-5-hydro3yacetophenone. The product is more toxic than the parent drug, when examined by a luminescent bacteria test. This is... 

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