Session 8 Flashcards
(16 cards)
Describe the terms affinity intrinsic efficacy and efficacy
Affinity - the likelihood of a ligand binding to its target
Intrinsic Efficacy - the ability of a ligand to activate a receptor once it is bound
Efficacy - the ability of a ligand to cause a response (intrinsic efficacy plus cell/tissue dependent events).
An antagonist has affinity but no efficacy
How are drug-receptor interactions measured?
By binding of a radioligand
What is the name and symbol given to:
The concentration of ligand that a receptor has 50% occupancy
The maximal binding capacity of a receptor
And what is the use of each?
Kd, dissociation constant. A measure of affinity.
Bmax, maximum binding capacity. A measure of receptor number.
What is the name and symbol given to:
The effective concentration of ligand giving 50% of the maximal response
The maximal response of a receptor
And what is the use of each?
EC50, a measure of potency. It is governed by affinity and efficacy.
Emax, maximal response
What is IC50?
Inhibitory concentration giving half the maximum inhibition
What is the difference between concentration and dose?
Concentration - known concentration of the drug at the site of action
Dose - when the concentration at the site of action is unknown
Discuss affinity and efficacy of two common drugs used to treat asthma
Salbutamol - B2 agonist. Only 20 fold higher affinity for B2 but utility enhanced by B2 selective efficacy (limits B1 side effects) and route of administration (oral spray).
Salmeterol - longer acting B2 agonist and has a high B2 selective affinity but no selective efficacy (selectivity based on affinity) and is insoluble.
For any ligand-receptor complex what factors can influence potency?
Cell/tissue dependent factors including receptor number (affinity and intrinsic efficacy are fixed)
What are partial agonists and what are their properties?
Agonists that can’t produce a maximal response even with full receptor occupancy. EC50=Kd. They can be more or less potent than full agonists.
They have a lower intrinsic ACTIVITY (related to maximal amplitude of response) and hence lower efficacy.
Why can partial agonists be advantageous?
They can allow a more controlled response, they work in the absence of endogenous ligand and can act as an antagonist if high levels of the full agonist is present.
Explain the concept of spare receptors
In some cases, less than 100% receptor occupancy will give maximal response (EC50
Explain a clinical use of a partial agonist
Buprenorphine has a higher affinity but a lower efficacy than morphine - it is a partial agonist of the m-opioid receptor. This can reduce change of respiratory depression whilst still providing pain relief.
Buprenorphine can be used as a gradual a withdrawal from heroin addiction and prevent the use of other opioids by blocking their action.
Give a therapeutic example of a reversible competitive antagonist
Naloxone - high affinity competitive antagonist at m-opioid receptors used to reverse opioid mediated depression
Give a therapeutic example of an irreversible competitive antagonist
Phenoxybenzamine - non selective irreversible A1 adrenoreceptor antagonist used in hypertension episodes in pheochromocytoma (a tumour of the adrenal gland which causes excessive Catecholamine synthesis leading to vasoconstriction.
What are the different types of antagonist?
Reversible competitive antagonism
Irreversible competitive antagonism
Non competitive antagonism (allosteric binding)
Why are allosteric sites useful therapeutic targets?
They provide diversity amongst receptor subtypes.
