1. Option D Medicinal Chemistry

2. Health and the Human Body
The human body maintains an intricate balance of thousands of chemical reactions.
These systems must respond to constantly changing demands from the individual’s activities.
These systems are subject to challenges from defects and malfunctions resulting from
genetic abnormalities.
environmental challenges.
changes accumulated through age.
attacks from microorganisms. 2

3. Lines of Defense Barriers to prevent entry Skin Mucous membranes
Closures and secretions of natural openings: lips, eyelids etc.
Defense against attack invaders
White blood cells (Phagocytes)]
Blood clotting to prevent blood loss
Inflammatory response.
Immune system
Antibodies.
Memory cells to enable the body to fight repeat invasions. 3

4. Origins of Pharmacology
From earliest times people have used natural substances such as medicinal herbs to
-- relieve pain
-- heal injuries
-- cure diseases
Some folk remedies contained certain active ingredients that were of medicinal value. 4

5. Examples of Folk Remedies
Morphine
extracted from poppy used to treat pain in the 19th century.
Salicylic acid
extracted from willow bark an a precursor to aspirin.
Quinine
Used in South America to treat malaria. 5

6. Definition of a Medicine
Any chemical substance that
Alters a physiological state
Alters mood or emotions
Alters incoming sensory sensations
Sometimes it is difficult to determine whether a drug has any medicinal value.
The legitimate purpose of a drug is usually to improve health.
Use of drugs in some cases is controversial. 6

7. The Placebo Effect
Healing is a complex interaction between mind and body that is not entirely understood.
The Placebo Effect Merely taking any medicine may trigger responses in the body that result in changes in the mental/emotional or physiological states of the person without having any medicinal action.
Video 7

8. Drugs and Medicines Melatonin Codeine
Access to drugs and medicines is controlled in most countries but the definition of what constitutes a drug may vary.
Examples:
Melatonin
Codeine 8

9. Research, Development and Drug Testing
Development of new drugs is long and expensive process
Several stages in development include:
Isolation or chemical synthesis
Laboratory studies
Animal testing to determine LD50
Clinical testing to determine effectiveness
Approval by the FDA for market 9

10. Research, Development and Drug Testing
The development of a new drug is a time consuming process
Determination of the Lethal Dose or LD50. This is the concentration that will kill 50% of the animals in a test sample
The Effective Dose or ED50. is the concentration necessary to bring about a noticeable effect in 50% of the test sample
The Therapeutic Index is the ratio of
LD50.
ED50. 10

11. Therapeutic window
A therapeutic window is the range of dosage between the minimum required to cause a therapeutic effect and the level which produces unacceptable toxic effects.
The therapeutic window may also be used to describe the range of concentrations of drug in the blood plasma that gives safe, effective therapy

12. Video
Developing new drug

13. Video
Clinical Trials
All drugs that are approved for market must be clinically tested multiple times
Most clinical tests are done on volunteers using a double blind study
Some of the volunteers receive a placebo while others receive the therapeutic medicine
Neither the researcher nor the participants know in advance who receives which 13

14. Drug Development
All medicines have some side effects and the appropriate dosage must be determined.
To determine the following must be considered:
Lethal Dose or LD50
Effective Dose or ED50
Therapeutic Index
Toxic Range or Toxic Dose or TD50
Therapeutic Level
Sub-therapeutic level 14

15. Contraindications or Side Effects
Contraindications are additional and often undesirable effects that result from the use of a particular drug to treat a particular condition.
Side effects are somewhat relative depending on the reason the drug is prescribed 15

16. Risk to Benefit Ratio
The prescribing physician must weigh the benefits from the use of a drug against the undesirable side effects when determining a suitable level of risk
The level of risk that is acceptable is related to the severity and the degree to which the condition is life threatening
Examples: Chemotherapy, Pain Killers etc 16

17. Tolerance
Over time the body adapts the presence of a drug
The person receiving the drug needs ever larger doses to achieve the original effect.
Tolerance results in increased risks of dependency/addiction
Increased risks of toxic levels
Possibility of immunity in anti-bacterials. 17

18. Tolerance Tolerance may be developed for two possible reasons
Repeated use of the drug stimulates increased metabolism of that drug –the body is able to prepare the drug more quickly for excretion so that lower levels remain in the body to cause an effect.
The body may adapt so that it off sets the effect of the drug – for example, by desensitising the target receptors with which the drug binds so that it is not able to produce its effect.

19. Addiction/dependence
Although` drug addiction and dependence are usually associated with illicit drugs, addiction can also occur with therapeutic drugs.
A common type of drug that people become dependent on are central nervous system depressants belonging to the class of benzodiazepines, such as diazepam (Valium®) and nitrazepam (Mogadon®).

20. Addiction/dependence
Drug addiction can physiological and Physical Physiological dependence – The drug taker craves if deprived for short time, because he feels good while taking that drug Physical dependence - Body can not function without the drug Drug dependence and tolerance are closely related – Over-prescription is the main reason.

21. Methods of Administering Drugs
Drugs must reach blood stream to be transported to critical tissues.
The method of administration determines rate at which the drug is absorbed in the blood.
Five common points of entry:
Oral
Inhalation/ Pulmonary
Topical
Injection
Anal/Rectal

22. Methods of Administering Drugs
Injection methods
Intradermal
Between layers of skin
Subcutaneous
Under the skin
Intramuscular
In the muscle
Intravenous
Directly in the vein

24. Bioavailability
Bioavailability is the fraction of the administered drug that reaches the target part of the human body.
The proportion of an administered drug dose that reaches the general blood circulation – and is then available to travel around the body to where it is needed (its site of action) – is known as the ‘bioavailability’ of that drug.

25. Bioavailability
If the drug is given as intervenous injection, it bioavailability is 100%
Not all drug is bioavailable if taken orally.
Water soluble drug is more available in digestive trace and water solubility also affect how well it is transported in blood plasma
Fat soluble drug can pass through cell membrane more quickly.

26. Bioavailability
a -Isoniazid is water soluble due to presence of polar groups, it is used to treat tuberculosis b- Griseofulvin is virtually insoluble in water

27. Drug receptor interaction
A lot of drug act by binding with some receptors in body
Receptors are usually protein in cell membrane or cytoplasm

28. A drug can act in various ways on receptors
It can bind to a cell-membrane protein receptor, mimicking the effect of the normal molecule that binds and cause a series of reactions in a cell – i.e. it turns a particular process in the cell on/off ; in this case the drug is called a receptor agonist
It can bind to a cell-membrane protein receptor so that the normal messenger molecule can’t – it prevents a particular response from a cell; in this case the drug is called a receptor antagonist.