Indomethacin Suppositories Research Articles

Vision loss: another ERCP-related adverse event, also known as isolated bilateral lateral geniculate body infarction

A 22-year-old healthy woman experienced intermittent epigastric pain 3 weeks after an uncomplicated pregnancy. Cholecystitis was diagnosed on the basis of US, and cholecystectomy was scheduled in 2 weeks. Because of the persistence of intermittent pain and mild laboratory evidence of cholestasis, with bilirubin total of 1.6 mg/dL, the patient underwent preoperative ERCP because of a concern for choledocholithiasis, despite normal common bile duct (CBD) on US (A) and no symptoms of cholangitis. ERCP with precut sphincterotomy to facilitate CBD cannulation and subsequent balloon-sweep revealed a normal cholangiogram (B). An indomethacin suppository was given. Within 24 hours after ERCP, the patient experienced severe epigastric pain. Acute pancreatitis was diagnosed on the basis of lipase 2200 units/L. Intravenous fluids were started 12 hours later. Simultaneously, the patient experienced rapidly progressing, painless, bilateral vision loss, necessitating transfer to our hospital. Her pain resolved within 72 hours; however, the result of neurologic examination was pertinent for persistent profound bilateral vision loss but was otherwise nonfocal, with normal fundoscopic examination results. Magnetic resonance imaging of the brain revealed bilateral lateral geniculate body infarcts (C). Given the temporal relationship to post-ERCP pancreatitis, a watershed infarction was suspected, likely resulting from temporary hypotension. The result of a comprehensive evaluation for other causes of stroke, including vasculitis and hypercoagulability, was negative. Because potentially severe ERCP-related adverse events can occur, the correct procedure indication is crucial.

A Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis in Patients with Suspected Type 3 Sphincter of Oddi Dysfunction.

Recent data have suggested that rectal indomethacin can also reduce the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The aim of this study was to determine whether prophylactic rectal indomethacin with PD stenting would reduce the incidence and severity of PEP compared to PD stenting alone in patients undergoing manometry for suspected SOD type 3. A retrospective review of consecutive patients who underwent an ERCP with manometry for suspected SOD type 3 was performed. Patients were divided into two groups: (a) those who received a prophylactic PD stent (n=285) and (b) those who received a prophylactic PD stent and a single dose of 100-mg indomethacin suppositories after ERCP (n=57). The rate of PEP was compared between the two groups. The two patient groups were similar with regard to patient and procedure risk factors for PEP. Post-ERCP pancreatitis developed in 22% patients. There was no significant difference in the incidence of PEP in the PD stent group compared to the PD stent and indomethacin group (23 vs. 18%, respectively; p=0.39). Moderate-to-severe pancreatitis developed in 21 (7%) patients in the PD stent group compared to 5 (9%) patients in the PD stent and indomethacin group (p=0.78). Among patients with PEP, the median length of hospital stay was not significantly longer in the PD stent group compared to the PD stent and indomethacin group (6 vs. 4days, respectively; p=0.11). In patients with suspected SOD type 3, prophylactic rectally administered indomethacin with PD stenting was not observed to affect the incidence or severity of post-ERCP pancreatitis when compared to PD stenting alone.

Comparison of indomethacin suppository and lidocaine cream on post-episiotomy pain: A randomized trial.

Background:One of the most important problems after episiotomy is perineal pain which is more severe on the first day of postpartum period. The aim of this study was to compare the analgesic effects of indomethacin suppository and lidocaine cream in the management of post-episiotomy pain.Materials and Methods:In a randomized, controlled trial, 60 primiparous women who had mediolateral episiotomy received 50 mg indomethacin suppository (n = 30) or 2% lidocaine cream (n = 30) in the postpartum period in Hajar Hospital in Shahrekord (Iran). The mean severity of post-episiotomy pain was assessed with the first complaint and at 6, 12, and 24 h after the delivery, and compared in the two groups. The visual analog scale (VAS) was used for pain recording and data were analyzed with independent-samples t-test, χ2, and Fisher's exact tests, and significance was defined as P < 0.05.Results:With the first complaint of pain, the mean intensity of pain was 4.9 (1.9) in the indomethacin group and 4.9 (1.8) in the lidocaine group, and the difference was not significant (P = 0.25). Six hours after birth, it was 3.3 (1.3) in the indomethacin group and 3.2 (1.9) in the lidocaine group, and there was not a significant difference between the two groups (P = 0.90). No significant difference was found between the two groups at 12 h after birth [2.3 (1.7) vs 2.5 (1.7); P = 0.59]. Also, the difference was not significant at 24 h after birth [1.5 (1.3) vs 1.8 (1.3); P = 0.31].Conclusions:It was concluded from the study that indomethacin suppository and lidocaine cream have similar efficacy on episiotomy pain relief on the first day of postpartum period.

