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JNCI Cancer Spectrum Mar 2023Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as... (Review)
Review
BACKGROUND
Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.
METHODS
We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 liveborn offspring). We reviewed prescribed medications from mothers' medical records to identify those who received Bendectin during pregnancy. Diagnoses of CRC in adult (aged ≥18 years) offspring were ascertained by linkage with the California Cancer Registry. Cox proportional hazards models were used to estimate adjusted hazard ratios, with follow-up accrued from birth through cancer diagnosis, death, or last contact.
RESULTS
Approximately 5% of offspring (n = 1014) were exposed in utero to Bendectin. Risk of CRC was higher in offspring exposed in utero (adjusted hazard ratio = 3.38, 95% confidence interval [CI] = 1.69 to 6.77) compared with unexposed offspring. Incidence rates of CRC were 30.8 (95% CI = 15.9 to 53.7) and 10.1 (95% CI = 7.9 to 12.8) per 100 000 in offspring exposed to Bendectin and unexposed, respectively.
CONCLUSIONS
Higher risk of CRC in offspring exposed in utero may be driven by dicyclomine contained in the 3-part formulation of Bendectin used during the 1960s. Experimental studies are needed to clarify these findings and identify mechanisms of risk.
Topics: Adult; Female; Humans; Pregnancy; Antiemetics; Colorectal Neoplasms; Dicyclomine; Mothers; Prenatal Exposure Delayed Effects
PubMed: 36895101
DOI: 10.1093/jncics/pkad021 -
Dementia & Neuropsychologia 2023Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial... (Review)
Review
UNLABELLED
Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings.
OBJECTIVE
The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies.
METHODS
This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software.
RESULTS
Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders.
CONCLUSION
The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.
PubMed: 37261256
DOI: 10.1590/1980-5764-DN-2022-0053 -
British Journal of Pharmacology Sep 1986The selectivity profiles of the muscarinic receptor antagonists dicyclomine and trihexyphenidyl have been examined in binding and functional studies and compared with...
The selectivity profiles of the muscarinic receptor antagonists dicyclomine and trihexyphenidyl have been examined in binding and functional studies and compared with those of pirenzepine and atropine. Dicyclomine, trihexyphenidyl and pirenzepine demonstrated the highest affinity for the M1 muscarinic receptor subtype as revealed in competition experiments against [3H]-pirenzepine labelling of cortical membranes. Their affinity values lay in a narrow range (3.7-14 nM) approaching that of atropine (1.6 nM). Competition experiments against [3H]-N-methylscopolamine in cardiac and glandular (salivary) membranes revealed differences between the drugs examined. Dicyclomine, trihexyphenidyl and pirenzepine displayed low affinity for the cardiac and intermediate affinity for the glandular receptors. Thus, the drugs appeared to discriminate between the M1 (cortical) and the peripheral muscarinic subtypes (cardiac and glandular). However, atropine displayed similar affinities for either subtype with IC50s varying only slightly (1.6-4.6 nM). The rank order of selectivity was: pirenzepine greater than dicyclomine greater than trihexyphenidyl greater than atropine. Mirroring the binding data, pirenzepine, dicyclomine and trihexyphenidyl showed a tenfold greater ability at inhibiting M1-receptor mediated ganglionic responses (McN A-343 pressor effect in pithed rats and nictitating membrane contraction in cats) than at inhibiting peripheral muscarinic responses in the heart and cardiovascular smooth muscle (vagal bradycardia in rats and cats and vagally-induced vasodilatation in cats). The muscarinic antagonists so far examined can be categorized into two groups. Trihexyphenidyl, dicyclomine and pirenzepine, included in one group, are characterized by a higher affinity for the neuronal (M1) muscarinic receptor, hence they antagonize functional responses mediated by the M1 subtype. Atropine, a member of the other group, shows essentially no selectivity. 6 Differentiation of M1 and peripheral muscarinic receptor subtypes appears to be a property not confined to tricyclics such as pirenzepine but shared by diverse chemical structures. Both trihexyphenidyl and dicyclomine appear to be useful pharmacological tools in the classification of muscarinic receptor subtypes.
Topics: (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; Animals; Blood Pressure; Cyclohexanecarboxylic Acids; Decerebrate State; Dicyclomine; Electric Stimulation; In Vitro Techniques; Male; Pirenzepine; Rats; Rats, Inbred Strains; Receptors, Muscarinic; Trihexyphenidyl; Vagus Nerve
PubMed: 2432979
DOI: 10.1111/j.1476-5381.1986.tb11123.x -
British Medical Journal (Clinical... Oct 1985
Topics: Abnormalities, Drug-Induced; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Infant, Newborn; Pregnancy; Pyridines; Pyridoxine; Risk; United Kingdom
PubMed: 3929963
DOI: 10.1136/bmj.291.6500.918 -
Gastroenterology and Hepatology From... 2022As few randomized clinical trials have verified the efficacy of selective and norepinephrine reuptake inhibitors in IBS, the current study made an inclusive comparison...
