Topical Calcium Channel Blockers Research Articles

Anal fissures: An update on treatment options.

Anal fissure (AF) is the second most common anorectal complaint in healthcare settings. The presentation might be acute or chronic, characterised by severe pain with defaecation that persists for one to two hours. Non-surgical and surgical interventions are available based on the severity and persistence of the fissure. The aim of this article is to review the pathophysiology, clinical presentation andmanagement of AF under current guidelines. The aetiology of AF is unclear, although it is commonly associated with local trauma or associated chronic conditions. Acute AF is first treated with conservative therapy, including dietary fibre and sitz baths. Addition of topical nitrates, topical calcium channel blockers or botulinum toxin injection is indicated with failure of conservative treatment or at medical discretion. Surgical options are considered if AF persists despite treatment. Most present as hypertonic, but special consideration is needed for hypotonic or secondary presentations.

Topical Calcium channel blockers for effective post operative analgesia for hemorrhoidectomy patients; A Randomized Control Trial at a Tertiary Care Hospital.

Objective: To compare the mean pain scores after hemorrhoidectomy in patients given topical calcium channel blocker and patients being given routine post-operative treatment only. Study Design: Randomized Controlled Trial. Setting: Surgical Department of Holy Family Hospital. Period: 7th January 2022 to 7th July 2022. Material & Methods: Patients fulfilling the inclusion criteria were divided into two groups. Group A patients will receive topical calcium channel blockers whole group B will receive conventional analgesic medications. Patients in both groups underwent open hemorrhoidectomy under saddle block anesthesia. At the end of procedure, a lignocaine gel-soaked pack was placed in rectum which was removed after 6 hours. The post-operative treatment of test group was similar in all regards except that they were given 2% diltiazem ointment to apply to perianal region twice a day. Oral stool softeners were started after NPO duration. The patients were advised to start warm sitz bath and application of 2% lignocaine gel to perianal region 12 hourly after removal of pack. The patients in both groups were compared for the degree of pain on the second post-operative day using visual analogue scale. Results: In this study, on comparison of mean pain scores after hemorrhoidectomy in patients given topical calcium channel blocker and patients being given routine post-operative treatment only shows that pain in Group-A was 5.89+0.80 and in Group-B 3.60+0.77, p value was 0.0001. Conclusion: Topical Calcium Channel Blockers are effective in managing post hemorrhoidectomy pain.

A Pilot, Prospective, Randomized-Controlled Study to Evaluate the Efficacy and Safety of Arsha Hita™ in the Treatment of Anal Fissures.

Introduction Anal fissures are tears in the anal canal that cause pain, bleeding, and spasms. They can be treated with non-operative options such as sitz baths, local anesthetics, topical nitrates, oral fiber, and calcium channel blockers, but some patients require surgery. Topical nitrates have side effects such as severe headaches, while topical calcium channel blockers can cause itching. There is a need to explore alternative treatments with fewer side effects. This proof-of-concept pilot study aimed to compare the efficacy and safety of a combination of Arsha Hita™ tablets and ointment (Shree Dhootapapeshwar Limited, Mumbai Maharastra, India) (test treatment) with a combination of lidocaine 1.5% w/w + nifedipine 0.3% w/w cream for local application and Isabgol powder (6 g) orally as an active comparator (standard treatment), which is the standard treatment of anal fissures as per the Association of Colon and Rectal Surgeons of India (ACRSI) guidelines. Methodology This study was a single-center, prospective, randomized-controlled study conductedin Karnataka, India. Participants were screened for anal fissures and randomized to receive either standard treatment (Group A) or test treatment (Group B) for 14 days, and were re-evaluated after two, four, and six weeks. The study assessed signs and symptoms related to anal fissures, such as pain post-defecation on Visual Analog Scale (VAS), bleeding per anus grading, wound healing grade, stool consistency, and stool frequency. Compliance, inter-current illness, and concomitant therapy were noted at each visit. The study used independent sample t-tests to compare variables at baseline and chi-square or Fisher's exact tests to compare the number/proportion of participants achieving primary and secondary endpoints. Mann-Whitney U test was used to compare median composite scores at baseline and Visit 4, and Friedman's two-way analysis of variance was used to compare median composite scores across the four visits (p < 0.05 was considered significant). Descriptive analysis was used to assess VAS, bleeding, and healing grades. Results The study included 53 participants with anal fissures, of which 25 out of 27 allocated in Group A (two drop-outs) received standard treatment, and all 26 allocated in Group B received Arsha Hita treatment. At the end of the study, 11 participants in Group B achieved a 90% reduction in composite scores compared to only three patients in Group A (p<0.05). Both groups showed improvement in pain on defecation, severity of bleeding, healing of anal fissure wound, and participant's and physician's global impression score. Group B had significantly better results in terms of VAS score, resolution of per-anal bleeding, and physician's global impression score (p<0.05). There were no adverse events in either group during the six-week treatment period. Conclusion The pilot study provides evidence that the combination of Arsha Hita tablets and Arsha Hita ointment may be more effective and safer for treating anal fissures than the standard treatment. The test treatment group experienced greater pain relief, complete resolution of per-anal bleeding, and better global impression scores than the standard treatment group. These findings suggest the need for further research through larger, randomized controlled trials to determine the efficacy and safety of Arsha Hita in treating anal fissures.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anal Fissures.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anal Fissures.

