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Indian Journal of Pharmaceutical... 2014Liquid chromatographic method was developed for simultaneous quantitative determination of dicyclomine hydrochloride, mefenamic acid and paracetamol in their combined...
Liquid chromatographic method was developed for simultaneous quantitative determination of dicyclomine hydrochloride, mefenamic acid and paracetamol in their combined dosage form. The separation was achieved using a C18 column (250×4.6 mm id, 5 μm) using acetonitrile:20 mM potassium dihydrogen phosphate 70:30 (v/v) adjusted to pH 4 using orthophosphoric acid as mobile phase at a flow rate of 1 ml/min and detection at 220 nm. Separation was completed within 12 min. The retention times of dicyclomine hydrochloride, mefenamic acid and paracetamol were 3.8, 9.3 and 2.5 minutes respectively. The proposed method was found to have linearity in concentration range of 10-100 μg/ml for dicyclomine hydrochloride, 0.05-10 μg/ml for mefenamic acid and 0.1-20 μg/ml for paracetamol. The developed method has been statistically validated and was found to be simple, precise, reproducible and accurate. The developed and validated method was successfully used for the quantitative analysis of commercially available dosage form.
PubMed: 25593386
DOI: No ID Found -
British Journal of Pharmacology Sep 19901. The effect of atropine on the nociceptive system was examined in mice and rats by use of the hot-plate, writhing and tail-flick tests. 2. Atropine dose-dependently...
1. The effect of atropine on the nociceptive system was examined in mice and rats by use of the hot-plate, writhing and tail-flick tests. 2. Atropine dose-dependently produced analgesia, no effect and hyperalgesia. Analgesia was observed in both species with doses ranging from 1 to 100 micrograms kg-1 while hyperalgesia was obtained with 5 mg kg-1. 3. Atropine antinociception was prevented by pirenzepine (0.1 microgram per mouse, i.c.v.), dicyclomine (10 mg kg-1, i.p.), atropine-methylbromide (0.5 microgram per mouse, i.c.v.) and hemicholinium-3 (1 microgram per mouse, i.c.v.). Naloxone (1 mg kg-1, i.p.), alpha-methyl-p-tyrosine (100 mg kg-1, s.c.) and reserpine (2 mg kg-1, i.p.) were ineffective. 4. The site of atropine analgesia is in the CNS since it exerts its antinociceptive effect also when injected i.c.v. (1-10 ng per mouse). Moreover drugs which do not cross the blood-brain barrier, such as hemicholinium-3, pirenzepine and atropine methylbromide, were unable to antagonize atropine analgesia if administered i.p. 5. Atropine also in vitro, showed a biphasic action on electrically-evoked guinea-pig ileum contractions. Concentrations between 10(-14) and 10(-12) M increased electrically and nicotine-evoked contractions but did not affect acetylcholine- and oxotremorine-evoked contractions. Concentrations above 10(-9) M inhibited both electrically- and drug (acetylcholine, nicotine and oxotremorine)-evoked contractions while they were ineffective on unstimulated ileum. 6. On the basis of the above findings, amplification of cholinergic transmission by very low doses of atropine is postulated, through a selective blockade of presynaptic muscarinic autoreceptors, as the likely mechanism of action. 7. Atropine antinociception, unlike oxotremorine antinociception, was obtained without any impairment of mouse rota-rod performance. 8. The antagonism by pirenzepine and dicyclomine of oxotremorine and atropine antinociception suggests that M1 muscarinic receptor subtypes are responsible for cholinergic analgesia.
Topics: Analgesics; Animals; Atropine; Dicyclomine; Electric Stimulation; Guinea Pigs; Ileum; In Vitro Techniques; Injections, Intraventricular; Male; Mice; Muscle, Smooth; Naloxone; Oxotremorine; Pain; Parasympatholytics; Pirenzepine; Postural Balance; Rats; Rats, Inbred F344; Rats, Inbred Strains; Reaction Time; Sensory Thresholds
PubMed: 2282466
DOI: 10.1111/j.1476-5381.1990.tb12087.x -
Indian Journal of Psychiatry 2020
PubMed: 33896989
DOI: 10.4103/psychiatry.IndianJPsychiatry_562_19 -
Revista de Gastroenterologia de Mexico 2012Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit.
