Chemistry of Paracetamol

Research papers on Chemistry of Paracetamol analysis

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1. Seminar’s Research article: Chemistry of Paracetamol 1

2. The modern pharmacology of paracetamol, mechanism of action, toxicity and Properties. Garry G. Graham Et al. Inflammopharmacology | Springer , 21(3 ), 201-232. Research Title 2

3. Paracetamol referred as 4-hydroxyacetanilide | para-hydroxyacetanilide is an important end-product for Chemists Is an important precursor used in the synthesis of some other Organic compounds . Paracetamol is an analgesic Its popular because its easy access In other hand, adverse effect stands pronounced when it’s not taken in its rightful dosage when it is taken in addition to some other food or drug . Abstract 3

4. Garray G. Discuss The historical changes of this important compound That has undergone till date, I ts preparation by the chemist Analgesic its Dosage Its adverse effect as well as its usage. This is a very helpful drug which becomes a poison in the presence of other drugs such as warfarin and care should be taken when handling this drug. Abstract 4

5. Introduction The painkilling properties of paracetamol discovered by accident when a similar molecule (acetanilide) given as patient's prescription for about 100 years ago. One of these compounds is  N -acetyl- para -aminophenol That is acetaminophen  and  paracetamol  (from  para -acet yl- am ino-phen ol ). The paracetamol provides the painkilling properties but the aniline is toxic. Paracetamol has a very similar structure to  aspirin Because of this they are recognized by the same enzyme. This enzyme is responsible for the biosynthesis of  prostaglandins which are involved in the dilation of blood vessels that causes the pain experienced in a headache. Reduction of the amount of prostoglandin, therefore, helps prevent headaches and other pain. Acetanilide Paracetamol Aniline 5

6. Chemical Properties of Paracetamol: Preparation of Paracetamol: The lone pair of electrons on the amine of 4-aminophenol attacks the C=O bond of acetic anhydride causing it to break. Nitrogen has a positive charge But regains electrons by losing a proton . The negative charge on the oxygen comes back in to reform the C=O bond . This causes the other C-O bond to break. The result is: An amide bond formation A carboxylic acid by-product. 6

7. Structure Elucidation: Paracetamol (p-Hydroxyacetanilide) undergoes usual reaction of Phenols because of the presence of its hydroxyl functional groups. It undergoes reactions such as: A cetylation Oxidation R eacts with sodium hydroxide I t gives a positive test to iron (iii) chloride test based on the presence of the phenolic group. Paracetamol (acetaminophen) contains three functional groups: Hydroxyl group (OH) A mide group ( HN-CO-CH 3 ) A romatic group (benzene ring ) 7

8. Dosage and Adverse Effect of Paracetamol: Dosage: Although the maximum daily dosage has become somewhat controversial in recent years It’s generally recommended to follow the dosing instructions on the package. For children , dosing for most medications is based on the child’s weight. For adults and children 12 years of age and older, The recommended dose of acetaminophen is 650 to 1000mg every 4 to 6 hours as needed, not to exceed 4000mg in 24 hours. Children under 12 years of age, The recommended dose of acetaminophen is 10 to 15mg/kg every 4 to 6 hours, not to exceed 5 doses (50 to 75mg/kg) in 24 hours . Adverse Effect of Paracetamol: Fever and Body Temperature. Inflammation. Platelet Aggregation 8

9. Conclusion Various stories are heard about this very helpful at the same time deadly drug. While some appreciate it for its: Relief of muscle and joint pain C old and flu symptoms C ommon headache A nti-inflammatory functions O thers curse it for its ability to lead to renal and hepatic complications in the human body. 9

10. Conclusion In this article, one of its chemistry that should be taught to all is the drug interaction of this very powerful drug. In the presence of other drugs like warfarin, it causes excessive bleeding, patients should also stay away from Alcohol when taking this drug. Its adverse effects that results from overdozage should not be taken lightly as it can lead to range of sicknesses from: Skin rashes Vomiting to even a damaged liver or kidney Therefore the right dosage should be given to the patient and the patients should adhere to it. 10

11. 2 nd Research Paper 11

12. PARACETAMOL: MECHANISM OF ACTION, APPLICATIONS AND SAFETY CONCERN MARTA J. B. Et al. Department of Pharmacology, Pharmacology and Clinical Pharmacology at the Medical University of £ Ûdü , 7/9, 90-752 £ Ûdü , Poland Research Title 12

13. Paracetamol is one of the best: General M ost frequently used painkiller Antipyretic medicines all over the world Accessible without a recommendation It is the medicine of choice in patients that cannot be cured with non-steroidal anti-inflammatory drugs (NSAID ), like People with bronchial asthma Peptic ulcer disease Hemophilia Children under 12 years of age etc. Abstract 13