Strategies to Reduce Post-Hemorrhoidectomy Pain: A Systematic Review.

Background and Objectives: Excisional hemorrhoidectomy is considered as a mainstay operation for high-grade hemorrhoids and complicated hemorrhoids. However, postoperative pain remains a challenging problem after hemorrhoidectomy. This systematic review aims to identify pharmacological and non-pharmacological interventions for reducing post-hemorrhoidectomy pain. Materials and Methods: The databases of Ovid MEDLINE, PubMed and EMBASE were systematically searched for randomized controlled trails (published in English language with full-text from 1981 to 30 September 2021) to include comparative studies examining post-hemorrhoidectomy pain as their primary outcomes between an intervention and another intervention (or a sham or placebo). Results: Some 157 studies were included in this review with additional information from 15 meta-analyses. Fundamentally, strategies to reduce post-hemorrhoidectomy pain were categorized into four groups: anesthetic methods, surgical techniques, intraoperative adjuncts, and postoperative interventions. In brief, local anesthesia-alone or combined with intravenous sedation was the most effective anesthetic method for excisional hemorrhoidectomy. Regarding surgical techniques, closed (Ferguson) hemorrhoidectomy performed with a vascular sealing device or an ultrasonic scalpel was recommended. Lateral internal anal sphincterotomy may be performed as a surgical adjunct to reduce post-hemorrhoidectomy pain, although it increased risks of anal incontinence. Chemical sphincterotomy (botulinum toxin, topical calcium channel blockers, and topical glyceryl trinitrate) was also efficacious in reducing postoperative pain. So were other topical agents such as anesthetic cream, 10% metronidazole ointment, and 10% sucralfate ointment. Postoperative administration of oral metronidazole, flavonoids, and laxatives was associated with a significant reduction in post-hemorrhoidectomy pain. Conclusions: This systematic review comprehensively covers evidence-based strategies to reduce pain after excisional hemorrhoidectomy. Areas for future research on this topic are also addressed at the end of this article.

COVID-19-related acro-ischemia and topical calcium channel blockers: A useful therapeutic adjunct

COVID-19-related acro-ischemia and topical calcium channel blockers: A useful therapeutic adjunct

The Effect of Nonoperative Management of Chronic Anal Fissure and Hemorrhoid Disease on Bowel Function Patient-Reported Outcomes

Nonoperative management has been reported to decrease symptoms from common anorectal conditions such as chronic anal fissures and hemorrhoids. The effects of these interventions on bowel function are unknown. This study aims to perform a prospective evaluation of patient-reported outcomes of bowel function on nonoperative management for chronic anal fissures and hemorrhoid disease. This is a prospective, observational study. Patient-reported outcome measures were collected from the clinical practice of the division of colon and rectal surgery at a tertiary colon and rectal surgery referral center. All patients received standardized dietary counseling including fiber supplementation as well as toileting strategies. Those with chronic anal fissures were also prescribed topical calcium channel blockers. The Colorectal Functional Outcome questionnaire was administered at baseline and at first follow-up visit. The primary outcomes measured were the mean change in patient-reported bowel function scores after nonoperative management for each disease and in aggregate. A cohort of 64 patients was included, 37 patients (58%) with chronic anal fissure and 27 patients with hemorrhoid disease. Incontinence, social impact, stool-related aspects, and the global score were observed to have statistically significant improvement in the aggregate group. When analyzed by diagnosis, hemorrhoid disease demonstrated a statistically significant improvement in incontinence and stool-related aspects, whereas chronic anal fissure was associated with a statistically significant change in social impact, stool-related aspects, and the global score. This study was limited by the small cohort size and unclear patient adherence to medical management. Nonoperative management of chronic anal fissures and hemorrhoid disease is associated with significant improvement in patient-reported outcome scores in several domains, suggesting that dietary counseling and medical therapy should be the first-line outpatient therapy for these diseases. See Video Abstract at http://links.lww.com/DCR/A726.

What is the best treatment for chronic anal fissures in adults?

