Lecture 33 - Drugs Acting Through Receptors 3

Question 1

How can partial agonists lead to antagonism?

Answer 1

They are taking up space on the receptors, so the full agonist isn’t having as much of a response

Question 2

Draw a concentration response curve of an agonist, when a partial agonist is and isn’t present

Answer 2

Slide 2

Question 3

What happens to the response of a full agonist when the concentration of the partial agonist is increased?

Answer 3

As we get more and more partial agonist, the dose-response curve of the full agonist is shifted further to the right

More and more full agonist is required to get the maximum response

Question 4

What are some pharmalogically important partial agonists?

Answer 4

Buprenorphine

Salbutamol

Pindolol

Question 5

What is the function of Buprenorphine?

Answer 5

Treatment for opiate dependence

Question 6

What is the function of Salbutamol?

Answer 6

B2 partial agonist

Question 7

What is the fuction of pindolol?

Answer 7

Beta blocker

Lowers blood pressure

Question 8

What is insurmountable antagonism?

When does this happen?

Answer 8

The maximum can no longer be reached

Irreversible antagonism

Question 9

Describe a situation of mechanistic antagonism

Answer 9

Nifedipine is an antagonist of NA, but it doesn’t bind the a-adrenoceptor

In binds to the L-type Ca channel

Ca can’t come into the cell

There is no smooth muscle contraction

Question 10

Describe an example of functional antagonsim

Answer 10

ACh effect on Ad on heart rate

Each of the ligands is an agonist, but they act on different receptors

The different receptors bring about opposing responses in the cell

Question 11

What are the two types of functional interaction?

Answer 11

Antagonism

Synergy

Question 12

Give an example of functional synergy

Answer 12

NO: turns on Guanylate cyclase

Sildenafil: inhibits phosphodiesterase

Question 13

What happens to the response due to B2 activation with increasing amounts of ACh?

Answer 13

Less response

Question 14

What is the duty cycle of B1-adrenoceptors?

Answer 14

Recycling of receptors from the surface

Not all receptors are put back in the membrane, however

Question 15

What is the central axiom of pharmacology?

Answer 15

All drugs have more than one action, at different concentrations

Question 16

What is interesting about Yohimbine?

Answer 16

Low concentration: a2 blocker
Intermediate concentration: a1 blocker
High concentration: local anaesthetic

Question 17

Describe a situation where there are ‘spare receptors’

Answer 17

There is a non-competitive antagonist present, but the maximum effect is still produced.

This is because there are still enough receptors that can be engaged to produce the full response

Question 18

Is functional antagonism competitive or non-competitive?

Why?

Answer 18

Non-competitive, because the two ligands do not have an effect on each other.

Question 19

What is the definitive feature of competitive antagonism?

Answer 19

The two ligands effect each other, thus, the interaction is

Concentration specific

Act on the same active site

Question 20

What is the parasympathetic effect on heart rate and BP?

Answer 20

Slows Heart rate

Decreases BP

Question 21

Describe the interaction between Adrenaline and ACh in the smooth muscle of the lung

Answer 21

Function antagonism

No ACh: Adrenaline leads to relaxation of smooth muscle

Some ACh: Max still reached, but a greater concentration of AD is required (curve shifted to the right)

Lots of ACh: max not reached.

Question 22

Under what conditions will a receptor not be transported back to the membrane during the duty cycle?

Answer 22

In response to the agonist

Question 23

Describe the process of desensitisation

Answer 23

1. Agonist binds to the receptor
2. Receptor is phosphorylated on internal tail
3. Recruitment of a protein
4. System marked for internalisation and processing (Clathrin coated pit forms)
5. Receptor degrade
6. Loss of receptor density, desensitisation