Drugs and Receptors

Question 1

Why is it important to measure a drug’s molarity rather than it’s weight?

Answer 1

The same weight of different drugs will have very different concentrations.
The concentration of drug molecules around the site of action is what is critical in determining drug action.

Question 2

What two factors determine the action of a drug?

Answer 2

Affinity - ability to bind to a receptor

Intrinsic efficacy - ability to activate the receptor

Question 3

Describe an agonist.

Answer 3

A ligand which causes a response.

Has both affinity and intrinsic efficacy.

Question 4

Describe the difference between intrinsic efficacy and efficacy.

Answer 4

Intrinsic efficacy - ability to activate a receptor.

Efficacy - ability of a receptor to exert a response. Is cell and tissue dependent.

Question 5

Describe an antagonist.

Answer 5

Blocks the effect of an agonist.

Has affinity ut no intrinsic efficacy.

Question 6

What is Bmax?

Answer 6

The maximum binding capacity

Question 7

What is the Kd of a drug?

Answer 7

The amount of drug required to bind half the receptors on a cell.

Question 8

What is EC50?

Answer 8

A measure of agonist potency.
Is the effective concentration that gives 50% of the maximum response.
Depends on affinity, intrinsic efficacy and tissue-specific components.

Question 9

Describe what is meant by dose.

Answer 9

The amount of a drug given to a patient.

Question 10

Describe what is meant by functional antagonism, using airway bronchoconstriction as an example.

Answer 10

When a function is antagonised by the activation of an opposing function, rather than directly through a receptor.

Contraction of smooth muscle in the bronchioles is functionally antagonised by the activation of beta-2 adrenoceptors which trigger relaxation.

Question 11

Why is a selective beta-2 agonist important in treating asthmatics?
Give two examples of drugs used.

Answer 11

Beta adrenoceptors are found elsewhere in the body so can produce unwanted side effects if not specific enough, such as in the heart where they increase the rate and force of contraction.

Salbutamol and salmeterol.

Question 12

Describe the difference in method of selectivity between salbutamol and salmeterol.

Answer 12

Salbutamol - poorly selective agonist for beta-2 adrenoceptors. Has beta-2 selective efficacy and the route of administration also helps in selectivity.

Salmeterol - Very selective for beta-2 adrenoceptors based on affinity rather than efficacy.

Question 13

How can IV salbutamol cause angina when being used to treat a severe asthmatic attack?

Answer 13

It causes increased force and rate of contraction in the heart.
If the person has some occlusion of the coronary arteries, this will cause angina as there is not sufficient perfusion for the activity of the cardiac muscle.

Question 14

What does EC50 depend on?

Answer 14

Affinity and intrinsic efficacy.

Cellular/tissue-dependent factors (including number of receptors).

Question 15

If there is a discrepancy between a binding curve and response curve in a graph of binding/response against drug concentration, what does this indicate?

Answer 15

There are spare receptors because when there is a lower proportion of receptors activated, where is still a 100% effect.

Question 16

Why do catalytically active receptors allow a cell to have spare receptors?

Answer 16

There are amplications in the signalling pathway which allows a greater response with a smaller activation of receptors.

Question 17

Describe partial agonism.

Answer 17

There are no spare receptors so insufficient efficacy for a maximal response.
It’s maximum response is linked directly to efficacy.
Can be compound and system-dependent.

Question 18

On a graph of response against the concentration of a drug (log10), how would you determine intrinsic activity?

Answer 18

The maximum response, indicated by the height of the curve.

Question 19

On a graph of response/binding against the concentration of a drug (log10), how would you determine efficacy?

Answer 19

The difference between the binding and response curve.

Greater difference = greater efficacy

Question 20

Describe reversible competitive antagonism.

Answer 20

More antagonism means that there is more competition, but this can be overcome by increasing agonist concentration.
Causes a parallel shift to the right of agonist concentration-response curve.

Question 21

What is IC50?

Answer 21

The concentration of antagonist giving 50% inhibition.

Question 22

How can naloxone be used as an ‘antidote’ to heroin overdose?

Answer 22

High affinity competitive antagonist at the mu-opioid receptor so can reverse respiratory depression.

Question 23

Describe irreversible competitive antagonism.

Answer 23

When the antagonist dissociates slowly or not at all.
The effect is unsurmountable.
Causes a parallel shift to the right of the agonist concentration-response curve.
At higher concentrations, the maximum response is suppressed.

Question 24

Describe how phenoxybenzamine can be used to treat pheochromocytoma.

Answer 24

It is a tumour of Chromaffin cells in the adrenal gland which can produce a lot of adrenaline, leading to a hypertensive crisis.
Phenoxybenzamine covalently binds to alpha-1 adrenoceptors to reduce the effect.

Question 25

Describe non-competitive antagonism

Answer 25

The antagonist binds to the allosteric site rather than orthosteric where the ligand binds.
Has a similar effect to irreversible competitive antagonism.

Question 26

Describe how ketamine acts on ligand-gated NMDA receptors.

Answer 26

They are excitatory receptors which are found in the brain and usually agonised by glutamate.
Ketamine binds with the channel, decreasing central excitation so is analgesic at low concentration.
Has a distinctly different site to glutamate.

Question 27

Give two mechanisms for drug elimination from the body and indicate the tissues where this mechanism occurs.

Answer 27

Solubility by glucuronidation or conjugation in the liver.

Glomerular filtration in the kidney.