https://www.youtube.com/watch?v=yAednonQ-Qo
OPTION D: MEDICINAL CHEMSITRY
D.1 Pharmaceutical Products and Drug Action
Drug: A chemical that causes a physiological change in the body. This includes changes for the
better and for the worse
Medicine: A substance that is used for the treatment or prevention of disease. They may be
natural or synthetic and contain beneficial drugs
o Therapeutic Effect: The beneficial effect of medicine on the body
Drugs and medicine are commonly taken to improve health (but not always) as they can assist
the body in its natural healing process
Most drugs need to be absorbed into the bloodstream to be effective. The method of
administration determines the speed which it is absorbed and the route taken.
o Subcutaneous (under the skin) – e.g. dental injections
Parenteral o Intravenous (into the vein, fastest method of injection) – e.g. local
(by injection)
anaesthetics
o Intramuscular (into the muscle) – e.g. many vaccines
o Inhalation (vapour breathed in) – e.g. cigarettes
o Oral (taken by mouth) – e.g. tablets
o Rectal (through the anus) – e.g. laxatives for constipation
o Drugs may also be applied topically (in the form of creams) to limit the effect to the site
Bioavailability: The fraction of the administered dosage that reaches the target part of the
human body. It is affected by factors such as:
o The method of drug administration
Drugs administered intravenously have a bioavailability of 100% as they are
delivered directly into the bloodstream
Drugs administered orally are broken down during digestion reducing
bioavailability (approx. four times lower than intravenous drugs)
o Polarity of a drug (affects its solubility)
For a drug to be readily absorbed it must be largely hydrophobic (lipid soluble)
but still have some solubility in aqueous solutions
Very hydrophilic drugs cannot cross cell membranes (composed of lipids)
o Functional Group (affects solubility)
Water solubility depends on a molecules ability to form H-bonds and ionise
Therapeutic window: range of dosages between the minimum amounts of the drug that produce
the desired effect and an adverse effect (measures
safety of a drug)
54
, o A wide therapeutic window means there is a wide margin between effective and toxic
doses (= safer drug)
o A narrow therapeutic window means a small increase in the effective dose may produce
toxic effects
Therapeutic Index: The ratio between the dosage of a drug that causes a toxic effect and the
dosage that causes a therapeutic effect
𝐋 𝟓𝟎 %
o TI for animals =
𝟓𝟎 % .
𝐓 𝟓𝟎 𝐱 x %
o TI for humans =
𝟓𝟎 % .
o Drugs with a low therapeutic index need to be controlled very carefully as exceeding an
effective dose could cause toxic or fatal consequences
o For ethical and economic reasons, animal and human tests of drugs should be kept to a
minimum
At the molecular level, drugs interact with enzyme binding sites or cellular receptors
o At enzymes, most drugs act as inhibitors where normal biological activity is prevented
The activity of the drug depends on its structure as the greater the fit between
the drug and the receptor the greater the activity
As drugs interfere with biological processes they can also cause unwanted side-effects
o These can be benign such as drowsiness or nausea or serious such as organ damage
o The administration of the drug may be altered to minimise side-effects e.g. a drug with
severe side effects may be taken orally for a slower delivery rather than intravenously
Another factor to consider is the tolerance of the drug as when some drugs are taken regularly
the effective action of the drug can decrease with exposure
o Therefore, higher doses are needed to produce the same effect
Drug addiction or dependence is the compulsive desire of the user to take a drug regardless of
the health problems it might cause
o Usually occurs when a person has become dependent on a drug, and suffers from
withdrawal symptoms when it is not taken
o Addiction becomes particularly dangerous when combined with drug tolerance and can
lead to overdoses
When administering drugs the risk to benefit ratio needs to be considered and whether the
negative side-effects/addictive properties outweigh the therapeutic effects
Drug development is a long and complex process which takes many years. Stages include:
o Drug Discovery (Research) – identification of a lead compound which shows promising
activity towards a specific biological target. It can be isolated from natural products or
synthesised in a lab
o OR Drug Design – relies on knowledge or drug-receptor interactions by designing a drug
with a complementary structure to a specific biological target using technology. The
molecule is then synthesised and tested and the model can be refined if necessary
o Optimisation (Development) – The effectiveness of the lead compound is optimised by
synthesising and testing many chemically related compounds. The drug must have
limited side-effects and be accessible with minimal environmental damage
o Preclinical Trials – Drug is tested on animal/bacterial cultures to determine TI
55
OPTION D: MEDICINAL CHEMSITRY
D.1 Pharmaceutical Products and Drug Action
Drug: A chemical that causes a physiological change in the body. This includes changes for the
better and for the worse
Medicine: A substance that is used for the treatment or prevention of disease. They may be
natural or synthetic and contain beneficial drugs
o Therapeutic Effect: The beneficial effect of medicine on the body
Drugs and medicine are commonly taken to improve health (but not always) as they can assist
the body in its natural healing process
Most drugs need to be absorbed into the bloodstream to be effective. The method of
administration determines the speed which it is absorbed and the route taken.
