Receptor basics and mechanisms Flashcards
What is tissue selectivity?
Certain tissues exhibit certain receptors, hence why different drugs disproportionately affect different tissues
What is chemical sensitivity?
Only specific drug structures bind to receptors
What is amplification?
Small number of drug/receptor interactions initiate significant biological effects
Define agonist
Drug which binds to a receptor to produce a biology cellular response, therefore have affinity and efficacy
Define antagonist
Drug which binds to a receptor but does not produce a biological cellular response- antagonists bind to receptors and prevent agonists producing effects, therefore these only have affinity
Define affinity
The extent or fraction to which a drug binds to receptors at any given drug concentration
Define efficacy
Ability to initiate a physiological response through interaction with the receptor
Is binding to receptors reversible or irreversible?
Reversible, as most agonists and antagonists bind reversibly, as their they bind to their receptor and then dissociate from it
What is KA?
- Measures affinity
- KA is the affinity at equilibrium, and assesses the affinity of an agonist to a receptor
- Every drug has its own KA value
What does a smaller KA mean?
- The agonist has a greater affinity for a receptor than a drug with a higher KA value. This is because the KA value will show fewer free receptors, meaning most are bound to a agonist-receptor complex.
What is EC50?
- Measures efficacy
- Half maximal effective concentration, describes how well an agonist produces an action assessed by the effective concentration producing 50% of a maximal response.
- Assesses how well an agonist produces an action.
- This value can be used to compare drug potency
What is drug potency determined by?
- Affinity and Efficacy
Affinity (KA) and efficacy (EC50) of an agonist are not…?
Equal, as you don’t need full occupancy of receptors to produce a maximum response
Why don’t receptors need to be full to produce a maximum response?
- This is because receptors amplify signals, so only a small number of drug receptor interactions produce biological effect, hence why drugs work at such low concentrations
What is the effect of competitive antagonism on concentration-response curves?
Antagonist binds to and competes at the same site as the agonist, as both antagonist and agonist compete for the same receptor binding site
Curve shifts to right, as EC50 will increase due to great concentration of agonist needed to have greater affinity than antagonist. Maximal biological response is unchanged.
What are receptors?
- Molecular structures (mainly proteins) that receive input and produce an effect through activation of single transduction pathways
- Are associated with the plasma-membrane and permit communication between the outside and inside of a cell- although some are found inside the cell
- Receptors recognise endogenous chemicals (naturally occurring such as neurotransmitters) and also recognise and bind to drugs
What happens when a chemical signal reaches a receptor
- Chemical signal binds to receptor
- This causes a change in receptor protein conformation
- Signal transduction
- Cellular response
What are the 4 types of receptors?
- Ligand- gated receptors
- G-protein coupled receptors (GPCRs)
- Tyrosine kinose receptors
- Intracellular/ nuclear receptors
What happens when an agonist binds to a receptor?
It produces an agonist receptor reaction, leading to a conformation change in receptor allowing it to initiate a biological response in the cell.
What bonds can drugs form with receptors?
- Hydrogen bonding
- Ionic bonding
- Van der Waal’s forces (London forces)
- Covalent bonding
What bonds allow for easier reversible binding and good dissociation and why?
Hydrogen, ionic and van der waal’s due to their forces being relatively weak
What bond leads to irreversible binding and poor dissociation?
Covalent bonding due to its strong stable bonds