M&R 8.1 - Drugs and Receptors Flashcards
What is meant by the affinity of a drug?
The ability of a drug to bind to its biological target e.g. a receptor
What is meant by the efficacy of a drug?
The ability of a drug to generate a response upon binding
What is meant by intrinsic efficacy?
The ability of an agonist to activate a receptor
What does efficacy depend on?
- Efficacy
- Influential factors to the response e.g. cell-tissue dependent factors
What is Kd?
- The concentration of a drug/ligand supplying 50% of the receptors (dissociation constant)
- Measurement of affinity
- Lower Kd = Higher affinity
What is Bmax?
- The maximum binding capacity between a ligand and its receptors
- Indicates number of receptors
When would radioligands be used?
- To obtain information about binding
- Low radioligand = low binding
When would a concentration-response curve be used?
When measuring a response in cells/tissues
When would a dose-response curve be used?
When measuring a response in a whole animal
What is Emax?
Maximum response of a drug
What is EC50?
- The effective concentration giving 50% of the maximal response
- A measure of potency
What is potency?
- A combination of both affinity and efficacy
- The concentration of a drug required to give 50% of the maximal response
What does potency depend on?
- Affinity
- Efficacy
- Needs to generate a MEASURABLE RESPONSE
What is the relevance of measuring efficacy in relative terms?
- Agonists with different Emax = different efficacy
BUT
- Agonists with same Emax may have different efficacy as affinity could differ
How does dose differ to concentration?
- Dose = concentration of the drug at a site of unknown action (mg or Mgk-1)
- Concentration = known concentration of a drug at a site of action
What is an agonist?
- A molecule that activates a receptor
- Fits binding site fully
What are the features of an agonist?
Have:
- Intrinsic efficacy
- Efficacy
- Affinity
What is an antagonist?
A molecule that blocks the ability of an agonist by blocking the binding site without causing a conformational change
What are the features of an antagonist?
- ONLY HAS AFFINITY
- Doesn’t cause a response so has no intrinsic efficacy
How does Salbutamol compare with Salmeterol?
- Salbutamol has a higher affinity for Beta-2 adrenoceptors than Beta-1
- Salbutamol has a Beta-2 selective efficacy
- Salmeterol has a higher affinity for Beta-2 adrenoceptors than Beta-1
- Salmerterol has no selective efficacy (prevents side effects and Beta1 activation through affinity)
How is the route of administration of Salbutamol significant?
- Gives another element of selectivity
- Limits Beta-1 activation and other side effects
- Can be given by drip to a severely ill patient but that then loses the selectivity
