Pharm - Lecture 2 Flashcards
What is affinity?
An equilibrium state; the concentration of the drug that occupies 50% of the receptors is equal to the affinity; Affinity = K subD; Aff = k sub12/ k sub1; Aff is NOT EC50
What are k sub1 and k sub2?
K sub1 = the rate of approach (of drug to receptor); k sub 2 = the rate of dissociation
When affinity increases the numeric value of the constant (K subD) does what?
Decreases
Re: k sub1 and k sub2, which tends to remain constant for all drugs?
k sub1
As k sub2 decreases we say that…
affinity increases/is high(er)
What units is K subD expressed in?
molar units (typically, nM)
All binding curves will look like what?
A sigmoidal function
Law of mass action
Y = [D]/(K sub D + [D])
Affinity refers to the binding behavior of ligands and receptors; efficacy refers to what?
The subsequent biological response/effect
Is the relationship between biological response and the # of receptors occupied linear?
No [flesh this out more]
What is potency
The concentration of drug at which you get half of the maximum biological response
EC50 is what?
EC50 = numeric value of potency
What is a high efficacy agonist?
EC50
Who proposed that the EC50 = K subD
AJ Clark
What AJ clark correct?
No
What’s “in between” the EC50 and K subD?
Signal transduction (the strength of the cranking?)
What’s another name for a high efficacy agonist?
a super agonist
What’s another name for a low efficacy agonist?
a partial agonist
What is a low efficacy agonist?
EC50 > K subD; An agonist (a drug) that only approaches/achieves the EC50 at higher concentrations than would be predicted if the relationship between the binding curve and the efficacy curve was 1 to 1 (i.e., equal to K subD)
intrinsic efficacy
[UC]
clinical efficacy
[UC]
what is an antagonist?
A drug that has no INTRINSIC efficacy (but can have high clinical efficacy); but has high affinity; will block the response of exogenous (e.g., other drugs) and endogenous (i.e., neurotransmitters) agonists; their ability to do so is related to dose (i.e., concentration of antagonist)
What NT operates at the neuromuscular junction?
acetylcholine; on nicotinic-acetylcholine receptors
Where does curare act? How? To what result?
At the NM junction; acts as antagonist to acetylcholine; death by suffocation (turns off the diaphragm)
Two difference kinds of antagonists?
Competitive and non-competitive
Is curare comp or non-comp?
competitive
How do you surmount the action of a competitive antagonist? This behavior represented graphically is called what?
increase the concentration of the agonist; parallel shift to the right (of the DR curve)
What’s the difference between comp and non-comp antagonists?
Comp antagonists fight of the same receptor cites; a non-comp antagonist changes the receptor site conformation
Non-comp antagonism results in what kind of change to the DR curve?
There is a downward shift; can’t surmount it
Most drugs are comp or non-comp antagonists?
Non-comp
what is an inverse agonist
negative intrinsic efficacy; for example: suppose have a muscle tissue prep, with agonist the thing contracts, with an antagonist nothing happens (but you need more agonist to get the response you want), with an inverse agonist the thing relaxes below baseline level of activity
