Lecture 9.2: The Clinical Significance of Receptor Regulation Flashcards
What is a Ligand?
Any molecule or atom that irreversibly binds to a receiving protein molecule, otherwise known as a receptor
What is the Affinity of a drug?
Measure of the ability of a drug (ligand) to form a drug-receptor complex
What is the Efficacy of a drug?
Measure of the ability of that complex to produce a response
What is an Agonist?
A drug that has efficacy (leads to a response)
What is an Antagonist?
A drug that has an affinity, but no efficacy, and impairs the ability of an agonist to bind
What is a Full Agonist?
Efficacy equal to the endogenous agonist
What is a Partial Agonist?
Ceiling effect of drug
What is a High Efficacy Agonist?
Low proportion of receptors needed to produce maximal response
Competitive vs Non-Competitive Agonist/Antagonist
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
What is Intrinsic Receptor Regulation?
Receptors initiate regulation of a variety of events and are themselves subject to regulatory and homeostatic
controls
What can affect Receptor Regulation? (3)
- Intrinsic Regulation
- Disease States
- Drugs
What is Super/Hypersensitivity?
Refers to an enhanced response to an agonist, hypersensitivity may occur as a result of unmasking of receptors or accentuation of signal amplification
What is Synergism?
When two receptors produce a combined effect that is
greater than the sum of their individual effect
What is Upregulation?
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
Cellular Mechanisms of Increased Response (3)
- Super/Hypersensitivity
- Synergism
- Upregulation
Cellular Mechanisms of Decreased Response (4)
- Desensitization
- Downregulation
- Tachyphylaxis
- Tolerance
What is Drug Desensitisation?
Refers to a reduced response to an agonist drug due to over activation of a receptor
Types of Drug Desensitisation (3)
- 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
What is Downregulation?
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
How does Downregulation occur?
Occurs through endocytosis
What is Tolerance?
Tolerance refers to a gradual decreased response to a drug, requiring a higher dose of drug to achieve the same initial response
What is Tachyphylaxis?
It is a rapid decrease in response to an agonist drug following repeated administration within a brief
period, an acute form of desensitisation
What is Myasthenia Gravis?
It is an autoimmune disorder in which antibodies destroy nicotinic acetylcholine receptors [nAChR] located in skeletal muscle
What is excess bronchoconstriction caused by?
- Increase parasympathetic tone (mAch receptors)
- Decreased sympathetic stimulation (β adrenoceptors)
What drugs can cause bronchoconstriction? (2)
- Beta Blockers
- Aspirin
What can abrupt discontinuation of beta-blockers can lead to? (3)
- Tachycardia
- Hypertension
- Angina
How does β-blocker cessation cause tachycardia and hypertension?
- 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
