Lecture 6 Part 1 Flashcards
Once a drug is bound to its receptor, what can happen?
it can elicit 2 types of responses:
-agonist action (stimulant effect)
-antagonist action (block the activity)
true or false
if a drug has a stimulating effect, it has agonist action
true
true or false
if a drug blocks activity, it has agonist action
FALSE – antagonist action
what was one of the 1st proposed theories of drug-receptor interaction and subsequent events?
who proposed it?
the occupancy theory - tissue response is proportional to the number of receptors occupied
proposed by Clark and Gaddum
according to the occupancy theory proposed by Clark and Gaddum, more receptors occupied =………
greater activity
according to the dose response curve for acetylcholine, as the concentration of Ach increases, what happens?
the % response (% contraction of rat jejunum) increases until its flattened out
as mentioned, in the dose response curve for acetylcholine, as the concentration of acetylcholine increases, the % response increases until its FLATTENED OUT.
according to the occupancy theory, what is going on at this point where the curve is flattened out?
all the receptors are occupied at this point
HOWEVER, it is now known that only a small fraction of receptors (not all) need to be occupied to obtain this maximal, flattened out response
true or false
the muscarinic effects of acetylcholine cause the contraction of smooth muscle
true
scenario: analogues of acetylcholine are able to contract smooth muscle to the same degree as acetylcholine, but HIGHER DOSES are required to produce the SAME EFFECT.
these analogues are said to possess……..
the same INTRINSIC ACTIVITY as acetylcholine (because they all can reach the same maximum) but LOWER AFFINITY for the receptor (because higher doses are required to produce the same effect)
how can affinity of acetylcholine analogues to their receptor be estimated?
by comparing the concentration of drug required to produce the pharmacological response equivalent to the conc required by a STANDARD DRUG (typically, the dose required to produce a 50% response is compared)
why is the %response of 50% used to estimate the affinity of a drug to its receptor?
at a % response of 50%, the sigmoidal curve is usually linear and thus easier to identify
what does EC 50 mean
half maximal effective concentration
halfway between the baseline and maximal effect
the occupancy theory was modified how and by whom
Ariens and Stephenson modified the occupancy theory to include the antagonists.
they divided the drug-receptor interaction into 2 steps:
- Combination of drug and receptor (initial affinity)
- Production of effect (intrinsic activity)
true or false
only agonists may have structural features that contribute to drug-receptor affinity, but ANY DRUG possesses the intrinsic activity
FALSE
any drug may have structural features that contribute to drug-receptor affinity, but ONLY AGONISTS possess the intrinsic activity
identify the type of drug
Shows decreased response. This is attributed to a decrease in intrinsic activity. The affinity for the receptor may increase, decrease, or remain equivalent
PARTIAL AGONIST
explain what partial agonists are
they’re able to have the same, increased, or decreased affinity to the receptor, but it shows a decreased response – only partial efficacy. (decrease in intrinsic activity)
name the type of drug
No response. the drug is either inactive or it is an antagonist
type of drug cannot be identified with a dose response curve.
need different methods to identify if binding or not – add something that’s known to bind, see if you get displacement. isotope labeling is another technique
identify the type of drug
as the concentration of drug increases, the response increases until it flattens out and there is no further response
agonist
identify the type of drug
Gives same maximal response, but higher dose is required to get the maximal response
it is an agonist (bc it can produce same maximal response) with LOWER AFFINITY
true or false
an agonist with lower affinity as different intrinsic activity than the original agonist
FALSE – same intrinsic activity, but lower affinity for the receptor
true or false
if a drug is found to be inactive/an antagonist from a dose response curve, more information is needed to confidently determine if the drug is inactive or an antagonist
true
who introduced the rate theory for drug-receptor interactions?
peyton
according to the rate theory, if a drug has a fast forward reaction with the receptor (binding) and a slow reverse reaction (unbinding), the drug is a __________
antagonist
according to the rate theory, if a drug has a fast forward reaction with the receptor (fast binding) and a fast reverse reaction (fast unbinding) the drug is a __________
agonist
who proposed the macromolecule Perturbation theory?
belleau
the Macromolecule Perturbation Theory is meant to explain what?
the agonist, partial agonist, and antagonist nature of drugs
explain the macromolecule perturbation theory
the interaction of drugs with receptors (macromolecules) can produce:
-SCP (specific conformational changes)
-NSCP (nonspecific conformational changes)
-SCP + NSCP
if a drug binds to its receptor and causes SCP, it causes activity is an agonist
if it causes NSCP, it has no activity and is an antagonist
if both, it is a partial agonist
true or false
NSCP (non specific conformational changes) are not productive
true
the rate theory was used to explain what that the occupancy theory could not explain?
an initial “spike” in drug response that then settles down and levels off
initial spike occurs before equilibrium is reached
the drug-receptor interaction is complicated and often times involves…..
a second messenger
who modified the occupancy theory?
ariens and stephenson – included the antagonists.
drug-receptor interaction in 2 steps:
1. combination of drug and receptor (initial affinity)
2. production of effect (intrinsic activity)
true or false
antagonists can have the same affinity as agonists
TRUE – antagonists just do not have intrinsic activity (production of effects), but they can bind to the receptor with the same affinity
if size of the drug fits between agonist and antagonist, what can happen?
SCP and NSCP can flip back and forth — partial agonist
