51. Introduction to drug action Flashcards
what are the 4 receptor superfamilies:
ligand-gated ion-channel receptors,
G-protein-coupled receptors, kinase-linked receptors
nuclear receptors.
what are the four drug targets
receptors, ion channels, enzymes and transport/channel proteins.
what is a ligan
A substance that is bound to a protein.
what is affinity
the tendency of a ligand to bind to its receptor
what is an agonist
A ligand that binds to a receptor and alters the receptor state resulting in a biological response.
what is an antagonist
A drug that reduces the action of another drug, generally an agonist. Many antagonists act at the same receptor macromolecule as the agonist.
what is a partial agonist
An agonist that cannot elicit as large an effect (even with 100% receptor occupancy) as can another agonist acting through the same receptors in the same tissue
what is efficacy
the tendency for an agonist to activate the receptor state resulting in a biological response
and the maximum response achievable from a drug
what is - Drug Potency -
the concentration or amount needed to produce a desired effect (e.g., EC50).
describe - Drug selectivity –
the degree to which a drug has affinity for its intended target to the exclusion of other (‘off’) targets.
The greater the selectivity for the intended target, the greater the likelihood that the drug will evoke the intended physiological mode of action and less the likelihood that the drug will evoke an adverse effect by acting at ‘off’ targets.
Dose
- a specified quantity of drug administered once or at stated intervals. Doses can be relative to body weight (e.g., mg/kg).
From the dose-response curve, we can estimate the …..
ED50 (note, not the EC50!).
what is drug specificity
- To be useful, a drug must act selectively for a specific receptor, i.e., it must have a high degree of specificity for the binding site of the receptor.
The Relationship Between Ligand Concentration and Receptor Occupancy. What is the equation.
Hill- Langmuir equation
what is the EC50
Concentration of agonist that elicits half maximal effect
The lower the conc. of the drug the …..the affinity
greater
The lower the Ka that ………..the affinity
greater
describe competitive antagonism
Binding of agonist and antagonist occur at same (orthosteric) site - competitive
competitive antagonism causes a …..shift of agonist conc. response curve with no depression in maximal response
right
describe non competitive antagonism
Agonist binds to normal site and antagonist binds to separate (allosteric) site - not competitive
If both antagonist and agonist occupy sites simultaneously, can activation occur
no
what does an agonist and non competitive antagonist do to the agonist conc. response curve
Depress the slope and maximum response curve, but do not cause a rightwards shift
what does an agonist and competitive antagonist do to the agonist conc. response curve
shifts right but no depression of curve and no decrease in maximal
the disassociation equilibrium constant is …
Ka
the disassociation equilibrium constant Ka is equal to what
the concentration of ligand required to occupy 50% of the receptors
higher pEC50 values indicate what
higher potency
The lower the IC50, the …….
the greater the affinity!
a lower IC50 means the drug is very potent and binds strongly to its target, showing high affinity. It’s like needing fewer strong magnets to hold something in place tightly
the lower the Ki…..
the greater the affinity.
what drug is an antagonist at NET and SERT
Amitriptyline
A + R <—> AR <—> AR*
which bit of this is governed by efficacy
state 2 the activated receptor AR*
A + R <—> AR <—> AR*
which bit of this is governed by affinity
State one the ligand receptor complex AR
………..activates muscarinic acetylcholine receptors which then leads to a contraction of the smooth muscle of the ileum
Carbachol
Carbachol activates muscarinic acetylcholine receptors which then leads to a contraction of the smooth muscle of the ……
ileum
