Receptors and basic pharm Flashcards
the -olol suffix defines drug as a _
beta blocker
How many FDA approved drugs are there
3000-6000
point being too many
top 10 causes of death in the US 1. 2. 3. 4. accidents 5. stroke 6. alzheimer's and dementia 7. diabetes 8. influenza and pneumonia 9. kidney disease 10. suicide
- heart disease
- cancer
- chronic lower respiratory disease
drugs exert their effects by binding to a _
a receptor (protein)
drugs bind to receptors(proteins) and receptors act as a _
signal transducer
they bind a ligand and send some sort of signal to the cell machinery to produce a physiological effect
drugs that actively produce a physiological effect are called _
agonists
drugs that block the action of agonists (drugs that actively produce effects)
antagonists
a binding curve of drug being bound to a receptor vs. free drug concentration looks like a _
a rectangular hyperbola
that has practical implications that we should know
having 100% of the receptor bound by drug is a limit approached as the drug concentration _
gets very high
the dissociation constant describing drug binding to its receptor is defined as the concentration of drug providing _
the concentration of a drug providing 1/2 maximal binding
semilog plots (drug bound to receptor) vs log (free drug) provide _ curves that allow a more complete range of data to be shown
sigmoidal curve
a vast majority of drugs function by interacting with _ and either facilitating (agonist drugs) or blocking (anatagonist drugs) their function
receptor proteins
the drug _ stimulates salivation by the submaxillary gland
the drug _ blocks this effect
pilocarpine
the drug atropine blocks this effects
the beginning of the _ theory of pharmacology
A(pilocarpine)
B(atropine)
Y(receptor)
AY and BY both formed, quantity of AY and BY depending on the relative masses of A and B present and their relative affinity for Y
receptor theory
pilocarpine and atropine produce their effects by acting upon _ receptor proteins of salivary glands
muscarinic acetylcholine receptors
this is why muscarininc antagonists (blockers) can produce xerostomia
Nicotine acts upon the _ and not upon the axon-endings. It has been shown that _ acts upon the same muscle substance as nicotine.
since this accessory substance is the recipient of stimuli which it transfers to the contractile material. we may speak of it as the receptive substance of the muscle
muscle substance
curare
in all cells two consitituents at least must be distinguished
- substance concerned with _
- _ especially liable to change and capable of setting the chief substance in action
- substance concerned with carrying out the cheif functions of the cells, such as contraction secretion, the formation of special metabolic products
- receptive substances
interaction of a drug with a receptor is based on the law of mass action which is
Kd (dissociation constant =
concentration R x concentration of L divided by concentration of RL
interaction of a drug with a receptor is based on the law of _
the law of mass action
the proposition that the rate of a chemical reaction is directly proportional to the product of the activities or concentrations of the reactants.[1] It explains and predicts behaviors of solutions in dynamic equilibrium. Specifically, it implies that for a chemical reaction mixture that is in equilibrium, the ratio between the concentration of reactants and products is constant.
description of how a plot of drug (L) bound to receptor (R) vs. drug concentration (L) should look
[RL] = [Rt][Lf]/(kd+[Lf])
[RL]/[Rt] = _
thus, 10% to 90% binding takes place over a _ fold concentration range, with 50% binding taking place when the free ligand concentration is equal to the _
law of mass action
= fraction bound
or = [Lf]/9kd+[Lf])
y=x/(c+x)
rectangular hyperbola
over an 81 fold
50% binding when free ligand concentration is equal to kd
as Lf approaches infinity, RL/Rt apprroaches 1
what does this mean
once the drug concentration is high enough basically all of he receptor will contain bound drug
at RL/Rt = 1/2 , Lf=kd
by definition, the equilibrium or dissociation constant describes the drug concentration required for _ binding to the receptor
1/2 maximal binding
is it possible that to drugs L1 and L2 act at the same receptor site but require vastly different concentrations to achieve the same effect?
absolutely. the amount of drug bound to the receptor would depend on both the concentration of drug available for binding as well as the Kd. if drug L1 has a much higher kd than drug L2, more of drug _ will be required to achieve binding equivalent to that of the other
L1
if X amount of drug produces a certain effect, 2X amount of drug will produce roughly twice as much of an effect?
