Basic pharmacology

Question 1

What are signs of receptor action?

Answer 1

1. Dose responsivness to ligand
2. Saturability of effect
3. Reversibility of effect

Question 2

Define efficacy (in a ligand)

Answer 2

Ability of a ligand to produce effect (full agonist has efficacy of 1)

Question 3

Explain pharmacological efficacy.

Answer 3

1. Receptors have two conformations in equilibrium, active and inactive
2. If ligand alters equilibrium of receptor conformations, it is an agonist. (most drugs are antagonistic or partial agonists)
3. If ligand makes a submaximal change in equilibrium, it is a partial agonist

Question 4

Define potency.

Answer 4

A dose required for a specific effect (focus on receptor or outcome, identification of target levels is crutial)

“If you need a low dose and have a high effect fast, then you have a potent drug”

Question 5

Define competitive antagonist.

Answer 5

1. Binds to the same site as agonist
2. If bound, prevents agonist binding
3. Excess agonist will compete off antagonist, if antagonist binds reversibly

Question 6

Define non-competitive antagonist .

Answer 6

1. Don’t share binding site with agonist
2. Cannot be competed away by agonist
3. Prevent effect upon agonist binding
4. Reduce agonist Emax rather than potency
5. Effect on agonist dose curve like irreversible antagonist

Question 7

Desensitisation and tachyphylaxis

Answer 7

• Change in receptor (ex. phosphorylation),
• loss of receptor (internalization),
• exhaustion of mediator,
• increased metabolic degradation of the drug,
• physiological adaptation,
• active extrusion of drugs from cells.

Question 8

Explain constitutively active receptors.

Answer 8

1. In rest state they are largely active
2. With ligand are they mostly inactive (Ligands causing shift to inactive receptor are called inverse agonists)

Question 9

What happens when a competitive agonist binds irreversible?

Answer 9

• agonist cannot compete it away from the receptor
• the dose-response curve will not only be shifted to the right
• the maximal effect produced by the agonist will also be limited