MEDCHEM: nitrates

Very fast acting; some are used in emergency situations

Biochemical mechanism of action: induce the product “NO” after metabolism that causes smooth muscle relaxation through activating the enzyme guanylate cyclase. The later converts GTP into cGMP, the actual vasodilator

Esters of nitric acid (inorganic acid = no carbons) with poly-ols is called inorganic esters.

Very lipophlic drug (because of the ester nature, no strong polar groups); absorbed quickly which is good for use in emergencies.

Being an ester, it moisture and heat sensitive; so should not be stored in the bathroom cabinet where heat and moisture exist.

• quickly hydrolyzed by serum esterase into the two products : glyceryl-dinitrate+nitrate ions, The dinitrate is inactive, and the nitrate ions “-NO3 “ is acted upon by an enzyme called aldehyde dehydrogenase that reduces nitrite ions “-NO2 “ and further reduces it into nitric oxide “NO”, the actual stimulator of the enzyme Guanylate cyclase.

  = label nitroglycerin as a pro-drug

nitroglycerin

NO activates guanylate cyclase. what is the pathway?

GTP to cGMP via guanylate cyclase, then cGMP to GMP via PDE

isosorbide dinitrate

isosorbide mononitrate

hydralazine

Ranolazine

sildenafil

tadalafil

avanafil