Body
defences:
9.
Introduction to drugs - medicines and their
development and testing for treating diseases
Doc Brown's Biology exam study revision notes
Sub-index of notes: Our body's defence mechanisms against infections from
pathogens, help from vaccines & drugs
(9a) Introduction to drugs - medicines for treating diseases
For more on drugs, solvents and alcohol see
Keeping healthy - non-communicable diseases
- risk factors
Drugs are substances that affect
how the body works.
A drug can be defined as any
substance taken into the body that modifies or affects chemical
reactions in the body - which of course can be helpful and harmless,
but also harmful, especially is use is abused.
Most drugs are proven safe
medicines to use, but some are potentially dangerous if misused.
Many drugs can be bought directly
from a pharmacy, but others can only be obtained from a doctors
prescription.
The first thing you should appreciate
is the difference between 'feeling better' and being 'cured'!
If you are injured, some of your
sensory nerve endings send pain messages to the brain - an unpleasant
experience.
Painkillers block these nerve
impulses, reducing pain sensation and making you feel better.
Some painkillers were originally
derived from plants e.g. an aspirin like molecule is found in willow
bark and opiates are extracted from the poppy flower.
From these naturally occurring
molecules, lots of synthetic derivatives have been developed like
codeine.
Some drugs like aspirin or
paracetamol relieve pain and reduce discomfort i.e. reduce the symptoms,
but they do not counteract the disease you are suffering from e.g. a
virus giving you a headache - but pain killers are better than nothing
and enable to carry on with life with less discomfort while your body's
immune system fights the infection.
Such drugs do NOT cure you
because they do NOT kill the pathogen causing the disease in the
first place.
Lots of other drugs such as cold
remedies, decongestants, analgesic pain killers etc., cannot destroy
e.g. the cold or flue virus but do make you feel a lot better and
help you get a better night's sleep!
Other drugs e.g. the antibiotic
penicillin do kill or inhibit the growth of certain bacterial
infections by interfering with the pathogen's metabolism e.g. the
biochemical processes that build bacterial cell walls.
(See section on
healthy2defence-10.htm)
However, they are not a 'blanket
cure', different types of bacteria require different types of antibiotic
and the correct match is required to effect a cure.
Note that nothing is perfect in
medicinal treatments!
Whether the drug is a painkiller,
antibiotic, antiviral etc. people can suffer adverse effects e.g.
some people exhibit an allergic
reaction to penicillin.
Some drugs are expensive and
maybe need to be taken for a long time, without the outcome being
wholly effective - doctors have to make some crucial judgements on
what to prescribe.
Medical practitioners have to
'juggle' costs versus benefits, especially the more expensive the
treatment.
There are also problems from the
development of
antibiotic-resistant bacteria like MRSA 'superbugs'
For more on drugs, solvents and alcohol see
Keeping healthy - non-communicable diseases
- risk factors
(9b) Developing and
testing
new
drugs and medicines
See
also
Products of the
Chemical & Pharmaceutical Industries & impact on us
(GCSE chemistry
For more on drugs, solvents and alcohol see
Keeping healthy - non-communicable diseases
- risk factors
It has been known for some time that
plants produce a wide range of chemicals to defend themselves against
attack from e.g. insect pests or pathogen microorganisms.
Historically, currently and in the
future, these substances provide a basis for developing drugs to treat
human diseases.
Even some of our current medications
come from knowledge of plants giving us many traditional
herbal recipes e.g.
(i) The painkiller aspirin
was developed from chemicals in willow plants that reduce fever and
reduce pain in childbirth.
(ii) Drugs like digitalis
have developed from chemicals found in foxglove plants and are used
to treat heart conditions.
Many antibiotics are made from
growing microorganisms (first found by 'accident'!) e.g.
(i) The famous scientist
Alexander Fleming noticed in some petri dishes used for
investigating bacteria, a mould had grown, but the area
around the mould was free of bacteria.
He realised that the mould
(in this case Penicillium notatum), was producing a chemical
that killed the bacteria.
This chemical was extracted
and named penicillin, and proved to be a very effective
antibiotic in killing various bacterial infections.
(ii) These days pharmaceutical
companies grow fungi and other microbes on a large scale and extract
the antibiotic molecules in the laboratory.
