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MEBO versus topical Diltiazem versus a combination of both ointments in the treatment of acute anal fissure: a randomized clinical trial protocol.
El Charif, MH, Doughan, S, Kredly, R, Kassas, S, Azab, R, Sbaity, E
BMC complementary medicine and therapies. 2021;(1):75
Abstract
BACKGROUND Anal fissure is a common complication of the anorectal region and one of the most reported causes of anal pain. Acute anal fissure can be cured by surgery or medical treatment. There is an increase in the use of topical therapy for the treatment of anal fissures. A common topical drug used is Diltiazem (DTZ), a calcium-channel blocker, which relaxes the anal sphincter and thus promotes healing of the anal fissure. Moist exposed burn ointment (MEBO) is an ointment that is effective for the treatment of burns and wound healing and is becoming popular in the treatment of anal fissures. METHODS This is a 1:1:1 randomized, controlled, parallel design, with endpoint measures of change in pain score, wound healing, defecation strain score and patient's global impression of improvement. The study will be conducted at AUBMC over a 10-week period. Patients will be randomized to three treatment arms: MEBO, Diltiazem, and a combination of MEBO and Diltiazem ointments. DISCUSSION The results of this study will allow physicians to assess the efficacy and safety of MEBO in the treatment of acute anal fissure, and also in comparison to Diltiazem. This trial will generate evidence-based conclusions regarding the use of a herbal/natural-based product (MEBO ointment) for the treatment of anal fissures. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT04153032 . Clinical Trial Registration Date: 06-NOVEMBER-2019.
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Topical diltiazem for pain after closed hemorrhoidectomy.
Rodríguez-Wong, U, Ocharán-Hernández, ME, Toscano-Garibay, J
Revista de gastroenterologia de Mexico. 2016;(2):74-9
Abstract
BACKGROUND Anal sphincter spasm contributes to the appearance of postoperative pain following hemorrhoidectomy. AIM: To determine the efficacy of topical diltiazem in the control of post-hemorrhoidectomy pain. MATERIAL AND METHODS A randomized, prospective, experimental, double-blind study was conducted on 2 groups of patients in the postoperative period of closed hemorrhoidectomy. Each group consisted of 17 patients. Group A received topical diltiazem in the anal region 3 times a day and group B received a placebo. Ketorolac was administered to both groups as rescue therapy. RESULTS In group A, the mean score on the visual analog scale was 2.97±1.18cm at 24h, 1.51±1.18cm at 48h, and 0.84±0.92cm at 72h. In group B, it was 6.82±1.9cm at 24h, 5.3±1.66cm at 48h, and 4.32±2.13cm at 72h (P<.001, 95% CI). The mean number of analgesic doses in group A was 2.41±0.87 at 24h, 1.11±0.85 at 48h, and 0.94±0.96 at 72h. In group B, it was 3.82±0.52 at 24h, 3.64±0.70 at 48h, and 2.88±1.26 at 72h (P<.001, 95% CI). CONCLUSIONS In this study, topical administration of diltiazem resulted in a statistically significant reduction of postoperative pain in patients that underwent closed hemorrhoidectomy.
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Magnesium sulfate or diltiazem as adjuvants to total intravenous anesthesia to reduce blood loss in functional endoscopic sinus surgery.