EVIDENCE-BASED ANSWER For medical treatments, topical nitroglycerin, topical calcium channel blockers, and botulinum toxin injections are effective in about half of patients but nitroglycerin has more adverse effects than the other agents and has a high recurrence rate in chronic anal fissure. Lateral internal sphincterotomy results in long-term cure rates of more than 90% and less than a 5% risk of incontinence (SOR: A, meta-analyses of RCTs). Medical therapies are usually recommended first, but lateral internal sphincterotomy is the treatment of choice for refractory anal fissures (SOR: C, expert opinion).

A prospective randomized double-blind study of pain control by topical calcium channel blockers versus placebo after Milligan-Morgan hemorrhoidectomy.

Post-hemorrhoidectomy pain is significantly associated with a hypertonicity of the internal anal sphincter. We evaluated the effects of topical diltiazem, a calcium channel blocker, in reducing pain after hemorrhoidectomy. Purpose of our study was to determine difference in extent of pain control by application of topical calcium channel blocker (diltiazem 2%) versus placebo ointment. This was a prospective randomized double-blind clinical study conducted at Sawai Man Singh Hospital, Jaipur, from May 2016 to May 2017. Sixty patients, who had undergone hemorrhoid, were randomly assigned to receive 2% diltiazem ointment (n = 30) or a placebo ointment (n = 30) postoperatively. Ointments were applied to the perianal region three times daily for 7days. Pain scores were recorded using visual analog scale at 6, 24, and 48h and seventh day postoperatively and number of analgesic doses consumed by patients in the first 3days. Patients using the diltiazem ointment had significantly less pain and greater benefit than those in the placebo group throughout the first postoperative week (p < 0.001) except for reading at 6h. Also, there was significantly less number of analgesic doses consumed in the diltiazem group compared to the placebo group. Perianal application of 2% diltiazem ointment after hemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial.

Cutting-edge Advancement in the Therapy of Glaucoma

Glaucoma is the second most prevalent eye condition, after cataracts, known to cause irreversible blindness in the world. Currently, the only modifiable risk factor for the progression of this disease is intraocular pressure (IOP). This article aims to evaluate the hypotensive potential of topical calcium channel blockers in glaucoma management, based on our current knowledge about this disease. A comprehensive literature search was conducted on Medline, PubMed, and Google Scholar databases in April 2013. Search temporal limits included articles published from 1996 to 2013 with the purpose of providing the most recent evidence. Studies were queried using the following keywords in various combinations: glaucoma, calcium channel blockers, glaucomatous optic neuropathy, neuroprotection, topical calcium channel blockers. The articles of high or medium clinical and preclinical relevance were selected for review. Multiple studies have shown the relevancy and effectiveness of topical calcium channel blockers as an alternative hypotensive therapy in glaucoma management. Taken into account that not all calcium channel blockers are equally effective, the challenge for future research will be to determine the best type of calcium channel blocker.

Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid-induced Glaucoma.

ABSTRACTPurpose: To evaluate the effect of 0.125% verapamil and 0.5% diltiazem eye drops on intraocular pressure (IOP) in steroid-induced glaucoma in rabbit eyes.Methods: A total of 18 rabbits with steroid-induced glaucoma were divided into three groups (A, B and C; n = 6 each). Right eyes in groups A, B and C received 0.5% diltiazem, 0.125% verapamil and 0.5% timolol eye drops twice daily for 12 days, respectively; whereas, left eyes received distilled water. IOP was measured with Tono-pen XL at baseline, day 4, day 8, and day 12 of treatment.Results: Both 0.5% diltiazem and 0.125% verapamil eye drops significantly reduced IOP compared to control eyes (p < 0.05). Reduction of IOP by 0.5% diltiazem, 0.125% verapamil eye drops were comparable to 0.5% timolol. No surface toxicity or systemic side effects were noted during the study period.Conclusion: Calcium channel blockers, verapamil, and diltia-zem significantly reduced IOP in rabbiteyes. This group of drugs may have a potential role in treatment of glaucomaHow to cite this article: Ganekal S, Dorairaj S, Jhanji V, Kudlu K. Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid-induced Glaucoma. J Current Glau Prac 2014;8(1):15-19.

Comparative study of local calcium channel blocker application and lateral internal sphincterotomy in the treatment of chronic anal fissure: study of 50 cases.

