Lecture 17 And 18 Flashcards
(24 cards)
What is an orphan receptor?
One for which its ligand is not known
What is a ligand?
Something that binds to a receptor eg drug or hormone
Why is molarity of ligand important to use?
Concentration is most important measurement for drugs and their targets. Two samples of drug that are the same weight can have different molarities
What is intrinsic efficacy?
Ability of an agonist to activate a receptor after it has bound to it.
What is efficacy?
A measure of the ability of a ligand to cause a physiological response. Efficacy is governed by intrinsic efficacy and other factors that influence the response.
How is ligand binding measured?
Using radioactively labelled ligand. Can measure proportion of bound and unbound receptors and calculate Kd.
What is Kd?
Measure of ligand affinity for receptor
What is EC50?
Measured from a concentration response curve it acts as a measure of drug efficacy and potency is indicated by the EC50 value.
What does potency depend on?
Both affinity and intrinsic efficacy and cel-tissue dependent factors including the number of receptors available.
What is a cell tissue dependent factor when it comes to drug action?
Receptor number- often less than 100% receptor occupation will give 100% response and this is due to spare receptors being present. Not all receptors need activation to get full response.
Why do we see spare receptors?
Allow amplification in signal transduction
Response can be limited by a post receptor event
What is the advantage of spare receptors?
Allow for increased sensitivity
For example if 20,000 receptors and 10,000 of them spare then only Kd concentration required to elicit a maximal response.
How can changing tissue receptor number affect agonist potency and maximal response?
If 100,000 receptors only 10% occupancy for full response.
If 10,000 receptors 100% occupancy for full response
If 5,000 receptors 100% occupancy will only give half the response.
How does receptor number change?
Increase with low activity (increased sensitivity)
Decrease with high activity (lowered sensitivity)
What is a partial agonist?
Intrinsic efficacy not as good as its affinity. Doesn’t elicit a full response.
A partial agonist cannot elicit a full response unless there are spare receptors present
Partial agonist use?
Can allow a more controlled response
Can act as an antagonist if levels of agonist are high.
Eg heroin
Role of burprenorphine in heroin addiction
Has a higher affinity so binds better than morphine but is a partial agonist and has lower efficacy. Doesn’t cause respiratory depression.
It or methadone can be used in the management of opioid dependence
Why would a heroin addict who accidentally takes buprenorphine instead become very ill?
Withdrawal or abstinence syndrome and partial agonism.
Withdrawal syndrome- receptor number lowered from taking heroin. It’s absence now means endogenous ligand cant do their job.
Partial agonism- buprenorphine not giving full effect, lowered potency and so withdrawal symptoms
Secondary effect is that after time receptor number will go back up. If patient relapses then original dose will be far too much and very dangerous ( overdose)
What are the three types of antagonism?
Reversible competitive
Irreversible competitive
Non-competitive antagonism
What is IC50?
Concentration of antagonist which gives 50% response.
IC50 will depend on agonist concentration as if more agonist present more antagonist will be required
What is the key thing about competitive antagonism?
It is surmountable meaning that it can be overcome by increasing drug concentration
Why is Naloxone an important drug?
Competitive antagonist at opioid receptors. Can be used to treat respiratory depression in heroin overdose.
What is the key point about irreversible antagonism?
It is non surmountable and if spare receptors used up by it it will reduce the ability to get a maximal response
Non competitive antagonism?
Ligand can bind to allosteric or orthosteric site. Can enhance or reduce effects of agonists.
Similar effects to non competitive antagonism. Need to do further experiments to confirm
