Lecture 5

Question 1

Name 2 types of targets for drug action

Answer 1

1. Drugs that are dependent on chemical properties and do not interact with cellular components.
   - E.g. Antacids –Magnesium hydroxide, aluminium hydroxide gel.
2. Drugs that combine with specific molecular components – receptors

• Lipids
• DNA
• Proteins

Question 2

*What are the 4 classes of protein receptors?

(We are focussing on main 2)

Answer 2

1. enzymes
2. carrier molecules
3. ion channels
4. classical transmembrane receptors.

Question 3

Define a INHIBITOR

Answer 3

A substrate that binds to a protein target (enzyme) and normal reaction is inhibited

Examples

Neostigmine acting on ACH-esterase

Aspirin acting on cyclo-oxygenase (COX) Signalling pathway

Question 4

Define a FALSE SUBSTRATE

Answer 4

(drug) undergoes chemical transformation to form

abnormal metabolite

Examples:
DOPA => Noradrenaline (normal substrate)

Methyl DOPA => Methylnoradrenaline (false substrate)

Question 5

Define PRO DRUG

Answer 5

Pro-drug- conversion of inactive drug to active drug by enzyme, usually in liver

EXAMPLES:

Cortisone => Hydrocortisone

Azathioprine (immunosuppressant) => Mercaptopurine

Question 6

List some TRANSDUCTION MECHANISMS of an Agonist

Answer 6

1. Ion channel modulation
2. Enzyme activation/inhibition
3. Receptor tyrosine kinase
4. DNA transcription

Question 7

*List 4 classes of TRANSMEMBRANE PROTEIN RECEPTORS

Answer 7

1. Oligomeric or Ligand-gated ion channels = 4/5 anchored channel lining
2. 7 - transmembrane spanning receptors
3. Single transmembrane spanning receptors
4. Intracellular Steroid/thyroid receptors

Question 8

How are receptors classified?

Answer 8

1. PHARMACOLOGICAL (50 receptors characterised)
   Physiological mediator
   Exogenous drug / ligand
2. MOLECULAR (1500 receptors characterised)

Question 9

*Give an example of a receptor that couples to INHIBITORY G PROTEIN (Gi)

Answer 9

Inhibitory alpha 2-adrenergic receptor

Question 10

*Give an example of a receptor that couples to

G PROTEIN (Gs)

Answer 10

Beta adrenergic receptor

Question 11

*List a variety of 2nd messenger molecules

Answer 11

1. cyclic AMP
2. cyclic GMP
3. IP3
4. diacylglycerol
5. nitric oxide

Question 12

*Name the enzymes responsible for the SYNTHESIS & HYDROLYSIS of cyclic AMP

Answer 12

ATP => (Adenylyl Cyclase) => Cyclic AMP => (Phosphodiesterase) => AMP

Question 13

*What is the MOLECULAR STRUCTURE of Cyclic AMP

Answer 13

Adenine + Ribose = Adenosine (nucleoside)

Question 14

*Distinguish between the nicotinic and muscarinic acetylcholine receptors by their molecular structures.

Answer 14

Muscarinic = C9 H20 NO2

(From mushroom - one pentagon with everything attached)

Nicotinic = C10 H14 N2

(From plant - hexagon attached to pentagon)

Question 15

*Give examples of drugs that function through NON-PROTEIN drug receptors

(i.e. Lipid & DNA)

Answer 15

Lipid = nitrous oxide

DNA = Mitomycin