Lecture 5 (Drug Receptor Interactions) Flashcards
When we don’t know the endogenous ligand for a receptor it is called an ______ ________
orphan receptor
binding is _____
specific
There is a ____ binding capacity for receptors
finite
- meaning there are only a limited number of receptors
- it is possible for binding to be matured (all the receptors are occupied)
receptors are ___ specific
tissue
Drugs bind to receptors using the same interactions that drugs form with solvents as discussed in lecture 2 on solubility:
What are these interactions?
- dispersion forces (london forces)
- dipole-dipole bonding
- this one is not as important)
- H-bonding (a special kind of dipole dipole bonding)
- ionic bonding
- ion-dipole bonding
For protein interactions - dispersion forces are referred to as ??
hydrophobic interactions
What is KD?
not the delicious cheesy macaroni treat
dissociation constant bitches
-it tells you what side of the rxn that it favours
either free drug and free receptor OR drug-receptor complex
Units of KD?
mol/L or M
if KD is small = ?
there is more DR (and therefore more biological response)
*also indicates tight binding
1/KD = KA = ?
affinity constant
units of KA ?
L/mol or M^-1
higher the affinity constant = ?
tighter the binding
if KD = 1 microM what does this mean?
1 microM [drug] will produce half maximal receptor binding
KD = ?
[drug] at which you get half maximal binding
[drug] at which 1/2 Rt (total receptors) is bound to drug
efficacy
constant of proportionality which measures the ability of the drug to produce an effect by forming a drug receptor complex
Eobs = alpha [DR]
alpha = efficacy (intrinsic activity)
Emax is achieved when ?
Emax = maximal effect
all receptors are mound to the drug
What is ED50?
[drug] and 1/2 Emax
concentration of drug which produces half of the maximal effect
T or F: KD and ED50 have the same value
true man
lower ED50 = ?
more potent
potency is ____ of efficacy
independent
What is an agonist?
-they bind to receptors and have affinity for the receptor which produce an effect (they have intrinsic activity) or response
What is a full agonist?
it binds to the receptor and is capable of producing the same maximal response as the endogenous agonist
What is a partial agonist?
it can bind to the receptor but produces a smaller maximal response.
-therefore it has lower intrinsic activity than a full agonist which is capable of eliciting a maximal response
What is an antagonist?
an antagonist binds to receptors and has affinity for the receptor but has NO INTRINSIC ACTIVITY
-no efficacy (no response)
Describe the spare receptors theory
- it is frequently found that for the same drug KD > ED50
- this means that the maximal effect is still being achieved without binding to all of the receptors
*potential of signal amplification
(see slide 22)
Two most important types of antagonists?
competitive
non-competitive
Describe competitive antagonists
compete for the same binding site as the drug/agonist/endogenous ligand
If antagonists binds = no response
If drug binds = response
Can you overcome a competitive antagonist? If so, how?
Yes you can
-increase amount of agonist
What is competitive antagonism characterized by?
An increase in apparent Kd
OR
Decrease in affinity of drug
Describe non-competitive antagonists
they don’t compete for the same binding site
the Antagonist binds to the Receptor at a different spot than the agonist but even if the drug still binds - it cannot produce a response when the antagonist is present.
Affinity of the drug for the receptor does not change!!!
-it does with competitive antagonists
*reduces maximal efficacy
non-competitive antagonism is characterized by?
reduction in the apparent number of receptors
with non-competitive antagonists … KD = ?
stays the same
Can non-competitive antagonists be overcome with increasing agonist?
NO WAY MAN
-only competitive antagonism can be overcome this way
understand slide 30
kay ma’am
