Kaplan Chapter 2 Flashcards
(25 cards)
How do pharmacologic antagonists work on receptors?
they work on same receptor
How do physiologic antagonists work on receptors?
different receptors
2 agonists with opposing action antagonize each other
How do chemical antagonists work on receptors?
They form a complex between effector drug and another compound; no receptor involved
How does potentiation of a drug work?
They increase the potency of another drug
Formula for TI (therapeutic index).
TI = TD50/ED50
(TD stands for toxic dose)
What are some things that act as intracellular receptors?
thyroid hormones
gonadal steroids
vit D.
Gs pathway has what downstream messengers?
AC (adenylyl cyclase)
cAMP (second messenger)
protein kinase A
Which receptors work through the Gs pathway?
B1, B2, B3, D1
Gi pathway has what downstream messengers?
AC (adenylyl cyclase)
cAMP (second messenger)
protein kinase A
Which receptors act through Gi pathway?
the “MAD 2”
muscarinic M2
alpha 2
Dopamine 2
The Gq pathway acts through what messengers?
IP3 DAG pathway
Describe IP3 DAG pathway?
Phosphlipase C cleaves PIP2 into IP3 and DAG
IP3 releases Ca2+ from SR
DAG activates protein kinase C which causes phosphorylation of tissue specific enzymes
Which receptors act through the Gq pathway?
M1
M3
alpha 1
Nicotinic receptors are coupled to what types of channels?
directly to ion channels
Describe JAK STAT pathway?
transmembrane receptor activates JAK
JAK activates STAT (signal transducers and activators of transcription)
STATs dimerize, dissociate and cross nuclear membranes and modulate gene transcription.
cGMP messengers act on what?
vascular smooth muscle to cause vasodilation
cGMP is associated with what messengers in its signaling pathway? How does it work to cause vasodilation?
GC
cGMP (second messenger)
then cGMP dephosphorylates myosin light chain preventing interaction with actin and causing vasodilation
What molecules act on cGMP pathway? Also what is an example of drug associated with this molecule.
NO (nitric oxide) which activates GC thus increasing cGMP in smooth muscle
i.e nitroglycerin
What endogenous compounds increase synthesis of NO?
the vasodilators bradykinin and histamine
What are examples of compounds that bind to receptors that function as transmembrane enzymes?
insulin and growth factor
How do hormones that act on transmembrane enzymes work?
Membrane-spanning macromolecules with recognition sites for binding of insulin and growth factors located externally and a cytoplasmic domain that usually functions as tyrosine kinase.
Binding of ligand causes conformation change (dimerization) so the tyrosine kinase domain becomes activated
This leads to phosphorylation of tissue specific substrate enzymes
Formula for clearance that factors in area under the curve?
Cl= (f x dose)/AUC
Formula for clearance that doesn’t factor in AUC?
Cl= amount drug cleared/cleared from plasma
Hendersohn-Hasselback equation?
pH= pKa + log ionized conc./unionized concentration