Aravindan, A, Subramanium, R, Chhabra, A, Datta, PK, Rewari, V, Sharma, SC, Kumar, R
Journal of clinical anesthesia. 2016;:179-85
Abstract
STUDY OBJECTIVE This study was designed to know whether addition of magnesium sulfate (MgSO4) or diltiazem to total intravenous anesthesia (TIVA) (propofol) aided reduction in blood loss during functional endoscopic sinus surgery (FESS). The secondary outcomes measured were surgeon's assessment of the surgical field and hemodynamics. DESIGN Randomized, double-blinded, placebo-controlled trial. SETTING Operating room. PATIENTS Forty-five American Society of Anesthesiologists I and II adult patients (18-60years) undergoing FESS. INTERVENTIONS All groups received propofol-fentanyl TIVA. Patients were randomly allocated to 1 of the 3 groups (MgSO4 group, n=15; diltiazem group, n=15; saline group, n=15). MEASUREMENTS Intraoperative bleeding was quantified, and quality of surgical field was graded. Hemodynamic parameters were recorded. MAIN RESULTS Addition of both MgSO4 and diltiazem significantly reduced blood loss (240 and 350mL) in comparison to control group (415mL) (P=.003). The surgical field was significantly better in the MgSO4 group compared with the diltiazem (P=.028) and saline groups (P=.0001). CONCLUSION It was concluded that the addition of both MgSO4 and diltiazem to TIVA propofol results in significant reduction in blood loss and significant improvement in the quality of surgical field during FESS without causing any adverse effects on the hemodynamics or on the recovery from anesthesia. The surgical field in the MgSO4 group was significantly better than that in the diltiazem group (P=.04).
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Diltiazem vs. Metoprolol in the Management of Atrial Fibrillation or Flutter with Rapid Ventricular Rate in the Emergency Department.
Fromm, C, Suau, SJ, Cohen, V, Likourezos, A, Jellinek-Cohen, S, Rose, J, Marshall, J
The Journal of emergency medicine. 2015;(2):175-82
Abstract
BACKGROUND Diltiazem (calcium channel blocker) and metoprolol (beta-blocker) are both commonly used to treat atrial fibrillation/flutter (AFF) in the emergency department (ED). However, there is considerable regional variability in emergency physician practice patterns and debate among physicians as to which agent is more effective. To date, only one small prospective, randomized trial has compared the effectiveness of diltiazem and metoprolol for rate control of AFF in the ED and concluded no difference in effectiveness between the two agents. OBJECTIVE Our aim was to compare the effectiveness of diltiazem with metoprolol for rate control of AFF in the ED. METHODS A convenience sample of adult patients presenting with rapid atrial fibrillation or flutter was randomly assigned to receive either diltiazem or metoprolol. The study team monitored each subject's systolic and diastolic blood pressures and heart rates for 30 min. RESULTS In the first 5 min, 50.0% of the diltiazem group and 10.7% of the metoprolol group reached the target heart rate (HR) of <100 beats per minute (bpm) (p < 0.005). By 30 min, 95.8% of the diltiazem group and 46.4% of the metoprolol group reached the target HR < 100 bpm (p < 0.0001). Mean decrease in HR for the diltiazem group was more rapid and substantial than that of the metoprolol group. From a safety perspective, there was no difference between the groups with respect to hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (HR < 60 bpm). CONCLUSIONS Diltiazem was more effective in achieving rate control in ED patients with AFF and did so with no increased incidence of adverse effects.
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Pharmacokinetic interactions between the orexin receptor antagonist almorexant and the CYP3A4 inhibitors ketoconazole and diltiazem.
Dingemanse, J, Cruz, HG, Gehin, M, Hoever, P
Journal of pharmaceutical sciences. 2014;(5):1548-56
Abstract
Almorexant, a tetrahydroisoquinoline orexin receptor antagonist and first representative of a new class of compounds for the treatment of insomnia, is a substrate of the cytochrome P450 3A4 isoenzyme (CYP3A4). Two randomized two-way crossover studies were performed in healthy subjects investigating the pharmacokinetic interaction between almorexant and the CYP3A4 inhibitors ketoconazole and diltiazem. When administered as a single dose of 100 mg almorexant during steady state of ketoconazole (400 mg once daily for 14 days) or diltiazem treatment (300 mg once daily for 11 days), the exposure to almorexant was 10.5- and 3.5-fold, respectively, greater when compared with almorexant alone. Exposure to the phenol metabolites M3 and M8 increased in the presence of the CYP3A4 inhibitors, whereas that to M6 (dealkylated metabolite) decreased. Concomitant ketoconazole decreased formation of the dehydrogenated metabolite M5 and diltiazem increased concentrations of this metabolite. Higher almorexant exposure was associated with an increased incidence of typical almorexant-related adverse events such as fatigue (both studies) and somnolence (ketoconazole study only). The present results indicate that dose adaptation must be considered when almorexant would be coadministered with inhibitors of CYP3A4.
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Evaluation of the efficacy of a combination of diltiazem and periprostatic nerve block in pain control during transrectal ultrasonography-guided biopsy of the prostate.
Jindal, T, Mandal, SN, Biswas, G, Karmakar, D
Annals of the Royal College of Surgeons of England. 2013;(5):361-4
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Abstract
INTRODUCTION The choice of analgesia during prostate biopsy remains controversial. The pain has dual origin: from the insertion of the probe as well as the biopsy itself. Periprostatic nerve block (PPNB) is currently the gold standard modality for decreasing pain of prostate biopsy but it does not alleviate the pain of probe insertion. A randomised controlled trial was performed to test the efficacy and safety of the combination of topical application of diltiazem gel and PPNB for pain control during transrectal ultrasonography guided prostate biopsy. METHODS A total of 73 patients who were to undergo their first prostate biopsy were randomised to receive either 2ml of 2% topical diltiazem gel or a placebo 15 minutes before the biopsy. All the patients then had a PPNB using 1% lignocaine. A ten- point visual analogue scale was used to record the pain immediately after the insertion of the probe and during the biopsy. Any adverse effects were also recorded. RESULTS There was no significant difference in the mean age and prostate volumes between the groups. There was a significantly lower mean pain score due to probe insertion in those patients who received topical diltiazem than in the placebo group (p<0.0001). There was no significant difference between the pain scores during the biopsy itself between the two groups. CONCLUSIONS Topical diltiazem significantly reduces the pain of probe insertion during prostate biopsy and can be used effectively as an adjuvant to PPNB.
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A randomized, prospective, double-blind, placebo-controlled trial of the effect of diltiazem gel on pain after hemorrhoidectomy.
Sugimoto, T, Tsunoda, A, Kano, N, Kashiwagura, Y, Hirose, K, Sasaki, T
World journal of surgery. 2013;(10):2454-7
Abstract
BACKGROUND Spasm of the internal anal sphincter is considered to be one of the causes of pain in anal diseases. We have evaluated the effects of topical diltiazem on postoperative pain after hemorrhoidectomy. METHODS Sixty-two patients were randomly assigned to receive a 2 % diltiazem gel (n = 32) or a placebo gel (n = 30) after hemorrhoidectomy. Patients applied the gel to the anal region three times per day for 14 days. Pain both in the resting state and on defecation ranged from 0 to 10 on a numerical rating scale, and the number of prescribed loxoprofen tablets (Loxonin) were recorded and confirmed daily by telephone. Any morbidity during the follow-up period was recorded. RESULTS Both pain scores during defecation and the number of analgesic tablets consumed tended to be lower in the diltiazem group, although they did not reach statistical significance (P = 0.09, P = 0.12, respectively). Total number of complications was significantly higher in the diltiazem group, but each incidence of complications, including itching sensation, headache, and dizziness was not statistically different. CONCLUSIONS Perianal application of 2 % diltiazem gel after hemorrhoidectomy has the potential to reduce postoperative pain during defecation.
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Comparison of topical isosorbide mononitrate, topical diltiazem, and their combination in the treatment of chronic anal fissure.
