Disease relevance of Constipation

• Prucalopride, a full 5HT(4) agonist that has been promising in idiopathic chronic constipation, may also be limited by toxicity [1].
• A patient with chronic constipation developed liver injury and leukopenia following the ingestion of Doxidan, a combination drug consisting of danthron and dioctyl calcium sulfosuccinate [2].
• Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia [3].
• Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05) [4].
• CONCLUSION: Functionally distinct alpha(2A) and alpha(2C) adrenoceptor and serotonin transporter polymorphisms are associated with constipation and high somatic symptoms in patients with lower functional gastrointestinal disorders, although the strength of the genetic contribution to the phenotype is unclear [5].

Psychiatry related information on Constipation

• The treatment of chronic idiopathic constipation consisted of education, faecal disimpaction, prevention of future impaction, and promotion of regular bowel habits with dietary fibre and milk of magnesia, and finally toilet training of the preschool child [6].
• In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients [7].
• We investigated the utility and tolerability of donepezil in nongeriatric affective illness for treatment of psychotropic-induced memory loss, dry mouth, and constipation [8].
• CONCLUSION: Urinary symptoms were found in a significant number of children who had functional constipation and encopresis [9].
• OBJECTIVES: FG syndrome is an X-linked recessive mental retardation syndrome with ano-rectal anomalies, constipation, and occasional urinary incontinence [10].

High impact information on Constipation

• OBJECTIVE: To evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone-induced constipation [11].
• Constipation (15%) and headaches (10%) were most frequent complaints for verapamil vs fatigue (18%) and dizziness (7%) for propranolol [12].
• Eight of the loperamide-treated subjects experienced constipation compared with one in the bismuth subsalicylate-treated group; otherwise, there was no difference in minor side effects experienced between both treatment groups [13].
• Nonresponders were randomized to either 5 weekly biofeedback sessions (n = 54) or polyethylene glycol 14.6-29.2 g/day plus 5 weekly counseling sessions in preventing constipation (n = 55) [14].
• The mRNA expression of Galpha q was lower and the progesterone receptors were overexpressed in patients with chronic constipation compared with controls [15].

Chemical compound and disease context of Constipation

• Novel approaches include alosetron; a 5-HT(3) antagonist, tegaserod, a partial 5-HT(4) agonist, kappa-opioid agonists, and neurokinin antagonists to address the remaining challenging symptoms of pain, constipation, and bloating [16].
• The distribution of serotonin and dopamine beta-hydroxylase was examined in sigmoid colon specimens from patients with severe idiopathic constipation and control patients with carcinoma of the rectum or colon [17].
• Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder [18].
• Dioctyl sodium sulphosuccinate in constipation [19].
• The results were related to mouth-to-caecum (MCTT) and large bowel transit times (LBTTs) in 4 groups of 8 individuals: (1) non-acromegalic controls, (2) acromegalics untreated with octreotide, (3) acromegalics on long-term octreotide, and (4) patients with constipation [20].

Biological context of Constipation

• CONCLUSIONS: Slow transit chronic constipation in women may be caused by down-regulation of contractile G proteins and up-regulation of inhibitory G proteins, probably caused by overexpression of progesterone receptors [15].
• The second positive AM case, a 69-year-old white man who presented with painless rectal bleeding and clinical symptoms of an intestinal constipation showed a novel missense mutation (C1327T leading to R443W conversion) in BRAF exon 11 [21].
• Moreover, SNPs in the MDR1 gene did not identify patients with an increased risk for vincristine-induced constipation [22].
• Other examples of potential therapeutic applications for the guanylin family of cGMP-regulating agonists are: (1) the irritable bowel syndrome (IBS) with constipation, (2) salt-dependent forms of high blood pressure, (3) liver regeneration and repair, and (4) respiratory diseases such as asthma [23].
• This article reflects the current state of our understanding of their mechanisms of action and their clinical utility in treating disorders of gastrointestinal motility, including gastroesophageal reflux, gastroparesis, small-intestinal dysmotility, and constipation [24].

Anatomical context of Constipation

• Decreased colonic concentrations of vasoactive intestinal peptide (a candidate nonadrenergic, noncholinergic inhibitory neurotransmitter) may be associated with diminution of inhibitory innervation of colonic circular smooth muscle in some patients with idiopathic chronic constipation [25].
• Multiple sclerosis is a central nervous system disease frequently accompanied by urinary symptoms and severe constipation [26].
• Late complications included constipation in one patient (treated with diet alteration), granulation tissue in seven patients (treated with silver nitrate cautery), and accidentally dislodged tubes in three patients (two successfully replaced at home and one replaced at the radiology suite) [27].
• Of the 77 children 59 (76%) had recurrent urinary tract infections, 38 (49%) had associated bladder instability, 19 (24%) had vesicoureteral reflux and 44 (58%) had constipation [28].
• Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear [29].

Gene context of Constipation

• Since CCK is involved in sensory and motor responses to distension in the intestinal tract, it may contribute to the symptoms of constipation, bloating and abdominal pain that are often characteristic of functional gastrointestinal disorders in general and irritable bowel syndrome (IBS), in particular [30].
• RESULTS: Somatostatin levels were higher in patients with constipation (basal level, controls vs patients, 31 vs 57 pmol/L, p < 0.05, median values; peak level, 48 vs 60, p < 0.05) [31].
• Differential alterations in tachykinin NK2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation [32].
• Idiopathic slow-transit constipation is not associated with mutations of the RET proto-oncogene or GDNF [33].
• Furthermore, in the patients with colonic inertia, the percentages of strongly and moderately stained PYY-positive cells were higher in the right-side colon than in the left (P < 0.01) [34].

Analytical, diagnostic and therapeutic context of Constipation

• Twenty-one patients with refractory idiopathic constipation underwent studies of segmental colonic transit of radiopaque markers and anorectal manometry to determine the utility of these tests in planning therapy and in predicting subsequent clinical outcome [35].
• PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial [36].
• Visual analogue scale scores for constipation were significantly higher during treatment with verapamil; scores for other possible side effects and for overall wellbeing were similar [37].
• In steroid-treated patients, prevention of constipation might avert this serious complication, while early diagnosis will improve the outcome [38].
• Two retarded male cousins with odd facies, hypotonia, and severe constipation: possible examples of the X linked FG syndrome [39].

References