Achalasia medical therapy: Difference between revisions

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Latest revision as of 15:37, 27 November 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Twinkle Singh, M.B.B.S. [2], Ahmed Younes M.B.B.CH [3]

Overview

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.

Medical Therapy

Botulinum Toxin

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]

Oral Pharmacotherapy

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]

Pharmacotherapy	Dose	Time to maximum effect	Duration of effect	% of symptomatic improvement'
Nifedipine	10-30 mg, sublingually 30-45 min before meals	20-45 min	30-120 min	0-75 %
Isosorbide dinitrate	5 mg, sublingually 10-15 min prior to meals	3-27 min	30-90 min	53-87 %
Botulinum toxin	100 units of toxin placed by sclero-needle in at least 4 quadrants just above the squamocolumnar junction

Contraindicated medications

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

ACG Clinical Guideline: Diagnosis and Management of Achalasia^[1]

Recommendations for the Management of Achalasia

"1. Pharmacologic therapy for achalasia is recommended for patients who are unwilling or cannot undergo definitive treatment with either PD or surgical myotomy and have failed botulinum toxin therapy (strong recommendation, low-quality evidence)."

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Vaezi MF, Pandolfino JE, Vela MF (2013). "ACG clinical guideline: diagnosis and management of achalasia". Am J Gastroenterol. 108 (8): 1238–49, quiz 1250. doi:10.1038/ajg.2013.196. PMID 23877351.
↑ Zhao X, Pasricha PJ (2003). "Botulinum toxin for spastic GI disorders: a systematic review". Gastrointest Endosc. 57 (2): 219–35. doi:10.1067/mge.2003.98. PMID 12556788.
↑ ^3.0 ^3.1 Boeckxstaens GE, Zaninotto G, Richter JE (2014). "Achalasia". Lancet. 383 (9911): 83–93. doi:10.1016/S0140-6736(13)60651-0. PMID 23871090.

Template:WS Template:WH

[pmid23877351-1] 1.0 ^1.1 ^1.2 ^1.3 Vaezi MF, Pandolfino JE, Vela MF (2013). "ACG clinical guideline: diagnosis and management of achalasia". Am J Gastroenterol. 108 (8): 1238–49, quiz 1250. doi:10.1038/ajg.2013.196. PMID 23877351.

[pmid12556788-2] Zhao X, Pasricha PJ (2003). "Botulinum toxin for spastic GI disorders: a systematic review". Gastrointest Endosc. 57 (2): 219–35. doi:10.1067/mge.2003.98. PMID 12556788.

[pmid23871090-3] 3.0 ^3.1 Boeckxstaens GE, Zaninotto G, Richter JE (2014). "Achalasia". Lancet. 383 (9911): 83–93. doi:10.1016/S0140-6736(13)60651-0. PMID 23871090.