AIMS
To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS.
METHODS
We carried out a systematic review and meta-analysis of randomized controlled clinical trials on antispasmodic agents for IBS treatment. Clinical trials identified from January 1960 to May 2011 were searched for in MEDLINE, the Cochrane Library, and in the ClinicalTrials.gov registry. Treatment response was evaluated by global improvement of symptoms or abdominal pain, abdominal distention/bloating, and frequency of adverse events. The effect of antispasmodics vs placebo was expressed in OR and 95% CI.
RESULTS
Twenty-seven studies were identified, 23 of which fulfilled inclusion criteria. The studied agents were pinaverium bromide, mebeverine, otilonium, trimebutine, alverine, hyoscine, alverine/simethicone, pinaverium/simethicone, fenoverine, and dicyclomine. A total of 2585 patients were included in the meta-analysis. Global improvement was 1.55 (CI 95%: 1.33 to 1.83). Otilonium and the alverine/simethicone combination produced significant values in global improvement while the pinaverium/simethicone combination showed improvement in bloating. As for pain, 2394 patients were included with an OR of 1.52 (IC 95%: 1.28 a 1.80), favoring antispasmodics.
CONCLUSIONS
Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations.
Topics: Drug Therapy, Combination; Humans; Irritable Bowel Syndrome; Parasympatholytics; Randomized Controlled Trials as Topic
PubMed: 22672854
DOI: 10.1016/j.rgmx.2012.04.002 -
The Cochrane Database of Systematic... Aug 2011Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control.
OBJECTIVES
The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.
SEARCH STRATEGY
Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review.
SELECTION CRITERIA
Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included.
MAIN RESULTS
A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review.
AUTHORS' CONCLUSIONS
There is no evidence that bulking agents are effective for treating IBS. There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures.
Topics: Abdominal Pain; Antidepressive Agents; Dietary Fiber; Humans; Irritable Bowel Syndrome; Parasympatholytics; Phytotherapy; Plantago; Randomized Controlled Trials as Topic
PubMed: 21833945
DOI: 10.1002/14651858.CD003460.pub3 -
Evidence-based Complementary and... 2020Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage...
MATERIALS AND METHODS
Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage parameters of the hematoxylin and eosin-stained and periodic acid-Schiff-alcian blue-stained sections of the colon were scored to be assessed. Possible antispasmodic mechanism was studied on isolated rabbit jejunum, while antibacterial activity was assessed for microbes implicated in IBD.
RESULTS
In AA-induced colitis, Flaxseed oil was found to be more effective in reducing mortality and colonic ulcers than Fs.Cr at 500 mg/kg dose. Fs.Cr was more efficacious in increasing mucin content as compared to oil, exhibiting slightly greater anti-inflammatory effect (50% vs 35%) and reducing depth of lesion (55% vs 42.31%, respectively). Antispasmodic activity of Fs.Cr (0.03 and 0.1 mg/ml) was mediated by phosphodiesterase inhibitors (PDEI, possibly PDE-4 subtype) with a resultant increase in cAMP levels. Flaxseed oil PDEI activity was mild (1 and 3 mg/ml). Fs.Cr (0.1 and 0.3 mg/ml) was potent in exhibiting anticholinergic activity, similar to dicyclomine, whereas Flaxseed oil showed anticholinergic effect at 1 and 3 mg/ml. Flaxseed oil (9 and 14 g/ml) was bactericidal against enteropathogenic (EPEC), enterotoxigenic (ETEC), and enteroaggregative (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100 g/ml.
CONCLUSIONS
Results of this study, taken together with previous studies, suggest that Flaxseed possesses anti-inflammatory, antibacterial, and antispasmodic action through multiple pathways and thus offers promising potential to be developed for IBD.
