Anal fissure medical therapy: Difference between revisions
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{{Anal fissure}} | {{Anal fissure}} | ||
{{CMG}};{{AE}}{{ADS}} | {{CMG}}; {{AE}}{{ADS}} | ||
==Overview== | ==Overview== | ||
Most common cause of anal fissure is straining when constipated. For treatment of [[constipation]], [[Constipation medical therapy#Medical Therapy|click here]]. Anal fissures in infants usually self-heal without anything more than frequently changing diapers and treating [[constipation]] if it is the cause. The topical therapy is the first line of treatment along with dietary and other conservative measures. [[Analgesic|Analgesia]] with [[lidocaine]] and vasodilators like [[nitroglycerin]] and [[nifedipine]] are chiefly used for the topical management. [[Botulinum toxin]] can be effective in 89% cases. It is reserved for the people who can't undergo [[surgery]] for high risk of incontinence. | |||
==Medical Therapy== | ==Medical Therapy== | ||
*For many years up until 1995, customary treatment included warm baths, topical anesthetics, stool bulking agents, mechanical anal stretching, and, sometimes, surgery. In 1995, doctors began using nitroglycerine cream (topical 1 percent isosorbide dinitrate) but found it less acceptable for long-term use due to patients developing a tolerance to the drug. In 1998, Italian researchers reported injecting [[botulinum toxin]] into the anal sphincter to promote healing by relieving anal spasm through relaxation of the muscle. | *For many years up until 1995, customary treatment included warm baths, topical [[Anesthesia|anesthetics]], stool bulking agents, mechanical anal stretching, and, sometimes, surgery. In 1995, doctors began using [[nitroglycerine]] cream (topical 1 percent [[isosorbide dinitrate]]) but found it less acceptable for long-term use due to patients developing a tolerance to the drug. In 1998, Italian researchers reported injecting [[botulinum toxin]] into the anal [[sphincter]] to promote healing by relieving anal spasm through relaxation of the muscle. | ||
* Most common cause of anal fissure is straining when constipated. For treatment of constipation, [[Constipation medical therapy#Medical Therapy|click here]] | * Most common cause of anal fissure is straining when constipated. For treatment of [[constipation]], [[Constipation medical therapy#Medical Therapy|click here]]. | ||
===Symptomatic=== | ===Symptomatic=== | ||
* Most anal fissures are shallow or superficial (less than a quarter of an inch or 0.64 cm deep). These fissures self-heal within a couple of weeks. Furthermore, the treatment used for [[hemorrhoid]] such as eating a high-fiber diet, using a stool softener, taking a painkiller and having a | * Most anal fissures are shallow or superficial (less than a quarter of an inch or 0.64 cm deep). These fissures self-heal within a couple of weeks. Furthermore, the treatment used for [[hemorrhoid]] such as eating a high-fiber diet, using a stool softener, taking a painkiller and having a sitz bath can help. | ||
* Preferred regimen, | * Preferred regimen, sitz bath: anus to be immersed in warm water for 10-15 minutes q8-12h for 4 weeks.<ref name="pmid25022811">{{cite journal |vauthors=Wald A, Bharucha AE, Cosman BC, Whitehead WE |title=ACG clinical guideline: management of benign anorectal disorders |journal=Am. J. Gastroenterol. |volume=109 |issue=8 |pages=1141–57; (Quiz) 1058 |year=2014 |pmid=25022811 |doi=10.1038/ajg.2014.190 |url=}}</ref><ref name="pmid16916391">{{cite journal |vauthors=Gupta P |title=Randomized, controlled study comparing sitz-bath and no-sitz-bath treatments in patients with acute anal fissures |journal=ANZ J Surg |volume=76 |issue=8 |pages=718–21 |year=2006 |pmid=16916391 |doi=10.1111/j.1445-2197.2006.03838.x |url=}}</ref><ref name="pmid22336789">{{cite journal |vauthors=Nelson RL, Thomas K, Morgan J, Jones A |title=Non surgical therapy for anal fissure |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003431 |year=2012 |pmid=22336789 |doi=10.1002/14651858.CD003431.pub3 |url=}}</ref><ref name="pmid3011180">{{cite journal |vauthors=Jensen SL |title=Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran |journal=Br Med J (Clin Res Ed) |volume=292 |issue=6529 |pages=1167–9 |year=1986 |pmid=3011180 |pmc=1340178 |doi= |url=}}</ref><ref name=":0">{{cite journal |author=Nelson R |title=Non surgical therapy for anal fissure |journal=Cochrane database of systematic reviews (Online) |volume= |issue=4 |pages=CD003431 |year=2006|pmid=17054170}}</ref> | ||
===Pediatric=== | ===Pediatric=== | ||
* Anal fissures in infants usually self-heal without anything more than frequently changing diapers and treating constipation if it is the cause. | * Anal fissures in infants usually self-heal without anything more than frequently changing diapers and treating [[constipation]] if it is the cause. | ||
===Chemical Sphincterotomy=== | ===Chemical Sphincterotomy=== | ||
* Painful deep chronic fissures, will not heal because of poor blood supply caused by sphincter spasm. Traditionally, surgical operations were required which are both painful and associated with various long-term complications, particularly incontinence in a small proportion of cases. | * Painful deep chronic fissures, will not heal because of poor blood supply caused by sphincter spasm. Traditionally, surgical operations were required which are both painful and associated with various long-term complications, particularly incontinence in a small proportion of cases. | ||
* | * [[Botulinum toxin]] injection, administered by [[colorectal]] surgeons, can also be used to relax the [[sphincter]] muscle and its use for this condition was first investigated in 1993.<ref>{{cite journal |author=Jost W, Schimrigk K |title=Use of botulinum toxin in anal fissure|journal=Dis Colon Rectum |volume=36 |issue=10 |pages=974 |year=1993 |id=PMID 8404394}}</ref> [[Botulinum toxin]] can provide relief in 89% cases.<ref name="pmid17604520">{{cite journal |vauthors=Radwan MM, Ramdan K, Abu-Azab I, Abu-Zidan FM |title=Botulinum toxin treatment for anal fissure |journal=Afr Health Sci |volume=7 |issue=1 |pages=14–7 |year=2007 |pmid=17604520 |pmc=2366122 |doi=10.5555/afhs.2007.7.1.14 |url=}}</ref> Combination of medical therapies may offer up to 98% cure rates.<!-- | ||
--><ref>{{cite journal |author=Tranqui P, Trottier D, Victor C, Freeman J |title=Nonsurgical treatment of chronic anal fissure: nitroglycerin and dilatation versus nifedipine and botulinum toxin|journal=Canadian journal of surgery. Journal canadien de chirurgie |volume=49 |issue=1 |pages=41-5|year=2006 |pmid=16524142|url=http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/cjs/vol-49/issue-1/pdf/pg41.pdf|format=PDF}}</ref><ref name="pmid22336789">{{cite journal |vauthors=Nelson RL, Thomas K, Morgan J, Jones A |title=Non surgical therapy for anal fissure |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003431 |year=2012 |pmid=22336789 |doi=10.1002/14651858.CD003431.pub3 |url=}}</ref> | |||
*[[Botulinum toxin]] is reserved for the people who can't undergo surgery due to high risk for incontinence.<ref name="pmid9293930">{{cite journal |vauthors=Jost WH |title=One hundred cases of anal fissure treated with botulin toxin: early and long-term results |journal=Dis. Colon Rectum |volume=40 |issue=9 |pages=1029–32 |year=1997 |pmid=9293930 |doi= |url=}}</ref><ref name="pmid10492136">{{cite journal |vauthors=Jost WH, Schrank B |title=Repeat botulin toxin injections in anal fissure: in patients with relapse and after insufficient effect of first treatment |journal=Dig. Dis. Sci. |volume=44 |issue=8 |pages=1588–9 |year=1999 |pmid=10492136 |doi= |url=}}</ref> | |||
