Medication Summary
Medical therapy is the first line of treatment for esophageal spasm. Because the etiology is unknown, all medical therapies are directed at symptoms, not the etiology. Proton pump inhibitors may be useful for associated gastroesophageal reflux disease. Calcium channel blockers and nitrates may decrease pain associated with esophageal spasms. Botulinum toxin decreases acetylcholine available at nerve endings. Imipramine improves pain by an unknown mechanism of action.
Calcium channel blockers
Class Summary
Calcium channel blockers reduce the amplitude of contractions. In nutcracker esophagus, calcium channel blockers effectively reduce the amplitude of contractions, but chest pain often is not reduced. Whether calcium channel blockers decrease the force of contraction of muscle or decrease the underlying stimulus is unknown.
Diltiazem (Cardizem, Cartia XT, Dilacor XR, Diltzac, Tiazac, Diltia XT)
Diltiazem is FDA approved for hypertension, vasospastic angina, and chronic stable angina. It decreases calcium ion flux across cell membranes in smooth muscle, thereby relaxing the vascular smooth muscle.
Nitrates
Class Summary
Like calcium channel blockers, nitrates may decrease the pain associated with esophageal spasm. The mechanism of action is unknown, but it may be related to decreasing vasospasm in the brainstem, similar to calcium channel blockers, or it may be due to a direct effect on the myocytes.
Isosorbide dinitrate (Dilatate SR, Isordil, Isoditrate ER)
The approved indication is for angina pectoris. Isosorbide dinitrate relaxes vascular smooth muscle by stimulating the intracellular cyclic GMP. By decreasing left ventricular pressure and dilating the arteries, it reduces cardiac oxygen demand.
Tricyclic antidepressants
Class Summary
These agents, specifically imipramine, have been shown to decrease chest pain of no apparent cause on angiography. Studies specifically evaluating nutcracker esophagus are not yet available. The mechanism of action of imipramine is not known.
Imipramine (Tofranil, Tofranil PM)
Imipramine decreases pain in patients with chest pain of no apparent cause on angiography, which may be esophageal spasm. This is not an FDA-approved use. The mechanism of action is not known. The primary use of imipramine is in the treatment of depression.
Toxins (botulinum toxin)
Class Summary
This class binds receptors in nerve endings, decreasing the release of acetylcholine. Injecting botulinum toxin endoscopically above the lower esophageal sphincter (LES) improves the symptoms of patients with esophageal spasms. However, the effect is temporary and the response decreases with repeated injections.
Botulinum toxin (BOTOX®)
Botulinum toxin treats excessive abnormal contractions associated with blepharospasm. It binds to receptor sites on motor nerve terminals and inhibits the release of acetylcholine, which, in turn, inhibits the transmission of impulses in neuromuscular tissue.
Phosphodiesterase-5 Enzyme Inhibitors
Class Summary
These agents can relax smooth muscle.
Sildenafil (Revation, Viagra)
Sildenafil acts by inhibiting cGMP-specific phosphodiesterase type 5, an enzyme that promotes the degradation of cGMP, thereby enhancing the effects of nitric oxide-activated increases in cGMP, resulting in smooth muscle relaxation.
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Barium swallow demonstrates diffuse uncoordinated contractions of the esophagus in a patient with diffuse esophageal spasm.
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This is normal esophageal manometry tracing with normal amplitude of the contractions. The contractions are coordinated because the contractions in the proximal esophagus (top of image) occur before the contractions further distal in the esophagus.
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Esophageal manometry tracing demonstrates diffuse esophageal spasm. Note the multiple uncoordinated contractions in the third tracing from the distal esophagus.
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Esophageal manometry tracing demonstrates nutcracker esophagus. Note the excessive amplitude of the contractions.
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High-resolution manometric display of a normal esophageal swallow using esophageal pressure topography. Image courtesy of Wikimedia Commons.