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Achalasia}}
-{{CMG}}
+{{CMG}} {{AE}} {{TS}}, {{AY}}
 ==Overview==
+[[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.
 ==Medical Therapy==
-*Medication:
+===Botulinum Toxin===
-**Intra-[[sphincter]]ic injection of [[botulinum toxin]] (or botox), to paralyze the lower esophageal sphincter and prevent [[spasm]]s.  As in the case of botox injected for cosmetic reasons, the effect is only temporary, and symptoms return quickly in most patients. Botox injections cause scarring in the sphincter which may increase the difficulty of later [[Heller myotomy]].  This therapy is only recommended for elderly patients who cannot risk surgery.
+Intra-[[sphincter]]ic injection of [[botulinum toxin]] (or botox), to paralyze the lower esophageal sphincter and prevent [[spasm]]s.  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.<ref name="pmid23877351">{{cite journal| author=Vaezi MF, Pandolfino JE, Vela MF| title=ACG clinical guideline: diagnosis and management of achalasia. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 8 | pages= 1238-49; quiz 1250 | pmid=23877351 | doi=10.1038/ajg.2013.196 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23877351  }} </ref>  [[Botox]] injections cause scarring in the sphincter which may increase the difficulty of later [[Heller myotomy]].
-::* 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. As it is the excitatory neurons that release acetylcholine, a decrease in LES tone is observed.
+'''Indications'''
-::*:* It has also been shown that BoTox interferes with cholinergic signaling in the myenteric nervous system that supplies smooth muscle, and hence also decreases smooth muscle contractility.
+* For patients who cannot risk surgery
-::* 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.
+* As an adjunct to [[myotomy]] to treat residual [[Lower esophageal sphincter|LES]] spasms
-::*:* 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%.
+'''Mechanism of Action'''
-::* BoTox is very well tolerated, and only ~ 5% develop symptomatic gastroesphageal reflux disease (GERD).
+* 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|presynaptic nerve terminal]].  Decrease in [[acetylcholine]] results in [[Lower esophageal sphincter|decreased LES]] tone.
-::* The technique is currently being refined with even better results when injection is guided by endoscopic ultrasound.
+* It has also been shown that Botox interferes with [[cholinergic]] signaling in the [[Myenteric plexus|myenteric]] neurons that supplies [[smooth muscle]], and hence also decreases smooth muscle [[contractility]].
-::* Some surgeons believe that BoTox can increase the difficulty of future surgery, and therefore recommend it only for patients who are not candidates for dilation or surgery.
+* Relief was associated with a reduction in [[Cardia|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|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)<ref name="pmid12556788">{{cite journal| author=Zhao X, Pasricha PJ| title=Botulinum toxin for spastic GI disorders: a systematic review. | journal=Gastrointest Endosc | year= 2003 | volume= 57 | issue= 2 | pages= 219-35 | pmid=12556788 | doi=10.1067/mge.2003.98 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12556788  }} </ref><ref name="pmid23877351">{{cite journal| author=Vaezi MF, Pandolfino JE, Vela MF| title=ACG clinical guideline: diagnosis and management of achalasia. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 8 | pages= 1238-49; quiz 1250 | pmid=23877351 | doi=10.1038/ajg.2013.196 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23877351  }} </ref><ref name="pmid23871090">{{cite journal| author=Boeckxstaens GE, Zaninotto G, Richter JE| title=Achalasia. | journal=Lancet | year= 2014 | volume= 383 | issue= 9911 | pages= 83-93 | pmid=23871090 | doi=10.1016/S0140-6736(13)60651-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23871090  }} </ref>
-**Drugs that reduce LES pressure may be useful, especially as a way to buy time while waiting for surgical treatment.  These include [[calcium channel blockers]] such as [[nifedipine]], and [[nitrates]] such as [[isosorbide dinitrate]] and [[nitroglycerin]].  Unfortunately, many patients experience unpleasant side effects such as [[headache]] and swollen feet, and these drugs often stop helping after several months.
-:* Nitrates,
+{{#ev:youtube|xKetB4qNaI8}}
-:* Aminophylline,
-:* Terbutaline
+===Oral Pharmacotherapy===
-:* Ca++ channel blockers
+Drugs that reduce [[Lower esophageal sphincter|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.
-:*:* Decreases LES tone
-:*:* Usually only provide minimal relief.
+'''Indications'''
-:*:* As the pills themselves can get stuck in the esophagus, this can complicate the disease.
+*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]]<ref name="pmid23877351">{{cite journal| author=Vaezi MF, Pandolfino JE, Vela MF| title=ACG clinical guideline: diagnosis and management of achalasia. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 8 | pages= 1238-49; quiz 1250 | pmid=23877351 | doi=10.1038/ajg.2013.196 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23877351  }} </ref><ref name="pmid23871090">{{cite journal| author=Boeckxstaens GE, Zaninotto G, Richter JE| title=Achalasia. | journal=Lancet | year= 2014 | volume= 383 | issue= 9911 | pages= 83-93 | pmid=23871090 | doi=10.1016/S0140-6736(13)60651-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23871090  }} </ref>
+{| class="wikitable"
+|-
+|'''Pharmacotherapy '''|| align="center" |'''Dose'''||'''Time to maximum effect'''|| '''Duration of effect'''||'''% of symptomatic improvement''''
+|-
+|[[Nifedipine]] ||10-30 mg, sublingually<br>30-45 min before meals  ||20-45 min||30-120 min||0-75 %
+|-
+|[[Isosorbide dinitrate]] ||5 mg, sublingually<br>10-15 min prior to meals ||3-27 min ||30-90 min||53-87 %
+|-
+|[[Botulinum toxin]]|| colspan="4" |100 units of toxin placed by sclero-needle in at least 4 quadrants just above the squamocolumnar junction
+|}
+===Contraindicated medications===
+{{MedCondContrAbs
+|MedCond = Achalasia|Alendronate|Etidronic acid|Hyoscyamine|Ibandronic acid|Orphenadrine}}
+==ACG Clinical Guideline: Diagnosis and Management of Achalasia<ref name="pmid23877351">{{cite journal| author=Vaezi MF, Pandolfino JE, Vela MF| title=ACG clinical guideline: diagnosis and management of achalasia. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 8 | pages= 1238-49; quiz 1250 | pmid=23877351 | doi=10.1038/ajg.2013.196 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23877351  }} </ref>==
+===Recommendations for the Management of Achalasia===
+{| class="wikitable"
+|-
+| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' Pharmacologic therapy for achalasia is recommended for patients who are unwilling or cannot undergo definitive treatment with either PD or surgical myotomy and have failed botulinum toxin therapy (''strong recommendation, low-quality evidence'').<nowiki>"</nowiki>
+|-
+|}
 ==References==
+{{Reflist|2}}
-{{Reflist|2}}
+[[Category:Gastroenterology]]
+[[Category:Otolaryngology]]
+{{WS}}
+{{WH}}