Organic Nitrates

Products

Nitrates are commercially available in the form of chewable capsules, transdermal patches, infusion preparations, ointment, sustained-release tablets, sustained-release capsules, and sprays. As the first representative, nitroglycerin was already produced in the 19th century and used for the treatment of angina pectoris. Nitrates are thus among the oldest synthetic drugs.

Structure and properties

Organic nitrates are esters of nitric acid with polyols (alcohols) such as glycerol: -C-O-NO2. The pure substances are explosives, which are also used as explosives (e.g., dynamite). However, in the drugs they are present in a stabilized form and are not explosive.

Effects

Nitrates (ATC C01DA) have vasodilator, antihypertensive, antianginal, and antispasmodic properties. They relax vascular smooth muscle as well as smooth muscle of the bronchi, urinary tract, gallbladder, bile duct, esophagus, and intestines. Nitrates are prodrugs with high first-pass metabolism. The effects are due to the release of nitric oxide (NO), which relaxes smooth muscle. NO stimulates guanylate cyclase and increases the intracellular concentration of cyclic guanosine monophosphate (cGMP). Nitrates are active on veins, arterioles, arteries, and coronary arteries and mediate the following effects:

  • Dilatation of blood vessels; at low doses, this is primarily veins, but at higher doses, it is also arteries
  • Lowering blood pressure
  • Reduction of preload, reduction of blood return to the heart.
  • Reduction of oxygen consumption of the heart muscle.
  • Reduction of peripheral resistance (reduction of afterload).

Indications

  • For the treatment of attacks and prevention of angina pectoris attacks.
  • Coronary heart disease
  • Heart failure
  • Post-myocardial infarction, acute myocardial infarction.
  • Arterial pulmonary hypertension
  • Anal fissure see under nitroglycerin ointment

Dosage

According to the professional information. Dosage depends on the drug and indication. Because of high first-pass metabolism, nitrates are also administered sublingually and transdermally. Because tolerance can occur during therapy with nitrates, breaks in therapy of 8 to 12 hours at night are recommended for transdermal patches.

Active Ingredients

Not or no longer on the market in many countries:

Contraindications

Contraindications include (selection):

For complete precautions, see the drug label.

Interactions

Other antihypertensive drugs and other substances that affect blood pressure may potentiate the antihypertensive effect of nitrates. Phosphodiesterase-5 inhibitors such as sildenafil, tadalafil, vardenafil are contraindicated because they may cause a dangerous drop in blood pressure.

Adverse effects

The most common possible adverse effects include headache (“nitrate headache”), hypotension, tachycardia (rapid pulse), flushing, nausea, vomiting, and fatigue. Headache is most common during the first few days of therapy. Tolerance may occur with continuous use.