Drug receptor interactions Flashcards
How many of the top drugs on the market target G-protein coupled receptors?
34 of top 100
What is an agonist drug?
drug that binds to a receptor and elicits a biological process
What is an antagonist drug?
Drug that blocks the action of an agonist compound: commonly binding to a receptor without eliciting a biological response
What is a partial agonist drug?
An agonist drug that produces a biological effect but never the maximal of which the tissue is capable-posses antagonist properties
What is an inverse agonist drug?
Agonist that produces an opposing biological response to that observed by a full agonist
What is affinity?
Ability of a drug molecule to bind to a receptor site
What is efficacy?
Ability of a drug to elicit a biological response from a drug receptor interaction
What is occupation governed by?
Affinity
What is activation governed by?
Efficacy
How do most agonists bind to receptors?
Reversibly
Why do most agonist bind reversibly?
Relatively weak attractions such as Hydrogen bonding, ionic bonding and van der waal’s forces between the receptor and agonist, therefore easy dissociation
How do some agonist bind to receptors in rare cases?
Irreversibly
Why do agonist rarely bind irreversibly?
Interactions between receptor and agonist are by stable strong bonds such as covalent bonds. These are relatively strong therefore have poor dissociation
What is the B-max?
Maximum amount of receptors the drug can bind to
What is the Kd?
Amount of drug needed to occupy half the number of maximum receptor
What is the relationship between kd and affinity?
The higher the Kd, the lower the affinity
Does each drug have its own unique Kd value?
Yes, each drug has its own kd
What is the law of mass action dependent on?
Dependent on the concentration of the reactants involved
What is the law of mass action?
Rate of a chemical reaction is directly proportional to the product of the activities or concentrations of the reactants
What are the predictions the law of mass makes?
Low[A]- Few AR interactions
Increase[A]- More AR interactions
Continue to increase[A]- Few Rfree, reaction reaches maximal
The points on increase in biological affect against Log[A]
(a)Threshold concentration
(b)EC50=effective concentration giving 50% biological response
Used to compare drug potency
(c)Maximal concentration
Why is the threshold concentration, EC50 and maximal concentration important values?
They’re important for determining drug doses
Is affinity and efficacy equal?
No these values are not equal as full occupancy is not required to give a maximum response
What do receptors do to signals?
Receptors amplify signals so only a small number of drug-receptor interactions produce biological effects
Where are partial agonists present and what is there affinity and efficacy like?
Present at receptors-high affinity, low efficacy
What do partial agonists reduce?
Reduce withdrawal effects
Reduce additive highs
Heroin-induced highs are reduced in the presence of partial agonist
What do receptors only bind?
Receptors only bind agonists or antagonists
What do agonist and antagonist do in competitive antagonism and how do they bind?
Agonist and Antagonist compete for same binding site
Agonist and antagonist both bind reversibly
What is competitive antagonism dependent on?
Dependent on two equilibrium constants, KA and KAnt
If Kantagonist
Agonist has greater affinity for receptors than agonist
How can the binding of antagonist to receptors be overcome?
Increasing the concentration of agonist
Reponse against Log[A[
- In presence of antagonistic concentration- effect of curve is shifted to the right
- Shift to right is linearly related to concentration of antagonist
- Linear part of the curve is parallel
- Same maximal response is obtained-if you increase concentration of agonist you will outcompete antagonist
What happens during an overdose?
- Receptors overloaded and the pharmacological effect exceeds high
- This results in respiratory depression
- Eventually leading to death
What is non-competitive antagonism and how does it work?
- Antagonist binds to a different site from the agonist
- Causes 3D shape of the receptor to change and this will therefore not allow agonists to bind
- Fewer number of receptors available for agonist to bind to
- This blocks the pharmacological effect
What is irreversible antagonism and how does it work?
- Antagonist bind irreversibly to either agonist or non-agonist binding sites on receptors through covalent bonds
- Reduces number of receptors the agonist bind to
- There is still a pharmacological affect however the maximum response is reduced a lot compared to agonist alone
How does asprin work to inhibit COX activity?
- Acetylsalicylic acid’s acetyl group forms an irreversible covalent bond with active site of enzyme
- This blocks the receptor site and inhibits COX activity.
