Receptors Flashcards
(17 cards)
Define Receptor
a component of a cell that interacts with a drug and initiates the chain of biochemical events.
non - covalent (reversible) bonds strength (H-L)
Ionic
Hydrogen
hydrophobic
Van der Waals
Define Median effective dose
ED50: does that produces 50% of the observed effect.
Therapeutic Index
TI = TD50/ED50
Should be >than 1 by a LARGE margin to be safe
Define Ligands
anything that binds to the receptor: Agonist, Antagonist,
Receptor six properties
Recognition: allow recognition and binding
Saturability: exists in finite number
Reversibility: Non-covalently bonded.
Stereoselectivity: should recognize only one naturally occuring optical isomers
Agonist specificity: structurally related bind well
Tissue specificity: binding in tissues known to be sensitive
Conformational selection (not fixed)
- receptor is spontaneously changing between conformations
- Each drug SELECT and STABILIZE one PARTICULAT conformation
- If the drug (agonist) stabilizes perper conform, then this binding = biological activity
Agonist
proper conformation, exposing activation domain needed
Antagonist
Bind to the receptor but does NOT expose activation domain. UNABLE to activate receptor at ALL, regardless of dose and only blocks agonist from activating receptor (sometime use as agonist overdose
Law of mass action
rate of any reaction is proportional to the sum of the masses of the reactants.
Kd=([reactants][products])/[reactant x product]
Dissociation constant (Kd) purpose
Ka indicate how strongly drug bind to recepor, Kd - how easily drug dissociate from receptor
Low Kd or High Ka: preferred drug design, as drug bond longer to the receptor (longer duration)
Receptor binding curves
Receptor binding vs conc. (how conc affect the receptor binding)
Kd: in practical - indicates the conc. required to saturate 50% of the receptor
Dose - response curves
Dose vs biological effect.
It’s similar to receptor binding curves, as the biological effect are directly relate to binding of the drug to its receptor
Phases of the Dose - response curves
1: dose too low, receptor just beginning to respond
2: dose increases, more receptors are occupied
3: no further increase in response as ALL available receptors are saturated
Partial agonist
Able to activate receptor but not completely -> unable to cause FULL activation. REGARDLESS of Dose. (dose response curve lowers)
Agonist vs Antagonist (competitive: same binding site)
Agonist vs non-competitive Antagonist
Antagonist effect eventually would be eliminated as agonist increase.
NCA effect could NOT be eliminated by increasing agonist because NCA does not compete for the same site, it also changes the conformation of receptor
Consequences of Increasing Antagonist
Competitive: curve shift right
Non-competitive: curve lowers