AIM
As few randomized clinical trials have verified the efficacy of selective and norepinephrine reuptake inhibitors in IBS, the current study made an inclusive comparison between them, and their effectiveness in IBS-C was proven.
BACKGROUND
Irritable bowel syndrome with constipation (IBS-C) is a functional bowel disorder characterized by changes in bowel movements and abdominal pain in the absence of identifiable structural abnormalities. Despite much progress in the treatment of other types of IBS, limited treatments are available for IBS-C.
METHODS
The study population comprised 182 IBS-C patients who were randomly divided into 3 groups according to treatment type. One group was given 20 mg of dicyclomine and fluoxetine, the second group received dicyclomine along with duloxetine hydrochloride, and the third group received dicyclomine only for two months. The severity of symptoms was recorded by questionnaire at the beginning and end of the treatment.
RESULTS
The average age and BMI of the patients were 28.5 ± 5.2 years and 25.2 ± 2.4 kg/m2, respectively. Duloxetine was more effective than fluoxetine in reducing flatulence (=0.043), abdominal pain intensity (≤0.046), and duration (≤0.003), in increasing the quality of life (≤0.046), and the frequency of fecal excretion in patients (≤0.004).
CONCLUSION
Based on the study findings, fluoxetine and duloxetine had greater therapeutic effects on all symptoms of IBD than dicyclomine, with duloxetine, specifically, being more effective than fluoxetine. Further studies on larger groups are suggested to determine the best dosage and identify any potential side effects of these drugs.
PubMed: 35611252
DOI: No ID Found -
Molecules (Basel, Switzerland) Oct 2021is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for...
is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of in diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of (Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K (80 mM)-induced, and carbachol (1 µM)-induced jejunum contractions in a concentration-dependent manner similar to dicyclomine and dantrolene. Pp.Cr showed a rightward parallel shift of concentration-response curves (CRCs) of Cch after a non-parallel shift similarto dicyclomine and shifted CRCs of Ca to rightward much likeverapamil and dantrolene, demonstrating the coexistence of antimuscarinic and Ca antagonistic mechanism. Furthermore, Pp.Cr, dicyclomine, and dantrolene relaxed K (80 mM)-induced and Cch (1 µM)-induced tracheal contractions and shifted rightward CRCs of Cch similar to dicyclomine, signifying the dual blockade. Additionally, Pp.Cr also relaxed the K (80 mM)-induced and phenylephrine (1 µM)-induced aortic contraction, similarly to verapamil and dantrolene, suggesting Ca channel antagonism. Here, we explored for the first time thespasmolytic and bronchodilator effects of Pp.Crand whether they maybe due to the dual blockade of Ca channels and muscarinic receptors, while the vasodilator effect might be owing to Ca antagonism. Our results provide the pharmacological evidence that could be a new potential therapeutic option to treat gastrointestinal, respiratory, and vascular diseases. Hence, there is a need for further research to explore bioactive constituent of as well as further investigation by suitable experimental models are required to further confirm the importance and usefulness of in diarrhea, asthma, and hypertension treatment.
Topics: Animals; Biological Products; Bronchodilator Agents; Calcium Channel Blockers; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Mice; Molecular Structure; Muscarinic Antagonists; Parasympatholytics; Parmeliaceae; Spectrum Analysis; Toxicity Tests, Acute; Vasodilator Agents
PubMed: 34770756
DOI: 10.3390/molecules26216348 -
American Journal of Public Health Dec 1986In a case-control study spanning five years' experience at Group Health Cooperative of Puget Sound, we could demonstrate no plausible association between the use of...
In a case-control study spanning five years' experience at Group Health Cooperative of Puget Sound, we could demonstrate no plausible association between the use of spermicides, oral contraceptives, Bendectin, or antibiotics prior to conception and the occurrence of 73 nontraumatic stillbirths.
Topics: Abnormalities, Drug-Induced; Adult; Anti-Bacterial Agents; Contraceptives, Oral; Dicyclomine; Doxylamine; Drug Combinations; Female; Fetal Death; Health Surveys; Humans; Pregnancy; Pyridines; Pyridoxine; Spermatocidal Agents
PubMed: 3777291
DOI: 10.2105/ajph.76.12.1428 -
The Cochrane Database of Systematic... Nov 2013Irritable bowel syndrome (IBS) is a common, chronic disorder that leads to decreased health-related quality of life and work productivity. Evidence-based treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Irritable bowel syndrome (IBS) is a common, chronic disorder that leads to decreased health-related quality of life and work productivity. Evidence-based treatment guidelines have not been able to give guidance on the effects of homeopathic treatment for IBS because no systematic reviews have been carried out to assess the effectiveness of homeopathic treatment for IBS. Two types of homeopathic treatment were evaluated in this systematic review. In clinical homeopathy a specific remedy is prescribed for a specific condition. This differs from individualised homeopathic treatment, where a homeopathic remedy based on a person's individual symptoms is prescribed after a detailed consultation.
OBJECTIVES
To assess the effectiveness and safety of homeopathic treatment for treating IBS.
SEARCH METHODS
We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), Cochrane IBD/FBD Group Specialised Register, Cochrane Complementary Medicine Field Specialised Register and the database of the Homeopathic Library (Hom-inform) from inception to February 2013.
SELECTION CRITERIA
Randomised controlled trials (RCTs), cohort and case-control studies that compared homeopathic treatment with placebo, other control treatments, or usual care, in adults with IBS were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the risk of bias and extracted data. The primary outcome was global improvement in IBS. The overall quality of the evidence supporting this outcome was assessed using the GRADE criteria. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous outcomes and the risk ratio (RR) and 95% CI for dichotomous outcomes.
MAIN RESULTS
Three RCTs (213 participants) were included. No cohort or case-control studies were identified. Two studies published in 1976 and 1979 compared clinical homeopathy (homeopathic remedy) to placebo for constipation-predominant IBS. One study published in 1990 compared individualised homeopathic treatment (consultation plus remedy) to usual care (defined as high doses of dicyclomine hydrochloride, faecal bulking agents and diet sheets asking the patient to take a high fibre diet) for the treatment of IBS in female patients. Due to the low quality of reporting in the included studies the risk of bias in all three studies was unclear on most criteria and high for some criteria. A meta-analysis of two small studies (129 participants with constipation-predominant IBS) found a statistically significant difference in global improvement between the homeopathic remedy asafoetida and placebo at a short-term follow-up of two weeks. Seventy-three per cent of patients in the homeopathy group improved compared to 45% of placebo patients (RR 1.61, 95% CI 1.18 to 2.18). There was no statistically significant difference in global improvement between the homeopathic remedies asafoetida plus nux vomica and placebo. Sixty-eight per cent of patients in the homeopathy group improved compared to 52% of placebo patients (1 study, N = 42, RR 1.31, 95% CI 0.80 to 2.15). GRADE analyses rated the overall quality of the evidence for the outcome global improvement as very low due to high or unknown risk of bias, short-term follow-up and sparse data. There was no statistically significant difference found between individualised homeopathic treatment and usual care (1 RCT, N = 20) for the outcome "feeling unwell", where the participant scored how "unwell" they felt before, and after treatment (MD 0.03; 95% CI -3.16 to 3.22). None of the included studies reported on adverse events.
AUTHORS' CONCLUSIONS
A pooled analysis of two small studies suggests a possible benefit for clinical homeopathy, using the remedy asafoetida, over placebo for people with constipation-predominant IBS. These results should be interpreted with caution due to the low quality of reporting in these trials, high or unknown risk of bias, short-term follow-up, and sparse data. One small study found no statistically difference between individualised homeopathy and usual care (defined as high doses of dicyclomine hydrochloride, faecal bulking agents and diet sheets advising a high fibre diet). No conclusions can be drawn from this study due to the low number of participants and the high risk of bias in this trial. In addition, it is likely that usual care has changed since this trial was conducted. Further high quality, adequately powered RCTs are required to assess the efficacy and safety of clinical and individualised homeopathy compared to placebo or usual care.
Topics: Adult; Constipation; Dicyclomine; Dietary Fiber; Female; Ferula; Homeopathy; Humans; Irritable Bowel Syndrome; Male; Phytotherapy; Randomized Controlled Trials as Topic
PubMed: 24222383
DOI: 10.1002/14651858.CD009710.pub2 -
Archives of Disease in Childhood Oct 1985
Topics: Animals; Circadian Rhythm; Colic; Dicyclomine; Food Hypersensitivity; Humans; Infant; Infant, Newborn; Intestines; Milk; Mothers; Tobacco Smoke Pollution
PubMed: 3840672
DOI: 10.1136/adc.60.10.981