Drug Target Sites - Receptors Flashcards
Potency
dose required for effect
Agonist
drug which acts on a receptor and produces a response (increase or decrease of activity in a cell)
Antagonist
A drug which prevents the response to an agonist
Drug Receptors Control…
- selectivity of drug effect
- magnitude of response
- mechanisms to mimic/prevent physiological functions
Unit of dose: Micrograms
(10-6 grams)
Unit of Dose: Nanomoles
(10-9 moles)
Unit of concentration: Micromolar
(10-6 moles per litre)
Unit of concentration: Nanomolar
(10-9 moles per litre)
Drug-Receptor Interaction
An agonist binds to its receptor with weak bonds: -electrstatic forces -van der waals -h bonds [AR] ====> Effect
Stereo-selective
Ligand/receptor interactions are defined in 3D
-hence display selectivity for one stereo-isomer of a ligand over another
[A]
Agonist conc
[AR]
Agonist-receptor conc
[Rt]
total receptor conc
Kd
Dissociation constant
Magnitude of response
hyperbolic relationship
LOG DOSE - response curves
sigmoid in shape
Info from LOG dose response curves:
- threshold dose
- max dose
- effective dose range
- half-maximal effective dose (ED50)
POTENCY
related to affinity of drug for receptor
-ED50 usually index of potency
EFFICACY
-an index of the max response a drug can induce (effectiveness)
FULL AGONISTS
- have high efficacy
- produce maximum response
PARTIAL AGONISTS
- have low efficacy (<1.0)
- fail to produce max. response
ANTAGONISTS
-block the actions of agonists
-they may:
act on same receptor site as agonist
act at diff. site in the pathway leading to the response
-activate an opposing physiological mechanism
-interact chemically with the agonist
COMPETITIVE ANTAGONISTS
- antagonists with act on the same receptor site as the agonist
- have high affinity for the receptor
- have no efficacy at the receptor
- doesnt produce effect
REVERSIBLE competitive antagonists
-Surmountable
-weak bonds
-agonist is competitive and reversible
(curve shifts to right, )
IRREVERSIBLE competitive antagonists
- Insurmountable
- covalent bonds
- curve has depressed maximum response
Receptor reserve
-powerful agonists do not need to occupy all the receptors to produce the max response
(<5%)?
-full agonists occupy a small % of the receptors to produce max response (HIGH EFFICACY)
-partial agonists cannot produce the max response even when they occupy all the receptors (LOW EFFICACY)
NON-COMPETITIVE ANTAGONISTS
can:
- act at diff site-activate opposing physiological mechanism
- interact chemically with agonist
Inverse Agonism
an inverse agonist is a ligand that binds to the receptor and limits agonism-independent activity
Allosteric ligands
- Ligands that bind to the same region of the receptor as the natural hormone/neurotransmitter are termed ‘ORTHOSTERIC’
- There are potentially many other sites on receptors to which synthetic ligands may bind - such ligands are termed ‘ALLOSTERIC’
- these do not produce an effect in isolation but only modulate the effect of an orthosteric ligand
Positive allosteric ligands
enhance the funciton of an orthosteric ligand
Negative allosteric ligands
reduce the function of an orthosteric ligand
