Killing Pain- On the market
30 years have passed without the release
of a new class of analgesic, yet demand rises every year.
In the USA alone, there are over 30 million people suffering
chronic pain. The business is worth millions, yet though there
are many marketed brands of painkillers, but operate via only
2 mechanisms, non-steroidal anti-inflammatories, (NSAIDs)
NSAIDs such as aspirin, ibuprofen all
operate by the same mechanism. When cells are damaged,
they release chemicals called prostaglandins. These
trigger the pain. 3 enzymes, known as Cox-1, Cox-2 and
Cox-3 synthesize the prostaglandins, and NSAIDs work
by inhibiting one or more of these enzymes. Selective
inhibition prevents stomach lining corrosion, which
is a side effect for drugs like asprin which inhibit
all 3 enzymes. Anyone who has taken Neurofen for an
ailment will know however that these analgesics are
not very potent, and they operate to reduce inflammation,
so are not useful for disorders such as cancer.
Opioids however can much more potent,
and so may be used for chronic pain.
So what is wrong with morphine?
Morphine, codeine, demerol are all examples
of opioids. These work by binding to opoid receptors along
the pain pathway through the central nervous system. Naturally,
the body produces endorphins (or enkephalins) to dampen pain
signals when required. Morphine and related opioids are very
effective pain killers, like endorphins, but, unlike the natural
products, they are highly addictive, and have large range
of problems and side effects:
Tolerance builds up on exposure so more and more
is required for the same effect
The synapses become desensitised, and if drug is
stopped, patient will suffer withdrawl symptoms
Dizziness, nausea and sedation
CNS: euphoria, dysphoria, weakness, insomnia, visual
Gastrointestinal: constipation, anorexia
Cardiovascular: Flushing of face, palpitation,
Allergies: Urticaria and other skin rashes, edema.
Endorphins do not have these
difficulties as they are broken down much faster
by the body. Endorphins cannot be used as drugs
since they are formed form 5 amino acids, so ingestion
would cause breakdown in the stomach, and injection
would not deliver them to the neurones, as they
are too large.