Pre-operative rectal indomethacin for reduction of postoperative nausea and vomiting after laparoscopic cholecystectomy: a double-blind randomized clinical trial.

To evaluate the effect of pre-operative indomethacin suppository on postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy. A double blind placebo-controlled randomized clinical trial. Hazrat Rasoul Akram Hospital, Tehran, Iran, from February 2010 to September 2012. One hundred and thirty patients, scheduled for laparoscopic cholecystectomy, were randomly divided into case and control groups. Sixty-five patients received indomethacin suppository and 70 patients received rectal placebo in the case and control groups respectively. All patients underwent the same protocol in laparoscopic surgery and anesthesia, then nausea and vomiting was recorded after 1, 6, 12 and 24 hours postoperatively and compared between the two groups. Independent-sample t test or Mann-Whitney tests were used for statistical analysis. Level of statistical significance was set at P ² 0.05. Patients' nausea was statistically lower in the case group at the 1st hour (43.1 vs. 92.9%), 6th hour (20.0 vs. 68.6%) and 12th hour (7.7 vs. 24.3%) after surgery (for all periods, P < 0.001). Fewer patients in the case group experienced vomiting at the first (13.8 vs. 51.4%) and 6th hour (0 vs. 20%) after surgery (for both P < 0.001). The use of pethidine was also statistically less in the case group in the same hours after surgery (for all of them, P < 0.001). Rectal indomethacin before laparoscopic cholecystectomy led to lower postoperative nausea and vomiting.

Combination of tocolytic agents for inhibiting preterm labour.

Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a wide range of drugs that can inhibit labour to prolong pregnancy. This may gain time to allow the fetus to mature further before being born, permit antenatal corticosteroid administration for lung maturation, and allow time for intra-uterine transfer to a hospital with neonatal intensive care facilities. However, some tocolytic drugs are associated with severe side effects. Combinations of tocolytic drugs may be more effective over single tocolytic agents or no intervention, without adversely affecting the mother or neonate. To assess the effects on maternal, fetal and neonatal outcomes of any combination of tocolytic drugs for the treatment of preterm labour when compared with any other treatment, no treatment or placebo. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014) and reference lists of retrieved studies. We included randomised controlled trials comparing a combination of tocolytic agents, administered by any route or any dose, for inhibiting preterm labour versus any other treatment (including other combinations of tocolytics or single tocolytics), no intervention or placebo. Two review authors independently assessed study reports for eligibility, carried out data extraction and assessed risk of bias. Eleven studies met our inclusion criteria. Two studies did not report any outcome data relevant to the review, so the results of the review are based on nine trials that contributed data. Primary outcomes were perinatal mortality, serious maternal or infant outcomes, adverse drug reactions, birth before 48 hours of trial entry, birth before 34 weeks' gestation and preterm neonates delivered without a full course of antenatal steroids completed 24 hours before birth. The quality of evidence in included trials was mixed; only three of the trials were placebo controlled.The included trials examined seven different comparisons: intravenous (IV) ritodrine plus oral or IV magnesium (sulphate or gluconate) versus IV ritodrine alone (three trials, 231 women); IV ritodrine plus indomethacin suppositories versus IV ritodrine alone (one trial, 208 women); IV ritodrine plus vaginal progesterone versus IV ritodrine alone (one trial, 83 women); IV hexoprenaline sulphate plus IV magnesium hydrochloride versus IV hexoprenaline sulphate alone (one trial, 24 women); IV fenoterol plus oral naproxen versus IV fenoterol alone (one trial, 72 women); oral pentoxifylline plus IV magnesium sulphate plus IV fenoterol versus IV magnesium sulphate plus IV fenoterol (one trial, 125 women); and, IV terbutaline plus oral metoprolol versus IV terbutaline alone (one trial, 17 women). Few studies with small numbers of women were available for each comparison, hence very little data were pooled in meta-analysis. In all trials, not many of the primary outcomes were reported.Three trials examined intravenous (IV) ritodrine plus IV or oral magnesium (sulphate or gluconate) compared with IV ritodrine alone. One study, with 41 women, reported more adverse drug reactions in the group receiving the combined tocolytics (risk ratio (RR) 7.79, 95% confidence interval (CI) 1.11 to 54.80). Two trials reported discontinuation of therapy due to severe side effects (results were not combined due to high statistical heterogeneity, I² = 83%); one trial reported increased severe side effects in the group receiving IV ritodrine alone (RR 7.79, 95% CI 1.11 to 54.80, 41 women); in the other trial there was no clear difference between groups (RR 0.23, 95% CI 0.03 to 1.97, 107 women). Other primary outcomes were not reported.One trial assessed IV ritodrine plus indomethacin suppositories versus IV ritodrine alone. There were no significant differences between groups for perinatal mortality or serious neonatal morbidity. Results for other primary outcomes were not reported.There were no significant differences between groups receiving IV ritodrine plus vaginal progesterone compared with IV ritodrine alone for most outcomes reported, although the latency period (time from recruitment to delivery) was increased in the group receiving the combination of tocolytics.For other combinations of tocolytic agents, primary outcomes were rarely reported and for secondary outcomes results did not demonstrate differences between groups. It is unclear whether a combination of tocolytic drugs for preterm labour is more advantageous for women and/or newborns due to a lack of large, well-designed trials including the outcomes of interest. There are no trials of combination regimens using widely used tocolytic agents, such as calcium channel blockers (nifedipine) and/or oxytocin receptor antagonists (atosiban). Further trials are needed before specific conclusions on use of combination tocolytic therapy for preterm labour can be made.

A comparative study on relieving post-episiotomy pain with diclofenac and indomethacin suppositories or placebo

In this study, we compare the prophylactic efficacy of a diclofenac suppository and an indomethacin suppository on decreasing post-episiotomy pain. A total of 90 women with 2nd-degree episiotomy were assigned to receive a single dose of diclofenac suppository (30), indomethacin suppository (30) or placebo (30), according to randomised blocks. The pain was assessed at 1, 2, 4, 6 and 12 hours after receiving analgesia, using the two methods of pain score and visual analogue. This study showed that in the group given diclofenac or indomethacin, at all the assessed hours, the pain measured was considerably less than in the suppository-free group (p < 0.05). Comparing the diclofenac and indomethacin groups, there were only significant differences in the 4 and 12 hour measurements: the diclofenac was more effective than the indomethacin (4th hour), but due to a shorter half-life, the diclofenac group in the 12th hour had more pain (p < 0.05). Diclofenac suppository is recommended at 4-hour intervals for all patients, without internal disorders, to decrease episiotomy pain.

A Randomized Trial of Rectal Indomethacin and Sublingual Nitrates to Prevent Post-ERCP Pancreatitis

Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.

The Comparison of Periprostatic Nerve Blockage with the Combination of Perianally and Intrarectally Lidocaine Gel and Intrarectally Indomethacin Suppository in the Control of Pain Related to Transrectal Ultrasound Guided Prostate Biopsy Procedure

