Vasodilators/Vasoconstricters Flashcards
why does increasing K+ channel opening relax vascular smooth muscle?
the harder it is to depolarize the membrane enough to open Ca2+ gated channels
name the 3 K+ channel openers
minoxidil, diazoxide, adenosine
side effect of minoxidil
hypertrichosis (excess hair)
diazoxide administration and uses
IV for drug-resistant HTN
inhibits release of insulin
used for hypoglycemia secondary to hyperinsulinemia
what does adenosine do to the membrane?
hyperpolarization and relaxation
what does adenosine bind
A1 a GPCR
what is adenosine used for
coronary stress test
supraventricular arrhythmias
what does adenosine activate that kicks K+ out of the cell?
GIRK
what happens in vascular endothelium
calcium-calmodulin activates eNOS which helps convert arginine to NO
where is eNOS found
endothelium
where is guanylate cyclase found
vascular smooth muscle
what does NO do in smooth muscle
binds heme group on guanylate cyclase and stimulates cGMP and activation of protein kinase g
how does protein kinase G relax smooth muscle? (4 ways)
inhibits Cav 1.2
stimulation of Ca/K channels (BKca)
decreased MLC phosphorylation
enhanced Ca uptake in ER (phospholambam)
organic nitrates MOA
non selective vasodilators
breakdown to NO (bioactivation)
do organic nitrates require functional endothelium
no
what are nitrates used for?
sublingually for angina
oral for prolonged prophylaxis
what happens with continuous admin of nitrates”?
tolerance
asian population has an allele that decreases efficacy of what?
glycerol trinitrate
lys 504 allele
sodium nitroprusside dilates what
veins and arterioles
what is sodium nitroprusside metabolized to and where?
in erythrocytes to NO and CN which limits duration of treatment (toxic)
what does hydralazine dilate?
arterioles
what does hydralazine interfere with
release of Ca from ER
what can hydralazine be combined with?
isobride dinitrate in BiDil which is useful for African Americans with CHF
what does human type B natriuretic peptide do?
activates guanyl cyclase domain
increases cGMP
B type peptide drugs
nesiritide and sacubitril
what is nesiritide used for?
acutely decompensated HF
how does nesiritide work?
binds and activates membrane bound guanyl cyclase
how does sacubitril work?
inhibits neprilysin which breaks down BNP
so we have increased BNP and enhanced action
increased bradykinin so don’t use with ACE inhib
PDE3 inhibitors
amrinone and milrinone
PDE5 inhibitors
dipyridamole, sildenafil, tadalafil, vardenafil
what does PDE3 prefer
cAMP
what does PDE5 prefer
cGMP
what are PDE3 inhibitors used for?
IV for CHF
what has 10 fold selectivity over inhibiton of PDE6?
sildenfail (blue vision)
what pde is predominant in the corpus cavernosum?
PDE5
where is PDE6 located?
retina
PDE5 with longest duration of action?
tadalafil
PDE5 with shortest time to onset
vardenafil
PDE5 contraindicated with what?
nitrates
endothelium receptor antagonists
-entans
bosentan, macitentan
what do bosentan and macitentan do
blcok ETa and ETb
what does ambrisentatn do
block ETa
what are the -entan endothelien antagonists used for
pulmonary arterial hypertension
what are the -entans contraindicated in and why
pregnancy, hepatotoxicity
what do prostacyclin analogs do
relax pulmonary vascular smooth muscle
where is prostacyclin produced?
endothelium
what are the prostacyclin analogs?
PGI2, treprostinil, Iloprost, selexipag
activator of sGC drug
riociguat
what does riociguat do?
increases cGMP concentration in vascualr smooth muscle
what is riociguat a substrate for?
pgp, CYP 1A1, 3A
alpha 1 agonist drugs
epinephrine, phenylephrine, midodrine, droxidopa