Bulus, H, Varol, N, Tas, A, Coskun, A
Asian journal of surgery. 2013;(4):165-9
Abstract
BACKGROUND/OBJECTIVE Chronic anal fissure is a painful condition that is associated with an increase in internal anal sphincter pressure. The main aim of this study is to evaluate the efficacy and adverse effects of topical isosorbide 5 mononitrate and topical diltiazem, when administered either as single agents or in combination, in the treatment of anal fissure. METHODS Patients with chronic anal fissure were enrolled in the study. They were randomized into three groups: Group A (0.2% isosorbide 5 mononitrate users), Group B (2% diltiazem users), and Group C (2%diltiazem + 0.2% isosorbide 5 mononitrate users). Pain was evaluated using a visual analog scale (VAS). Level of strain during defecation was graded on a 4-point scale. RESULTS A total of 55 patients were enrolled in the study. The average ages of patients in Groups A, B, and C were 37.94 ± 16.19, 42.83 ± 13.21, 40 ± 13.58 years, respectively. After treatment, pain completely abated in 55.6% of patients in Group A, 27.8% (n = 5) in Group B, and 42.1% (n = 8) in Group C. The decreases in average VAS values prior to and after treatment in Groups A, B, and C were statistically significant (p values 0.0001, 0.001, and 0.0001, respectively). Average strain scores prior to and after treatment were 2.11/0.72 for Group A, 2.17/0.94 for Group B, and 1.95/0.47 for Group C. Strain during defecation prior to and after treatment in Groups A, B, and C was statistically significant (p values 0.001, 0.001, and 0.003, respectively). CONCLUSION Topical diltiazem and a combination of nitrate and diltiazem can be used in the treatment of anal fissure. However, the agents are not significantly superior each other.
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Effect of different durations and formulations of diltiazem on the single-dose pharmacokinetics of midazolam: how long do we go?
Friedman, EJ, Fraser, IP, Wang, YH, Bergman, AJ, Li, CC, Larson, PJ, Chodakewitz, J, Wagner, JA, Stoch, SA
Journal of clinical pharmacology. 2011;(11):1561-70
Abstract
Understanding how inhibition of cytochrome P4503A (CYP3A) affects the metabolism of a new drug is critical in determining if a clinically relevant drug interaction will occur. Diltiazem interaction studies assess a given compound's sensitivity to moderate CYP3A inhibition. The present study compared the effect different durations and formulations of diltiazem (extended release [XR] and conventional release [CR]) had on the single-dose pharmacokinetics of midazolam. The geometric mean ratio (GMR; midazolam + diltiazem(XR × 5 days)/midazolam + diltiazem(XR × 2 days)) for midazolam AUC(0-∞) was 0.98 (90% confidence interval [CI], 0.87, 1.10). The GMR (midazolam + diltiazem(XR × 2 days)/midazolam + diltiazem(CR × 2 days)) for midazolam AUC(0-∞) was 0.82 (90% CI, 0.73, 0.92). Simcyp simulations accurately predicted the observed clinical results only when a hepatic CYP3A degradation rate (k(deg)) different from that provided by the software was used. The data suggest that dosing diltiazem XR for 2 days predicts the change in midazolam AUC as reliably as 5 days of XR dosing and 2 days of CR dosing. In addition, the authors believe that a hepatic CYP3A kdeg of 0.03 h(-1) should be considered for future Simcyp studies.
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Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: from retrospective to prospective.
Li, JL, Wang, XD, Chen, SY, Liu, LS, Fu, Q, Chen, X, Teng, LC, Wang, CX, Huang, M
The pharmacogenomics journal. 2011;(4):300-6
Abstract
The impact of CYP3A5*3, a CYP3A5 nonexpresser genotype, on inhibitory effects of diltiazem on tacrolimus metabolism has not been assessed. In retrospective study, when coadministered with diltiazem, mean increments in dose-adjusted C(0D7), C(max) and AUC(0-12 h) for tacrolimus were larger in CYP3A5 expressers than in CYP3A5 nonexpressers (48.7 vs 3.7%, 31.7 vs 17.2% and 38.2 vs 18.5%, respectively). Subsequently, a prospective study was carried out, patients were randomized to algorithm-predicted dosing or standard dosing. For CYP3A5 expressers, an algorithm guided by CYP3A5 and diltiazem significantly reduced tacrolimus maintenance dosage (P=0.009) and improved the accuracy of tacrolimus initial dose, resulting in reduction in out-of-range C(0) after initial dose (P=0.002) and dose adjustments (P=0.004). However, for CYP3A5 nonexpressers, primary end points were not achieved, and tacrolimus-sparing effect of diltiazem was not remarkable. Our study results show that CYP3A5 genotype-guided tacrolimus-diltiazem combination is a promising therapy in renal transplant recipients in the early postoperative stage.