Flashcards in Pharmacodynamics (session 6) Deck (29):
How do drugs exert an effect?
By binding to a target
True or false: the concentration of drug molecules around receptors is critical in determining drug action
True or false: most drugs bind irreversibly to receptors
FALSE - reversibly
What does a ligand need in order to bind to a receptor?
Affinity for the receptor
What is the ability to generate a response called?
What is intrinsic efficacy?
The ability to switch a receptor on
What is the difference between agonists and antagonists?
Agonists have intrinsic efficacy and efficacy
Antagonists have affinity only (no efficacy or intrinsic efficacy)
How do we measure drug-receptor interactions by binding?
By binding of a radioactively labelled ligand (radioligand) to cells or membranes prepared from cells (many cells/many receptors)
What is Bmax?
Maximum binding capacity (info about receptor number)
What is Kd?
Dissociation constant-index of affinity, tells you about the strength of the interaction. Concentration of ligand required to occupy 50% of the available receptors
What does a low value of Kd mean?
What is EC50?
Effective concentration giving 50% of the maximal response - measure of agonist potency
What does EC50 depend on?
Affinity and intrinsic efficacy and cell/tissue-dependent factors such as the number of receptors
What effect do beta2-adrenoceptors have on asthma?
Relaxation of airways
Why is it hard to design a drug that only targets beta2-adrenoceptors?
The binding site for beta1 and beta2 are very similar
What is sensitivity?
Concentration of ligand that causes a response
Why have spare receptors?
Increase sensitivity to a ligand-allows responses at low concentrations of agonist
Why do morphine doses have to be increased, even if the pain is the same?
System becomes less sensitive
Give an example of a full agonist
What is the relevance of partial agonists? (3)
1. Can allow a more controlled response
2. Work in the absence or low levels of ligand
3. Can act as an antagonist if there are high levels of full agonist
What is an example of a partial agonist and what is its clinical implication?
Opioids - for pain relief but cause respiratory depression (can lead to death as it inhibits respiration)
What is buprenorphine used for clinically?
To enable gradual withdrawal of morphine and prevent use of heroin
What does reversible competitive antagonism rely on?
Dynamic equilibrium between ligands and receptors - increasing concentration of antagonist leads to antagonist out competing agonist and response is inhibited
What is IC50?
Concentration of antagonist giving 50% inhibition
Naloxone is a high affinity, competitive antagonist at mu-opioid receptors. Why might such a compound be useful clinically?
Reversal of opioid-mediated respiratory depression-high affinity so it will compete effectively with other opioids (eg heroin) for receptors
When does irreversible competitive antagonism occur?
When the antagonist dissociates slowly or not at all
What is the difference between reversible and irreversible competitive antagonism?
Reversible is surmountable (adding more agonist nullifies the effect of the antagonist) whereas irreversible is non-surmountable
What is the site where endogenous ligands bind to a GPCR called?