Aims : In this study, we aimed to evaluate the effectiveness of the use of periprostatic nerve blockage with the combination of perianally and intrarectally lidocaine gel and intrarectally indomethacin suppository in the control of pain related to the TRUS-Bx procedure. Materials and Methods : The data of 88 patients who underwent TRUS-Bx were retrospectively evaluated. The sample were divided in two groups according to the type of topical anesthesia previous to TRUS-Bx. In group 1 (n=42), while the combination of perianally and intrarectally lidocaine gel with intrarectally indomethacin suppository were applied to provide local anesthesia, a periprostatic nerve blockage by using 10 ml of %1 lidocaine solution were also performed in addition to this combination in group 2 (n=46). Ten point linear visual analog scale (VAS) was used to evaluate the pain. While VAS-1 score evaluated the pain that occured during TRUS probe placement and/or manipulations, VAS-2 score analysed the pain that occurred during the performation of needle biopsy. Results : The mean ages, PSA values, and prostate volumes were similar between two groups (P= 0.437, P= 0.187, P= 0.194; respectively). The analysis of the pain related to TRUS probe placement and manipulation showed that VAS-1 score was found 2.72 ± 0.7 and 2.68 ± 08, respectively. The comparison of VAS-1 scores revealed that there was no statistically significant difference between two groups. Nevertheless, VAS-2 score, which evaluated the pain during the needle biopsy, was determined 5.36 ± 1.08 in group 1 and 2.13 ± 0.76 in group 2. It was found that VAS-2 score was significantly lower in group 2 (P= 0.001). Conclusion : Our study revealed that periprostatic nerve blockage provided additional improvement in the control of pain related to only the step of needle biopsy in TRUS-Bx procedure.

Influence of Excipient Hydroxyl Value on the In‐vitro Release of Indomethacin Suppositories

The release rates of indomethacin from suppositories prepared with excipients of different hydroxyl values were examined by the Muranishi dialysis method. All the excipients tested had an inhibitory effect on the indomethacin release in comparison with the original powder. However, the greatest inhibition of the indomethacin release was observed when excipients of very low (OH 45) hydroxyl values were used. Excipients of an optimal range of hydroxyl values at about 15–30 are suggested to be most appropriate for the preparation of indomethacin suppositories.

Analgesic Efficacy of Interpleurally Administered Morphine and Fentanyl After Posterolateral Thoracotomy

Pain control is a major concern in post-thoracotomy patients. The current prospective randomized double-blind study was designed to evaluate the analgesic effects of morphine and fentanyl given interpleurally after posterolateral thoracotomy. Thirty patients undergoing elective posterolateral thoracotomy in a teaching hospital in Tehran were divided into 3 groups with equal number of patients. Patients in group IPM, IPF1 and IPF2 received 0.1 mg/kg morphine sulfate, 5 µg/kg fentanyl and 2.5 µg/kg fentanyl in a total volume of 40 ml injected via an intrapleural catheter placed in the pleural space before the closure of chest. Subsequent doses of interpleural injections were administered at 4 and 8 h after operation. The intensity of pain was evaluated at rest and with coughing just before each interpleural injection and 30 min afterwards using a 10 point visual analogue scale (VAS). If patients needed additional analgesia, indomethacin suppository and intravenous morphine were given during the 20-h postoperative study period. In all of the 3 study groups VAS scores were significantly reduced 30 min after interpleural administration of the study solutions (p

Comparison of the efficacy of diclofenac and indomethacin suppositories in treating perineal pain after episiotomy or laceration: a prospective, randomized, double-blind clinical trial

To compare the results in terms of effectiveness, side effects, and patient satisfaction when diclofenac and indomethacin suppositories were used for the relief of perineal pain after episiotomy or tearing during childbirth. A total of 200 women who had undergone mediolateral episiotomy or suffered lacerations while giving birth vaginally were randomly assigned to receive either rectal diclofenac or indomethacin. Pain ratings were recorded before the administration of drugs and at 1, 3, 6, 9, 12, and 24 h after the first dose on a 10 cm visual analog scale. Side effects and overall opinion on the two treatments were assessed at 24 h. The prophylactic use of diclofenac suppositories reduced perineal pain more than the use of indomethacin suppositories, although the difference was not significant. Overall additional analgesia requirement was correspondingly lower in the diclofenac group. There were no significant differences in overall patient satisfaction between the two groups. Since the two analgesics were rated similarly and gave satisfactory pain relief, diclofenac may be preferred because it is administered in a single dose and requires less nursing time to dispense and is a substantially less costly alternative to the new pain treatment technologies currently in use.