*Preferred regimen (1): Botulinum toxin type A (Botox) 10 Units (0.2 ml of 50 U/mL) intrasphincteric q30 days for 16 months.<ref name="pmid9435326">{{cite journal |vauthors=Maria G, Cassetta E, Gui D, Brisinda G, Bentivoglio AR, Albanese A |title=A comparison of botulinum toxin and saline for the treatment of chronic anal fissure |journal=N. Engl. J. Med. |volume=338 |issue=4 |pages=217–20 |year=1998 |pmid=9435326 |doi=10.1056/NEJM199801223380402 |url=}}</ref> | |||
--><ref>{{cite journal |author= | |||
* [[Botulinum toxin]] | |||
===Topical medical therapy=== | ===Topical medical therapy=== | ||
The topical therapy is the first line of treatment along with dietary and other conservative measures. Analgesia and vasodilators are chiefly used for the topical management.<ref name="pmid3011180">{{cite journal |vauthors=Jensen SL |title=Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran |journal=Br Med J (Clin Res Ed) |volume=292 |issue=6529 |pages=1167–9 |year=1986 |pmid=3011180 |pmc=1340178 |doi= |url=}}</ref><ref name="pmid29132530">{{cite journal |vauthors=Davies D, Bailey J |title=Diagnosis and Management of Anorectal Disorders in the Primary Care Setting |journal=Prim. Care |volume=44 |issue=4 |pages=709–720 |year=2017 |pmid=29132530 |doi=10.1016/j.pop.2017.07.012 |url=}}</ref><ref name="pmid27041801">{{cite journal |vauthors=Schlichtemeier S, Engel A |title=Anal fissure |journal=Aust Prescr |volume=39 |issue=1 |pages=14–7 |year=2016 |pmid=27041801 |pmc=4816871 |doi=10.18773/austprescr.2016.007 |url=}}</ref><ref name="pmid11052511">{{cite journal |vauthors=Carapeti EA, Kamm MA, Phillips RK |title=Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects |journal=Dis. Colon Rectum |volume=43 |issue=10 |pages=1359–62 |year=2000 |pmid=11052511 |doi= |url=}}</ref><ref name="pmid11298624">{{cite journal |vauthors=Knight JS, Birks M, Farouk R |title=Topical diltiazem ointment in the treatment of chronic anal fissure |journal=Br J Surg |volume=88 |issue=4 |pages=553–6 |year=2001 |pmid=11298624 |doi=10.1046/j.1365-2168.2001.01736.x |url=}}</ref><ref name="pmid12195195">{{cite journal |vauthors=Jonas M, Speake W, Scholefield JH |title=Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a prospective study |journal=Dis. Colon Rectum |volume=45 |issue=8 |pages=1091–5 |year=2002 |pmid=12195195 |doi= |url=}}</ref> | The topical therapy is the first line of treatment along with dietary and other conservative measures.<ref>{{cite journal |author=Haq Z, Rahman M, Chowdhury R, Baten M, Khatun M |title=Chemical sphincterotomy--first line of treatment for chronic anal fissure |journal=Mymensingh Med J |volume=14|issue=1 |pages=88-90 |year=2005 |id=PMID 15695964}}</ref> Analgesia and vasodilators are chiefly used for the topical management.<ref name="pmid3011180">{{cite journal |vauthors=Jensen SL |title=Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran |journal=Br Med J (Clin Res Ed) |volume=292 |issue=6529 |pages=1167–9 |year=1986 |pmid=3011180 |pmc=1340178 |doi= |url=}}</ref><ref name="pmid29132530">{{cite journal |vauthors=Davies D, Bailey J |title=Diagnosis and Management of Anorectal Disorders in the Primary Care Setting |journal=Prim. Care |volume=44 |issue=4 |pages=709–720 |year=2017 |pmid=29132530 |doi=10.1016/j.pop.2017.07.012 |url=}}</ref><ref name="pmid27041801">{{cite journal |vauthors=Schlichtemeier S, Engel A |title=Anal fissure |journal=Aust Prescr |volume=39 |issue=1 |pages=14–7 |year=2016 |pmid=27041801 |pmc=4816871 |doi=10.18773/austprescr.2016.007 |url=}}</ref><ref name="pmid11052511">{{cite journal |vauthors=Carapeti EA, Kamm MA, Phillips RK |title=Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects |journal=Dis. Colon Rectum |volume=43 |issue=10 |pages=1359–62 |year=2000 |pmid=11052511 |doi= |url=}}</ref><ref name="pmid11298624">{{cite journal |vauthors=Knight JS, Birks M, Farouk R |title=Topical diltiazem ointment in the treatment of chronic anal fissure |journal=Br J Surg |volume=88 |issue=4 |pages=553–6 |year=2001 |pmid=11298624 |doi=10.1046/j.1365-2168.2001.01736.x |url=}}</ref><ref name="pmid12195195">{{cite journal |vauthors=Jonas M, Speake W, Scholefield JH |title=Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a prospective study |journal=Dis. Colon Rectum |volume=45 |issue=8 |pages=1091–5 |year=2002 |pmid=12195195 |doi= |url=}}</ref> | ||
====Topical analgesic==== | ====Topical analgesic==== | ||
*Preferred regimen: [[Lidocaine]] | *Preferred regimen: [[Lidocaine]] gel 2-5% to be applied locally as needed. | ||
====Topical vasodilators==== | ====Topical vasodilators==== | ||
*Preferred regimen (1): [[Nitroglycerin]] 0.2 or 0.4% ointment to be applied rectally q12h for 8 weeks. | *Preferred regimen (1): [[Nitroglycerin]] 0.2 or 0.4% ointment to be applied rectally q12h for 8 weeks.<ref>{{cite journal |author=Loder P, Kamm M, Nicholls R, Phillips R |title='Reversible chemical sphincterotomy' by local application of glyceryl trinitrate |journal=Br J Surg |volume=81 |issue=9|pages=1386-9 |year=1994 |id=PMID 7953427}}</ref><ref>{{cite journal |author=Watson S, Kamm M, Nicholls R, Phillips R |title=Topical glyceryl trinitrate in the treatment of chronic anal fissure |journal=Br J Surg |volume=83 |issue=6 |pages=771-5|year=1996 |id=PMID 8696736}}</ref><ref>{{cite journal | author = Simpson J, Lund J, Thompson R, Kapila L, Scholefield J | title = The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children. | journal = Med Sci Monit | volume = 9 | issue = 10 | pages = PI123-6 | year = 2003 | id = PMID 14523338}}</ref> | ||
*Preferred regimen (2): [[Nifedipine]] 0.2-0.3% ointment to be applied topically q6-12h. | *Preferred regimen (2): [[Nifedipine]] 0.2-0.3% ointment to be applied topically q6-12h.<ref>{{cite journal |author=Antropoli C, Perrotti P, Rubino M, Martino A, De Stefano G, Migliore G, Antropoli M, Piazza P |title=Nifedipine for local use in conservative treatment of anal fissures: preliminary results of a multicenter study |journal=Dis Colon Rectum |volume=42 |issue=8 |pages=1011-5|year=1999 |id=PMID 10458123}}</ref><ref>{{cite journal |author=Katsinelos P, Kountouras J, Paroutoglou G, Beltsis A, Chatzimavroudis G, Zavos C, Katsinelos T, Papaziogas B |title=Aggressive treatment of acute anal fissure with 0.5% nifedipine ointment prevents its evolution to chronicity |journal=World J Gastroenterol |volume=12 |issue=38|pages=6203-6 |year=2006 |id=PMID 17036396| url=http://www.wjgnet.com/1007-9327/12/6203.asp}}</ref> | ||
*Alternative regimen (1): [[Diltiazem]] 2% rectal gel q8h for 8 weeks. | *Alternative regimen (1): [[Diltiazem]] 2% rectal gel q8h for 8 weeks.<ref>{{cite journal |author=Carapeti E, Kamm M, Phillips R |title=Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects |journal=Dis. Colon Rectum |volume=43 |issue=10 |pages=1359-62 |year=2000|pmid=11052511}}</ref> | ||
*Alternative regimen (2): [[Bethanechol]] 0.1% rectal gel q8h for 8 weeks. | *Alternative regimen (2): [[Bethanechol]] 0.1% rectal gel q8h for 8 weeks. | ||
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[[Category:Medicine]] | |||
[[Category:Gastroenterology]] | |||
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Latest revision as of 20:24, 29 July 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]
Overview
Most common cause of anal fissure is straining when constipated. For treatment of constipation, click here. Anal fissures in infants usually self-heal without anything more than frequently changing diapers and treating constipation if it is the cause. The topical therapy is the first line of treatment along with dietary and other conservative measures. Analgesia with lidocaine and vasodilators like nitroglycerin and nifedipine are chiefly used for the topical management. Botulinum toxin can be effective in 89% cases. It is reserved for the people who can't undergo surgery for high risk of incontinence.
