Chemistry of Paracetamol

Seminar’s Research article:
Chemistry of Paracetamol
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The modern pharmacology of paracetamol, mechanism
of action, toxicity and Properties.
Garry G. Graham Et al.
Inflammopharmacology | Springer , 21(3), 201-232.
Research Title
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 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
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 Garray G. Discuss
 The historical changes of this important compound
 That has undergone till date,
 Its 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
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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-acetyl-amino-phenol).
• 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
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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.
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Structure Elucidation:
 Paracetamol (p-Hydroxyacetanilide) undergoes usual reaction of Phenols because of
the presence of its hydroxyl functional groups.
o It undergoes reactions such as:
o Acetylation
o Oxidation
o Reacts with sodium hydroxide
o It gives a positive test to iron (iii) chloride test based on the presence of the phenolic group.
 Paracetamol (acetaminophen) contains three functional groups:
o Hydroxyl group (OH)
o Amide group (HN-CO-CH3)
o Aromatic group (benzene ring)
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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
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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
• Cold and flu symptoms
• Common headache
• Anti-inflammatory functions
• Others curse it for its ability to lead to renal and hepatic
complications in the human body.
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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.
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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
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 Paracetamol is one of the best:
 General
 Most 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
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 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
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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.
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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.
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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.
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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.
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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.
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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.
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Chemistry of Paracetamol

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