Constipation

There are two different mechanisms behind ordinary causes of constipation, functional and outlet obstructions. Functional constipation is caused by the slower movement of the colon, peristalsis, which comes with old age, often in combination with less physical activity and less intake of fibre containing food. Outlet obstruction is a result of incapacity to empty the rectum from faeces often due to too large masses of stool blocking the anus. It can also be caused by anal stricture from haemorrhoids or scar tissue caused by fissures. 

Many diseases that can cause physical inactivity and decreased intake of fluids and food can have constipation as a common symptom. Acute infections with dehydration or chronic diseases as heart failure, diabetes, Parkinson s disease, obstructive pulmonary disease or terminal cancer, are some. 

Anticholinergic drugs (e.g. tricyclic antidepressants, urological spasmolytics) 

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Morphine and its salts are very valuable analgesic drugs but are highly addictive. In addition to suppression of pain, morphine causes constipation, decreases pupillary size and depresses respiration. Only the (-l-)-stereoisoraer is biologically active. They appear to produce their effects on the brain by activating neuronal mechanisms normally activated by... 

Celiac Disease. A disturbance of the lower gastroiatestiaal tract, celiac disease is a chronic disease characterized by loss of appetite and weight, depression and irritabiUty, and diarrhea frequendy followed by constipation (35). One of the more disturbiag features of ceHac disease is the large, frothy, foul-smelling stools. The disease may develop ia childhood or later ia life. Frequendy, the patients who develop the disease ia adulthood report having had some of the symptoms duting childhood. 

Prior to this work, dietary fiber, of which ceUulose is oae of the more important constituents, was considered important primarily as a means of preventing or overcoming constipation. Otherwise, dietary fiber was considered to be a metaboHcally iaert substance. A large variety of diseases such as appendicitis, hiatus hernia, gallstones, ischemic heart disease, diabetes, obesity, dental caries, and duodenal ulcers are now suspected to be associated with the consumption of a highly refined diet (42). 

Workers who produce or use lead should be aware of possible ha2ards. Symptoms of chronic lead poisoning include fatigue, headache, constipation, uneasy stomach, irritabiHty, poor appetite, metallic taste, weight loss, and loss of sleep. Most of these same symptoms also occur in many common illnesses, such as the flu, thus a physician must rely on tests, such as blood lead analysis, to determine chronic lead poisoning. 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

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. 

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

Toxic effects of propranolol are related to its blocking P-adrenoceptor blocking actions. They include cardiac failure, hypotension, hypoglycemia, and bronchospasm. Propranolol is lipophilic and crosses the blood—brain barrier. Complaints of fatigue, lethargy, mental depression, nightmares, hallucinations, and insomnia have been reported. GI side effects include nausea, vomiting, diarrhea, and constipation (1,2). 

The side effects and toxic reactions to verapamil iaclude upper GI upset, constipation, di22iaess, headaches, flushing and burning, edema, hypotension, bradycardia, and various conduction disturbances. Verapamil has negative iaotropic activity and may precipitate heart failure ia patients having ventricular dysfunction (1,2). 

Adverse effects with atropine therapy include dry mouth, myosis, loss of visual accommodations, constipation, and urinary retention. The dmg can also produce flushing, hyperthermia, delirium, tachycardia, and exacerbate glaucoma (85). 

The side effects or toxic effects that the calcium antagonists have in common are hypotension, facial flushing, headache, di22iness, weakness, sedation, skin rash, edema, constipation, and abdominal discomfort (nausea, vomiting, and epigastric pressure). 

Because colestipol and cholestyramine are not absorbed, but simply pass through the body by the GI tract, few severe side effects occur. Patients often complain of distaste and constipation, however. More severe side effects such as GI bleeding ate relatively uncommon (151). 

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. 

USP (Oncovin) vindesine sulfate [59917-39 ] C43H55N5O7 -H2S0 852.01 (50) chil-dren lymphocytic leukemia Hodgkin s disease non-Hodg-kin s lymphomas Wilm s tumor neuroblastoma rhabdomyosarcoma, investigational dmg (paresthesias, foot drop, double vision, etc) constipation ileus alopecia leu-kopenia (occasional) ... 

Side effects associated with narcotics include nausea, anorexia, and constipation most of them also diminish ciUary activity and produce a drying effect on the respiratory tract mucosa. 

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]... 

A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide... 

Opioids G-protein coupled p-, 5-, k-receptors l cAMP l Ca2+ currents t K+ currents l Excitability of peripheral and central neurons l Release of excitatory neurotransmitters p, 5 sedation, nausea, euphoria/re-ward, respiratory depression, constipation k dysphoria/aversion, diuresis, sedation... 

Antidepressants Noradrenaline/5-HT transporters Na+, K+ channels l Noradrenaline/ 5-HT reuptake l Na+ currents t K+ currents l Excitability of peripheral and central neurons Cardiac arrhythmia, myocardial infarction, sedation, nausea, dry mouth, constipation, dizziness, sleep disturbance, blurred vision... 

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