o Subcutaneous (under the skin) – e.g. dental injections
Parenteral o Intravenous (into the vein, fastest method of injection) – e.g. local
(by injection)
anaesthetics
o Intramuscular (into the muscle) – e.g. many vaccines
o Inhalation (vapour breathed in) – e.g. cigarettes
o Oral (taken by mouth) – e.g. tablets
o Rectal (through the anus) – e.g. laxatives for constipation
o Drugs may also be applied topically (in the form of creams) to limit the effect to the site
Bioavailability: The fraction of the administered dosage that reaches the target part of the
human body. It is affected by factors such as:
o The method of drug administration
Drugs administered intravenously have a bioavailability of 100% as they are
delivered directly into the bloodstream
Drugs administered orally are broken down during digestion reducing
bioavailability (approx. four times lower than intravenous drugs)
o Polarity of a drug (affects its solubility)
For a drug to be readily absorbed it must be largely hydrophobic (lipid soluble)
but still have some solubility in aqueous solutions
Very hydrophilic drugs cannot cross cell membranes (composed of lipids)
o Functional Group (affects solubility)
Water solubility depends on a molecules ability to form H-bonds and ionise
Therapeutic window: range of dosages between the minimum amounts of the drug that produce
the desired effect and an adverse effect (measures
safety of a drug)
54
, o A wide therapeutic window means there is a wide margin between effective and toxic
doses (= safer drug)
o A narrow therapeutic window means a small increase in the effective dose may produce
toxic effects
Therapeutic Index: The ratio between the dosage of a drug that causes a toxic effect and the
dosage that causes a therapeutic effect
𝐋 𝟓𝟎 %
o TI for animals =
𝟓𝟎 % .
𝐓 𝟓𝟎 𝐱 x %
o TI for humans =
𝟓𝟎 % .
o Drugs with a low therapeutic index need to be controlled very carefully as exceeding an
effective dose could cause toxic or fatal consequences
o For ethical and economic reasons, animal and human tests of drugs should be kept to a
minimum
At the molecular level, drugs interact with enzyme binding sites or cellular receptors
o At enzymes, most drugs act as inhibitors where normal biological activity is prevented
The activity of the drug depends on its structure as the greater the fit between
the drug and the receptor the greater the activity
As drugs interfere with biological processes they can also cause unwanted side-effects
o These can be benign such as drowsiness or nausea or serious such as organ damage
o The administration of the drug may be altered to minimise side-effects e.g. a drug with
severe side effects may be taken orally for a slower delivery rather than intravenously
Another factor to consider is the tolerance of the drug as when some drugs are taken regularly
the effective action of the drug can decrease with exposure
o Therefore, higher doses are needed to produce the same effect
Drug addiction or dependence is the compulsive desire of the user to take a drug regardless of
the health problems it might cause
o Usually occurs when a person has become dependent on a drug, and suffers from
withdrawal symptoms when it is not taken
o Addiction becomes particularly dangerous when combined with drug tolerance and can
lead to overdoses
When administering drugs the risk to benefit ratio needs to be considered and whether the
negative side-effects/addictive properties outweigh the therapeutic effects
Drug development is a long and complex process which takes many years. Stages include:
o Drug Discovery (Research) – identification of a lead compound which shows promising
activity towards a specific biological target. It can be isolated from natural products or
synthesised in a lab
o OR Drug Design – relies on knowledge or drug-receptor interactions by designing a drug
with a complementary structure to a specific biological target using technology. The
molecule is then synthesised and tested and the model can be refined if necessary
o Optimisation (Development) – The effectiveness of the lead compound is optimised by
synthesising and testing many chemically related compounds. The drug must have
limited side-effects and be accessible with minimal environmental damage
o Preclinical Trials – Drug is tested on animal/bacterial cultures to determine TI
55
