Lecture 3

Question 1

How drugs work?

Answer 1

Receptors (usually extracellular) bind to ligand (drug), agonist or antagonist, which can activate or supress functions, restoring balance.

Question 2

Affinity?

Answer 2

Strength of binding

Question 3

Efficacy?

Answer 3

Success of producing desired response

Question 4

Antagonist - affinity/efficacy?

Answer 4

Has affinity but not efficacy e.g. antihistamine

Question 5

Down-regulation?

Answer 5

Occurs in response to a chronically high concentration of ligand. Down-regulation will decrease the sensitivity (desensitise) of the cell response to frequent or intense stimulation.

Question 6

Up-regulation?

Answer 6

Chronic stimulation at very low levels of a ligand requires increased sensitivity at receptor level. Greater numbers of receptor will ensure increased sensitivity

Question 7

First messenger?

Answer 7

Ligand (drug) - doesn’t enter cell

Question 8

What does binding of first messenger to its receptor do?

Answer 8

Initiates series of chemical changes (activation of intracellular second messengers) in the cell

Question 9

Examples of intracellular second messengers?

Answer 9

Cyclic nucleotides e.g. cAMP
Inositol trisphosphate (IP3) and diacylglycerol (DAG)
Calcium ions (Ca2+)

Question 10

What does signal transduction result in?

Answer 10

Direct opening of ion channels

Direct activation of an enzyme

Indirect activation/inactivation of enzyme
Indirect opening/closing of ion channel
Involves a G-protein (molecular switch)

Question 11

Example of receptor-operated ion channels and agonist?

Answer 11

Binding of GABA to GABAa receptor causes opening of Cl- channels

Question 12

Role of Ca2+ as second messenger?

Answer 12

Activation of specific protein kinases, ion channels
Regulation of activity of many enzymes
(effects are concentration dependant)

Question 13

Examples of Ca2+ channel blockers?

Answer 13

Nifedipine, verapamil - can be
used to modulate muscle contraction.

Question 14

Targets for drugs in GI tract?

Answer 14

Histamine receptors
e.g. Ranitidine
Target: Parietal cells – decreased gastric acid secretion

Opioid receptors
e.g. Loperamide
Target: Myenteric plexus/opioid receptors – decreased peristalsis, increases tone of anal sphincter (partly via Ca2+ channel blockade)