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Old 02-23-2012
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Drug Drugs acting via cGMP

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 unwrapped around vascular endothelium.
NO activates guanylyl cyclase → ↑cGMP → dephosphorylates myosin light chain kinase → smooth muscle relaxation
Note, tolerance develops rapidly

Addressed by telling patient 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
venodilator = reduces preload; AE: SLE like syndrome
Know that ANP (Atrial Natriuretic Peptide) acts by activating guanylyl cyclase
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