Achalasia medical therapy

Botulinum toxin, calcium channel blockers and nitrates are the most commonly used medical therapies for achalasia. However, they are not very effective and used only when pneumatic dilation and surgical procedures cannot be performed in high risk patients.

Intra-sphincteric injection of botulinum toxin (or botox), to paralyze the lower esophageal sphincter and prevent spasms. As in the case of botox injected for cosmetic reasons, the effect is only temporary, and symptoms return quickly in most patients. First month response rates are > 75% but they need repeat injections every 6-24 months.^[1] Botox injections cause scarring in the sphincter which may increase the difficulty of later Heller myotomy.

Indications

• For patients who cannot risk surgery
• As an adjunct to myotomy to treat residual LES spasms

Mechanism of Action

• Botox acts as a zinc-dependant protease and cleaves a protein called SNAP-25. This results in a block of acetylcholine release from the presynaptic nerve terminal. Decrease in acetylcholine results in decreased LES tone.
• It has also been shown that Botox interferes with cholinergic signaling in the myenteric neurons that supplies smooth muscle, and hence also decreases smooth muscle contractility.
• Relief was associated with a reduction in LES pressure by 40%, an increase in esophageal diameter by 17%, and a reduction in esophageal retention of 33%.

Adverse Effects

• Botox is very well tolerated, and only ~ 5% develop symptomatic gastroesophageal reflux disease (GERD).
• 16-25% rate of developing chest pain
• Mediastinitis (rare)
• Allergic reaction to egg protein (rare)
• Higher rate of subsequent surgical complications
• 50% relapse rate
• Requirement for repeat injections (Pasricha et.al. showed that 90% of patients experienced immediate relief, however only 65% have relief at 6 months, and only 42% are symptom free at one year)^[2][1][3]

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Drugs that reduce LES pressure may be useful, especially as a way to buy time while waiting for surgical treatment. Calcium channel blockers such as nifedipine, and long acting nitrates such as isosorbide dinitrate and nitroglycerin are the two most commonly used groups of medications.

Indications

• Drugs are the least effective mode of treatment. They are used temporarily before the more effective mode of treatment such as pneumatic dilation and myotomy can be used.
• High risk patients who cannot undergo surgical procedures.
• Patients who refuse pneumatic dilation or myotomy.
• Patients in whom repeated injections of botulinum toxin fail to relieve symptoms.

Mechanism of action

• They cause smooth muscle relaxation which leads to reduction in lower esophageal sphincter pressure and helps in esophageal emptying.

Adverse Effects

• Headache
• Hypotension
• Pedal Edema
• Usually only provide minimal relief.
• As the pills themselves can get stuck in the esophagus, this can complicate the disease.

Other uncommon drugs which can be used in achalasia management: Sildenafil, Theophyllin, Atropine, Dicyclomine, Cimetropium Bromide, Terbutaline^[1][3]

Achalasia is considered an absolute contraindication to the use of the following medications:

• Alendronate
• Etidronic acid
• Hyoscyamine
• Ibandronic acid
• Orphenadrine

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