Lecture 9.2: The Clinical Significance of Receptor Regulation

Question 1

What is a Ligand?

Answer 1

Any molecule or atom that irreversibly binds to a receiving protein molecule, otherwise known as a receptor

Question 2

What is the Affinity of a drug?

Answer 2

Measure of the ability of a drug (ligand) to form a drug-receptor complex

Question 3

What is the Efficacy of a drug?

Answer 3

Measure of the ability of that complex to produce a response

Question 4

What is an Agonist?

Answer 4

A drug that has efficacy (leads to a response)

Question 5

What is an Antagonist?

Answer 5

A drug that has an affinity, but no efficacy, and impairs the ability of an agonist to bind

Question 6

What is a Full Agonist?

Answer 6

Efficacy equal to the endogenous agonist

Question 7

What is a Partial Agonist?

Answer 7

Ceiling effect of drug

Question 8

What is a High Efficacy Agonist?

Answer 8

Low proportion of receptors needed to produce maximal response

Question 9

Competitive vs Non-Competitive Agonist/Antagonist

Answer 9

Competitive: Competes with the agonist for the same binding site
Non-Competitive: Binds to a different site, inducing conformational change which alters the ability of receptor to bind agonist

Question 10

What is Intrinsic Receptor Regulation?

Answer 10

Receptors initiate regulation of a variety of events and are themselves subject to regulatory and homeostatic
controls

Question 11

What can affect Receptor Regulation? (3)

Answer 11

• Intrinsic Regulation
• Disease States
• Drugs

Question 12

What is Super/Hypersensitivity?

Answer 12

Refers to an enhanced response to an agonist, hypersensitivity may occur as a result of unmasking of receptors or accentuation of signal amplification

Question 13

What is Synergism?

Answer 13

When two receptors produce a combined effect that is
greater than the sum of their individual effect

Question 14

What is Upregulation?

Answer 14

An increase in the number of receptors due to prolonged deprivation of receptors of interacting with
their physiological neurotransmitter, by expressing more receptors, there is a greater probability that a hormone will bump into and stimulate its receptor

Question 15

Cellular Mechanisms of Increased Response (3)

Answer 15

• Super/Hypersensitivity
• Synergism
• Upregulation

Question 16

Cellular Mechanisms of Decreased Response (4)

Answer 16

• Desensitization
• Downregulation
• Tachyphylaxis
• Tolerance

Question 17

What is Drug Desensitisation?

Answer 17

Refers to a reduced response to an agonist drug due to over activation of a receptor

Question 18

Types of Drug Desensitisation (3)

Answer 18

• Receptor mediated (loss of function/number of
  receptors)
• Non receptor mediated (reduction in signaling or 2o
  messengers, increase in metabolism of drug,
  pathophysiological adaptation)
• Dependence

Question 19

What is Downregulation?

Answer 19

Refers to a reduction in the total number of
receptors available to be stimulated due to prolonged receptor activation, this decreases the cell’s
sensitivity to an agonist or drug

Question 20

How does Downregulation occur?

Answer 20

Occurs through endocytosis

Question 21

What is Tolerance?

Answer 21

Tolerance refers to a gradual decreased response to a drug, requiring a higher dose of drug to achieve the same initial response

Question 22

What is Tachyphylaxis?

Answer 22

It is a rapid decrease in response to an agonist drug following repeated administration within a brief
period, an acute form of desensitisation

Question 23

What is Myasthenia Gravis?

Answer 23

It is an autoimmune disorder in which antibodies destroy nicotinic acetylcholine receptors [nAChR] located in skeletal muscle

Question 24

What is excess bronchoconstriction caused by?

Answer 24

• Increase parasympathetic tone (mAch receptors)
• Decreased sympathetic stimulation (β adrenoceptors)

Question 25

What drugs can cause bronchoconstriction? (2)

Answer 25

• Beta Blockers
• Aspirin

Question 26

What can abrupt discontinuation of beta-blockers can lead to? (3)

Answer 26

• Tachycardia
• Hypertension
• Angina

Question 27

How does β-blocker cessation cause tachycardia and hypertension?

Answer 27

• β-blocker decrease adrenergic stimulation
• Thus decrease heart rate
• Thus decrease coronary vasoconstriction
• This leads to β receptor up-regulation (they are
  competitive antagonists)
• If there is β-blocker withdrawal when receptor
  numbers are higher
• It leads to increased sympathetic activity