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PHRM 844 > Vasodilators/Vasoconstricters > Flashcards

Vasodilators/Vasoconstricters Flashcards

1
Q

why does increasing K+ channel opening relax vascular smooth muscle?

A

the harder it is to depolarize the membrane enough to open Ca2+ gated channels

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2
Q

name the 3 K+ channel openers

A

minoxidil, diazoxide, adenosine

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3
Q

side effect of minoxidil

A

hypertrichosis (excess hair)

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4
Q

diazoxide administration and uses

A

IV for drug-resistant HTN
inhibits release of insulin
used for hypoglycemia secondary to hyperinsulinemia

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5
Q

what does adenosine do to the membrane?

A

hyperpolarization and relaxation

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6
Q

what does adenosine bind

A

A1 a GPCR

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7
Q

what is adenosine used for

A

coronary stress test
supraventricular arrhythmias

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8
Q

what does adenosine activate that kicks K+ out of the cell?

A

GIRK

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9
Q

what happens in vascular endothelium

A

calcium-calmodulin activates eNOS which helps convert arginine to NO

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10
Q

where is eNOS found

A

endothelium

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11
Q

where is guanylate cyclase found

A

vascular smooth muscle

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12
Q

what does NO do in smooth muscle

A

binds heme group on guanylate cyclase and stimulates cGMP and activation of protein kinase g

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13
Q

how does protein kinase G relax smooth muscle? (4 ways)

A

inhibits Cav 1.2
stimulation of Ca/K channels (BKca)
decreased MLC phosphorylation
enhanced Ca uptake in ER (phospholambam)

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14
Q

organic nitrates MOA

A

non selective vasodilators
breakdown to NO (bioactivation)

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15
Q

do organic nitrates require functional endothelium

A

no

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16
Q

what are nitrates used for?

A

sublingually for angina
oral for prolonged prophylaxis

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17
Q

what happens with continuous admin of nitrates”?

A

tolerance

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18
Q

asian population has an allele that decreases efficacy of what?

A

glycerol trinitrate
lys 504 allele

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19
Q

sodium nitroprusside dilates what

A

veins and arterioles

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20
Q

what is sodium nitroprusside metabolized to and where?

A

in erythrocytes to NO and CN which limits duration of treatment (toxic)

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21
Q

what does hydralazine dilate?

A

arterioles

22
Q

what does hydralazine interfere with

A

release of Ca from ER

23
Q

what can hydralazine be combined with?

A

isobride dinitrate in BiDil which is useful for African Americans with CHF

24
Q

what does human type B natriuretic peptide do?

A

activates guanyl cyclase domain
increases cGMP

25
B type peptide drugs
nesiritide and sacubitril
26
what is nesiritide used for?
acutely decompensated HF
27
how does nesiritide work?
binds and activates membrane bound guanyl cyclase
28
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
29
PDE3 inhibitors
amrinone and milrinone
30
PDE5 inhibitors
dipyridamole, sildenafil, tadalafil, vardenafil
31
what does PDE3 prefer
cAMP
32
what does PDE5 prefer
cGMP
33
what are PDE3 inhibitors used for?
IV for CHF
34
what has 10 fold selectivity over inhibiton of PDE6?
sildenfail (blue vision)
35
what pde is predominant in the corpus cavernosum?
PDE5
36
where is PDE6 located?
retina
37
PDE5 with longest duration of action?
tadalafil
38
PDE5 with shortest time to onset
vardenafil
39
PDE5 contraindicated with what?
nitrates
40
endothelium receptor antagonists
-entans bosentan, macitentan
41
what do bosentan and macitentan do
blcok ETa and ETb
42
what does ambrisentatn do
block ETa
43
what are the -entan endothelien antagonists used for
pulmonary arterial hypertension
44
what are the -entans contraindicated in and why
pregnancy, hepatotoxicity
45
what do prostacyclin analogs do
relax pulmonary vascular smooth muscle
46
where is prostacyclin produced?
endothelium
47
what are the prostacyclin analogs?
PGI2, treprostinil, Iloprost, selexipag
48
activator of sGC drug
riociguat
49
what does riociguat do?
increases cGMP concentration in vascualr smooth muscle
50
what is riociguat a substrate for?
pgp, CYP 1A1, 3A
51
alpha 1 agonist drugs
epinephrine, phenylephrine, midodrine, droxidopa
52

PHRM 844 (16 decks)

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