756: Analgesic Efficacy of Interpleurally Administered Morphine and Fentanyl After Posterolateral Thoracotomy

Pain control is a major concern in post-thoracotomy patients. The current prospective randomized double-blind study was designed to evaluate the analgesic effects of morphine and fentanyl given interpleurally after posterolateral thoracotomy. Thirty patients undergoing elective posterolateral thoracotomy in a teaching hospital in Tehran were divided into 3 groups with equal number of patients. Patients in group IPM, IPF1 and IPF2 received 0.1 mg/kg morphine sulfate, 5 μg/kg fentanyl and 2.5 μg/kg fentanyl in a total volume of 40 ml injected via an intrapleural catheter placed in the pleural space before the closure of chest. Subsequent doses of interpleural injections were administered at 4 and 8 h after operation. The intensity of pain was evaluated at rest and with coughing just before each interpleural injection and 30 min afterwards using a 10 point visual analogue scale (VAS). If patients needed additional analgesia, indomethacin suppository and intravenous morphine were given during the 20-h postoperative study period. In all of the 3 study groups VAS scores were significantly reduced 30 min after interpleural administration of the study solutions (p<0.05). However, inter-group comparisons revealed no significant differences for VSA scores, supplemental analgesic usage and systemic side effects. Briefly, interpleural morphine and fentanyl following thoracotomy produce equal analgesia without major side effects.

Formulation development and release studies of indomethacin suppositories

Indomethacin suppositories were prepared by using water-soluble and oil soluble suppository bases, and evaluated for in vitro release by USP I and modified continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5%) was further studied on in vitro release of the medicament. Release rate was good in water-soluble suppositories bases in comparison to oil soluble suppositories bases. Release was found to be greater in modified continuous flow through bead bed apparatus. When surfactant was used in low concentration then release rate was much greater, as compared to high concentration. When stability studies were performed on the prepared indomethacin suppositories it was found that suppositories made by water-soluble base had no significant changes while suppositories prepared by oil soluble bases, had some signs of instability.

Acute Renal Failure in Four HIV-Infected Patients: Potential Association with Tenofovir and Nonsteroidal Anti-Inflammatory Drugs

Acute Renal Failure in Four HIV-Infected Patients: Potential Association with Tenofovir and Nonsteroidal Anti-Inflammatory Drugs

Urinary nitrite excretion and urinary variables in patients with primary nocturnal frequency of micturition: effects of indomethacin suppositories

Urinary nitrite excretion was measured in patients with primary nocturnal frequency of micturition (PNFM) and in normal individuals. Effects of indomethacin suppository on urine volume and other urinary variables were evaluated. The study comprised seven patients with PNFM and seven healthy control (age range 30-45 years). Nitrite was assayed in spot morning urine samples; urine volume, urine osmolality and electrolytes, serum osmolality and electrolytes and functional bladder capacity (FBC) were assayed. Both groups were then given 100 mg of indomethacin suppository daily for a maximum of 10 days and urinary variables were re-evaluated during day 10. Results showed that urinary nitrite excretion of patients with PNFM was greater than that of the normal subjects (230+/-62 umol/l vs. 42+/-30 umol/l, P<0.05). The mean (SD) 24 h urine volume and osmolality, the night urine volume and osmolality, serum osmolality, FBC, creatinine clearance, fractional excretion of sodium (FENa), fractional excretion of potassium (FEK), and urinary excretion of glucose and potassium were lower in patients with PNFM as compared with normal individuals, although not statistically significantly so, except for FBC that was significantly lower in the patients. Urinary excretion of sodium, calcium, chloride, phosphorus, magnesium, day-night urinary volume ratio, spot morning osmolality, nocturnal index, and nocturnal polyuria index were higher in patients with PNFM. Indomethacin decreased the 24 h urinary volume by 21%, creatinine clearance by 12%, osmolar clearance by 14% and urinary protein excretion by 38% in the patients. These variables decreased by 26, 45, 17 and 12% respectively in the healthy subjects, whereas 24 h urinary protein excretion increased mildly by 9%. Indomethacin increased day-night urinary volume ratio by 73% in the healthy subjects. It might be concluded that urinary nitrite excretion, urinary excretion of sodium, chloride, phosphorus, calcium, and magnesium increased and FBC decreased in patients with PNFM; Indomethacin decreased urinary volume, FENa, FEK, osmolar clearance, and free water clearance in the healthy subjects and the patients. These might explain the mechanism of action of indomethacin to reduce frequency of voiding. The possible interaction of prostaglandin and NO in the pathogenesis of PNFM is discussed.

