Vasodilators Flashcards by Eli Lee

why does increasing K+ channel opening relax vascular smooth muscle

K+ flux sets the membrane potential
the longer the K+ channels are open, the closer the membrane potential is to K+ equilibrium potential
the closer the membrane potential is to the K+ equilibrium potential, the harder it is to depolarize the membrane enough to open voltage gated Ca2+ channels

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drugs that are K+ channel agonists/openers

Minoxidil
Diazoxide
Adenosine

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minoxidil metabolism

prodrug
activated in vivo by sulfotransferase 1A1

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what is minoxidil used with

with loop diuretics and beta blockers

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effects of minoxidil

very potent vasodilator - effective in severe, drug resistant forms of htn

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what may contribute to minoxidil efficacy

cAMP PDE inhibition

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minoxidil structure

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diazoxide indication

used IV to tx acute htn

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effects of diazoxide

very potent vasodilator - effective in severe, drug resistant forms of htn

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diazoxide moa

inhibits release of insulin from pancreatic beta cells

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diazoxide structure

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what does adenosine bind to

A1 receptor- a GPCR

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what does adenosine do

increases conductance of a K+ channel

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what is adenosine used for

supraventricular arrhythmias
coronary stress test

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where is the nitric oxide synthase

vascular endothelium

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where does NO diffuse to

vascular smooth muscle

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what is found in vascular smooth muscle

guanylate cyclase

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how can NO directly relax smooth muscle

by being exogenously applied

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where does NO bind and then what does it do

NO binds to heme iron prosthetic group in guanylate cyclase, stimulating production of cGMP and activating protein kinase G (cGKI)

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how does protein kinase G relax smooth muscle

inhibition of L-type Ca2+ channels (Cav1.2)
stimulation of Ca2+ activated K channels (BKca)
decreased MLC phosphorylation (myosin phosphatase 1)
enhanced Ca2+ uptake in to ER (phospholamban)

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what are features of organic nitrates

non-selective vasodilators
breakdown to NO
don’t require functional endothelium
acute or chronic admin

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types of organic nitrates/nitrites

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organic nitrates PK

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organic nitrates indications

given sublingually in tx of acute angina attacks
given orally or transdermally for prolonged prophylaxis
tolerance occurs with continuous admin

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pharmacogenetics of glycerol trinitrate

glu 504 Lys polymorphism in ALDH-2 glu 504 is 10x more efficient in metabolizing GTN

what likely accounts for lack of efficacy of GTN in large % of asian pop

30-50% of asian pop has at least one Lys 504 allele

what is the diff in activation of GTN and ISMN/ISDN

ISMN and ISDN activation is ALDH-2 independent

what is the mechanism of cell damage initiated by hyperglycemia

AGE precursor methylglyoxal inhibits vasorelaxation stimulated by acetylcholine/NO

sodium nitroprusside (SNP) indication

given IV for acute management of hypertensive crisis and severe decompensated hf

SNP effects

dilates veins and arterioles

SNP metabolism

metabolized in erythrocytes to NO, 4CN-, and cyanmethemoglobin

hydralazine effects

dilates arterioles preferentially

hydralazine moa

moa not clear appears to interfere with release of Ca from the ER may also prevent oxidation of NO

what can hydralazine induce

Lupus-like syndrome

what does BiDil (the combo of hydralazine + ISDN) do

antioxidant activity potentiates vasodilatory activity of ISDN BiDil decreases mortality in AA w CHF

what is the human type B natriuretic peptide (BNP) drug

natrecor (nesiritide)

natrecor indication

given IV in acutely decompensated HF

what does natrecor bind to and do

binds to and activates membrane bound guanylate cyclase in vascular smooth muscle and endothelial cells

where is natrecor metabolized

synthesized and secreted from heart muscle in response to increased blood volume

natriuretic peptide mechanism

neprilysin (a protease) inhibitor drug

sacubitril

what is sacubitril

a prodrug activated by esterases

sacubitril moa

prevents breakdown of BNP, enhancing its action (also angiotensin 2 and bradykinin)

what is sacubitril not used with

ACE inhibitors

sacubitril indication

tx hf

sacubitril combo product

ARNI - combination with ARB valsartan (entresto)

what drugs inhibit breakdown of cGMP/AMP

PDE

PDE3 inhibitor structures

what is the mechanism for controlling smooth muscle tone

what drug class is amrinone/milrinone

PDE3 (cAMP) inhibitor

amrinone/milrinone effect

direct positive inotropic effect on myocardium. minimal chronotropic effect. direct vasodilatory effect on vascular smooth muscle.

how is amrinone/milrinone given

amrinone/milrinone indication

used mainly in ACUTE chf ONLY

what is sildenafil a potent and specific inhibitor of

cGMP PDE5

how selective is sildenafil for each PDE

10 fold more selective for PDE5 inhibition over PDE6 inhibition 4000 fold more selective for PDE5 inhibition over PDE3 inhibition

what can PDE6 inhibition lead to

bluish vision

what does sildenafil lack

systemic vasodilation

PDE5 inhibitor structures

all very similar vardenafil has extra methyl group and nitrogen

levitra pk

shorter time to onset than viagra more selective for PDE5 than viagra

cialis pk

more selective for pde5 than viagra longer duration of action than viagra or levitra

why is PDE5 inhibitors CI w organic nitrates

both drugs increase accumulation of cGMP, leading to precipitous drop in BP

endothelial signaling

what are bosentan (tracleer) and macitentan (opsumit) used for

pulmonary arterial htn

tracleer and opsumit moa

endothelin receptor antagonists block both ETa (VSM) and ETb (VSM + endothel) receptors

tracleer and opsumit MW

low

ambrisentan (letairis) moa

blocks only ETa receptors

what is letairis CI for

pregnancy

what sex are tracleer, opsumit, and letairis available for

female

PGI2, iloprost, selexipag effect

relax pulmonary vascular smooth muscle

PGI2, iloprost, selexipag indication

tx pulmonary arterial htn

PGI2 dosage form

iloprost dosage form

inhalation

selexipag dosage form

oral

PGI2, iloprost, selexipag structures

riociguat (adempas) indication

tx pulmonary arterial htn

riociguat (adempas) moa

potentiates NO effect stimulates sGC activity allosterically increases cGMP conc in VSM

what is riociguat (adempas) not combined with

nitrates or PDE5 inhibitors

riociguat (adempas) CI

pregnancy

riociguat (adempas) risk

hemorrhage

what is riociguat (adempas) substrate for

P-gp, CYP1A1, CYP3A

what sex can take riociguat (adempas)

females only

why are PDE5 inhibitors indicated for PAH

PDE5 is expressed in vascular smooth muscle of lungs both are thought to enhance vasodilatory effect of NO

which PDE5 inihibitors are indicated for PAH

sildanifil cialis

Vasodilators Flashcards

(83 cards)