3- Pharmacodynamics Flashcards
additive vs. synergistic
drug A = 20 drug B = 20
A+ B = 40 = additive
A+B = 90 = synergistic
estrogen receptor
vitamin A/retinoic acid receptor
intracellular receptors
bind lipophillic agents
intracellular receptors
consequence of ligand binding is a change in gene activity(transcription)
often an intracellular receptor
single membrane spaning domain with extracelullar ligand binding area and intracellular enzymatic activity area
intrinsic enzymatic activity receptor
tyrosine kinases
receptor with intrinsic enzymatic activity
epidermal growth factor receptor
insulin receptor
transforming growth factor receptor
receptors with intrinsic enzymatic activity
leptin receptor
erythropoietin
interleukin-3
receptors that directly associate with intracellular enzymes
nAchR
ligand-gated ion channel
rhodopsin frizzled odorant receptors smoothened receptors beta adrenergic receptors
7MSR aka serpentine or heptahelical receptors
can 7MSR mediate signals that are independent of gprtn signaling
yes
can mediate signals that require coupling to a g prtn OR are independent of gprtn signaling
downregulation
continued stimulation of a receptor leads to a decreased number of receptors
upregulation
continued exposure of a receptor to an inhibitor causes a increase in number of receptors
decreased physiological response to the same amount of drug
tolerance
increased physiological response to the same amount of drug
sensitization
equation for dissociation constant Kd
kd = (concentration of drug x concentration of ligand) / concentration of receptor bound drug
point at which half the receptors are occupied with ligand and half the receptors are free
Kd dissociation constant
higher affinity = ____________ Kd
lower Kd
the lower the Kd (or less drug required for half maximal occupancy), the greater the binding affinity of that drug
concentration of drug that produces a half-maximal response
EC50
comparing the EC50 of drugs tells you …
potency
comparing the Emax of drugs tells you …
efficacy
a drug that binds to a receptor and produces a response
agonist
a drug or ligand that binds to a receptor and inhibits the response produced by the agonist
antagonist
compete for the same binding site
competitive antagonist
bind to different sites
noncompetitive antagonist
induces a shift to the right in EC50 of dose curve but max effect is still achievable
competitive antagonist
max effect is still achievable because the antagonist can be outcompeted with higher concentrations of agonist but the EC50 of the agonist is increased
decrease in the maximal effect of the agonist without changing the binding affinity (EC 50 doesn’t change)
noncompetitive antagonist
drug that produces a lower maximal response compared to the agonist
partial agonist
overall result of increasing partial agonists =
blunted overall physiological response (see graphs)
dose at which 50% of individuals exhibit a specific quantal effect
ED50
dose at which 50% of individuals exhibit a toxic effect
TD50
dose at which 50% of individuals die
LD50
therapeutic index ID =
TD50 / ED50
a higher ID = ______________ safety
increased safety
more wiggle room between lethal and therapeutic doses