Background: The treatment of chronic anal fissure has changed greatly during the past two decades with ongoing research directed at lowering the internal anal sphincter tone and avoiding the risk of fecal continence disturbance. Glycerin trinitrate, topical calcium channel blockers and anal dilators and botulinum toxin injection alone are all known to be able to lower the internal anal sphincter tone but results have been disappointing in curing chronic anal fissure, often marginally better than to placebo. The surgical treatment in the form of lateral internal sphincterotomy is the gold standard for chronic anal fissure. Aims & Objective: The aim of this prospective study was to assess the efficacy of medical treatment in form of topical calcium channel blocker and surgery in the management of chronic anal fissure. The objective is to compare the efficacy with regard to complete healing, recurrence, incontinence and other complications after treatment with topical calcium channel blocker and lateral anal sphincterotomy. Material and Methods: From October 2010 to October 2012, 50 patients with typical chronic anal fissure completed the study. 25 patients were initially treated with topical calcium channel blocker for 8 weeks and rests 25 were treated with lateral anal sphincterotomy. During the follow-up healing rates, symptoms, incontinence scores, and therapy adverse effects were recorded. Results: Overall healing rates were 60% after 8 weeks therapy with topical calcium channel blocker. Whereas overall healing after lateral internal sphincterotomy group was 88% with no recurrence. Conclusion: Lateral internal sphincterotomy is far more effective than medical treatment, with significantly increased healing rates while avoiding risk of incontinence.

Non surgical therapy for anal fissure

Because of the disability associated with surgery for anal fissure and the risk of incontinence, medical alternatives for surgery have been sought. Most recently, pharmacologic methods that relax the anal smooth muscle, to accomplish reversibly what occurs in surgery, have been used to obtain fissure healing. To assess the efficacy and morbidity of various medical therapies for anal fissure. Search terms include "anal fissure randomized". Timing from 1966 to August 2010. Further details of the search below. Studies in which participants were randomized to a non-surgical therapy for anal fissure. Comparison groups may include an operative procedure, an alternate medical therapy or placebo. Chronic fissure, acute fissure and fissure in children are included in the review. Atypical fissures associated with inflammatory bowel disease or cancer or anal infection are excluded. Data were abstracted from published reports and meeting abstracts, assessing method of randomization, blinding, "intention to treat" and drop-outs, therapies, supportive measures (applied to both groups), dosing and frequency and cross-overs. Dichotomous outcome measures included Non-healing of the fissure (a combination of persistence and recurrence), and Adverse events (including incontinence, headache, infection, anaphylaxis). Continuous outcome measures included measures of pain relief and anorectal manometry. In this update 23 studies including 1236 participants is added to the 54 studies and 3904 participants in the 2008 publication, however 2 studies were from the last version reclassified as un included, so the final number of participants is 5031.49 different comparisons of the ability of medical therapies to heal anal fissure have been reported in 75 RCTs. Seventeen agents were used (nitroglycerin ointment (GTN), isosorbide mono & dinitrate, Botulinum toxin (Botox), diltiazem, nifedipine (Calcium channel blockers or CCBs), hydrocortisone, lignocaine, bran, minoxidil, indoramin, clove oil, L-arginine, sitz baths, sildenafil, "healer cream" and placebo) as well as Sitz baths, anal dilators and surgical sphincterotomy. GTN was found to be marginally but significantly better than placebo in healing anal fissure (48.9% vs. 35.5%, p < 0.0009), but late recurrence of fissure was common, in the range of 50% of those initially cured. Botox and CCBs were equivalent to GTN in efficacy with fewer adverse events. No medical therapy came close to the efficacy of surgical sphincterotomy, though none of the medical therapies in these RCTs were associated with the risk of incontinence. Medical therapy for chronic anal fissure, currently consisting of topical glyceryl trinitrate, botulinum toxin injection or the topical calcium channel blockers nifedipine or diltiazem in acute and chronic fissure and fissure in children may be applied with a chance of cure that is marginally better than placebo. For chronic fissure in adults all medical therapies are far less effective than surgery. A few of the newer agents investigated show promise based only upon single studies (clove oil, sildenifil and a "healer cream") but lack comparison to more established medications.

Topical verapamil lowers outflow facility in the rabbit eye.

Results of studies examining the mechanism of the ocular hypotensive effect of topical calcium channel blockers are controversial. Whereas evidence obtained in perfused human eyes indicates that these drugs lower intraocular pressure by increasing the aqueous humor outflow, tonographic studies in rabbits have revealed that they reduce both the aqueous humor outflow and inflow. In order to clarify such a discrepancy, the aim of this study was to assess whether the effect of topical verapamil on the facility of aqueous humor outflow in the rabbit eye was dose-related. Total outflow facility was determined by two-level constant pressure perfusion in anesthetized rabbits. The effect of 5 different concentrations on aqueous humor outflow at 60 minutes postdrug was studied in groups of 10 rabbits each. Baseline outflow facility was also determined in a group of 15 rabbits. In order to check the reliability of the method for detecting drug-induced changes in aqueous outflow, the effect of pilocarpine was also tested. Topical verapamil was shown to lower outflow facility in the rabbit eye in a dose-related fashion. On the contrary, topical pilocarpine was found to significantly increase outflow facility. Our data indicate that topical verapamil reduces outflow facility in the rabbit eye.