Pharmacology Pharmacodynamics and Mechanism of Action 3 — Questions and Answers
Question 1: An irreversible antagonist differs from a competitive antagonist primarily because it:
- Binds with lower affinity
- Cannot be overcome by increasing agonist concentration (Correct answer)
- Has a shorter duration of action
- Activates the receptor at high doses
Correct answer: Cannot be overcome by increasing agonist concentration
Irreversible antagonists form covalent bonds with the receptor, so increasing agonist concentration cannot fully displace them or restore maximal response.
Question 2: Which term describes the concept that a receptor can adopt an active conformation spontaneously, independent of agonist binding?
- Receptor spare capacity
- Constitutive activity (Correct answer)
- Receptor desensitization
- Pharmacological tolerance
Correct answer: Constitutive activity
Constitutive (basal) activity occurs when receptors spontaneously adopt an active conformation without agonist binding, producing measurable effects.
Question 3: Nitroglycerin exerts its vasodilatory effect by serving as a source of which signaling molecule?
- Prostacyclin (PGI2)
- Endothelin-1
- Nitric oxide (NO) (Correct answer)
- Adenosine
Correct answer: Nitric oxide (NO)
Nitroglycerin is bioconverted to nitric oxide, which activates soluble guanylyl cyclase to increase cGMP, causing smooth muscle relaxation.
Question 4: A drug that causes receptor desensitization through phosphorylation of the receptor by G protein-coupled receptor kinases (GRKs) is most likely:
- A nuclear receptor ligand
- An irreversible antagonist
- A sustained agonist (Correct answer)
- A pharmacokinetic inhibitor
Correct answer: A sustained agonist
GRKs phosphorylate activated GPCRs after sustained agonist exposure, leading to beta-arrestin recruitment and receptor desensitization.
Question 5: In a quantal dose-response curve, the ED50 represents the dose that produces the desired effect in what percentage of the population?
- 100%
- 25%
- 50% (Correct answer)
- 75%
Correct answer: 50%
ED50 in a quantal dose-response relationship is the dose producing the specified effect (e.g., analgesia) in 50% of the test population.
Question 6: Which enzyme is directly inhibited by sildenafil, leading to increased cGMP levels and penile erection?
- Adenylyl cyclase
- Phospholipase C
- Phosphodiesterase type 5 (PDE5) (Correct answer)
- Guanylyl cyclase
Correct answer: Phosphodiesterase type 5 (PDE5)
Sildenafil inhibits PDE5, which normally degrades cGMP, thereby prolonging cGMP-mediated smooth muscle relaxation and vasodilation.
Question 7: The term 'biased agonism' refers to a drug that:
- Activates only one receptor subtype
- Selectively activates specific downstream pathways of a receptor over others (Correct answer)
- Shows higher potency in one tissue versus another
- Requires a higher dose than a full agonist
Correct answer: Selectively activates specific downstream pathways of a receptor over others
Biased agonists preferentially activate one signaling pathway (e.g., G protein vs. beta-arrestin) over another at the same receptor, enabling pathway-selective pharmacology.
Pharmacology Pharmacodynamics and Mechanism of Action 3
An irreversible antagonist differs from a competitive antagonist primarily because it: