Vasodilators Flashcards
Types of vasodilators
cGMP modulators
K+ channel agonists
Endothelin receptor antagonists
PGI2 analogs - IP receptor agonists
Vasodilators that regulate membrane potential
K+ channel agonists
Minoxidil
K+ channel agonist
Activated by sulfotransferase 1A1
Used w loop diuretics and B-blockers
Used for resistant HTN
Admin PO
Diazoxide
Not often used now
Inhibits insulin release from pancreatic B-cells
Admin IV for HTN
Admin PO for hypoglycemia
Adenosine
GPCR - binds to A1 receptor
Promotes hyperpolarization -> relaxation
Admin IV for coronary stress test
Nitric oxide synthase
eNOS isoform -> activated by Ca-CAM in vasc endothelium -> NO diffuses to vasc smooth musc -> guanylate cyclase
NO uses
ACh relaxes smooth muscle via NO
Exogenously applied NO directly relaxes smooth muscle
NO MOA
No binds heme in guanylate cyclase -> stimulates prod of cGMP -> activates protein kinase G
cGKi MOA to relax smooth muscle
Inhibit Ca channels (Cav1.2)
Stimulate Ca-activated K channels (BKCa)
Decrease MLC phosphorylation (Myosin phosphatase 1)
Enhance Ca uptake in ER (phospholamban)
Organic nitrates
Non-selective vasodilators
Bioactivation
Don’t require functional endothelium
Organic nitrate drugs
Amylnitrite
Glyceryl trinitrate (GTN)
Pentaerythritol tetranirate (PETN)
Isosorbide dinitrate
Isosorbide mononitrate
Nitroprusside
Organic nitrate administration
Sublingual for angina
PO for prophylaxis
Tolerance with prolonged use
Munition workers incidents
Tolerance to glyceryl trinitrate
GTN and Lys 504
Lys 504 metabolizes GTN slower
Decreased GTN efficacy
Common in Asian population -> alc intolerance (asian flushing)
Cell damage via hyperglycemia
ACh/NO promotes vasorelaxation
Methylglyoxal inhibits vasorelaxation from ocurring