Release NO in smooth muscle which activates guanylyl cyclase and ↑ cGMP; smooth muscle relaxation in vessels ↓ venous return and heart size (10-30min)

Orthostatic hypotension, tachycardia, throbbing headache

First pass effect

methemoglobin regenerates cytochrome after cyanide poisoning

↑ NO which is an activator of guanylyl cyclase; cGMP dephosphorylates myosin light chains preventing interaction of myosin with actin (very similar to nitroglycerin)

Tolerance occurs if used more than a few hours without interruption

Synergistic hypotension with posphodiesterase type 5 inhibitors (sildenafil, etc)

Nonselective block of L-type calcium channels in vessels and heart

Atrioventricular block, acute heart failure, constipation, edema

Angina, hypertension, etc

Inhibit CYP450

Block of vascular L-type calcium channels > cardiac channels

Excessive hypotension

Does not ↓ AV conduction so can be used more safely than verapamil and diltiazem in presence of AV conduction abnormalities

Inhibits late sodium current in heart, also may modify fatty acid oxidation; reduces and improves efficiency of oxygen use by heart

QT interval prolongation

Inhibitors of CYP3A increase ranolazine concentration and duration of action

↑ cGMP by inhibiting its breakdown by phosphodiesterase 5. cGMP dephosphorylates myosin light chains causing relaxation of smooth muscle of corpora cavernosa required for erection.

Potentiate action of nitrates used for angina and severe hypotension and possibly MI can occur in men taking both drugs, blindness, altered color vision

Tadalafil (Cialis)
Vardenafil (Levitra)

Induce CYP450