Decisions - scientific and
commercial!
Any new drug must be targeted
at some specific medical condition where there is need - otherwise
it would not make commercial sense to develop a new pharmaceutical
product.
From a scientific point of
view, many drugs are designed to inhibit part of the chemistry
of a disease e.g. targeting a gene or a protein like an enzyme.
The target might be blocking
the action of an enzyme or a gene with a chemical agent (drug)
you can interfere with the development of a disease e.g. the
anti-cancer drugs used in chemotherapy treatments to reduce the
growth of tumour cells or kill them.
Studies of the genomes and
resulting proteins in both plants and animals are proving useful to
identify 'targets'.
You then have to find a
chemical that will have an effect on the target.
There are databases of
chemicals that have been screened by advanced analytical
techniques which can be consulted for likely effectiveness.
The screening might not
initially indicate the best molecule to 'hit the target' in a
biochemical sense, but, it may provide a useful starter
molecule.
You can then modify the
starter molecule to produce a variety of derivative molecules,
one of which might provide a more effective treatment. The
derivative molecules can be quite similar, but it is a sort of
'fine tuning' of their molecular structure to increase the
drug's effectiveness.
Today drugs are manufactured
on a huge scale in the pharmaceutical industry.
Chemists can synthesis molecules
based on naturally found organic compounds from plants and also lots
of molecules that have never existed in nature until synthesised in
a modern chemical laboratory.
Historically, most effective
drugs were discovered by accident e.g. somebody by chance notices
some effect of a chemical which might have a medical
application.
However, these days, research
is very systematic and we have an extensive database of
knowledge about the structure and properties of molecules AND how
diseases work.
Some drugs have been successfully
designed by computer software that can construct and display
molecular structure e.g. design a molecule with a shape to fit into
the active site of an enzyme to inhibit its action.
See
also
Products of the
Chemical & Pharmaceutical Industries & impact on us
(GCSE chemistry)
(9c) Developing a new drug - a lengthy and
costly process!
The drugs developed and produced by
the pharmaceutical industry are often very costly in the making for
several reasons
You have to carry out a lot of
research and development to find a suitable compound that performs an
effective medical treatment for some condition e.g. to reduce blood
pressure, kill cancer cells, slow down the development of dementia etc.
The compound must be tested, often
modified and retested.
All new potentially useful drugs must be fully
tested in trials including animal trials (controversial) and human
trials and this all takes time and money.
Until a drug has fully
passed all safety and effectiveness tests it cannot be marketed and sold
to medical institutions from hospitals to high street pharmacies etc. The
manufacturer must prove that any pharmaceutical product like a drug does
meet all legal requirements that it does actually work and is safe to
use.
The stages in the testing of a new
drug-medicine is summarised below:
Stage 1 Preclinical testing
(non-living animal testing):
Computer models can be used
initially to simulate a human's responses to a drug and can
identify possible effective drugs, but cannot possibly be as
accurate as actually using cell tissue cultures or live animals.
In preclinical testing the
drugs are tested on cultured human tissue cells in the laboratory.
However, these procedures
cannot be used to test drugs that affect a complex body system.
e.g. a drug for controlling
blood pressure must be tested on a
whole live animal with its complete intact circulatory system.
Stage 2 Preclinical testing
(live animal testing):
If the stage 1 tests prove
satisfactory, and no potential harmful effects are detected, you
can then move onto testing the drug on live animals.
This is to see whether the
drug works and producing the desired medical effect (this is
known as testing the efficacy of the drug).
You are also looking for
potential harmful side effects, including toxicity, from
using the new drug.
You are also investigating
the appropriate dosage in terms of concentration/amount and
frequency of administering the drug.
According to UK law, any new
drug must be tested on two different live mammals, but there are
objections to this on several grounds:
(i) Many people object on
the grounds it is cruel and unethical to use animals in
tests, but others think drug safety should override these
considerations i.e. avoid the use of a potentially dangerous
drug.
(ii) Animals used in
testing drugs are not quite the same as humans. Could their
biological differences give us false results in terms of the
efficacy of the drug when used on humans?
Stage 3 Clinical testing on
humans:
If the drug has passed all
the preclinical tests, you can then test it on human
volunteers in what is called a clinical trial - which
is just as complicated as any research laboratory testing.
