Pharmacodynamics Flashcards
What is a receptor?
component of a cell to which drug binds to initiate the chain of events that leads to a biological response
what is the duration of action for most drugs directly related to?
time the drug is bound to the receptor
what happens once the drug is cleared from the bloodstream?
actions will be terminated
what type of drug will persist for several weeks even after the drug has been cleared from the body?
corticosteroids
what happens when drugs irreversibly bind to an inhibit enzyme?
their effects persist much longer than the free drug in the plasma
what drug-receptor interactions are reversible?
electrostatic interactions, hydrogen bonds, van der waals forces, and hydrophobic interactions
what drug-receptor interactions are irreversible?
covalent binding
what is a intracellular receptor?
hormone or drug that crosses the plasma membrane that stimulates intracellular receptor
what hormones and drugs bind to intracellular receptors?
corticosteroids, mineralocorticoids, sex steroids, vitamin D, thyroid hormone
what binds to protein tyrosine kinase?
insulin, epidermal growth factor, platelet derived growth factor
which ligand-gated channels excites and which inhibits?
Nicotinic acetylcholine receptor - excitatory, depolarizes
GABA receptor - inhibitory, hyperpolarizes
what binds to the ligand-gated ion channels (specific for nicotinic vs GABA)?
Nicotinic - acetylcholine
GABA - GABA, benzodiazepines
Ca++/Na+ - glutamate
what happens when a drug binds a G-coupled receptor?
G-protein activates hydrolysis of GTP->GDP
What does receptors linked to Gs do to the formation of cAMP?
stimulate formation of cAMP
what does receptors linked to Gi do to the formation of cAMP?
inhibit formation of cAMP
what hormones and drugs bind to Gs to stimulate cAMP formation?
epinephrine (B1 and B2)
norepinephrine (B1)
isoproterenol (B1 and B2)
dobutamine (B1)
histamine (H2)
FSH
ACTH
what hormones and drugs bind to Gi to decrease cAMP formation?
norepinephrine (a2)
epinephrine (a2)
dexmedetomidine (a2)
acetylcholine (M2)
morphine (u,k,d)
serotonin (5-HT1)
what drugs and hormones bind to GQ to stimulate formation of IP3/DAG?
acetylcholine (M1 and M3)
norepinephrine, epinephrine (a1)
phenylephrine (a1)
serotonin (5-HT1c)
what are some non-receptor mediated effects?
simple chemical interactions with body components, other drugs, and infective agents
what does IP3 and DAG do?
IP3 stimulates Ca++ release from intracellular store
DAG stimulates protein kinase C -> Ca++ pumped out
second messenger, influx of Ca2+ into ER
how many drugs can combine with one receptor?
one drug
How is the amount of drug bound compared to the amount of free drug available?
negligible
what type of curve is this?
dose-response curve
what is EC50?
dose required for half maximal effect
what type of curve is this?
Quantal dose-response curve
which curve is in relation to a single animal and which is in relation to a population?
single animal - graded dose-response curve
population - quantal dose-response curve
which curve has a response of all or none?
quantal dose-response curve
How is the quantal dose-response curve obtained?
transformation of data used for frequency distribution plot
which curves can you use to calculate ED50?
quantal dose-response curve and dose-response curve
what is the equation for therapeutic ratio?
LD50/ED50
define affinity
measures binding of drug to receptor
what is Kd
concentration needed to produce half maximal binding
define potency
dose required to produce a given effect
define efficacy
degree of biological response produced by binding of a particular drug to the receptor
what is the relationship between potency and efficacy?
not related
define intrinsic aftivity
ability of a drug to initiate a response
synonymous with efficacy
what type of activity do agonists have?
affinity and intrinsic activity
what type of activity do antagonists have?
affinity and no intrinsic activity
what type of activity do partial agonists have?
affinity and lower intrinsic activity
what is drug X and Y in the top graph and then the bottom graph?
top
X and Y - full agonists
bottom
X and Y - partial agonists
what causes a maximum shift of receptors to the activated state?
agonist
what blocks a response to an agonist?
antagonist and partial antagonist to full agonist
what are the types of antagonists?
competitive
non-competitive
functional
chemical
what type of antagonist takes receptors out of play?
non-competitive
what type of antagonists bind to receptor and compete with agonist?
competitive
what type of antagonist produces opposing physiological effect?
functional (physiological)
what type of antagonist neutralizes chemically?
chemical
how much intrinsic activity to competitive antagonists have?
0
how does a competitive antagonist shift a dose response cuve?
to the right
which antagonist binds irreversibly to the receptor? what does this do to the agonist?
bind irreversibly to receptor so agonist cannot bind
How is EC50 affected by non-competitive antagonists?
might or might not change
maximum response is decreased
what produces a response but with lower efficacy?
partial agonists
How is tolerance seen in pharmacokinetics?
drug induces its own metabolism
drug may increase metabolism of another drug
dec plasma conc, dec biologic effect
How is tolerance seen in pharmacodynamics?
usually due to receptor down or up regulation
ex beta receptor agonists or antagonists (opioids)
How can increased drug activity be induced?
chemically induced, surgically induced, antagonist induced, deficiency in degrading enzymes, competition for binding sites, physiologic synergism
when do we see adverse effects?
when there are multiple responses to a drug due to the presence of multiple receptors being activated at different dose levels
what are drug examples that several dose-dependent responses can be obtained with one drug?
phenothiazines, antihistamines, CNS depressants
are drugs more selective or specific?
at most selective rarely specific
what are the two responses drug selectivity can have?
therapeutic and adverse
Define dose dependent toxicity
if an adverse reaction is mediated by the same receptor-effector mechanism
what is an overextensions of the therapeutic effect?
dose-dependent toxicity
what type of drug is added after the control?
competitive antagonist
what type of drug is added to epi in this curve?
non-competitive antagonist
what type of drug is each line?
