• Clinical science

Nitrates

Abstract

Nitrates are a class of medications that increase the release of nitric oxide (NO) in vascular smooth muscle cells, leading to smooth muscle relaxation and subsequent vasodilation. Veins are affected more than arteries, and most therapeutic effects of nitrates result from venous pooling and subsequently decreased preload. Rapid- and short-acting nitrates are primarily used in the symptomatic treatment of acute angina pectoris and hypertensive urgency. Side effects may include headache (nitrate-induced headache), gastroesophageal reflux, and hypotension with syncope. Prior intake of PDE-5 inhibitors significantly increases the risk of hypotension.

Agents and dosages

Agents Formulations Long- vs. short-acting Onset of action Duration of action
Nitroglycerin
  • Oral
  • Sublingual
  • Short
  • 2–5 minutes
  • 15–30 minutes
  • Transdermal patch
  • Long
  • 30 minutes
  • 8–14 hours

Isosorbide dinitrate

  • Sublingual
  • Short
  • 2–5 minutes
  • 1–2 hours
  • Oral
  • Long
  • 1 hour
  • 4-6 hours
Isosorbide mononitrate
  • Oral
  • Long
  • 30–45 minutes
  • 6–24 hours
Sodium nitroprusside
  • Intravenous

References:[1][2]

The authors cannot be held responsible for the contents provided being exhaustive, correct, or up to date. The contents have been meticulously researched by our editors. Especially updates regarding warnings and recommendations must be considered. Unless otherwise noted, the recommendations provided apply to adults.

Effects

  • Exogenous supply of nitric oxide (NO) through nitrate → activation of guanylyl cyclase → ↑ cyclic guanosine monophosphate (cGMP) → activation of protein kinase G
    • Increases SERCA activity → intracellular calcium → ↓ recruitment of contractile units → vasodilation
    • Increases myosin light chain phosphatase activity → ↓ phosphorylated myosinsmooth muscle relaxation → vasodilation
      • Peripheral vasodilation
        • Decreased preload through venous dilation (venous pooling); reduces myocardial wall tension; improved myocardial perfusion
        • Decreased afterload → reduces contraction effort ↓ myocardial oxygen demand
        • Dilates veins >>> arteries
      • Coronary dilationimproved myocardial perfusion
        • In patients with atherosclerotic CAD, arterioles are already dilated to maximize cardiac blood flow (due to flow-limiting stenosis) → difficult to dilate coronary vessels further → limited effect of nitrates
  • Anginal pain relief: preload through venous poolingheart size → ↓ oxygen demand → pain

References:[1]

Side effects

  • Circulatory dysregulation: hypotension, reflex sympathetic activity → reflex tachycardia → nitrate syncope
  • Nitrate-induced headache: vasodilation of the cerebral arteries
  • Gastroesophageal reflux: relaxation of the lower esophageal sphincter
  • Development of tolerance
    • Prevention: intermittent therapy with nitrate-free intervals of at least 8 hours
  • Cyanide toxicity after sodium nitroprusside infusion (see cyanide poisoning)
  • Monday disease”: Industrial workers who are exposed to nitrates during the work week develop a tolerance over the course of the week; no exposure during weekends leads to loss of tolerance. Reexposure on Monday causes dizziness and headache.

References:[1]

We list the most important adverse effects. The selection is not exhaustive.

Indications

References:[2][3][4]

Contraindications

References:[4]

We list the most important contraindications. The selection is not exhaustive.

last updated 11/09/2018
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