Drug Receptor Interaction Flashcards
What are the main receptor terms?
Agonist- A drug that binds to a receptor and elicits a biological response
Antagonist- A drug that blocks the action of an agonist compound: commonly by binding to a receptor without a biological response
Partial agonist- an agonist drug that produces a biological effect, but never the maximal of which the tissue is capable- partial agonists is possess antagonist properties
Inverse agonist- an agonist that produces an opposing biological response to that observed by a full agonist
Affinity- ability of a drug molecule to bind to a receptor site
Efficacy- ability of a drug to elicit a biological response from a drug receptor interaction
What happens when you use an agonist and an antagonist together?
An agonist and an antagonist used together result in less activation; similar to the effect of a partial agonist
What is an agonist like?
An agonist has both affinity and efficacy
Occupation governed by affinity
Activation governed by efficacy (A)
How do agonists bind to receptors?
Most agonists bind reversibly to their receptors
Agonist binds to receptor then dissociates
What are the different types of binding?
Hydrogen bonding, ionic bonding and Van der Waal’s forces- all are relatively weak resulting in reversible binding dissociation
Covalent binding are stable strong bonds resulting in irreversible binding and therefore poor dissociation
What determines drug affinity?
Reversible binding of an agonist to a receptor is governed by the Law of Mass Action
dependent on concentration of the reactants involved
Agonist- A
Receptor- Rfree
Agonist-receptor complex- AR
Association rate- K1
Dissociation rate- K-1
What does the Law of Mass Action predict?
Low [A]- lots of Rfree- few AR interactions
Increase [A]- more AR interactions- reaction driven to right
Continue increasing [A]- few Rfree- reaction reaches maximal
Bmax is the maximum amount of receptors bound by the agonists
Each drug has its own Kd value
Kd is a measure of affinity; concentration of the drug where 50% of the max. number of receptors are bound by the drug
Kd (affinity) is the ability of a drug molecule to bind to a receptor site
Kd is inversely correlated with affinity
The lower Kd the higher the affinity
What determines efficacy?
Similar principles to affinity but different measurement
Efficacy is the biological effect e.g. increase in heart rate
Pull graph up
a- threshold concentration; minimum concentration to induce an effect
b- EC50; effective concentration giving 50% biological response (the higher EC50 the lower the potency)
c- maximal biological effect (efficacy)
Potency refers to the concentration of the drug needed for the effect; the less concentration required, the more potent
What are partial agonists?
Partial agonists- e.g. Buprenorphine for opioid addiction
Present at receptors- high affinity but less efficacy
Reduces withdrawal effects
Reduces additive ‘highs’
Heroin-induced highs are reduced in presence of partial agonist
What is competitive antagonism?
Receptors only bind either Agonist (A) or Antagonist(AR)
A and Ant both bind reversibly
[A] must increase to overcome Ant binding to receptors
In the presence of the Ant concentration- effect of curve is shifted to right
Shift to right is linearly related to [Ant]
Linear part of curve is parallel
Same maximal response is obtained- if you increase [A] you will ‘out-compete’ the antagonist
This is called ‘surmountable’ antagonism
What is ‘non-surmountable’ antagonism?
Also known as non-competitive antagonism
Ant binds to a different site from the agonist e.g. ketamine blocks glutamine receptors by acting at a different site in the receptor structure to glutamate
What is Naloxone?
Naloxone is a competitive antagonist that competes with heroin in order to reverse an overdose
