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PARACETAMOL for
GPAT
D.Pharm, B.Pharm, and Pharm.D. (Pharmacy Exams)
RRB Pharmacist Recruitment Exam
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DPEE
Paracetamol is also known as acetaminophen
It is used as a common household analgesic and antipyretic.
It is a first choice for mild-to-moderate pain due to its efficacy, minimal toxicity, and low cost.
It is not used as an anti-inflammatory agent.
It was first synthesised by Harmon Northrop Morse, an American chemist, in 1878.
Phenacetin and paracetamol were first used by a German physician, Joseph von Mering in 1887.
After that paracetamol was not commonly used for 60 years because Mering assumed that paracetamol was more toxic than phenacetin and so he promoted phenacetin.
In 1940s it was found that paracetamol is a metabolite of phenacetin.
In 1953 paracetamol was marketed by Sterling-Winthrop Co.,in the United States of America.
Since 1970s, it became a widely used drug.
Paracetamol is considered as the safest pain-killer in the world.
It is available as OTC product.
It is also available in fixed-dose combinations containing narcotic analgesics (like tramadol, codeine), non-narcotic analgesics (like aspirin, ibuprofen and other NSAIDs), barbiturates, caffeine, antimigraine, hypnotics, antihistamines, antitussives, decongestants, expectorants, common cold medicine, and sore throat treatments.
It is the first-line analgesic in osteoarthritis.
It is not indicated for rheumatoid arthritis because rheumatoid arthritis is a chronic inflammatory condition.
Paracetamol is well tolerated and has a low incidence of GI side effects. It is an effective alternative to aspirin as an analgesic—antipyretic agent.
It is valuable for patients in whom aspirin is contraindicated (e.g., those with peptic ulcer, aspirin hypersensitivity, children with a febrile illness).
It does not prolong bleeding time, hypersensitivity reactions are rare; no metabolic effects or acid-base disturbances.
It does not have significant drug interactions.
Paracetamol can be administered to everyone (children, pregnant women, and elderly) except those with liver dysfunction.
It is contraindicated in severe hepatic impairment.
Acute overdosage of paracetamol can cause severe hepatic damage.
It is available in wide range of formulations including oral tablets, oral disintegrating tablets, chewable tablets, controlled-release tablets, dispersible tablets, liquid, injectables, and suppositories.
Mechanisms of Action
- Paracetamol produces analgesic effect by raising the threshold to painful stimuli.
- It produces antipyretic effects by inhibiting the hypothalamic heat-regulating centre.
- Its weak anti-inflammatory activity is due to inhibition of prostaglandin synthesis in the CNS.
- It is unable to inhibit COX in the presence of peroxides which are generated at sites of inflammation, but peroxides are not present in the brain.
- It is a poor inhibitor of PG synthesis in peripheral tissues, but more active on COX in the brain.
- Although paracetamol has been used clinically for more than a century, its mode of action has been demonstrated recently.
- It is demonstrated that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB(1) receptors.
- p-Aminophenol is an active metabolite of paracetamol.
- p-Aminophenol is conjugated (combined) with arachidonic acid by fatty acid amide hydrolase (an enzyme) to form N-arachidonoylaminophenol.
- N-arachidonoylaminophenol exerts analgesic effect through cannabinoid receptors.
ADME
Absorption: Well absorbed orally and rectally.
Distribution: Uniformly distributed into most body tissues. It crosses placenta and enters breast milk. Plasma protein binding is approx 10-25%.
Metabolism: Mainly metabolised in the liver via glucuronic and sulfuric acid conjugation.
Excretion: Conjugates excreted rapidly in urine.
Onset of action: Oral administration: <1 hour for analgesic and antipyretic effect
IV administration: 5-10 minutes for analgesic effect and antipyretic effect within 30 minutes.
Duration of action: Effects after an oral and IV administration last for 4-6 hours.
Therapeutic Uses
Analgesic and antipyretic
The adult oral and rectal dose is 0.5 to 1 g every 4-6 hours; total daily doses should not exceed 4000 mg (2000 mg/day for chronic alcoholics).
Paracetamol Intoxication
Paracetamol is generally a very safe drug if administered in normal therapeutic dose.
Overdose of paracetamol may cause irreversible liver failure.
N-acetyl-p- benzoquinoneimine (NAPQI) is one of the metabolites of paracetamol in body.
Normally, glutathione combines with the metabolite and removes it from body.
Normally, the level of glutathione is constant.
When a lot of paracetamol is taken, the glutathione levels are totally used up and the excess metabolite of paracetamol oxidizes thiol (-SH) groups of important hepatic enzymes and causes hepatic cell death, resulting in organ failure.
The antidote for paracetamol poisoning is a compound with a –SH group, usually intravenous Acetylcystine, or occasionally oral methionine.
• Paracetamol occurs as white crystalline powder. It is odourless and bitter in taste. It is less soluble in water, more soluble in boiling water, soluble in alcohol.
• Its aqueous solutions are slightly acidic in nature.
• Storage condition: Paracetamol is reasonably stable to heat, light and moisture. It should be stored in well closed containers, protected from light.
• Brand names of Paracetamol: Dolo, Crocin, Combiflam, Calpol.
MCQs
1. An active metabolite of paracetamol is _____.
a) p-Aminophenol
b) N-acetyl-P-benzoquinone imine
c) Salicylic acid
d) p-Nitrophenol
2. Chemical name of paracetamol is ______.
a) p-hydroxy acetanilide
b) 4-hydroxy acetanilide
c) 4-acetylamino phenol
d) All of these
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Blog content and MCQs have been taken from the following:
1) Essential Pharmacy Review for Drugs Inspector Exams by Nirali Prakashan, Pune
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2) Pharmacist Recruitment Exam by Nirali Prakashan, Pune
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Introduction to the Author
Dr. Pankaj M. Chaudhari is the Principal at Shakuntala Patil Bahuuddeshiy Sanstha, Shatabdi Institute of Pharmacy, Samsherpur, Bamdod, Dist. Nandurbar, 425412.
He has five books, two patents, six book chapters, one research grant, 56 Research & Review papers on his name.
He received Shikshak shree Award Delhi, in 2019.
He is a member of Board of studies (BOS member) in KBC NMU Jalgaon March 2023-2027 and a recognised Ph.D. Research Guide at KBC NMU, Jalgaon Feb 2022.
You can reach him at
Email -pmc15march@gmail.com
Contact no.- 9552185678
