drug receptor interactions Flashcards
what is an agonist ?
a drug or molecule which binds to the receptor will induce a pharmacological response.
◦ on the graph, as the concentration of the agonist increases, the pharmacoloigcal response increases, as agonists bind to the receptor inducing a response, and the more you increase the agonist the greater the pharmacolgical response.
◦ it will plateu . ie even if you continue to increase the agonists, the pharmacaological response will not increase.
what is an antagonist ?
the drugs will bind to the receptors, but will not induce a pharamacoloigcal response
◦ on the graph, even if you start increasing the concentration of the antagonist, the response will remain zero.
what is an antagonist + agonist ?
the antagonist will reduce the pharmacological activity of the agonist.
◦ ie if there is an agonist that binds to the receptor to induce a pharmocological response, and you start adding the antagonist, the antagonist will bind to the receptor and displace the agonist. since the antagonist doesnt induce activation, it will reduce the activity of the agonist. it blocks the effect of the agonist.
what is an inverse agonist
a drug that produces an opposing pharmacological response to that observed by a full agonist.
◦ e.g instead of contraction of the muscle, it will relax the muscle.
define affinity
- affinity is the measure of how tightly or loosely the drug binds to the receptor. does not affect the pharmocoloigcal response.
- some drugs can bind really tightly but does not induce a pharmocological response, e.g an antagonist.
define efficacy
• the ability of a drug to induce a pharmocological response
describe the affinity and efficacy of antagonist ?
• anatgonists have a high affinity but low efficacy.
how do drugs bind to receptor
• the drug will interact and bind to a specific pocket of the receptor. this interaction can have a high or low affinity.
• often have weak affinity so agonists often dissociate from the receptor. so there is binding to the receptor and then they dissociate.
• affinity depends on the bonds formed between the receptor and agonist. strong bonds - binding strong, weak bonds - binding weak.
• weak bonds
◦ hydrogen bonds, ionic bonds and van der waals forces.
◦ most common and there is reversible binding dissociation. ie the agonist will dissociate from the receptor.
• stable strong bonds
◦ covalent bonding
◦ irreversible binding, poor dissociation. binds for a long period of times. rare
• this explains why binding is reversible.
why is a drug receptor interaction reversible ?
his interaction is reversible because there are usually weak bonds between the agonist and receptor and so will dissociate.
what is the reversible binding of an agonist governed by ?
law of mass action
what does the law of mass action mean
low a conc - low ar interactions
as drug concentration increases, more receptors will be occupied so more drug-receptor complexes are being formed. it will eventually reach saturation.
free free receptors, so the reaction reaches maximal.
There is a maximum number of AR interactions due to finite number of receptors. Even if you increase the concentration of drugs, no more receptors will be occupied
what kind of plot can you identify Bmax and kd from
saturation binding curve
define Bmax
Bmax is the maximum amount of receptors bound by the drug.
define Kd
Kd is the amount of drug required to occupy half the receptors, its inversely coordinated with affinity. measurement of concentraion.
what does a small kd mean
• if there is a smaller Kd, the drug binds tightly to the receptor, and will require a smaller amount of the drug to achieve 50% of the Bmax.
what does a large kd mean
• if there is a larger Kd, the drug binds weakly to the receptor and so will require larger amounts of the drug to achieve 50% of the the Bmax.
why are there a maximal number of AR interactions ?
• There’s a maximal number of AR interactions due to a finite number of receptors.
what is kd a measure of
• kd is inversely correlated with affinity. the lower the kd, the higher the affinity.
what are the 3 characteristics given by a dose response curve?
• threshold conc is the minimum concentration of drug required to induce any pharmacological response.
ec50 - effective concentration giving 50 percent of the max biological response. depicts potency of the drug, the higher it is, the lower the potency
• The maximal biological effect : all drugs have a maximum pharmocological response that they can induce even if increase the concentration of the drug. this is known as efficacy
if drugs have the same efficacies what does this mean
they have the same max biological effect
draw a graph with 4 drugs that have the same efficacies and different potencies. explain why
x
do you need full occupancy to give a maximum response ? explain your answer
You do not need full occupancy to give a maximum response.
remember : receptors amplify signals, so only a small number of drug-receptor interactions can produce biogical effects.
give an example of a partial agonist
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.
describe the action of buprenorphine
◦ Heroine is really addictive because it binds to the opioid receptor with high efficacy and induces a sense of reward.
◦ if you take people of heroine they will go through withdrawal e.g pain
◦ solution : buprenorphine another opioid drug.
◦ it is a partial agonist with high affinity to the opioid receptor and because it has a higher affinity than heroine, so it will displace heroine from its bindng site. instead of heroine binding to the opioid receptor, there is the buprenorphine binding to the receptor.
◦ it is a partial agonist so it will induce a pharmacological effect ( rewarding) but the pharmocological effect is not as high as heroine. not as rewarding
◦ it is important that buprenorphine has a rewarding effect to reduce any withdrawal symptoms. the partial efficacy is enough to reduce withdrawal symptoms. an antagonist would have percipitated withdrawal symptoms whereas bphine would reduce.