PubMed: 32765633
DOI: 10.1155/2020/7974835 -
ELife May 2020Invasive fungal infections cause 1.6 million deaths annually, primarily in immunocompromised individuals. Mortality rates are as high as 90% due to limited treatments....
Invasive fungal infections cause 1.6 million deaths annually, primarily in immunocompromised individuals. Mortality rates are as high as 90% due to limited treatments. The azole class antifungal, fluconazole, is widely available and has multi-species activity but only inhibits growth instead of killing fungal cells, necessitating long treatments. To improve treatment, we used our novel high-throughput method, the overlap method (O2M) to identify drugs that interact with fluconazole, either increasing or decreasing efficacy. We identified 40 molecules that act synergistically (amplify activity) and 19 molecules that act antagonistically (decrease efficacy) when combined with fluconazole. We found that critical frontline beta-lactam antibiotics antagonize fluconazole activity. A promising fluconazole-synergizing anticholinergic drug, dicyclomine, increases fungal cell permeability and inhibits nutrient intake when combined with fluconazole. In vivo, this combination doubled the time-to-endpoint of mice with meningitis. Thus, our ability to rapidly identify synergistic and antagonistic drug interactions can potentially alter the patient outcomes.
Topics: Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Antagonism; Drug Evaluation, Preclinical; Drug Synergism; Female; Fluconazole; High-Throughput Screening Assays; Humans; Meningitis, Cryptococcal; Mice; Mycoses; Structure-Activity Relationship
PubMed: 32367801
DOI: 10.7554/eLife.54160 -
Iranian Journal of Pharmaceutical... 2011Pycnocycla spinosa Decne. ex Boiss. var. spinosa (Fam. Umbelliferae) is an essential oil-containing wild plant growing in central part of Iran. Hydroalcoholic extract of...
Pycnocycla spinosa Decne. ex Boiss. var. spinosa (Fam. Umbelliferae) is an essential oil-containing wild plant growing in central part of Iran. Hydroalcoholic extract of Pycnocycla spinosa has antispasmodic and antidiarrheal activity. The aim of this study was to further investigate antidiarrheal and small intestinal transit effect of P. spinosa extract for a comparison with loperamide and dicyclomine. Male mice fasted over night with free access to water, were treated with P. spinosa extract, loperamide, dicyclomine or vehicle (p.o.). After thirty min, castor oil was given orally to the animals. In separate groups, magnesium sulphate was given in the beginning and 30 min after the extract or drugs were administered. The onset and number of wet defecation on the absorbent paper was recorded for each animal for 2.5 h. In another group of mice, intestinal transit of charcoal meal after the administration of extract, loperamide or dicyclomine was determined and compared with the control group. P. spinosa extract sharply reduced castor oil and magnesium sulphate induced diarrhea. The extract, in dose of 1 mg/Kg, had antidiarrheal effect similar to loperamide (2 mg/Kg) and with dose of 0.5 mg/Kg, its antidiarrheal action was greater than that of dicyclomine (5 mg/Kg). Unlike dicyclomine, P. spinosa extract significantly reduced the small intestinal transit of charcoal meal. However, its inhibitory effect on intestinal transit was less than loperamide. This study shows that anti-diarrhea l effect of P. spinosa extract is similar to loperamide. The inhibition of intestinal propulsion is a most likely mechanism that may account for anti-diarrhea l activity of the extract.
PubMed: 24250420
DOI: No ID Found -
Indian Journal of Anaesthesia Apr 2020
PubMed: 32489212
DOI: 10.4103/ija.IJA_848_19 -
Paediatric Drugs Jun 2014Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for... (Review)
Review
Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis(®), and has been on the Canadian market since 1979, currently under the brand name Diclectin(®). The efficacy of Diclegis(®)/Diclectin(®) has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis(®)/Diclectin(®) for the treatment of NVP to justify its use as first-line treatment for NVP.
Topics: Antiemetics; Delayed-Action Preparations; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Nausea; Pregnancy; Pregnancy Complications; Pyridoxine; Treatment Outcome; Vomiting
PubMed: 24574047
DOI: 10.1007/s40272-014-0065-5