10/20

Question 1

vasodilators

Answer 1

cyclic GMP modulators:
-organic nitrates/nitrites
-PDE inhibitors
-vasoactive peptides
K+ channel agonists

Question 2

nitric oxide synthase

Answer 2

at the heart of the nitric oxide-cyclic GMP pathway
isoforms: nNOS (neuronal), iNOS (inducible), eNOS (endothelial)
NOS is in the vascular endothelium, and NO diffuses to the vascular smooth mucle

Question 3

___ is found in the endothelial cells of the vasculature

Answer 3

eNOS

Question 4

___ is found in the vascular smooth muscle

Answer 4

guanylate cyclase

Question 5

exogenously applied NO can

Answer 5

directly relax smooth muscle

Question 6

acetylcholine relaxes ___ via __

Answer 6

smooth muscle via NO

Question 7

NO binds to the __ group in __

Answer 7

heme iron prosthetic group in guanylate cyclase
-stimulates the production of cGMP and activating prokein kinase G
NO (heme) -> guanylate cyclase -> cGMP -> activates protein kinase G

Question 8

how does protein kinase G relax smooth muscle?

Answer 8

inhibition of L type Ca channels (Cav1.2)
stimulation of Ca activated K channels (BKca)
decrease MLC phosphorylation (myosin phosphatase 1)
enhanced Ca uptake into ER (phospholamban)

Question 9

organic nitrates

Answer 9

non-selective vasodilators, breakdown to NO (bioactivation - aldehyde dehydrogenase), don’t require functional endothelium, acute or chronic administration
tolerance occurs w continued administration

Question 10

phosphodiesterase inhibitors (PDE3)

Answer 10

amrinone and milirone
given IV
direct positive ionotropic effect on myocardium and minimal chronotropic effect
direct vasodilatory effect on vascular smooth muscle

Question 11

cGMP phosphodiesterase inhibtors (PDE5)

Answer 11

sildenafil is a potent and specific inhibitor f cGMP PDE5
10 fold selectivity over inhibition of PDE6 (bluish vision)
4000 fold selectivity over PDE3
predominant in the corpus cavernosum

Question 12

PDE5 drugs

Answer 12

tadalafil (cialis), vardenafil (levitra), sildenafil (viagra)
levitra - shorter time to onset and more selective for PDE5 than viagra
cialis - more selevtice for PDE5 than viagra, longer duration of action than viagra/levitra

Question 13

human type B natriuretic peptide

Answer 13

vasodilator
natrecor (Nesiiritide)
binds to and activates membrane-bound guanylate cyclase in vascular smooth muscle and endothelial cells

Question 14

K+ channel agonists/openers

Answer 14

vasodilators
K+ flux sets the membrane potential (longer the channels are open = closer the memrane potential is to the K+ equilibrium potential -> harder it is to depolarize the membrane enough to open voltage gated Ca channels)
EX: minoxidil, diazoxide

Question 15

minoxidil

Answer 15

activiated in vivo by sulfotransferase
use w loop diuretics and B blockers
potent vasodilator - effective in severe, drug resistant HTN

Question 16

diazoxide

Answer 16

used IV to treat acute HTN

very potent vasodilator - effective in severe, drug resistant HTN

Question 17

dilates arterioules preferentially

Answer 17

miscellaneous vasodilator
mechanism not clear, appears to interfere w release of Ca from ER
can induce a lupus-like syndrome

Question 18

adenosine

Answer 18

miscellaneous vasodilator
binds A1 receptor
increases conductance of a K+ channel hyperpolarization (relaxation)

Question 19

endogenous peptide vasoconstrictors

Answer 19

angiotensin
vasopressin
endothelin
urotensin

Question 20

endothelin receptor antagonsits

Answer 20

bosentan and macitentan

Question 21

uses for vasoconstrictors

Answer 21

hypotension
control blood flow (surgical procedures, nasal congestion, blood shot eyes)
cerebral arteries (migraine/ischemic damage)

Question 22

drugs used as vasoconsrtictors

Answer 22

a1 adrenergic receptor agonists: epinephrine, methoxamine, midodrine and metaraminol