Sesh 6- Pharmacodynamics Flashcards
What 3 general factors affect potency?
- Affinity-strength of binding
- Intrinsic efficacy- ability wto activate the receptor
- Cell/tissue-dependant factors
2+3= efficacy
Do G proteins bind GDP or GTP in their inactive state?
GDP
Do most drugs bind reversibly or irreversibly to receptors?
Reversibly
The affinity of a ligand for a receptor describes the ________ of binding.
Strength
What is the intrinsic efficacy of a ligand?
The ability of a ligand to activate the receptor.
*Applies to agonists only
What is meant by a ligand’s efficacy?
The ability of a ligand to produce a measurable biological response. This is governed by the intrinsic efficacy plus cell/tissue-dependant factors.
Do antagonists have intrinsic efficacy?
No, only affinity, as they bind to block the receptor.
How are drug-receptor interactions by binding measured?
By using a radioligand, you can calculate Bmax and Kd.
What does Bmax give information about?
The maximum binding capacity i.e. Number of receptors
Kd is an index of________ of a _________ for a __________.
- Affinity
- Ligand
- Receptor
Define Kd.
Kd is the dissociation constant. It is the concentration of ligand required to occupy 50% of the available receptors.
A drug binding curve plotted on a logarithmic scale produces a ________ shape plot.
Sigmoidal.
Define EC50.
The ligand concentration required to produce 50% of the maximal response (Emax).
The EC50 value of an agonist gives a measure of its _____________.
Potency.
What is functional antagonism?
Opposing a response in a way that is independent of the mechanism causing that response.
Give an example of a cell or tissue-specific factor that can influence drug potency.
The number of receptors in that cell or tissue.
Spare receptors increase the _______ of cells to a ligand, and increases the agonist ________.
- Sensitivity
- Potency
*ligand doesn’t need to occupy all receptors for max response.
Increasing the activation of a receptor pharmacologically, e.g. By dosing successively, will ___________ the receptor number.
Decrease/down regulate. This can lead to tolerance or tachyphylaxis.
Buprenorphine is a _____________ at the mu opioid receptor.
Partial agonist.
Why are partial agonists sometimes referred to as mixed agonist/antagonists?
Because if they have higher affinity for a receptor than another ligand, but lower efficacy, they can antagonise that ligand, and limit the response produced.
Partial agonism is dependent on the _______and _________.
- Compound
2. System-e.g. Receptor number can change a partial agonist into a full agonist
What is the IC50?
The concentration of antagonist needed to inhibit 50% of the max response. It is an index of antagonist potency.
Why is competitive inhibition surmountable?
If you increase the agonist concentration, it can compete with the antagonist for binding sites and eventually elicit the maximal response.
What type of antagonism is non-surmountable?
Irreversible competitive antagonism.
