Organic Nitrates

Organic nitrates work by relaxing vascular smooth muscle.  Nitric oxide is formed from these drugs, which causes vascular smooth muscle relaxation. Nitrates/nitrites are used in the treatment of angina and can also be used to reduce preload in the setting of pulmonary edema.  Reduction in preload assists in the treatment of angina by reducing oxygen demands on cardiac tissue. Additionally, dilation of coronary vasculature improves oxygen delivery.  Tolerance to these medications can develop. Headache is prominent and nitrates are contraindicated in combination with phosphodiesterase type 5 inhibitors (sildenafil and tadalafil) due to the combination causing extreme hypotension.  

Class Drugs

• Isosorbide dinitrate

• Isosorbide mononitrate

• Nitroglycerin

Class Mechanism of Action

Relaxes vascular smooth muscle

• Compounds convert to nitrite ions, then nitric oxide

• Nitric oxide increases cGMP levels, which leads to dephosphorylation of the myosin light chain in vascular smooth muscle, inducing vascular smooth muscle relaxation

Class Applications

Angina (Stable, unstable, variant angina)

• Dilation of large veins reduces preload, decreasing oxygen demand on cardiac tissue

• Dilation of coronary vasculature, increasing oxygen supply to cardiac tissue

• Nitrate free periods necessary to decrease tolerance

Class Adverse Effects

Contraindicated with phosphodiesterase type 5 inhibitors such as sildenafil and tadalafil

• Can cause extreme hypotension

Headache

Hypotension

Flushing

Tachycardia

Drug Table

Drug Name	Application	Comments	Image
Isosorbide Dinitrate		Long-acting (12-24 hrs)	"Ice" "Orb" "Die"
Isosorbide Mononitrate		Intermediate acting (~8 hours)	"Ice" "Orb" "Monocle"
Nitroglycerin		Short-acting: Sublingual tab or spray (~25 min); Intermediate-acting: Oral sustained release or transdermal (4-12 hrs.)	"TNT"