Session 8 Flashcards
How do all drugs exert their effects?
By binding to a target, majority are proteins.
Do drugs bind reversibly or irreversibly?
Reversibly with receptors.
What governs drug binding?
Association and dissociation rates.
What is the importance of concentration of drug molecules?
Concentration around the receptor is critical in determining drug action.
Drugs with equivalent molar concentrations have the same concentration of drug molecules.
Drugs with equivalent concentrations by weight may not.
What is the equation for grams per litre?
Molecular weight x Molarity
What is affinity?
The likelihood of a ligand binding to its target
What is efficacy?
Likelihood of activation.
Do Antagonists have affinity or efficacy?
Affinity only.
Do Agonists have affinity or efficacy?
Both.
How can binding information be found out?
By the binding of a radioligand.
What is Bmax?
The maximum binding capacity
What can the Bmax tell you?
The number of receptors
What is Kd?
The dissociation constant and concentration needed for 50% occupancy
What can you measure with the dissociation constant?
Affinity.
What does a low Kd value relate to?
A higher affinity.
When are concentration response curves used?
Measuring a response in cells/tissues.
When are dose response curves used?
When measuring a response in a whole animal.
What is Emax?
The maximum response.
What is EC50?
The effective concentration giving 50% of the maximal response.
It can be used to measure Potency
What is Potency?
Extra point - What governs it?
A combination of affinity and efficacy.
Extra point - The number of receptors.
If an agonist has the same Emax value, will the efficacy be the same? What id the efficacys were different?
Not necessarily. If the efficacys are different then the Emax value will be different.
What is the goal of treatment in asthma?
To activate Beta 2 adrenoceptors to relax the airways.
What is Salbutamol?
A beta 2 adrenoagonist. It is high affinity and Beta 2 selective efficacy. It has side effects and limits Beta 1 activation.
What is Salmeterol?
A longer acting Beta 2 adrenoagonist.No selective efficacy and prevents Beta 1 activation and side effects through difference in affinity only.
When can less than 100% receptor occupancy give 100% response?
When EC50 is smaller than Kd = 50% of the maximal response needs less than 50% of the receptor occupancy.
What effects the relationship between receptor occupancy and response?
It is non linear response and influenced by both transduction system and amplification (produced by second messengers) and properties of the tissue.
How do spare receptors increase the response of a cell?
They increase sensitivity and allow responses at low concentrations of agonists.
What does number of receptors have an effect on?
Potency
What are partial agonists?
An agonist that cannot produce a maximal effect even with full receptor occupancy.
What is the EC50 of a partial agonist equal to?
Kd
How can partial agoniosts be more or less potent than full agonsits?
Because potency is dependent on affinity and efficacy.
Is a partial agonist always a partial agonist?
No, it depends on the tissue and biological response.
Is Morphine a full or partial agonist?
A full agonist.
What is Buprenorphine and why is it used?
It is a partial agonist used for pain relief where possible as it doesn’t have the respiratory depression associated with morphine.
What are the 3 types of antagonists?
Reversible competitive
Irreversible competitive
Non competitive
What is the most common form of antagonism used in therapeutics?
Reversible competitive antagonism. It relies on a dynamic equilibrium between ligands and receptors.
What is IC50?
The concentration of antagonist that gives 50% inhibition.
How can reversible competitive antagonists be overcome?
By high concentrations of agonist so cause a parallel shift to the right of the agonist concentration response curve
What is a therapeutic example of a reversible competitive antagonist?
Naloxone - high affinity to opioid receptors. It is used to reverse respiratory depression caused by opioids.
When does irreversible competitive antagonism occur?
When the antagonist dissociates slowly or not at all. They cause a parallel shift to the right of the agonist concentration response curve.
What do irreversible competitive antagonists cause at high concentrations?
They suppress the maximal response as the spare receptors are filled by the antagonist so not enough are left free to create a response.
Give a therapeutic example of irreversible competitive antagonism.
Phenoxybenzamine is a non selective alpha 1 adrenoceptor blocker used in hypertension episodes in pheochromocytoma.(Tumour of the adrenal gland that released excessive adrenaline –> vasoconstriction)
What is non competitive antagonism?
The allosteric binding of an antagonist to a receptor that IS NOT the ligand binding site.
