Drug Targets, Agonists and Antagonists III

Question 1

What are antagonists and how do they differ from agonists?

Answer 1

Antagonists are molecules that reduce the actions of agonists (endogenous or drug molecules) by binding to receptors without evoking an active cellular response. They block receptors and are commonly referred to as blockers. Many clinically useful drugs are antagonists, such as β-blockers and antihistamines.

Question 2

Define competitive antagonism.

Answer 2

Competitive antagonists selectively bind to receptors but do not activate them. Instead, they block receptors, interfering with agonist-receptor interactions. Competitive antagonists have affinity for receptors but lack efficacy. They bind reversibly with receptors and compete with agonists for receptor occupancy.

Question 3

What is the mechanism of action of competitive antagonists?

Answer 3

Competitive antagonists bind to receptors in a reversible manner and compete with agonists for receptor binding sites. This competition reduces the ability of agonists to bind and activate the receptors, leading to a decrease in cellular response.

Question 4

Give examples of clinically useful competitive antagonists.

Answer 4

Examples of competitive antagonists include β-blockers used to treat hypertension and antihistamines used to relieve allergy symptoms. These drugs block specific receptors without activating them, thereby producing a passive response.

Question 5

How do competitive antagonists differ from agonists in terms of receptor binding?

Answer 5

Competitive antagonists have affinity for receptors but do not produce cellular activation (efficacy) like agonists. They selectively bind to receptors without initiating downstream signaling pathways, effectively blocking the actions of agonists.

Question 6

What type of binding do competitive antagonists exhibit with receptors?

Answer 6

Competitive antagonists bind to receptors in a reversible manner. This reversible binding allows them to compete with agonists for receptor occupancy and interfere with agonist-receptor interactions.

Question 7

What is the primary function of competitive antagonists?

Answer 7

Competitive antagonists selectively bind to receptors but do not activate them; instead, they block receptor activation by interfering with agonist-receptor interactions.

Question 8

What distinguishes competitive antagonists from agonists in terms of efficacy?

Answer 8

Competitive antagonists have affinity for receptors but lack efficacy, meaning they do not produce a biological response upon binding to the receptor.

Question 9

What is the relationship between the chemical structures of agonists and their competitive antagonists?

Answer 9

There is usually similarity in the chemical structures of agonists and their competitive antagonists, allowing them to compete for binding to the same receptor site.

Question 10

How do competitive antagonists bind to receptors?

Answer 10

Competitive antagonists bind reversibly to receptors, meaning their binding can be overcome by increasing the concentration of agonist.

Question 11

How does a competitive antagonist affect agonist binding in a biological system?

Answer 11

In the presence of a competitive antagonist, it competes with agonists for occupancy of receptors, reducing the number of receptors available for agonist binding and thereby diminishing the agonist’s effect.

Question 12

What effect does a competitive antagonist have on receptor occupancy by agonist molecules?

Answer 12

A competitive antagonist reduces receptor occupancy by agonist molecules because they compete for the same binding site on the receptor.

Question 13

How does increasing the concentration of an agonist affect receptor occupancy in the presence of a competitive antagonist?

Answer 13

Increasing the concentration of the agonist increases the probability of agonist molecules occupying receptors, overcoming the competition from the antagonist and evoking a response.

Question 14

Why is competitive antagonism considered “surmountable”?

Answer 14

Competitive antagonism is termed “surmountable” because increasing the concentration of the agonist can overcome the antagonistic effect by outcompeting the antagonist for receptor binding.

Question 15

Question: What happens to agonist dose-response curves when the concentration of antagonist molecules is increased?

Answer 15

Higher concentrations of agonist are required to evoke a response, leading to a parallel shift to the right on the agonist-dose response curves.

Question 16

Describe the effect of increasing antagonist concentration on agonist-dose response curves.

Answer 16

Increasing antagonist concentration results in a parallel rightward shift of the agonist-dose response curves.

Question 16

Does increasing antagonist concentration affect the slope of agonist-dose response curves?

Answer 16

No, there is no change in the slope of the curves when antagonist concentration is increased.

Question 17

What happens to the maximum response of agonist-dose response curves with increasing antagonist concentration?

Answer 17

The maximum response (efficacy) of the agonist remains unchanged despite increasing antagonist concentration.

Question 18

What is pA2 and what units does it have?

Answer 18

pA2 is an empirical measure of antagonist potency and does not have any units.

Question 19

What is irreversible competitive antagonism?

Answer 19

Irreversible competitive antagonism occurs when drugs chemically react with receptors, forming covalent bonds that dissociate very slowly or not at all from receptors.

Question 20

How do irreversible competitive antagonists differ from reversible competitive antagonists?

Answer 20

Irreversible competitive antagonists, once bound to receptors, exhibit non-surmountable antagonism and may leave insufficient vacant receptors for agonist molecules to evoke maximum responses.

Question 21

What do non-competitive antagonists do?

Answer 21

Non-competitive antagonists do not block the receptor binding sites for an agonist. Instead, they can bind to a different site on the receptors or block the signal transduction process initiated by receptor activation.

Question 22

Give an example of non-competitive antagonism.

Answer 22

An example of non-competitive antagonism is verapamil, which prevents smooth muscle contraction by blocking calcium (Ca2+) channels and reducing Ca2+ ion influx caused by various drugs.

Question 23

What is pharmacokinetic antagonism?

Answer 23

Pharmacokinetic antagonism occurs when one drug (antagonist) reduces the concentration of free drug by affecting drug absorption, renal elimination, or hepatic elimination. For example, phenobarbitone induces hepatic enzymes that can decrease the effectiveness of other drugs.

Question 24

Describe chemical antagonism.

Answer 24

Chemical antagonism involves the antagonist binding with a drug to form inactive or insoluble complexes. An example is protamine sulfate neutralizing the action of heparin or calcium ions chelating with tetracycline drugs.

Question 25

What characterizes physiological antagonism?

Answer 25

Physiological antagonism occurs when the antagonist has the opposite biological effect of the agonist. The antagonist, which can be an agonist itself, stimulates its own receptors to counteract the effect of the agonist. For instance, prostacyclin and thromboxane-A2 have opposing effects on platelet aggregation.

Question 26

Provide an example of physiological antagonism involving bronchodilation.

Answer 26

Salbutamol is an example of a drug that stimulates β2-receptors to cause bronchodilation, opposing the bronchoconstriction caused by leukotrienes stimulating leukotriene C4 receptors.