Medical Therapy
- For many years up until 1995, customary treatment included warm baths, topical anesthetics, stool bulking agents, mechanical anal stretching, and, sometimes, surgery. In 1995, doctors began using nitroglycerine cream (topical 1 percent isosorbide dinitrate) but found it less acceptable for long-term use due to patients developing a tolerance to the drug. In 1998, Italian researchers reported injecting botulinum toxin into the anal sphincter to promote healing by relieving anal spasm through relaxation of the muscle.
- Most common cause of anal fissure is straining when constipated. For treatment of constipation, click here.
Symptomatic
- Most anal fissures are shallow or superficial (less than a quarter of an inch or 0.64 cm deep). These fissures self-heal within a couple of weeks. Furthermore, the treatment used for hemorrhoid such as eating a high-fiber diet, using a stool softener, taking a painkiller and having a sitz bath can help.
- Preferred regimen, sitz bath: anus to be immersed in warm water for 10-15 minutes q8-12h for 4 weeks.[1][2][3][4][5]
Pediatric
- Anal fissures in infants usually self-heal without anything more than frequently changing diapers and treating constipation if it is the cause.
Chemical Sphincterotomy
- Painful deep chronic fissures, will not heal because of poor blood supply caused by sphincter spasm. Traditionally, surgical operations were required which are both painful and associated with various long-term complications, particularly incontinence in a small proportion of cases.
- Botulinum toxin injection, administered by colorectal surgeons, can also be used to relax the sphincter muscle and its use for this condition was first investigated in 1993.[6] Botulinum toxin can provide relief in 89% cases.[7] Combination of medical therapies may offer up to 98% cure rates.[8][3]
- Botulinum toxin is reserved for the people who can't undergo surgery due to high risk for incontinence.[9][10]
- Preferred regimen (1): Botulinum toxin type A (Botox) 10 Units (0.2 ml of 50 U/mL) intrasphincteric q30 days for 16 months.[11]
Topical medical therapy
The topical therapy is the first line of treatment along with dietary and other conservative measures.[12] Analgesia and vasodilators are chiefly used for the topical management.[4][13][14][15][16][17]
Topical analgesic
- Preferred regimen: Lidocaine gel 2-5% to be applied locally as needed.
Topical vasodilators
- Preferred regimen (1): Nitroglycerin 0.2 or 0.4% ointment to be applied rectally q12h for 8 weeks.[18][19][20]
- Preferred regimen (2): Nifedipine 0.2-0.3% ointment to be applied topically q6-12h.[21][22]
- Alternative regimen (1): Diltiazem 2% rectal gel q8h for 8 weeks.[23]
- Alternative regimen (2): Bethanechol 0.1% rectal gel q8h for 8 weeks.
References
- ↑ Wald A, Bharucha AE, Cosman BC, Whitehead WE (2014). "ACG clinical guideline: management of benign anorectal disorders". Am. J. Gastroenterol. 109 (8): 1141–57, (Quiz) 1058. doi:10.1038/ajg.2014.190. PMID 25022811.
- ↑ Gupta P (2006). "Randomized, controlled study comparing sitz-bath and no-sitz-bath treatments in patients with acute anal fissures". ANZ J Surg. 76 (8): 718–21. doi:10.1111/j.1445-2197.2006.03838.x. PMID 16916391.
- ↑ 3.0 3.1 Nelson RL, Thomas K, Morgan J, Jones A (2012). "Non surgical therapy for anal fissure". Cochrane Database Syst Rev (2): CD003431. doi:10.1002/14651858.CD003431.pub3. PMID 22336789.
- ↑ 4.0 4.1 Jensen SL (1986). "Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran". Br Med J (Clin Res Ed). 292 (6529): 1167–9. PMC 1340178. PMID 3011180.
- ↑ Nelson R (2006). "Non surgical therapy for anal fissure". Cochrane database of systematic reviews (Online) (4): CD003431. PMID 17054170.
- ↑ Jost W, Schimrigk K (1993). "Use of botulinum toxin in anal fissure". Dis Colon Rectum. 36 (10): 974. PMID 8404394.