14. Paracetamol is well accepted medicine and yields a small number of side effects from: The gastrointestinal territory, though, regardless of that, each year, it is seen as a progressively increasing in number of registered cases of paracetamol-induced liver alcoholism all around the world. Assuming the rising problem of the protection of paracetamol is questioned the rationality of the sale of medicine without a prescription . This work, in conjunction with the newest reports on the chemistry of action of paracetamol, trying to highlight that It is not a remedy without of side effects Particularly when is dosed often and in huge doses (> 4 g/day) There is a hazard of severe side effects. Abstract 14

15. Mechanism of action Owed to the deficiency of an anti-inflammatory constituent: Paracetamol has not been considered as a member of the NSAIDs family in pharmacological textbooks although, it has been continuously debated along with these drugs . Data concerning central action of paracetamol through its effect on descending steroinergic pathways do not exclude a hypothesis assuming the presence (or coexistence) of the inhibition of prostaglandin synthesis . It has been observed that in mouse brain and spinal cord Paracetamol is subject to deacetylation to p-aminophenol that in turn reacts with arachidonic acid affected by fatty acid amide hydrolase Resulting in the formation of an active metabolite of the drug, the fatty acid amide N-arachidonoylphenolamine (AM404). Summing up, paracetamol acts at all levels of pain stimulus conduction from the tissue receptors through the spinal cord to the thalamus and the cerebral cortex in which pain sensations are evoked. 15

16. SAFETY CONCERN Due to an easy overdose of paracetamol, the US FDA has proposed to implement new solutions Which to a certain degree would limit this growing problem . A decrease in the maximum permissible single dose of paracetamol from 1000 mg to 650 mg seems to be one of the crucial problems. It has been suggested that higher doses of this drug, i.e., above 325 mg should be available only by prescription . Another suggested solution postulated by FDA is that: Packaging should be labelled with the information bout the risk of liver damage caused by the overuse of the drug. 16

17. SAFETY CONCERN It also seems justifiable to use only one international name Either paracetamol Acetaminophen Not two different names of the same drug because it can be misleading for the patient. It should be remembered that a single dose of paracetamol should not exceed 1 g and daily dose 4 g The US FDA suggests these values should be decreased to 3.25 g - 0.65 g . 17

18. CONCLUSIONS Summing up, paracetamol mono-therapy is: Efficient Well tolerated by the majority of patients Safe We should, however , bear in mind that the paracetamol overuse or application even at therapeutic doses in some situations like Smoking Alcohol abuse Ingestion of other medicines may cause severe hepatic damage Thus , it is very important to the patient to be warned by doctors or pharmacists about the risk connected with the ingestion and particularly with the overuse of this drug . 18

19. CONCLUSIONS It appears in the light of new data that despite frequent application of paracetamol as An efficient analgesic Antipyretic drug The action of this medicament has not been completely understood This little unknown part may cause irreversible damage to the organism when the drug is overused . On the other hand, administered paracetamol at high doses inhibits platelet aggregation Which is very important in the treatment of patients with disorders of hemostasis . It should be remembered that despite the fact that paracetamol has a wide clinical application it is not a drug devoid of side effects . The aim of the present study was not to deny the rationality of paracetamol use But only to draw the attention of doctors prescribing this drug and pharmacists selling the drug as well patients taking it to the fact that this drug should be used only in situations which are indispensable. 19

20. References Abbadie C, Besson JM (1994) Chronic treatments with aspirin or acetaminophen reduce both the development of polyarthritis and Fos-like immunoreactivity in rat lumbar spinal cord. Pain 57:45–54 Abernethy DR, Greenblatt DJ, Ameer B, Shader RI (1985) Probenecid impairment of acetaminophen and lorazepam clearance : direct inhibition of ether glucuronide formation. J Pharmacol Exp Ther 234:345–349 Iloamaeke, I. M., and Iwuozor, K. O. (2018). Quality assessment of selected Paracetamol tablets sold at Bridge Head Market, Onitsha, Anambra state, Nigeria. British Journal of Pharmaceutical and Medical Research, 3 (5): 1190-1197. B. Alfio, CNS drug reviews, 2006, 12 (3-4), 251-260 . K . Ashutosh, New Age International (P) limited, Publishers,New delhi, 2004, 83-89 . E . Frank, Royal Society of Chemistry, London, 2002, 1-13. IARC, IARC Monograph on Paracetamol (Acetaminophen): An Updating of IARC Monographs, 1990, 1-50, 307-309. 20

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