vasodilators Flashcards
hockerman
what are the vasodilators that regulate membrane potential?
K+ channel agonists/openers (minoxidil, diazoxide)
adenosine
they reduce voltage-gated Ca2+ channel activity
what is the MOA of K+ channel agonsits?
K+ flux sets the membrane potentional –> The longer K+ channels are open, 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+ channel
what is minoxidil?
K+ channel opener and potent vasodilator activated in vivo by sulfotransferase 1A1
effective in severe, drug resistant forms of HTN
what drugs are used concurrently with minoxidil?
loop diuretics
beta blockers
what are the SE of minoxidil?
hypertrichosis
what is diazoxide?
K+ channel opener and potent vasodilator used IV to treat acute HTN or severe drug resistant form of HTN
what is the MOA of diazoxide in hypoglycemia?
inhibits release of insulin from pancreatic beta-cells, which treats hypoglycemia secondary to hyperinsulinemia
what is adenosine?
nucleoside given IV that binds to A1 receptor (GPCR)
increases conduction of a K+ channel to induce relaxation and hyperpolarization
what are the indications of adenosine?
coronary stress test
supraventricular arrhythmias
how does the vascular smooth muscle hyperpolarize?
via adenosine
G-beta, gamma binds and activates G-protein activated inwardly rectifying K+ channel (GIRK) –> conducts K+ efflux –> membrane hyperpolarizes
what vasodilators stimulate nitric oxide production?
organic nitrates/nitrites
hydralazine
human type B natriuretic peptide (BNP)
sacubitril
what is eNOS?
isoform of nitric oxide synthase that is located in vascular endothelium
activated by Ca2+-CAM
where does nitric oxide diffusion take place?
vascular smooth muscle (directly relaxes sm)
where is guanylate cyclase located?
vascular smooth muscle
what did nitric oxide use to be called?
endothelial derived relaxing factor (EDRF)
what is a partial inhibitor of acetylcholine?
L-NMMA
what drug relaxes smooth muscle via nitric oxide?
acetylcholine
how does smooth muscle relax via nitric oxide?
nitric oxide binds to heme iron prosthetic group in guanylate cyclase –> stimulates the production of cGMP and activates protein kinase G (cGKI)
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 into ER (phospholamban)
what are organic nitrates?
non-selective vasodilators that breakdown nitric oxide via bioactivation for acute or chronic administration
what are the types of organic nitrates/nitrites?
amylnitrite
glyceryl trinitrate (GTN)
pentaerythritol tetranitrate (PETN)
isosorbide dinitrate
isosorbide mononitrate
nitroprusside
what is PK of GTN?
3 minute half life
under 1% oral bioavailability
what is the PK of isosorbide dinitrate?
10 minute half life
20% oral bioavailability
what is the PK of isosorbide mononitrate?
280 minute half life
100% oral bioavailability
what are organic nitrates used for?
given sublingually for acute attacks of angina
given orally/transdermally for prolonged prophylaxis
tolerance occurs with continuous administration
what is sodium nitroprusside (SNP)?
vasodilator (veins and arterioles) given IV for acute management of HTN crisis and severe decompensated HF