Factors influencing the toxicity of paracetamol

The aim of the study was to investigate the in vitro quality of Paracetamol tablet marketed in Ethiopia. The study provide information about trend and characteristics of counterfeit and substandard paracetamol tablet, point out the relative variation of marketed paracetamol table in comparison with standard set by British Pharmacopeia (BP) 20 and United States Pharmacopeia (USP)21 and the degree of adherence of marketed tablet to the standard set by regulatory body in Ethiopia.

Holme JA & Jacobsen D (1986) Mechanism of paracetamol toxicity.

The active metabolite of Paracetamol believed to ..

Inhibition of prostaglandin synthesis in intact cells ..

This compound specifically inhibits glutathione synthesis without affecting any of the other enzyme systems pertinent to the mechanism of paracetamol toxicity (Miners et al., 1984).

What is the mechanism of absorption of paracetamol? …

The development of liver damage in mice, as indicated by elevation of alanine aminotransferase (ALAT) activity, was prevented completely by the intraperitoneal administration of L-methionine (1000 mg/kg; 6.7 mmol/kg) at the same time as oral administration of paracetamol (300 mg/kg; 1.98 mmol/kg) (Miners et al., 1984).

Since the first step in paracetamol metabolism is its bioactivation to NAPQI, inhibition of this process is, theoretically, of clinical relevance.

Update on its Analgesic Mechanism of Action

Paracetamol may be easily prepared in the laboratory by phenol with , separating the desired from the ortho- byproduct, and reducing the with . The resultant is then acetylated with . In this reaction, is strongly activating, thus the reaction only requires mild conditions (c.f. the nitration of benzene):

to be due to inhibition of prostaglandin synthesis.

Poor quality medicines do not meet official standard for strength, quality, purity, packaging and labeling. Use of counterfeit and substandard drugs bears serious health implication; such as treatment failure, adverse reactions, drug resistance, increased morbidity and mortality. In combating such type of problem studies on quality assurance take the big share. This study focus on investigation of the quality of paracetamol tablet which is registered by drug regulatory body of Ethiopia, Drug Administrative and Control Authority of (DACA) and which are not registered but marketed in Somale region of Ethiopia comparatively.

Effects of Paracetamol on NOS, COX, and CYP Activity …

Paracetamol consists of a ring core, by one group and the atom of an group in the para (1,4) . The amide group is (ethanamide). It is an extensively , as the on the hydroxyl oxygen, the benzene pi cloud, the nitrogen lone pair, the on the carbon, and the lone pair on the carbonyl oxygen are all conjugated. The presence of two activating groups also make the benzene ring highly reactive toward aromatic substitution. As the substituents are ortho,para-directing and para with respect to each other, all positions on the ring are more or less equally activated. The conjugation also greatly reduces the of the oxygens and the nitrogen, while making the hydroxyl acidic through delocalisation of charge developed on the .

an inhibition of prostaglandin synthesis in the central ..

Industrial preparation of paracetamol usually proceeds from . A one-step reductive acetamidation reaction can be mediated by thioacetate.

(inhibition of prostaglandin synthesis by ..

7 The data are consistent with the suggestion that inhibition of PGI2 synthesis in the peritoneal cavity by paracetamol is responsible for only a part of its antinociceptive activity in this test.