L4-5: Pharmacodynamics Flashcards
the duration of drug action is directly related to …..?
the time that the drug is bound to receptor
As the drug is _________ its action will be terminated
cleared from the bloodstream
drugs like corticosteroids act on _________ and alter the expression of specific ______
nuclear receptors, genes
MAO inhibitors, omeprazole, aspirin and DFP all ________ bind to and inhibit enzymes, causing their effects to last much longer than the free drug
irreversibly
how do drugs interact w/ ligand gated channels
- receptor is linked to an ion channel
- binding of NT or drug opens channel
- influx of ion depolarized (Na, Ca) or hyperpolarizes (Cl-) the cell
what type of receptors does Acetylcholine, GABA, Benzodiazepines and Glutamate have
ligand gated ion channels
the nicotinic ACh receptor is ________, it depolarizes the cell
excitatory
the GABA receptor is_______, it hyperpolarizes the cell
inhibitory
G-proteins stimulate binding and hydrolysis of _____ to _____ in response to binding of agonist to the receptor
GTP –> GDP
stimulation of G proteins amplifies the response caused by the bidning of the agonist
corticosteroids, mineralcorticoids, sex steroids, vit D and thyroid hormone are all waht types of receptors
intracellular
explain how corticosteroids are an exception to the rule that for most drugs - the duraction of action is directly related to the time the drug is bound to the receptor
corticosteroids act on nuclear receptors and alter gene expression. Altered gene expression can result for weeks even after the drug has been cleared from the body
explain how MAO inhibitors, omeprazole, aspirin and DFP are an exception to the rule that for most drugs - the duraction of action is directly related to the time the drug is bound to the receptor
these drugs irreversibly bind to and inhibit enzymes, their effects persist much longer than the free drug in plasma
the enzymes: tyrosine kinase, serine kinase and guanylyl cyalse are all enzymes that bind to ___________ regulated transmembrane proteins
allosterically regulated
allosterically regulated transmembrane proteins are polypeptides with a ________ binding domain and a ________ enzyme domain
extracellular hormone binding domain
cytoplasmic enzyme domain
ligand binding to allosterically regulated transmembrane proteins causes receptors to associate, stimulating _________
tyrosine kinase
the stimulation of tyrosine kinase in allosterically regulated transmembrane proteins results in the _______ of receptors and other downstream proteins
phosphorylation
Acetylcholine, GABA, benzodiazepines and Glutamate all have what type of ion channels
ligand gated
insulin, epidermal growth factor and platelet derived growth factor all have what type of receptors
protein tyrosine kinase
what is the receptor for ACh
nicotinic, Na
what is the receptor for GABA
GABA A, Cl-
what is the receptor for Benzodiazepines?
GABA A, Cl-
what are the ions associated with a glutamate receptor
Ca, Na
G proteins stimulate binding and hydrolysis of _____ to _____ in response to binding of agonist to receptor
GTP to GDP
stimulation of G proteins _______ the response to binding of agonist to the receptor
amplifies
receptors linked to G_ Stimulate the formation of cAMP
Gs
receptors linked to G_ inhibit formation of cAMP
Gi
what convertys ATP to cAMP
what breaks cAMP down to 5’AMP
adenylyl cylase
**PDE **breaks it down
cAMP binds to intracellular _______ which facilitates ______ of various proteins
protein kinase A
phosphorylation
Gq activates….
membrane phospholipase C
what happens after Gq activates membrane phospholipase C
hydrolysis of PIP2 into IP3 and DAG
what is the role of IP3 in polyphosphoinositide signaling
releases Ca from intracellular stores
what is the role of DAG in polyphosphoinositide signaling
stimulates protein kinase C
Gq stimulates the formation of what
IP3 and DAG from PIP2
drug response is directly related to the number of…
receptors occupied
when is drug and receptor response at its maximum
when all available receptor sites are occupied or bound to the drug
once all receptors are bound with drug, is there any effect of further addition of the drug
no additional response
quantal dose response curves relate the _______ of a drug to the _______ with which a designated response will occur within a population
dosages
frequency
what is the therapeutic ratio
LD50/ED50
is a drug with a large or small therapeutic window ‘safer’
larger theraeutic window
______ measures the binding of drug to receptor
affinity
what is the concentration needed to produce half max binding called
Kd
what is the degree of biological response produced by the bidning of a particular drug to a receptor
efficacy
not related to potency
intrinsic activity is the ability of a drug to ….. and is synonymous with efficacy
initiate a response
agonists have _____ and ______ activity
affinity and intrinsic
antagonists have affinity but no _______ activity
intrinsic
partial agonists (or antagonists) have affinity but lower ____ activity
intrinsic
a _______ binds to the receptor and initiates a response, causes a max shift of receptors to the activated state
agonist
ex: morphine
a ______ binds to the receptor but does NOT initiate a response
antagonist
blocks response to an agonist
ex: Naloxone
binds to the receptor and causes a response that is less that what would be produced by full agonist
partial agonist
ex: Buprenophine
_______ antagonists bind to receptor and compete w/ agonist
competitive
______ antagonists take receptors out of play
non competitive
______ antagonists produce opposing physiological effects
functional (physiological)
_______ antagonists have no intrinsic activity (no efficacy)
competitive
if agonist concentration is high enough, the effect of the __________ antagonist can be overcome
competitive
do competitive antagonists affect max response produced by agonist
NO
competitive antagonists shift the dose response curve to the ______
right
what is the effect of competitive antagonists on affinity
decrease it
(decreased Kd or EC50)
what type of antagonism is this
competitive
what is the effect of non-competitive antagonists on maximum response
decrease it
what type of antagonism is this
non competitive
what type of antagonism is this:
Epi reverses drop in bp caused by histamine in anaphylaxis
functional / physiological
type of antagonist that neutralizes a drug chemically
chemical antagonism
what type of antagonism is this:
herapin being neutralized by protamine
chemical
if ______ agonists are combined with full agonists, they will compete for the recetpor but produce a ________ response
partial
smaller
what type of agonist is this
partial
tolerance is the…
chronic administration of many drugs
what are the 2 types of tolerance
pharmacokinetic
pharmacodynamic
type of tolerance where the drug induces its own metabolism and may also increase metabolism of another drug
ex: barbiturates
pharmacokinetic tolerance
Metabolic
type of tolerance caused by the down or up regulation of a drug; includes beta receptor agonsits or antagonists
ex: opioids
pharmacodynamic tolerance
changes in the target tissue that makes them less sensitive to a given drug [ ]
T/F:drugs are at most ‘selective’, and rarely ‘specific’
T
what is dose dependent toxicity
an adverse reaction is mediated by the same receptor effector mechanism
ex: excessive sedation by sedative agent…overextension of the therapeutic effect
what are some examples of dose dependent toxicities
- excessive hypotension
- arrhythmias
- hypoglycemia
- hemorrhage
aminoglycosides cause what toxicity
reanl and ototoxicity
acetaminophen causes what toxicity
hepatotoxicity
chloramphenicol causes what type of toxicity
aplastic anemia
tetracycline causes what kind of toxicity
retardation of bone growth
