Vasodilators Flashcards
K+ channel agonists
The longer the K+ channels are open, the closer the membrane potential is to K+ equilibrium
The closer the membrane potential is to K+ equilibrium, the harder it is to depolarize the membrane enough to open voltage-gated Ca2+ channels
Minoxidil
Prodrug that is activated by sulfotransferase 1A1
Potent vasodilator by cAMP PDE inhibition effective in severe drug resistant HTN
HTN, alopecia
SE: hypertrichosis, reflex tachycardia, fluid retention
often used with loop diuretics and beta blockers
Diazoxide (oral, IV)
HTN, hyperinsulinemia
potent vasodilator–> effective in severe, drug resistant forms of HTN
Inhibits the release of insulin from pancreatic beta cells
Adenosine
Binds to A1 receptor that is coupled to specific K+ channels
A1 receptor is a Gi signaling pathway that allows Gby binding to GIRK and opening–> conducts K+ efflux and membrane hyperpolarization
GIRK is present is vascular smooth muscle, cardiac muscle, muscarinic receptors in atria
Results: increases conductance of K+ channel
coronary stress test and supraventricular arrhythmias
Nitric oxide production
NO is produced in vascular endothelium
L-arginine–>NOS–>L-Citrulline + NO
Major NO synthase in regulation of vascular tone is eNOS
In the endothelium, when there is an elevation of Ca2+ it will stimulate eNOS by binding to Ca-calmodulin
NO is then diffused into vascular smooth muscle–> activates guanylyl cyclase–> increase in cGMP–> relaxation of smooth muscle
NO binds to heme iron in guanylyl cyclase which stimulates production of cGMP and activates protein kinase G
Protein kinase G
inhibits Cav1.2
stimulates Ca2+ activated K+ channels
decreased MLC phosphorylation
enhances Ca2+ uptake in ER
Epoprostenol
IV
T1/2: 3-5 min
Treprostinil
oral, IV
T1/2: 4 hours
Iloprost
inhalation
T1/2: 30 min
Selexipag
oral
T1/2: 6-13 hours
