cGMP is High Yield

• Know that the drugs acting via cGMP are
• Nitrates (Nitroglycerin, isosorbide dinitrate)
• Increases production of cGMP
• Activation (denitration) to NO occurs within the smooth muscle cells enwrapped around vascular endothelium.
• NO activates guanylyl cyclase → ↑cGMP → dephosphorylates myosin light chain kinase → smooth muscle relaxation
• Note, tolerance develops rapidly
• Addressed by telling pt to take a break from the particular drug or Rx w/ a different anginal drug
• Occupation exposure → Monday Disease
• Nitroprusside
• Rx: Hypertensive emergencies
• Same mechanism as nitrates
• AE: Cyanide toxicity (rx: sodium thiosulfate)
• Sildenafil
• Decreased breakdown of cGMP
• Inhibits 5’-phosphodiesterase
• The enzyme that breaksdown cGMP
• Do not give a pt on a nitrate sildenafil (will synergistically cause their diastolic BP to fall through the floor!)
• Instead give Alprostadil
• If you accidentally did combine the 2 above what drug would you want to give?
• α-1 agonist
• Hydralazine
• dilates arterioles more than veins= reduces afterload; AE: SLE like syndrome
• Know that ANP (Atrial Natriuretic Peptide) acts by activating guanylyl cyclase