Pharmacodynamics II - Darmani Flashcards
Full agonist
Produce a maximal response which a given tissue is capable of producing
Partial agonist
- Produce a smaller maximal effect
- Occupy all of the available receptors to produce their effect
- Can antagonize the effects of a full agonist
- Can have a greater affinity for a particular receptor than a full agonist
Competitive antagonist
Do not produce any response
Efficacy
- The ability or strength of a drug to produce a maximal effect subsequent to binding to its appropriate receptor
- Dependent upon intrinsic efficacy and total receptor concentration
- Varies among tissues because it is dependent on receptor number
Efficacy limit for competitive antagonists
0
Efficacy limit for full agonist
1
Efficacy limit for partial agonist
Between 0 and 1
Intrinsic efficacy
- The amount of stimulus a drug molecule applies to the receptor
- Does not vary among tissues, but is a property of the drug molecule itself for any given type of receptor
Inverse agonists
Drugs that produce changes opposite to those produced by other agonists
Efficacy limit for inverse agonists
From -1 to 0
R*
Active form of GPCRs
R
Inactive form of GPCRs
How do full agonists affect GPCRs?
- Preferentially bind to and maximally enrich R*
* Maximally increase effector activity
How do partial agonists effect GPCRs?
- Show a weaker preference for R*
* Shift eq to a smaller extent
How do inverse agonists effect GPCRs?
- Bind preferentially to R
* Leads to a reduction in basal effector activity
How do silent antagonists effect GPCRs?
- Bind equally well to both R* and R
* Do not alter eq or effector activity
Extended Ternary Complex Model
Accounts for allosteric modulators and suggests that GPCRs may spontaneously adopt multiple active and inactive conformational states
Functionally selective agonists (aka biased agonists)
A unique drug that recognizes and stabilizes a chimeric conformation of a specific signaling pathway via a GPCR that activates multiple signals
Positive Allosteric Modulator
Increases affinity and/or efficacy of an agonist
Negative Allosteric Modulator
Decreases affinity and/or efficacy of an agonist
Potency
Refers to the dose or concentration of a drug required to produce a given effect
Spare Receptor
When the maximal response can be elicited by an agonist at a concentration that does not result in full occupancy of all available receptors
Protective Index
- Important measure of safety
* The ratio of ED50 (bad side effect):ED50 (actually doing its job)
Chemical Antagonism
Render the agonist pharmacologically inactive
Functional Antagonism
Interaction of two drugs whose independent opposing actions in the body tend to cancel each other out
Competitive Antagonism
Antagonist competes with the agonist for its binding site on the receptor
Noncompetitive Antagonism
Antagonist acts at a site other than the appropriate receptors for the agonist
Equilibrium Competitive
- Aka reversible competitive antagonism
* Key feature is surmountability expressed in a rightward parallel shift of the agonist log-dose response curve
Non-equilibrium Competitive
- Aka irreversible competitive antagonism
- Occurs when the antagonist dissociates very slowly, or not at all, from the receptors
- Results: no change in the antagonist occupancy takes place when the agonist is applied
