Constipation treatment

L.A. Sorbera, J. Castaner, N.E. Mealy, Lubiprostone. Treatment of constipation, treatment of irritable bowel syndrome, treatment of postoperative ileus, CIC-2 channel activator, Drugs Fut. 29 (2004) 336-342. 

Uses Pharmaceutical grade surfactant, solubilizer, wetting agent, dispersant for medicaments, as adjuvant in tablet formulation (improves tablet and dissolution chars.), esp. for constipation treatments/preventives Features Good stability, compat. 

Cetomacrogol 1000 BP solubilizer, condKioning shampoos DeTERIC CP-Na-38 DIsodlum oleamido PEG-2 sulfosuccinate Polyamodimethicone copolyol Unipol SH-100, SH-135 solubilizer, constipation treatments/ preventives DSS Tablet Grade... 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Balantidiasis in humans is manifest by chronic episodes of intermittent diarrhea and constipation, symptoms similar to those of amebiasis. The patient may also have abdominal pain, tenderness over the colon, anorexia, nausea, severe weight loss, and weakness. The disease may be fatal and, before the avakabihty of a treatment, was the cause of death in approximately 30% of infected individuals. 

Verapamil (Table 1), the first slow channel calcium blocker synthesized to selectively inhibit the transmembrane influx of calcium ions into cells, lowers blood pressure in hypertensive patients having good organ perfusion particularly with increased renal blood flow. Sustained-release verapamil for once a day dosing is available for the treatment of hypertension. Constipation is a prominent side effect. Headache, dizziness, and edema are frequent and verapamil can sometimes cause AV conduction disturbances and AV block. Verapamil should not be used in combination with -adrenoceptor blockers because of the synergistic negative effects on heart rate and contractile force. 

Cisapride (27) is effective in the treatment of re/Iux esophagitis and constipation, with a novel mechanism thought to involve acetylchohne release in the gut. It IS devoid of CNS and cardiac side effects [23]... 

Capecitabine is used for the treatment of colorectal and breast cancers. It is contraindicated in patients with known hypersensitivity to capecitabine or any of its components or to 5-fluorouracil and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. The use of capecitabine is restricted in patients with severe renal impairment. The drag can induce diarrhea, sometimes severe. Other side effects include anemia, hand-foot syndrome, hyperbilirubinemia, nausea, stomatitis, pyrexia, edema, constipation, dyspnea, neutropenia, back pain, and headache. Cardiotoxicity has been observed with capecitabine. A clinically important drag interaction between capecitabine and warfarin has been demonstrated. Care should be exercised when the drag is co-administered with CYP2X9 substrates. 

Antagonists of muscarinic acetylcholine receptors had widely been used since 1860 for the treatment of Parkinson s disease, prior to the discovery of l-DOPA. They block receptors that mediate the response to striatal cholinergic interneurons. The antiparkinsonian effects of drugs like benzatropine, trihexyphenidyl and biper-iden are moderate the resting tremor may sometimes respond in a favorable manner. The adverse effects, e.g., constipation, urinary retention, and mental confusion, may be troublesome, especially in the elderly. 

Several nonpeptidic, orally active vasopressin receptor antagonists have been developed. The dual V1A/V2R antagonist conivaptan is used in the treatment of hyponatraemia and could also become useful for diseases such as congestive heart failure, in which increased peripheral resistance and dilutional hyponatremia both are present [4]. Side effects of conivaptan include headache, injection site reactions, vomiting, diarrhoea, constipation and thirst. 

The expected outcomes for the patient may include an optimal response to dierapy, management of constipation, adequate nutritional status, and an understanding of and compliance witii die prescribed treatment regimen. 

Antimuscarinic drugs such as atropine have been used to modest effect in the treatment of PD for more than a century attenuating tremor and rigidity but with little effect on akinesia. Currently benzhexol and benztropine are sometimes added to levodopa therapy but peripheral effects such as dry mouth, blurred vision and constipation are unpleasant. They are also often used to counteract neuroleptic-induced extrapyramidal effects. 

Recommend lifestyle modifications and therapeutic interventions for the treatment of constipation. 

Constipation is a common complaint of patients seeking medical attention, and about one-third of patients with constipation seek medical treatment. Constipation occurs in approximately 20% of the population.2 Approximately 2.5 million physician visits and 90,000 hospitalizations per year in the United States are due to constipation3,4 Many medications and some disease states are associated with constipation. Constipation is associated with high socioeconomic costs and has considerable quality-of-life ramifications.5... 

Tegaserod maleate (Zelnorm) is a partial serotonin (5-HT4) receptor agonist that causes an increase in peristaltic activity and intestinal secretion and moderation of visceral sensitivity. It increases the frequency of bowel movements and reduces abdominal discomfort, bloating, and straining. It is indicated for the treatment of patients younger than 65 years of age who experience chronic idiopathic constipation. The most common adverse effects include headache, abdominal pain, diarrhea, and nausea. 

Lubiprostone (Amitiza), a bicyclic acid oral agent, is approved for treatment of chronic idiopathic constipation in adults. It has not been studied in children. Lubiprostone acts locally on intestinal chloride channels and increases intestinal fluid secretion, resulting in increased intestinal motility and thereby increasing the passage of stool.6... 

---