Basics. Exam 1 Flashcards
A vast majority of drugs function by interacting with _________.
Receptor Proteins
Receptor proteins will interact with drugs and either ______ or ______ their function.
facilitate
block
What kind of drugs will interact with receptor proteins and produce/facilitate an effect?
agonist drugs
What kind of drugs will interact with receptor proteins to block action or function?
antagonist drugs
Receptors act as _________ _______ by binding a drug and sending a signal to the cell machinery in order to produce a physiological effect.
signal transducers
Drugs that actively produce a physiological effect are called _______.
agonists
A binding curve of “drug bound to receptor” vs “free drug concentration” looks like a ___________.
rectangular hyperbola
Having what percent of bound receptor is the limit approached as drug concentration gets very high?
100%
What is the dissociation constant describing drug binding to its receptor?
the concentration of drug providing 1/2 maximal binding
What kind of plots will provide sigmoidal curves that allow a more complete range of data to be shown?
Semilog Plots (drug bound to receptor)
**Log plots show “free drugs”
Describe Langley’s studies in 1878 that led to the origin of “receptor theory.”
Pilocarpine stimulates salivation by the submaxillary gland. Atropine blocks this effect. Langley used a cat’s submaxillary gland and studied the effects of these two drugs. He found that AY (agonist) and BY (antagonist) both formed by the amount of A or B and their affinities for Y would determine the affect.
In Langley’s experiments on the submaxillary gland salivation: _______ was the agonist, _______ was the antagonist.
Pilocarpine (ag)
Atropine (ant)
What is the common receptor for acetylcholine?
muscarinic receptor
Pilocarpine (ag.) and atropine (ant.) produce their effects by acting upon __________ of salivary glands.
muscarinic acetylcholine receptor proteins
Muscarinic antagonists can produce _________.
xerostomia (block salivary gland stimulation)
Drugs A and B both can bind to a receptor Y. They compete based on _____ and ______.
- the amount of each that is present
- how well each can bind to the receptor
A __________ effect occurs when agonist binds to receptor.
biological
Langley’s later experiments described the fundamental _________ of pharmacology by looking at the effects of agonists/antagonists on ______ receptors of muscle.
signal transduction paradigm
nicotinic
What were the agonist and antagonist that Langley used in his second experiment on muscles?
Nicotine (agonist)
Curare (antagonist)
What are the agonist/antagonist pairs that Langley used on salivary glands? What about gastrocnemius muscle?
salivary: pilocarpine/atropine
muscle: nicotine/curare
What were the three varieties of muscle fibers that Langley used in his nicotine/curare experiment?
- Dennervated
- Native
- Electrically stimulated
Which type of muscle fiber saw no effect from curare (aka still contracted in the presence of curare)?
Muscle that was stimulate directly
Interaction of a drug with a receptor is based on _________.
The Law of Mass Action
Based on the law of mass action, at equilibrium the rate of ______ equals the rate of _______.
association
dissociation
What is the formula for the dissociation constant?
[R] [L] / [RL]
receptor concentration*free drug concentration
divided by bound receptor-drug concentration
What is the formula for a rectangular hyperbola?
y = x / (c+x)
The dissociation constant describes the drug _______.
concentration required for 1/2maximal binding to the receptor
Is it possible that two drugs L1 and L2 act at the same receptor site but require vastly different concentrations to achieve the same effect?
Yes!!
the amount of drug bound to the receptor would depend on both the concentration of drug AND the dissociation constant.
If Kd of L1> Kd of L2, more of drug 1 will be required to achieve binding equivalent to drug 2
True or False: If x amount of drug produces a certain effect, 2x amount of drug will produce twice the effect.
False. it depends where you are on the binding curve.
If the amount of drug bound to receptor is low, doubling the amount could roughly double the effect. If the amount of drug bound is high, doubling the amount of drug would _______.
have VERY LITTLE EFFECT
Why do pharmacologists prefer using semilog plots?
a need for data to be expressed over a 1000-fold range of drug concentrations cannot be met with a linear scale. semi-log plots relate data in an exponential relationship: one value has a large range, the other has a restricted range
In a rectangular hyperbola kinetic model for uptake-concentration, where is the largest change in uptake seen?
At low substrate concentrations there is a large change in uptake because almost all of the receptors are free. At higher concentrations, there are now fewer receptors
What is EC50?
the concentration of drug that produces 1/2 maximal effect.
quantitative description of drug ACTION
(vs. law of mass action= drug binding)
The __________ relates the amount of receptor, the concentration of drug, and the EC50.
pharmacological effect
True or False: EC50 can be less than Keq.
True
What is the difference between Keq and EC50?
Keq: how much does it take to get half bound
EC50: dose required to receive the desired effect; you may not need half bound to reach that effect.
The equation for pharmacological effect indicates that maximum effect is observed when the drug concentration greatly exceeds ______.
the EC50
What is the equation for pharmacological effect?
= k[Rt]*[D] / {EC50+ [D]}
D is drug concentration
Maximum effect is observed when the ______ greatly exceeds EC50.
drug concentration
True or False: Once the drug concentration reaches a certain level, addition of more drug will only alter the effect slightly.
False: addition of more drug will not produce any additional effect
Is EC50 the same as Keq?
No, often 1/2 maximal effect occurs at less than 1/2 maximal binding. Thus EC50 can be less than or equal to Keq
When both are given at their optimum concentrations, can methadone produce a larger opioid effect than buprenorphine?
Yes, some agonists are able to activate a higher fraction of receptors than others no matter what their relative binding affinities are.
At the same dose concentration, ______ agonists poorly activate receptors so much that their best could not achieve the maximum effect that ____ agonists can achieve.
Partial
Full
If methadone is the “full agonist,” what would be its “partial agonist” and “antagonist”?
partial: buprenorphine
antagonist: naloxone
Even among what appear to be full agonists, some cannot activate receptors as well as others. For example, when excess receptors are inactivated, a full agonist may only have a partial agonist response due to its inability to _____.
Activate Receptors that are available (while another full agonist may be proficient at converting receptors to an active state)
The ability of a drug to confer a response is known as ______.
efficacy
_______ refers to the relative ability of a drug to confer an effect.
Potency (aka: the concentration range where it works)
What two factors determine the potency of a drug?
- binding affinity
2. efficacy- ability to confer a response
Drugs with insufficient ______ will be partial agonists regardless of how well they bind to their receptor.
efficacy
Prior to Ahlquist’s experiments on receptor activation, it was believed that there were what two type of receptors?
Excitatory or Inhibitory
What did Ahlquist’s experiments prove?
He was testing agonists to determine their potency and determine whether they segregate according to whether they act on excitatory or inhibitory receptors. He found that the two groups were not Sympathin I and Sypathin E, but instead were alpha and beta adrenergic receptors characterized by pharmacology not the nature of their physiological response
There is only one adrenergic neurohormone, or sympathin, and it is identical with _______.
epinephrine
One drug can elicit ________ in different contexts.
different effects
There is no need for ______ -specific agonists and antagonists because one drug can elicit different effects (complexity).
receptor
