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9 Cards in this Set

  • Front
  • Back
Nitrates: MOA
-release of NO and/or nitrothiols
-activation of cytosolic guanylate cyclase to form cGMP
-cGMP activation of protein kinase phosphorylates proteins
-decrease in myosin light chain kinase causes dephosphorylation of myosin, relaxes vessels
Nitrates: Physiological Responses
-venodilation, reduced preload
-dilation of coronary vessels
-decreased TPR, caridac output
-reduced O2 demand
-decreased platelet adhesion
-reflex tachycardia
-balance 02 supply w/demand
Nitrates: Tolerance
-undergo bio-activation w/sulfhydryl groups:
-no cross tolerance w/NO
-sulfhydryl-reducing agents reverse
-N-Acetylcysteine reverses
-activation of counter-reg mechanisms (Ang II, etc)
-free radical hypothesis:
-interferes w/endothelium
Nitrates: Side Effects
-Headache
-Postural hypotension
-Reflex tachycardia
-Overdose: elevated methemoglobin
-Oral agents: nausea
-Patches: skin reactions
BiDil
Isosorbide Dinitrate + Hydralazine:
-fixed combo: 20 mg Iso, 37.5 mg Hydralazine
Sildenafil: MOA
-inhibits cGMP - PDE5 (PDE1-PDE11)
-NO released into corpus cavernosum to allow blood inflow and erection
-NO activates guanylate cyclase to make cGMP
Sildenafil: Side Effects
-Headache
-Flushing
-Dyspepsia
-Priaprism
-Visual disturbances (PDE6)
-Potentiates actions of nitrates and NO donors; may induce severe ischemia
Tadalafil
Cialis
-FDA 2002
-24 to 36 hr duration
-PDE5 selective
Vardenafil
Levitra
-Aug 2003
-Faster onset
-PDE5, some PDE6