Proposals have surfaced that paracetamol should be
reassessed to make a “safer” version of paracetamol without the liver-harming
side effects, even though paracetamol is the most widely exploited pain-killer
for everyone around the world and a good antipyretic (fever reducer). The well-known analgesic can be used safely however it can also be abused, either accidentally or intentionally, via overdose with amounts of over 10-15g [1]. So safer versions of paracetamol need to be found to try and prevent the incidence of “paracetamol poisoning” and the many deaths caused each year from it.
Paracetamol Synthesis
Paracetamol is synthesized from the starting product,
phenol, in a three step process:
1)
Nitration: the nitration of phenol to achieve two isomers; 2-nitrophenol and
4-nitrophenol. 4-Aminophenol is required to continue the reaction, which can be
easily extracted by steam distillation.
2)
Reduction: the extracted product, 4-nitrophenol, is reduced to produce
4-aminophenol.
3) Formation
of the amide: 4-aminophenol reacts with acetic anhydride to produce the final
product: paracetamol.
Where paracetamol is
used
The oblong shaped pill is the most used and most prescribed
painkiller. It is mainly used for mild to moderate pain relief and lowering
body temperature. The common analgesic can be combined with codeine to make co-codamol;
a stronger pain relief drug given usually to tackle acute amounts of pain such
as back, muscle and bone pain and also during cancer treatment for pain relief.
A study was conducted on paracetamol to detect if it affects
recovery time in patients with acute back pain in addition to pain relief. Even
though it might not have an input into recovery time, it’s still the most
recommended drug; when it comes to acute lower back pain. A study by GSK in
Australia found that compared with a placebo, paracetamol did not speed up
recovery time in patients with back pain, and it only gives temporary relief
from pain. [2]
Paracetamol Liver Damage
Paracetamol overdose causes paracetamol poisoning in the
liver, which in turn causes liver damage. The breakdown metabolites of
paracetamol cause liver toxicity. The harmful metabolites bind to liver cells
causing liver necrosis.
This toxicity is due to the chemical structure of the
compound and the way our bodies break it down; it is metabolised to a reactive
intermediate at high doses. When paracetamol is broken down in the liver a compound
called N-acetyl-p-benzoquinoneimine (NAPQI) which binds to the liver’s natural
antioxidant, glutathione. In cases of overdose NAPQI depletes the entire amount
of glutathione in the liver resulting in large concentrations of NAPQI being
left over in the liver which go on to damage the liver cells.
Loads of research goes into finding potential methods to producing
a better version of paracetamol that has minimum amount of side effects and
cannot be abused by overdose. The British Technology Group (BTG) has a patent
for a safer version of paracetamol, in which they claim that the new patent
makes poisoning by overdose highly unlikely. However this drug is still not
approved by the NHS and is not available in pharmacies yet as it is still under
testing.
Even though paracetamol is still the number one painkiller
(and also the cheapest to produce), there needs to be more research and talks
into discovering safer options to paracetamol and also to make them widely
available to the public, to try to eliminate possibilities of paracetamol abuse. During that time more projects can be
initiated to educate everyone on the correct use of paracetamol and the safe
dosages so to prevent or at least lower the cases of paracetamol poisoning in
the world.
References
[1] RSC
Paracetamol and Paracetamol synthesis reactions image - http://www.rsc.org/learn-chemistry/content/filerepository/CMP/00/000/047/Paracetamol_web.pdf
[2]Efficacy
of paracetamol for acute low-back pain: a double – blind, randomised controlled
trial. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60805-9/fulltext
[3] BTG
International Limited and Penn Pharmaceuticals “safer paracetamol” Patent, http://www.google.com/patents/US5716991
[4]Paracetamol
tablets image http://www.publicdomainpictures.net/view-image.php?image=73624&picture=medicine
[5] Pills in
blister pack http://www.publicdomainpictures.net/view-image.php?image=54900&picture=pills-in-blister-pack
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