no
it depends where you are on the binding curve, if the amount of drug bound to the rececptor is low, doubleing the amount of drug will indeed roughly double the amount of drug bounr to the receptor and could roughly double the effect, however if the amount of drug bound to the receptor is high, doubling the amount of drug would have very little effect
graph used to express data over a 1000-fold o more range of drug concentration
semilog plot
allows one to plot the full range of results. rectangular hyperbola turns into the familiar sigmoidal plot
_ refers to the relative ability of a drug to confer an effect, is a combo of affinity and efficacy
potency
law of mass action describes the _ of drugs
it does not accurately describe quantitative aspects of drug _ thus we use the concept or EC50
binding of drugs to receptors
not good at drug action
Delta = k[Rt][D] / EC50+ [D}
this is a representation of dose response data
this equation predicts the same shape as the law of mass action when you plot _ vs _
the most important difference is the term _
drug concentration vs effect
term EC50
delta - a quantitative representation of the pharmacological effect
k[Rt] - represents the pharmacological effect is a function that relates to the amount of receptor(R) and that the max effet is a fxn that relates to the total amount of receptor
EC50 - refers to the dose of drug that produces 1/2 max effect
[D] - refers to the concentration of drug
Delta = k[Rt][D] / EC50+ [D}
if delta describes a pharm effect, this equation is sating a max effect is observed when the [D] greatly excedds the EC50
[D]» EC50 then, deltamax ~kRt
there is a max pharm effect, once the drug concentration reaches a certain level addition of more drug does not produce an additional effect
if the [D] is equal to the value of EC50 then _
delta0.5 = 1/2kRt
this leads to a dose response curve
Ec50 is defined as the _
EC50 = [D] that provides 1/2 maximal effect
is EC50 the same as Keq since the former produces 1/2 max effect and the latter produces 1/2 max binding to receptor?
no because sometimes (often) one observes 1/2 max effects at less than 1/2 max binding
thus EC50 can be less than or equal to Keq
how is it that Methadone can prodice a larger opioid effect than Buprenorphine, even when both are given at their optimum concentrations
methadone - full agonist
buprenorphrine - partial agonist
some agonist are able to activate a higher fraction of receptors than others, INDEPENDENT of their relative binding affinities, in fact some agonists(partial agonists) are sufficiently poor at activation that their best is not good enough to achieve the maximum effect that other agonists (full agonists) can achieve
drugs with no efficacy are _
antagonists
binding affinity is one factor that determines the _ dependence of drug action.
the ability to confer the response (known as _) is another factor
the concentration dependence of drug action
efficacy
potency refers to the relative ability of a drug to confer an effect
- the potency of a drug ([D] range where it works) is determined by both its _ and _
- drugs with insufficient efficacy will be _ regardless of how well they bind to their receptor.
binding affinity and its efficacy (ability of drug to confer response)
- partial agonists
binding affinity is one factor that determines the concetration dependence of drug _
drug action
the ability to confer the response _, is another factor that determines the concentration dependence of drug action
efficacy
isoproterenol is the first _
beta selective agonist
adrenalin(epi) has _ and _ effects
2 receptors
2 agonists
excitatory effects (vasoconstriction, contraction of uterus)
inhibitory effects (inhibi of uterine contraction)
2 receptors - excitatory and inhibitory
2 agonists - sympathin E(excitatory)
sy,pathin I (inhib)
there are 2 distinct types of adrenotropic receptors as determined by their relative responsiveness to a series of sympathomimetic amines closely related structurally to epinephrine
the _ receptor is associated with most of the excitatory fxns and one inhib fxn
the _ adrenotropic receptor is associated with most of the inhib fxnx and one excitatory fxn..
_ is the one amine which is the most active on both the alpha and beta receptors
the alpha adrenotropic - most excitatory, one inhib
beta - most inhib and one excitatory (Ahlquist considered vasodilation inhibitory)
L-epinephrine most active on both the alpha and beta
the results support the theory that there is only one adrenergic neurohormone or sympathin and that sympathin is identical with epinephrine
characterize receptors by their _ not the nature of their physiological response
by their pharmacology
adrenergic receptor AR
alpha and beta AR receptors what are they
alpha 1-AR ~alpha1A-AR ~alpha1B-AR ~alpha1D-AR alpha 2-AR ~alpha2A-AR ~alpha2B-AR ~alpha2C-AR
Beta-AR
~beta1-AR
~beta2-AR
~beta3-AR
virtually all receptors are part of a _
one drug can elicit different effects in different contexts
- this underscores the need for receptor specific agonists and antagonists
- helps explain the complexity of drug action
gene family
