An analgesic is a drug acting to
relieve pain, and this group of drugs include aspirin, paracetamol and
ibuprofen[1].
These three
drugs all fall under the most common type of analgesic- non-opioid analgesics. This
group of simple painkillers work by blocking the COX-2 enzyme which is
responsible for pain and inflammation[2]. The stronger groups of
painkillers are compound and opioid analgesics, and these are widely used in
hospitals for severe pain.
Aspirin is one of the
most common analgesics used today[3]- the very first use of this
drug dates back to ancient Asian records 2400 years ago, as a related compound
from willow bark had been used to relieve pain and treat fevers[4]. The use of this compound
then grew in the 18th Century, with Edward Stone reading a paper to
the Royal Society of London on the effect of willow bark on Malaria. In the
1840s, nearly 100 years later, organic chemists identified this active
ingredient as salicin- which was found to be converted into salicylic acid in
the body by Pr. Von Nencki in 1870. This was then given to patients to help
with fevers, however a common and unpleasant side effect was soon discovered;
severe irritation of the lining of the mouth, gullet and stomach.
To combat this chemists made
sodium salicylate to cause less painful side effects, but it tasted awful and
so patients were not keen on taking it. This also caused patients to vomit and
so was not an ideal painkiller. In the 1890s Felix Hofmann of the Bayer (a
German pharmaceutical company) synthesized a similar drug which was found to
have good medicinal properties and be less irritable towards membranes in the
body; aspirin had now been made.
Aspirin,
or 2-Ethanoyloxybenenecarboxylic acid, was sent off for clinical trials and was
finally patented by Bayer in 1898[5].
John Vare won the Nobel Prize for medicine in 1982 for discovering that aspirin
inhibits the COX-2 enzyme in the prostaglandin pathway, and this drug is now
one of the most manufactured in the world, with 10 million kilograms being made
in the US each year.
An anaesthetic
is a drug that causes anaesthesia, which is a reversible loss of sensation[6].
These contrast with analgesics, which relieve pain without eliminating
sensation. These drugs are generally given to perform surgery or an invasive
surgery, which would be very painful if the area could be felt by the patient.
The main two types of anaesthetic are local and general anaesthetics.
Local
anaesthetic is a form of medication that causes reversible absence of pain
sensation in a localised area, although other senses can also be affected. Paralysis
can also be achieved by this type of anaesthetic when used on specific nervous
pathways[7]
(this is known as an epidural, and is commonly used during a caesarean section
during childbirth). The other two main types of local anaesthetic are topical
and subcutaneous anaesthesia. Topical
anesthesia is a local anesthetic which is applied directly to the skin- mostly in
the form of a gel or a cream. Subcutaneous anesthesia as local anesthetic
applied directly under the skin, mostly in the form of an injection,
targeted at the nerves which stimulate pain in that specific area.
A
common local anaesthetic is lidocaine[8],
and we can use this example to see how many other local anaesthetics work. The
main action of this drug is to inhibit the movement of sodium into nerve cells,
but why does this effectively stop the feeling of pain? Figure 5 shows a
representation of an electrical signal inside a nerve cell (axon), and how
sodium ions move through sodium channels to stimulate the feeling of pain[9].
It then shows how lidocaine- represented as a red circle- blocks these channels
and so does not allow the sodium to pass through the channel, and does not
allow the electrical signal travel to the brain.
Figure 6 is a magnified version of figure
5 and shows the cellular membrane interactions with the lidocaine molecules.
The 'sodium channel' spans the phospholipid bilayer on the membrane of the cell
and is extremely narrow. The anaesthetic
binds much more tightly to the channel when charged due to electrostatic
interactions, and so helps block the sodium channels and make the area
temporarily numb[10].
For more serious circumstances,
when a patient has to be completely unaware, doctors use general anaesthesia.
This renders patients unconscious with no perception or memory of the surgery
while it is happening. It also limits the physiological responses to invasive
procedures and surgical cuts, keeping blood pressure, stress hormone release
and heart rate constant during the operation.
General anaesthesia is still
quite a mystery to the scientific world[11],
as the biochemical mechanism which controls it is still speculated about. To
induce unconsciousness, anaesthetics have different sites of action and affect
the central nervous system at varying levels of severity. Common areas of the CNS
whose functions are often interrupted or changed during general anaesthesia
include the cerebral cortex, thalamus, and spinal cord.
Paul Ehrlich stated that drugs
act only when they are bound to their receptors; however, this concept does not
seem to apply in the case of general anaesthetics. There are two main reasons
to support this concept:
·
The molecular structures of these anaesthetics
are very simple and different to one another
Most general anaesthetics have very weak
affinities for their targets acting at much higher concentrations than most
other drugs
In 2015, roughly
15 million operations and minor procedures were carried out in the UK alone,
and this would never have been able to happen without anaesthetics.
[1]
http://www.nhs.uk/ipgmedia/national/Arthritis%20Research%20UK/Assets/Painkillers-analgesics.pdf
[2]
http://www.arthritisresearchuk.org/arthritis-information/drugs/painkillers.aspx
[3]
http://www.drugs.com/aspirin.html
[4]
https://en.wikipedia.org/wiki/Aspirin
[5]
https://en.wikipedia.org/wiki/History_of_aspirin#World_War_I_and_Bayer
[7] http://patient.info/doctor/practical-local-anaesthesia
[9] https://www.evidence.nhs.uk/formulary/bnf/current/15-anaesthesia/152-local-anaesthesia
[10] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2075196/
[11] https://www.newscientist.com/article/mg21228402-300-banishing-consciousness-the-mystery-of-anaesthesia/
