2. Outline
1. introduction
2. Metabolism
3. Classical synthesis method of paracetamol
4. Celanese method
5. pharmacokinetics
6. Pharmacodynamics
7. Side effect of paracetamol
8. overdose of paracetamol
9. precautions
3. 1. Introduction
Paracetamol is a painkilling (analgesic) medicine available over-the-
counter without a prescription.
Paracetamol can be used to:
ease mild to moderate pain ‐ for example, headaches, sprains,
or toothache
control a fever (high temperature,
also known as pyrexia) ‐ for example,
when someone has the flu (influenza).
4. Contin…
At a standard dose, paracetamol only slightly decreases body temperature; it is
inferior to ibuprofen in that respect, and the benefits of its use for fever are unclear.
Common brand names include Tylenol and Panadol.
Paracetamol is available in the following forms:
Tablets
Capsules
Suppositories
Soluble powders
Liquids
5. Contin…
Formula C8H9NO2
Molar mass 151.165 g·mol−1
Density 1.263 g/cm3
Melting point 169 °C (336 °F)
Solubility in water 7.21 g/kg (0 °C)
Drug class Analgesics and antipyretics
Bioavailability 63–89%
Protein binding negligible to 10–25% in overdose
Metabolism Predominantly in the liver
Onset of action By mouth – 37 minutes
Intravenous – 8 minutes
Elimination half-life 1.9–2.5 hours
6. 2. Metabolism of paracetamol
Paracetamol is metabolized primarily in the liver, mainly
by glucuronidation and sulfation, and the products are then
eliminated in the urine.
Only 2–5% of the drug are excreted unchanged in the urine.
Glucuronidation is facilitated by enzymes accounts for 50–70% of
the drug metabolism. Additional 25–35% of paracetamol is
converted to sulfate by sulfation enzymes.
8. This aminophenol goes to brain where it interacts with the cannabinoid
receptors. These receptors after interacting with aminophenol exhibits
analgesic effects.
9. 3. Classical synthesis method of paracetamol
The classical methods for the production of paracetamol involve
the acetylation of 4-aminophenol with acetic anhydride as the last
step. They differ in how 4-aminophenol is prepared. In one
method, nitration of phenol with nitric acid affords 4-nitrophenol,
which is reduced to 4-aminophenol by hydrogenation over Raney
nickel. In another method, nitrobenzene is
reduced electrolytically giving 4-aminophenol directly.
10.
11. 4. Celanese method of synthesis
An alternative industrial synthesis developed
at Celanese involves direct acylation of phenol with acetic
anhydride in the presence of hydrogen fluoride, conversion
of the resulting ketone to a ketoxime with hydroxylamine,
followed by the acid-catalyzed Beckmann rearrangement
13. 5. Pharmacodynamics
Paracetamol is a p-aminophenol derivative
that exhibits analgesic and antipyretic activity.
It does not possess anti-inflammatory activity.
Paracetamol is thought to produce analgesia
through a central inhibition of prostaglandin
synthesis.
Paracetamol appears to exert its effects
through two mechanisms: the inhibition
of cyclooxygenase and actions of its
metabolite AM404
14. 6. Pharmacokinetics
After being taken by mouth, paracetamol is rapidly absorbed from the small
intestine, while absorption from the stomach is negligible. Thus, the rate of
absorption depends on stomach emptying. Food slows the stomach
emptying and absorption, but the total amount absorbed stays
Paracetamol's bioavailability is dose-dependent: it increases from 63% for
500 mg dose to 89% for 1000 mg dose. Its plasma terminal elimination half-
life is 1.9–2.5 hours, and volume of distribution is roughly 50 L. Protein
binding is negligible, except under the conditions of overdose, when it may
reach 15–21%. The concentration in serum after a typical dose of
paracetamol usually peaks below 30 μg/mL (200 μmol/L). After 4 hours, the
concentration is usually less than 10 μg/mL (66 μmol/L).
15. 7. Side effects of paracetamol
Side effects from paracetamol are rare but can include:
an allergic reaction, which can cause a rash and swelling
flushing, low blood pressure and a fast heartbeat – this can
sometimes happen when paracetamol is given in hospital into a vein
in your arm
blood disorders, such as thrombocytopenia (low number of platelet
cells) and leukopenia (low number of white blood cells)
liver and kidney damage, if you take too much (overdose) – this can
be fatal in severe cases
16. Contin…
drowsiness and fatigue
rashes and itching.
Children may occasionally experience low blood sugar and tremors,
and feeling hungry, faint and confused after taking paracetamol.1
17. Paracetamol poisoning
Overdoses of paracetamol, that is, taking more than the recommended
maximum daily dose of paracetamol for healthy adults of three or four
grams, can cause potentially fatal liver damage.
Paracetamol toxicity is the foremost cause of acute liver failure.
Untreated paracetamol overdose results in a lengthy, painful illness. Signs
and symptoms of paracetamol toxicity may initially be absent or non-specific
symptoms. The first symptoms of overdose usually begin several hours after
ingestion, with nausea, vomiting, sweating, and pain as acute liver
failure starts People who take overdoses of paracetamol do not fall asleep or
lose consciousness, although most people who attempt suicide with
paracetamol wrongly believe that they will be unconscious by the drug.
18. 8. Overdose of paracetamol
Taking too much paracetamol, known as an overdose, can be very
dangerous.
There is no safe level of drug use. Use of any drug always carries some
risk – even medications can produce unwanted side effects.
Paracetamol affects everyone differently, based on:
size, weight and health
whether the person is used to taking it
whether other drugs are taken around the same time
the amount taken.
20. 9. Precautions
Always get advice before taking paracetamol if you:
have liver or kidney problems
have problems with alcohol, such as long-term alcohol misuse.
are very underweight
are taking other medications
