They all form covalent bonds with the receptor molecule
The more chiral a drug is the more ______ the binding.
selective
"Dextro" signifies the ____-enatiomer
S (+)
"Levo" signifies the ___-enatiomer
R (-)
With some racemic mistures the patient is receiving doses where 50% is either _________ or _________.
inactive
toxic
Racemic mixtures are sometimes used because of the _________ of the molecule in the body
biotransformation
bind to and activate the receptor
Agonists
What is an effector?
Binds to and indirectly activates the receptor via signal transduction that produces the effect
Some drugs mimic the effect of the receptor agonist by ________ the molecules responsible for terminating the action of the __________ agonist, and do NOT bind to the receptor but ______ the pharamcological effect
inhibiting
endogenous
amplify/extend
activates the receptor has maximum pharmacological effect
has high intrinsic efficacy
stabilizes receptor into the active conformation
Full agonists
activates the receptor
has a low pharmacological effect
has low intrinisc efficacy
can act as an agonist or antagonist
Partial agonists
does not activate the receptor
stabilizes the receptor in its inactive conformation
opposite effects of conventional agonists
Inverse agonists
enhances the efficacy/binding affinity of the agonists
bind to an allosteric site other than the binding site of the agonist
Allosteric agonists
aka allosteric activators
bind to but do not activate the receptor
block the binding of agonists
receptor specific
can be competetive/noncompetitive
Pharmacologic antagonists
aka blockers
aka receptor-specific antagonists
inhibit/reduce the binding affinity of the agonist
binds to allosteric sites on the receptor
non-competitive & receptor specific
not overcome by increasing concentration of the agonist
Allosteric antagonists
aka allosteric inhibitors
aka receptor-specific allosteric antagonists
aka noncompetitive allosteric antagonists
What does ADME stand for?
A-Absorption
D-Distribution
M-Metabolisim
E-Excretion
True or false, the Ri conformation is favored in equilibrium?
True-the inactive conformation is more stable
In the ___ confirmation the receptor can produce an effect in the _______ of a ligand.
Ra
absence
What is consitutive activity?
The effect produced in the absence of a ligand in Ra confirmation
What factors determine the degree of constitutive activity? (4 total)
1- The equilibrium between Ri and Ra
2- receptor density
3- concentration of coupling molecules
4- number of effector molecules
Humans exist in a _____ level of constitutive activity in the absence of an agonist
low
_____ agoinsts have a high affinty for binding to the _R__ confirmation and fully stabilize it.
Full
Ra
A partial agonist has an affinity for which form(s)?
Both the active and inactive
Partial agonists have what type of intrinsic efficacy?
low
In the presence of a full agonist a partial agonist acts as ___________
an antagonist (blocker)
Binding to a pharmacologic antagonist does what to the equilibrium?
It does NOT shift it
No effect will be observed
__________ has equal affinity for binding to both the Ra and Ri forms.
Pharmacologic antagonists
Inverse agonists have a higher affinity for binding to the _______ form of the receptor molecule
inactive
What two mechanisms terminate drug action at the receptor?
1- dissociation of the drug from the receptor
2- biosynthesis of a new receptor molecule
What is an inert binding site?
Binding of a drug to a nonregulatory inert molecule that will NOT alter the biologic function of response
Name 4 types of drug receptors:
1- regulatory proteins
2- enzymes
3- transport proteins
4- structural proteins
In what 3 ways does the receptor influence clinical use of drugs:
1- responsible for establishing the relationsihps between dose/concentration vs. pharmacologic effects
2- responsible for selectivity of drug action
3- mediate actions of agonists and antagonists
What is the name of this equation?
What does it tell us?
Graded dose-response curve
Concentration vs. effect
What is Emax?
Maxium response produced by the drug
Highest value on y-axis
Measures drug efficacy
What is EC50? (ED50)?
The concentration that produces 50% of the maximum effect
C=concentration
D=dose
EC50 and potency have a(n) ________ relationship
(When EC 50 is ____ potency is _____)
inverse
high
low
What is the name for this equation?
What does it tell us?
Graded dose-binding curve
Bound drug vs. Unbound drug
What is Bmax?
Total concentration of receptor sites that are bound to the drug
Maximum number of drug-receptor complexes you can form at the receptor site
What is KD?
What does it tell us?
Equilibrium dissociation constant
Characterizes affinity for binding
KD and binding affinity have a(n) ________ relationship
(When KD is ____ affinity is ______)
inverse
low
high
Emax and drug potency have a(n) _______ relationship
(When Emax is ____ drug efficacy is _____)
direct
low
low
Efficency in coupling is determined by what 2 things?
1- Initial conformational change in the receptor
2- Biochemical events (and how complicated they are)
Spare receptors are said to exist if.....
....the Emax(max pharmacologic effect) is obtained at less than max occupation of receptor molecules (Bmax)
If EC50 is ______ than the KD spare receptors are said to exist
lower
What does it mean when EC50 and KD are equal?
Spare receptors do not exist
Spare receptors are caused by what 2 mechanisims?
1- duration of activation may be much greater than the duration of the drug-receptor interaction
2- The number of receptor molecules may exceed the number of effector molecules
Sensitivity of a cell or tissue depends on what 2 things?
1- affinity of the receptor for binding of the agonist
2- degree of spareness of the receptor
Spareness and sensitivity have a _______ relationship
(____ spareness leads to ______ sensitivity in the tissue)
direct
high
high
reversibly bind to the same binding site of the agonist on the receptor molecule without activating the receptor
competitive antagonists
aka reversible
**RECEPTOR SPECIFIC
The success of competetive agonists depends on what 2 things?
1- its own concentration
2- concentration of the endogenous agonist
**you would have to adjust the dose frequently
irreversibly bind to the same binding site of the agonist without activating the receptor
noncompetitive antagonists
aka irreversible
**RECEPTOR-SPECIFIC
Irreversible binding can be caused by what 2 things?
1- extremely high affinity for that antagonist to bind
2- they form covalent bonds
Irreversible antagonists cause a ________ shift of the max in dose-response curve
downward
(tell you the receptors are being sealed up which is why you cannot see full max effect)
The duration of action of an irreverible antagonist depends on what?
The rate of turnover of receptor molecules
What is a disadvantage of irreversible antagonists?
there is no way to cure an overdose
Partial agonists produce a ______ response than do full agonists
lower
Partial agonists are also used as ________
competitive antagonists
What do these 3 drugs have in common?
protaminm dimercaprol, pralidoxime
They are all chemical antagonists
What is chemical antagonism?
Occurs when 1 drug prevents the second drug from binding to its receptor site
True or false, a chemical antagonist does not depend on interaction with the agonist's receptor
true, it is NOT receptor-specific
What do these 3 hormones have in common?
insulin, epinephrine, glucagon
They are all physiologic antagonists
What is physiologic antagonism?
The physiologic antagonist binds to a different receptor molecule producing an opposite effect than the drug it antagonizes
