Lecture 2 Part 1 Flashcards
(26 cards)
name 3 classes of proteins that have been clearly identified as drug receptors
enzymes
transport proteins
structural proteins
enzymes can function as receptors. are they more commonly activated or inhibited by drugs?
give an example
mainly inhibited
DHFR (dihydrofolate reductase) is the receptor for methotrexate (antineoplastic agent)
give an example of a structural protein that functions as a receptor
tubulin = receptor for colchicine.
anti inflammatory agent. tubulin responsible for maintaining cell integrity
give formula for “effect” of a drug
E = Emax * C / C + EC50
what is EC50
the concentration at which you get HALF OF THE MAXIMAL RESPONSE
when spare receptors are present, what does that indicate
means that the drug is very efficient because the maximal possible response that can be produced is accomplished without saturating all of the receptors
what is KD
equilibrium dissociation constant. – the concentration of free drug at which HALF MAXIMAL BINDING IS OBSERVED
KD characterizes the resceptor’s……
affinity for binding the drug
If KD is high……
affinity is LOW
what is BMAX
total concentration of receptor sites
what is B
drug bound to the receptors
an agonist that is at a concentration equal to KD will be occupying how many receptors
50%
half maximal response will be produced
what do receptor antagonists do
bind to the receptor but DONT ACTIVATE IT - block it
how can antagonists be divided
competitve (reversible) and noncompetitive (irreversible)
true or false
the Emax remains the same for any fixed concentration of competitive antagonist
TRUE, but the EC50 increases and thus the graph shifts to the right
the degree of inhibition produced by a competitive agonist depends on what
the concentration of the antagonist. more antagonist = more inhibition and more agonist is needed to achieve the same effects
phenoxybenzamine is what kind of antagonist
irreversible
explain how competitive antagonists are called reversible
by increasing the concentration of the agonist, the antagonist can be displaced
true or false
the Emax changes in the case of irreversible antagonists
true
HOWEVER, EC50 may not change
explain how phenoxybenzamine is an irreversible antagonist
used to control hypertension. covalently binds alpha-adrenoceptor in tumor of adrenal medulla to prevent catacholamines
the duration of action of an irreversible antagonist is mainly dependent on what
the rate of turnover of receptor molecules (and NOT its own rate of elimination)
this is bc once the antagonist occupies the receptor it doesnt have to be present in unbound form to inhibit agonist responses
what do alpha-adrenoceptors bind to?
catecholamines which act as agonists to increase blood pressure.
phenoxybenzamine prevents this by binding to the alpha adrenoceptors and thus preventing the catecholamines from binding
true or false
when bound, phenoxybenzamine will NOT be displaced from the receptor by the catecholamines
TRUE
not all methods of antagonism involve the interaction of drugs/endogenous molecules at a single type of receptor.
explain
there are chemical and physiologic antagonists
in chemical antagonists, 1 drug antagonizes the action of a 2nd drug by binding to and inactivating the drug
physiologic: the pancreas produces insulin to lower blood sugar. glucocorticoids work to INCREASE blood sugar by blocking the action of insulin