Thoracic epidural local anesthetics are ineffective in alleviating post-thoracotomy ipsilateral shoulder pain

Objective: This study was conducted to estimate the incidence and clinical predictors of post-thoracotomy shoulder pain and to determine the effectiveness of thoracic epidural block in alleviating this pain. Design: A prospective clinical trial. Setting: University teaching hospital. Participants and Interventions: Thirty-two adult patients undergoing elective thoracic surgery consented to participate in the study. All operations were open thoracotomies done by the same team of surgeons and anesthesiologists. A thoracic (T6) epidural catheter was placed before induction of general anesthesia. Each patient received 7 mL of lidocaine 2% epidurally and repeated doses of 5 mL of lidocaine 2% every half hour during the operation. Postoperatively, the occurrence of incision or ipsilateral shoulder pain was observed and treated with a maximal dose of 5 mL of lidocaine 2%. If ineffective, indomethacin suppository (nonsteroidal anti-inflammatory drug [NSAID]) was given. Variables such as patient’s age, sex, American Society of Anesthesiologists physical status, type, site and duration of surgery, duration of anesthesia, the resection of main bronchus, and the use of thoracostomy tubes were recorded. Measurements and Main Results: Postoperatively, 10 patients (31%) had shoulder pain, 4 patients (12.5%) complained of incision pain, and 2 (6.3%) complained of both incision and shoulder pain. A bolus of 5 mL of lidocaine 2% in the epidural catheter relieved incision pain in all the patients, but was ineffective for shoulder pain. Indomethacin suppository was effective in these patients. No correlation was found between any variable and the occurrence of shoulder pain. Conclusions: It is concluded that post-thoracotomy shoulder pain is a common problem, and the previously mentioned variables did not predict its appearance. Thoracic epidural block is effective in the treatment of incision but not shoulder pain. The NSAID indomethacin suppository was found to be effective for that problem.

In vitro drug liberation and kinetics of sustained release indomethacin suppository

The aim of this study was to formulate sustained release (SR) suppositories containing indomethacin (IND) microspheres. In the first part of the study, IND microspheres were prepared by solvent evaporation method. Ethyl cellulose was used as polymer. Shape and surface charactheristics, particle size and size distribution of microspheres were determined. The effect of drug: polymer ratio and stirring rate on microsphere formation, average particle size, drug loading capacity and in vitro IND release were investigated. The highest drug loading capacity was found with 1:1 drug–polymer ratio. Stirring rate caused insignificant effect on drug loading capacity but particle size. Increase in stirring rate resulted in a decrease in particle size. In the second part, SR suppositories were formulated by incorporating IND microspheres having the highest drug loaded. The bases used were PEG mixtures (400:1500:4000) and Witepsol H15. Qualitative controls and IND assay on the suppositories were carried out. The drugs released were evaluated by in vitro dissolution tests. Comparative results of SR suppositories containing IND microspheres with that of conventional ones showed that the former has sustained effect up to 480 min in vitro. Release results were evaluated kinetically and the data was fitted (Bt) a kinetics.

Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion.