- ↑ Radwan MM, Ramdan K, Abu-Azab I, Abu-Zidan FM (2007). "Botulinum toxin treatment for anal fissure". Afr Health Sci. 7 (1): 14–7. doi:10.5555/afhs.2007.7.1.14. PMC 2366122. PMID 17604520.
- ↑ Tranqui P, Trottier D, Victor C, Freeman J (2006). "Nonsurgical treatment of chronic anal fissure: nitroglycerin and dilatation versus nifedipine and botulinum toxin" (PDF). Canadian journal of surgery. Journal canadien de chirurgie. 49 (1): 41–5. PMID 16524142.
- ↑ Jost WH (1997). "One hundred cases of anal fissure treated with botulin toxin: early and long-term results". Dis. Colon Rectum. 40 (9): 1029–32. PMID 9293930.
- ↑ Jost WH, Schrank B (1999). "Repeat botulin toxin injections in anal fissure: in patients with relapse and after insufficient effect of first treatment". Dig. Dis. Sci. 44 (8): 1588–9. PMID 10492136.
- ↑ Maria G, Cassetta E, Gui D, Brisinda G, Bentivoglio AR, Albanese A (1998). "A comparison of botulinum toxin and saline for the treatment of chronic anal fissure". N. Engl. J. Med. 338 (4): 217–20. doi:10.1056/NEJM199801223380402. PMID 9435326.
- ↑ Haq Z, Rahman M, Chowdhury R, Baten M, Khatun M (2005). "Chemical sphincterotomy--first line of treatment for chronic anal fissure". Mymensingh Med J. 14 (1): 88–90. PMID 15695964.
- ↑ Davies D, Bailey J (2017). "Diagnosis and Management of Anorectal Disorders in the Primary Care Setting". Prim. Care. 44 (4): 709–720. doi:10.1016/j.pop.2017.07.012. PMID 29132530.
- ↑ Schlichtemeier S, Engel A (2016). "Anal fissure". Aust Prescr. 39 (1): 14–7. doi:10.18773/austprescr.2016.007. PMC 4816871. PMID 27041801.
- ↑ Carapeti EA, Kamm MA, Phillips RK (2000). "Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects". Dis. Colon Rectum. 43 (10): 1359–62. PMID 11052511.
- ↑ Knight JS, Birks M, Farouk R (2001). "Topical diltiazem ointment in the treatment of chronic anal fissure". Br J Surg. 88 (4): 553–6. doi:10.1046/j.1365-2168.2001.01736.x. PMID 11298624.
- ↑ Jonas M, Speake W, Scholefield JH (2002). "Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a prospective study". Dis. Colon Rectum. 45 (8): 1091–5. PMID 12195195.
- ↑ Loder P, Kamm M, Nicholls R, Phillips R (1994). "'Reversible chemical sphincterotomy' by local application of glyceryl trinitrate". Br J Surg. 81 (9): 1386–9. PMID 7953427.
- ↑ Watson S, Kamm M, Nicholls R, Phillips R (1996). "Topical glyceryl trinitrate in the treatment of chronic anal fissure". Br J Surg. 83 (6): 771–5. PMID 8696736.
- ↑ Simpson J, Lund J, Thompson R, Kapila L, Scholefield J (2003). "The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children". Med Sci Monit. 9 (10): PI123–6. PMID 14523338.
- ↑ Antropoli C, Perrotti P, Rubino M, Martino A, De Stefano G, Migliore G, Antropoli M, Piazza P (1999). "Nifedipine for local use in conservative treatment of anal fissures: preliminary results of a multicenter study". Dis Colon Rectum. 42 (8): 1011–5. PMID 10458123.
- ↑ Katsinelos P, Kountouras J, Paroutoglou G, Beltsis A, Chatzimavroudis G, Zavos C, Katsinelos T, Papaziogas B (2006). "Aggressive treatment of acute anal fissure with 0.5% nifedipine ointment prevents its evolution to chronicity". World J Gastroenterol. 12 (38): 6203–6. PMID 17036396.
- ↑ Carapeti E, Kamm M, Phillips R (2000). "Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects". Dis. Colon Rectum. 43 (10): 1359–62. PMID 11052511.