Agonists and Receptors Flashcards
(16 cards)
What does the Law of Mass Action state in pharmacology?
The rate of a chemical reaction is proportional to the concentrations of the reacting substances (drug [D] and receptor [R]).
In the reversible reaction D + R ⇌ DR, what do k1 and k2 represent?
k1: Rate constant for the forward (association) reaction
k2: Rate constant for the reverse (dissociation) reaction
What is the dissociation constant (KD)?
The drug concentration at which 50% of receptors are occupied. It reflects drug-receptor affinity (lower KD = higher affinity).
Term: Affinity Constant (KA)
The reciprocal of KD (i.e. KA = 1/KD). Describes potency—how strongly a drug binds to its receptor.
What does the variable “r” represent in receptor pharmacology?
Fractional occupancy—the proportion of total receptors that are bound by the drug.
r=[DR]/[Rt]
[DR] - conc of drug receptor complex
[Rt] - Total no. of receptors ([R] + [DR])
What happens to the dose-response curve as KD increases?
The curve shifts to the right, indicating lower affinity (more drug is needed to achieve the same receptor occupancy).
Term: ED50
Definition: The drug concentration at which 50% of the maximum effect is observed; equivalent to KD for full agonists.
What determines a drug’s response once it binds a receptor?
The fractional occupancy (r) and the intrinsic activity (e) of the drug.
E = er
Intrinsic Activity (e)
A measure of a drug’s ability to activate a receptor once bound. Ranges from -1 (inverse agonist) to +1 (full agonist).
What are full, partial and inverse agonists?
Full - A drug with intrinsic activity of 1, capable of producing a maximal response.
Partial - drug with 0 < e < 1, producing submaximal responses even with full receptor occupancy.
Inverse - A drug with e < 0, producing effects opposite to agonists by inhibiting constitutive receptor activity.
What effect does a partial agonist have on the dose-response curve?
Causes a downward shift (less maximal effect); if affinity is also lower, the curve also shifts right.
What happens on a graph when a drug’s KA (affinity) is higher?
The KD is lower, so the dose-response curve shifts left, indicating greater potency.
What does the vertical shift of a dose-response curve indicate?
A change in efficacy (intrinsic activity); full vs partial agonist.
Express observed response as a result of dissociation constant, drug concentration and efficacy
E = e[D] / KD + [D]
Why is understanding KD important in clinical pharmacology?
It helps determine dosing, potency, and predicts how a drug will compete for receptors with other agents.
Can two drugs have the same KD but different effects?
Yes. If they differ in intrinsic activity (e), they will produce different clinical responses.
