9 Pharmacodynamics Flashcards
What is an agonist and what do they require for it to function
Drugs activating the receptor
-Affinity for the receptor
-Intrinsic efficacy
What is an antagonist and what do they require for it to function
Drugs binding to receptor and blocking the binding of their ligands (exo/endogenous)
-Affinity for the receptor
How is binding measured? Give an example
Calculate the amount of (radio) ligand bound specifically to the receptor
e.g.) binding of fluorescent compounds
Difference between pharmacological efficacy and clinical efficacy
Pharmacological efficacy: The ability to activate a receptor and cause conformational change
Clinical efficacy: An indication of how well treatment succeeds in achieve in its aim
E.g.) does this drug lower BP
What is Kd and what does a lower value of this suggest
Index of affinity of the drug for the receptor
(half of Bmax)
Lower value = Higher affinity
-Lower conc. required to occupy 50% of receptors
E.g.) Drug A: Kd= 10^-9, Drug B: Kd=10^-3 (Both lnM)
Which has a higher affinity ?
Drug AA has a higher affinity
When is response against agonist be seen
-change in signalling pathway
-change in cell/tissue behaviour
e.g.) contraction
Response required drug efficacy (agonist)
What is the importance of affinity to ligands in pharmacological context ?
Give an example
High affinity allows binding at low conc. of hormones, neurotransmitters
e.g.) Opioid overdose used to be treated by naloxone since it is a high affinity antagonist of m-opioid receptors and outcompetes opioid
What is the relationship between the proportion of bound receptors and drug conc.
The proportion of bound receptors is logarithmically changing as the drug conc. increases
NOT linear
What is drug POTENCY and what does it depend on
How much drug you require to cause a response
It depends on
-affinity
-intrinsic efficacy
-cell/tissue -specific components (opening the door)
What is Bmax
Max. binding capacity of a receptor
(half of Bmax is EC50)
What is Emax
Max. threshold rate that a drug can act on a receptor
What is EC50
Drug Potency
-effective conc. giving 50% of the max. response
Difference between dose and concentration
Dose: Conc. at the site of action, generally unknown
E.g.) dose to a patient in in mg/kg
Conc.: known conc. of drug at site of action
What is the difference between selectivity and specificity in terms of ligand-receptor complexes
Specificity: The preference of a ligand for one specific receptor
Selectivity: The preference one a ligand for a receptor over another
How is selectivity/specificity achieved in drugs against asthma
Salbutamol:β2- selective efficacy
Salmeterol: no selective efficacy, selectivity based on affinity (β1-↑rate of heart contraction)
β2-adrenoreceptors opens up airways.
Salbutamol is a more suitable drug since it has selective efficacy to act on β2 than β1
Relationship between agonist affinity and agonist potency
Expectation: 100% binding, 100% response
Commonly seen: 50% binding, 100% response
The difference is caused by spare receptors
What does it mean when EC50 is less than Kd
There are spare receptors
-often seen when receptors are catalytically active e.g.) GPCR
Why do spare receptors exist
-Amplification in the signal transduction pathway
-Response is limited by a post-receptor event
What is the importance of spare receptors
Increase sensitivity/potency and allow responses at low. conc of agonist
What does the receptor no. depend on
-cell type
-level of activity
(low: increase in cell type, high: decrease in cell type)
What is intrinsic activity and how is it measured
Difference between full agonist and partial agonist
Full agonist: (often endogenous)
Partial agonist: lower intrinsic activity due to lower efficacy
What does partial agonist depend on
-ligand type
-receptor no.