To assess urinary nitrite excretion, a stable end product of nitric oxide (NO), in patients with enuresis and in normal controls, and to evaluate the effects of indomethacin (a potent prostaglandin synthesis inhibitor) on urinary nitrite excretion, other urinary variables and bladder capacity. The study comprised 10 patients with primary enuresis and 10 normal comparable controls (age range 6-14 years). Nitrite was assayed in 'spot' morning urine samples in both the enuretics and normal controls. Enuretics were then given 50 mg indomethacin suppositories each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes and urinary nitrite were assayed before indomethacin treatment and after 15 days of treatment. The mean (sd) urinary nitrite excretion was 24.4 (19.6) micromol/L in normal children and 275.9 (111.2) micromol/L in enuretics (P<0.05). With indomethacin, the urinary nitrite concentration was significantly decreased to 141 (45.1) micromol/L (P<0.05) and associated with a significant reduction in bed-wetting episodes and voiding frequency. The functional bladder capacity was <70% of the predicted value for age in six of the patients; they had significant improvements on indomethacin, to values similar to those in patients with a nearly normal functional bladder capacity. Indomethacin decreased the 24-h urinary volume by 41%, the night volume by 40%, clearance of free water by 46% and increased the day : night urinary volume ratio by 55%. The absolute amounts of urinary calcium, magnesium, phosphorus, urea, creatinine, and glucose were lower on indomethacin, although not statistically significantly so. Indomethacin decreased the 24-h urinary and 'spot' morning osmolality and osmotic clearance. There were no significant changes in serum osmolality and electrolyte concentrations. Indomethacin also decreased the absolute amount of urinary sodium, chloride and potassium, fractional sodium and potassium excretion, and filtered sodium. Creatinine clearance was decreased by 20% (P>0.05) and normal 24-h urinary protein was significantly lower, by 47%, after indomethacin treatment (P<0.05). Urinary nitrite excretion increased significantly in patients with primary nocturnal enuresis; indomethacin markedly reduced bed-wetting episodes and decreased the frequency of voiding in enuretics with small or normal functional bladder capacity, which was associated with a significant decrease in urinary nitrite excretion. Indomethacin reduced bed-wetting by decreasing the urine volume, clearance of free water and urinary electrolytes, and through possible effects on bladder and urethral contraction, by inhibiting NO and prostaglandin synthesis. NO and prostaglandins might be important in the pathogenesis of primary enuresis.

Effects of indomethacin suppository and lidocaine pomade for the relief of post-episiotomy pain

The aim of this study is to investigate the effectiveness of lidocaine pomade and indomethacin suppository for the relief of post-episiotomy pain. The study was carried out prospectively in 87 women aged between 17 and 39 years who delivered a live singleton and fetus at term between February and December 2000.

Effects of adding midazolam on the postoperative epidural analgesia with two different doses of bupivacaine

Study Objective: To investigate the interaction of midazolam with different doses of bupivacaine, by comparing the analgesic, sedative, and amnesic effects of continuous epidural midazolam with two different doses of bupivacaine. Design: Prospective, randomized study. Setting: Operating room and intensive care units of a university hospital. Patients: 100 ASA physical status I and II postgastrectomy patients (40–70 yrs) without any complications. Interventions: Patients were divided into four groups (n = 25) and administered continuous thoracic epidural infusion (40 mL/12 hr) of the drugs via a balloon infuser. The contents of the infuser (40 mL) were bupivacaine 180 mg with midazolam 20 mg (HM group), 90 mg with midazolam 20 mg (LM group), 180 mg without midazolam (HC group), or 90 mg without midazolam (LC group). As a rescue medication, 50 mg indomethacin suppository was the first choice, then IM pentazocine 15 mg. Measurements: Analgesia and sedation scores, blood pressure (BP), heart rate, respiratory rate, oxygen saturation, amnesia, the number of rescue medications, and time to the first rescue medication were monitored. The area under the curves (AUCs) of analgesia and sedation scores, and BP were calculated. Main Results: In the HM group, significantly better analgesia and sedation were obtained and the number of rescue medications given was the lowest of the four groups. The time to the first rescue medication was longest in the HM group, followed by the LM group, then the HC, and, finally, LC groups. The numbers of the patients with amnesia were greater in the HM and LM groups than the HC and LC groups. Blood pressure decreased significantly in the HM group but no treatment was necessary. The AUCs of analgesia and sedation scores, and BP were lowest in the HM group. Conclusions: Adding midazolam increased not only analgesic but also sedative effect with increasing dose of bupivacaine in a postoperative continuous epidural administration.