Medicines by Design – Storylines

MD1 – Alcohol in the blood

M   Alcohol is a XENOBIOTIC – a substance not in the body, but which affects it.

M   Xenobiotics includes foods, drugs (which alter the biochemical processes in our bodies) and poisons.

M   Ethanol is a source of energy but also depresses the activity of the central nervous system (CNS)

M   The effect depends on the amount taken (driving limit is 80mg/100cm3)

M   The concentration in the blood can be measured using a breathalyser due to the establishment of an equilibrium between alcohol in air in the lungs and the blood.

M   The old method of measurement used crystals of potassium dichromate which turned from orange to green. The new method uses the “Lion Alcometer” which measures the voltage produced as the ethanol is oxidised by the air.

M   If the breathalyser test is positive, a blood or urine sample is analysed by g.l.c. or the breath is checked by i.r. spectroscopy.

MD3 – Medicines that send messages to nerves

Þ    Designing a new medicine requires a biological understanding of the disease and a lead compound to provide clues as to where to start.

Þ    (This lead compound often comes from natural remedies or by an accidental discovery – e.g. penicillin)

Þ    Only about 1 in every 10000 compounds that are synthesised will survive the testing procedures and become commercially available.

Þ    Noradrenaline is a neurotransmitter. It’s effects include bronchiole dilation (needed by asthma sufferers) but it’s side effects mean that it cannot be used.

Þ    Chemists modified it to produce isoprenaline and then salbutamol.

Þ    Salbutamol has a very specific dilating effect on receptors of the airways and is metabolised very slowly due to the phenol group being changed.

Þ    The three structures shown above have a common part which binds to the receptor. This is called molecular recognition.

Þ    This common part is called the PHARMACOPHORE – a group of atoms which confers pharmacological activity.

Þ    Salbutamol is an AGONIST – it behaves like the body’s natural substance in binding and bringing about a response.

Þ    Other drugs act as ANTAGONISTS – they will compete for receptor sites but have no effect.

Þ    Propanolol is a very successful antagonist – it blocks the beta-receptors which control the heart muscle so stopping the heart rate from getting too high (it is a beta-blocker !)