Initially, the drug is
tested on healthy volunteers - this is the only way to
find out if there are any harmful side effects on a
healthy body working normally.
Initially it is unsuitable to
test the drug on sick people who are likely to be more
vulnerable to side effects.
At first very low doses of
the drug are administered to healthy people and then the dose is gradually
increased and the participants medical state closely
monitored.
If the results of the tests
on healthy individuals are good and meet any health and safety
criteria, the drug can then be tested on patients suffering
from the illness-disease the drug is designed to combat.
From these tests the optimum dose is found - that is the dose that is most
effective with the fewest side effects.
The safety and
effectiveness of the new drug must be thoroughly checked out.
This takes some time,
human drug trials may last for months or even years.
Sometimes this is due
to the long term progression of a disease e.g. cancer
and the time taken for the treatment to be shown to be
effective.
It might also be a
long time before the symptoms of side effects show up.
We now get into the practice
of how to get statistically valid results from real
patients.
To test the effectiveness of
a drug a group of patients are
randomly selected into two
groups.
One group is given the new
trial drug and the other group, the control group, a
placebo - a
substance that looks like the drug being tested, but has no
effect - it can be just a sugar pill.
The control group
(placebo group) of a clinical trial should be similar to the
people actually being treated with the trial drug e.g. of
similar age and gender.
Using a placebo ensures the
doctors can see the real difference the drug is having on the
patient's condition. This also allows for where the patient does
expect an improvement in their medical condition and might
actually feel better - even though unknowingly, nothing has been
taken to improve the medical situation!
In some trials on
seriously ill patients, placebos are not used -
it would be unethical not to allow all patients the same
chance of benefiting from the new drug.
In other trials
doctors might test new drugs against the best existing
treatment instead of testing against a placebo.
Note that that clinical trials must be blind, meaning, the patient in
the trial doesn't know whether they are getting the new drug
or a placebo, but the doctors do know who has the trialled
drug or the placebo.
Sometimes the clinical
trials are double-blind where neither the patients
nor the doctors know who has the drug or placebo until all
the results have been gathered and analysed. This ensures
the doctors administering, monitoring and analysing the drug
trial are not subconsciously influenced by their knowledge
of the patients.
Before any drug is approved
for use in our healthcare systems, the results of drug testing
trials must be peer reviewed by other equally qualified
medical practitioners.
This is essential to
avoid false or biased claims of the new drug's performance
in real patients.
Drug trials can also 'open-label'
where the doctor and the patient are aware of who is receiving
the drug. This can be used when comparing the effectiveness of
two similar drugs being trialled.
Peer reviewers must check the
validity of the drug trial e.g. has it been correctly
designed and rigorously carried out to the highest
scientific standards.
Finally, the drug can
only be approved for patients of the general public
after permission is granted by the appropriate medical agency if all health and safety criteria are
met. The rules are strict to ensure the drugs are as effective and safe to use as possible.
Thalidomide: A tragic classic case
of insufficient testing
Thalidomide is a drug that was developed as a
sleeping pill in the 1950s and was tested for its effectiveness, but only as a
sleeping pill.
Later it was also found to be effective in
relieving morning sickness in pregnant women.
However, the drug thalidomide had not been tested for use in pregnant
women, in particular it was not tested for relieving morning sickness.
Also, it was not known that the
drug could pass through the placenta and into the foetus (fetus), where
unfortunately, it caused abnormal limb development.
Thousands of babies were
affected and about half survived with missing limbs or malformed limbs.
Around 10 000 babies were affected
and only half of them survived.
It was only after many babies born to mothers
who took the drug were born with severe limb
abnormalities that the drug was then banned for this use.
As a
result, drug testing has become much more rigorous in an attempt to reduce the
incidence of serious side-effects from newly developed drugs..
More recently, thalidomide has been used
successfully in the treatment of leprosy and other
diseases including some cancers.
Learning objectives for this section on
?
Know that drugs for medical applications are
continuously being developed, but need thorough testing of their
safety and effectiveness
before their use is allowed in treating diseases
Know that trials of new drugs will involve testing
with cell cultures, animals and finally patients.
Know that thalidomide was tragic
classic case of inadequate testing of a pharmaceutical product.
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