Lec 3- Drug targets, Page 19-26

Question 1

What are the 4 most common drug binding proteins?

Answer 1

1. Enzymes
2. Carrier Proteins
3. Ion Channels
4. Receptors

Question 2

What are receptors?

Answer 2

They serve as recognition sites for specific endogenous compounds/ ligands

1. Neurotransmitters (noradrenaline)
2. Hormones (adrenaline: released from adrenal medulla and acts on the heart)
3. Local hormones/ Autacoids (prostaglandin: released and act upon the same/nearby tissue

Question 3

What is a ligand?

Answer 3

A molecule that binds to the specific binding site on a receptor. Endogenous (acetylcholine) or exogenous (atropine)

Question 4

How many binding sites do receptors have?

Answer 4

At least one

Question 5

Efficacy of receptors

Answer 5

Binding of endogenous ligands and some exogenous ligands
=> result in activation of intracellular signalling pathways (signal transduction)
- Drugs act to promote or inhibit process of signal transduction

Question 6

How does a ligand have its intended effect within the body?

Answer 6

It must bind to the target receptor with some specificity which is in part determined by the shapes of the ligand and the binding site(s) on the receptor

Question 7

What is affinity in the context of receptors?

Answer 7

Attraction of a ligand (drug) for a receptor

Question 8

What is efficacy (intrinsic activity) values? (Max effect and no effect)

Answer 8

Max effect = 1

No effect = 0

Question 9

To mimic, agonists have…

Answer 9

affinity and efficacy

Question 10

To prevent, antagonists have….

Answer 10

affinity but no efficacy

Question 11

What is the structure of receptors?

Answer 11

Usually membrane bound proteins but there are exceptions like steroid receptors

Question 12

How is the structure of receptors functionally important?

Answer 12

1. Specificity for ligand (+ stereospecificity)
2. Verification of receptor family subtypes (sequencing)
3. Intracellular signalling (transduction)

Nb: no drug is totally specific for a receptor family-> often lead to side effects (Eg. antihistamines)

Question 13

What are receptor based drug actions dependent upon?

Answer 13

1. Drug properties: selectivity for receptor subtypes

2. Tissue properties: Distribution of receptor subtypes throughout tissues (Eg. Histamines)

Question 14

What is selectivity?

Answer 14

• Preferential binding to a certain subtype that leads to a greater effect at the subtype than others
• Lack of selectivity can lead to unwanted drug effects
• how current antihistamines work :sensitivity for H1 receptors

Question 15

Name 3 benefits of selectivity (Histamines)

Answer 15

1. H1 antagonists for hayfever and allergy (chlorpheniramine, loratidine)
2. H2 antagonists are used for inhibition of gastric acid secretion (cimetidine)
3. H3 antagonists are primarily experimental tools but potentially useful in treating pain and inflammation (thioperamide)

Question 16

What are some problems of non-receptor specificity/selectivity?

Answer 16

1. NSAIDs inhibit cyclo-oxygenase but problems occur with ulcers, uncontrolled bleeding
2. COX II inhibitors are selective for the inducible form of cyclo-oxygenase w lil effect on constitutive form (rofecoxib, celecoxib)
3. Chemotherapy: supposed to be selective for cells/ organisms

Question 17

Receptor Occupancy Theory- drug effect

Answer 17

The number of receptors occupied

Question 18

Rate theory- drug effect

Answer 18

Rate of occupancy

Question 19

Two State Model

Answer 19

Receptors exist as active or inactive form

Question 20

Floating Receptor Model

Answer 20

The D-R complex may interact with a variety of effectors in the membrane to produce its effect

Question 21

Receptor Plasticity

Answer 21

• Receptor states and populations are not static
• Can alter due to physiological, pharmacological or pathological states
• Largely responsible for changes that occur in effectiveness of chronic drug (or endogenous compound) over time
  Eg. tolerance, insulin resistance