Achalasia medical therapy: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Achalasia}} | {{Achalasia}} | ||
{{CMG}} {{AE}} {{TS}} | {{CMG}} {{AE}} {{TS}}, {{AY}} | ||
==Overview== | ==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. | [[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== | ==Medical Therapy== | ||
===Botulinum Toxin=== | ===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. First month response rates are > 75% but they need repeat injections every 6-24 months. | 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]]. | ||
'''Indications''' | '''Indications''' | ||
* For patients who cannot risk surgery | * For patients who cannot risk surgery | ||
* As an adjunct to myotomy to treat residual LES spasms | * As an adjunct to [[myotomy]] to treat residual [[Lower esophageal sphincter|LES]] spasms | ||
'''Mechanism of Action''' | '''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|presynaptic nerve terminal]]. Decrease in [[acetylcholine]] results in [[Lower esophageal sphincter|decreased LES]] tone. | ||
* It has also been shown that | * 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]]. | ||
* 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%. | * 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''' | '''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 | * 16-25% rate of developing chest pain | ||
* [[Mediastinitis]] (rare) | * [[Mediastinitis]] (rare) | ||
* Allergic reaction to egg protein (rare) | * [[Allergic]] reaction to egg protein (rare) | ||
* Higher rate of subsequent surgical complications | * Higher rate of subsequent surgical complications | ||
* 50% relapse rate | * 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> | * 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> | ||
{{#ev:youtube|xKetB4qNaI8}} | |||
===Oral Pharmacotherapy=== | ===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. | 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. | ||
'''Indications''' | '''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. | *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. | *High risk patients who cannot undergo surgical procedures. | ||
*Patients who refuse pneumatic dilation or myotomy. | *Patients who refuse pneumatic dilation or [[myotomy]]. | ||
*Patients in whom repeated injections of botulinum toxin fail to relieve symptoms. | *Patients in whom repeated injections of [[botulinum toxin]] fail to relieve symptoms. | ||
'''Mechanism of action''' | '''Mechanism of action''' | ||
| Line 53: | Line 57: | ||
[[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> | [[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 || | |'''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 % | |[[Nifedipine]] ||10-30 mg, sublingually<br>30-45 min before meals ||20-45 min||30-120 min||0-75 % | ||
| Line 61: | Line 65: | ||
|[[Isosorbide dinitrate]] ||5 mg, sublingually<br>10-15 min prior to meals ||3-27 min ||30-90 min||53-87 % | |[[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 | |[[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== | ==References== | ||
{{Reflist|2}} | |||
{{ | [[Category:Gastroenterology]] | ||
[[Category:Otolaryngology]] | |||
{{WS}} | |||
{{WH}} | |||
Latest revision as of 15:37, 27 November 2017
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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
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]
{{#ev:youtube|xKetB4qNaI8}}
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.