Drug structure paracetamol

After oral administration, paracetamol is completely absorbed from the gastrointestinal tract with peak plasma concentrations being reached in less than an hour. The drug is eliminated by conjugation with glucoronic acid in the liver. The chemical structure is liable to oxidation. 

Benorylate (315) [4 -(acetamido)phenyl-2-acetoxybenzoate] is another example. It is the ester between two well-known antiinflamatory drugs, aspirin and paracetamol, and is employed in rheumatoid arthritis therapy. In view of the chemical structure with three photolabile groups (two esters and one amide), its possible phototoxicity has been investigated. From the preparative irradiations, it has been concluded that the PFR takes place with breaking of the central C—O bond to yield 5-acetamido-2 -acetoxy-2-hydroxybenzophenone (316). This product undergoes transacetylation to 5 -acetamido-2 -acetoxy-2-hydroxy-benzophenone (318) (Scheme 80) [300]. 

V.c.1.1. Cyclo-oxygenase inhibition. Inhibition of cyclo-oxygenase reduces the level of circulating prostaglandins and neurogenic inflammation. This is the mechanism of action of nonsteroidal antiinflammatory drugs (NSAID) and aspirin. The mode of action of paracetamol is less clear (inhibition of prostaglandins in the nociceptors of the posterior horn of the spinal cord and action on the supraspinal structures implicated in nociception). 

Some of the popularly used anti-inflammatory drugs, such as paracetamol, are not an NSAID but have analgesic/antipyretic properties. Paracetamol specifically has relatively weak anti-inflammatory activity. Once excreted, it gets reactivated in the environment through some microbially mediated transformation (Henschel et al., 1997). The exact mechanisms by which paracetamol relieves pain are not very clear. It has a chemical structure that resembles several estronegic compounds. 

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. 

A final example of the use of this strategy to examine futile deacetylation comes from work on the beta-blocking drug practolol where a radio-labelled 13C/14C drug was dosed to rats and the urine profiled by HPLC with UV, radioactivity, NMR and MS-MS detection [61]. As shown by the structure below, practolol can be considered to be an analogue of paracetamol with a beta-blocker side-chain ... 

Paracetamol (Acetaminophen and PCM) with a purity of >99 % was purchased from VWR International and was delivered as a white free flowing powder. The structural formula as well as an illustrative SEM image of the tmprocessed solute is shown in Fig. 24.2. Before S AS processing, PCM is crystalline (monoclinic form I). PCM itself is a well-known active pharmaceutical ingredient and an important bioactive compound, which is used as an antipyretic and analgesic drug [1]. 

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