7. Drugs and Receptors Flashcards
For drugs, why is molarity, mol/L, more important than concentration in g/L?
The CONCENTRATION of drug molecules around their site of action is critical in determining drug action.
Molarity (mol/L) gives a measure of the concentration of molecules.
Different substances have different MOLECULAR WEIGHT so drugs of same g/L will have different numbers of molecules.
What is meant by a drug’s affinity for a receptor?
Affinity is a measure of how LIKELY a drug is to BIND with a receptor.
What is the difference between a drug’s efficacy and its intrinsic efficacy?
Once bound to the receptor:
The drug’s INTRINSIC EFFICACY is its ability to ACTIVATE the RECEPTOR.
The drug’s EFFICACY is its ability to cause a RESPONSE in a CELL or tissue. Thus efficacy is itself composed of:
a) INTRINSIC EFFICACY (ability to activate receptor)
b) CELL/TISSUE FACTORS (e.g. post receptor events, receptor number, etc.)
Do all ligands (or drugs) have affinity and efficacy?
NO
a) AGONISTS have BOTH affinity and efficacy
(bind to and activate receptor, causing a cellular response)
b) ANTAGONISTS have ONLY affinity
(bind to but do not activate receptor thus no cellular response)
What is a radioligand?
Radioligands are radioactive forms of ligands.
They are used to MEASURE BINDING (i.e. AFFINITY).
Define dissociation constant.
Dissociation constant (Kd) is the CONCENTRATION of drug required to occupy HALF of all of the available receptors (Bmax).
Kd is INVERSELY proportional to AFFINITY.
What is Bmax?
Bmax is the MAXIMUM BINDING CAPACITY which is the level of binding achieved when the ligand (drug) is added in excess.
Bmax gives an indication of the NUMBER OF RECEPTORS.
What is the difference between concentration and dose?
CONCENTRATION is the quantity of substance per volume of space.
With regards to drugs:
a) CONCENTRATION is the KNOWN quantity of drug per volume at the SITE OF ACTION.
b) DOSE is a measure of a drug (e.g. mg/kg) ADMINISTERED to a patient, when the concentration at the site of action is unknown.
What is potency?
Potency is a measure of the AMOUNT of drug required to produce an effect of GIVEN AMPLITUDE.
It is determined by:
a) AFFINITY
b) INTRINSIC EFFICACY
c) CELL/TISSUE FACTORS
(note: (b) and (c) constitute efficacy)
What are EC50 and IC50?
EC50 and IC50 are measures of POTENCY.
EC50 is the EFFECTIVE CONCENTRATION of an AGONIST which produces 50% of maximal possible effect of that agonist.
IC50 is the INHIBITORY CONCENTRATION of an antagonist going 50% of maximal inhibition.
What is functional antagonism and why is it preferable?
FUNCTIONAL ANTAGONISM involves ACTIVELY producing an OPPOSITE ACTION to counteract an effect, instead of directly antagonising the receptor which may be involved in the problem.
It is preferable because we may not know exactly which receptors are involved in the disease process, but we know which receptors can be activated to oppose this process.
Salbutamol and Salmeterol are both used to treat asthma. Describe their selectivities?
SELECTIVITY describes how specific a drug is to the target (receptor).
Selectivity to B2 adrenoceptors is required because B1 adrenoceptor agonism can dangerously increase force and rate of contraction of the heart.
a) SALBUTAMOL:
- little selective affinity
- selective efficacy
- selective route of administration (except when given IV acutely - thus increases heart rate)
b) SALMETEROL:
- much selective affinity
What are spare receptors?
SPARE RECEPTORS are receptors which are in excess of that required to be occupied to deliver the MAXIMUM RESPONSE.
Spare receptors increase the SENSITIVITY therefore allow responses at LOWER CONCENTRATION of agonist.
With regards to drugs, what are the THREE types of antagonist?
- REVERSIBLE COMPETITIVE antagonist
- IRREVERSIBLE COMPETITIVE antagonist
- NON COMPETITIVE antagonist
