| CLINICAL PHARMACOLOGY
Dicyclomine relieves smooth muscle spasm of the gastrointestinal tract. Animal studies indicate that this action is achieved via a dual mechanism: (1) a specific anticholinergic effect (antimuscarinic) at the acetylcholine-receptor sites with approximately 1/8 the milligram potency of atropine (in vitro, guinea pig ileum); and (2) a direct effect upon smooth muscle (musculotropic) as evidenced by dicyclomine’s antagonism of bradykinin- and histamine-induced spasms of the isolated guinea pig ileum. Atropine did not affect responses to these two agonists. In vivo studies in cats and dogs showed dicyclomine to be equally potent against acetylcholine (ACh)- or barium chloride (BaCl2)-induced intestinal spasm while atropine was at least 200 times more potent against effects of ACh than BaCl2. Tests for mydriatic effects in mice showed that dicyclomine was approximately 1/500 as potent as atropine; antisialagogue tests in rabbits showed dicyclomine to be 1/300 as potent as atropine.
In man, dicyclomine is rapidly absorbed after oral administration, reaching peak values within 60-90 minutes. The principal route of elimination is via the urine (79.5% of the dose). Excretion also occurs in the feces, but to a lesser extent (8.4%). Mean half-life of plasma elimination in one study was determined to be approximately 1.8 hours when plasma concentrations were measured for 9 hours after a single dose. In subsequent studies, plasma concentrations were followed for up to 24 hours after a single dose, showing a secondary phase of elimination with a somewhat longer half-life. Mean volume of distribution for a 20 mg oral dose is approximately 3.65 L/kg suggesting extensive distribution in tissues.
In controlled clinical trials involving over 100 patients who received drug, 82% of patients treated for functional bowel/irritable bowel syndrome with dicyclomine hydrochloride at initial doses of 160 mg daily (40 mg q.i.d.) demonstrated a favorable clinical response compared with 55% treated with placebo. (p<.05). In these trials, most of the side effects were typically anticholinergic in nature (see table) and were reported by 61% of the patients.
Dosing (Adult): Usual: 10-20 mg orally or IM four times daily (up to 40 mg orally four times daily).
| INDICATIONS: Based on a review of this drug by the National Academy of Sciences – National Research Council and/or other information, FDA has classified the following indications as “possibly” effective: For use as adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis. May also be useful as adjunctive therapy in the treatment of duodenal ulcer. IT HAS NOT BEEN SHOWN CONCLUSIVELY WHETHER ANTICHOLINERGIC /ANTISPASMODIC DRUGS AID IN THE HEALING OF A DUODENAL ULCER, DECREASE THE RATE OF RECURRENCES OR PREVENT COMPLICATIONS.
Dosing (Adult): Usual: The dosage of Donnatal Extentabs® should be adjusted to the needs of the individual patient to assure symptomatic control with a minimum of adverse reactions. The usual dose is one tablet every twelve (12) hours. If indicated, one tablet every eight (8) hours may be given.
| Dosing (Adult): Usual: 7.5 to 15 mg orally 30 minutes before meals and at bedtime.
Supplied: [7.5, 15mg tablets]
| Brand Names: Mylanta Gas, Gas Relief, Gas-X, Major-Con, Phazyme, Flatulex, Mylicon, Maalox Anti-Gas.
INDICATIONS: used to relieve symptoms of extra gas such as belching, bloating, and feelings of pressure/discomfort in the stomach/gut.
Dosage – Oral:
Suspension, oral drops: 40 mg/0.6 mL (30 mL)
Tablet, chewable: 80 mg, 125 mg
| CLINICAL PHARMACOLOGY
Levsin® inhibits specifically the actions of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These peripheral cholinergic receptors are present in the autonomic effector cells of the smooth muscle, cardiac muscle, the sinoatrial node, the atrioventricular node, and the exocrine glands. At therapeutic doses, it is completely devoid of any action on autonomic ganglia. Levsin® inhibits gastrointestinal propulsive motility and decreases gastric acid secretion. Levsin® also controls excessive pharyngeal, tracheal and bronchial secretions.
Levsin® is absorbed totally and completely by sublingual administration as well as oral administration. Once absorbed, Levsin® disappears rapidly from the blood and is distributed throughout the entire body. The half-life of Levsin® is 2 to 3½ hours. Levsin® is partly hydrolyzed to tropic acid and tropine but the majority of the drug is excreted in the urine unchanged within the first 12 hours. Only traces of this drug are found in breast milk. Levsin® passes the blood brain barrier and the placental barrier.
Conventional hyoscyamine tablets may be administered orally or sublingually.
(Sustained-release): 1 to 2 capsules or tablets (0.375 to 0.75 milligram) every 12 hours; the dose may be adjusted to 1 capsule every 8 hours if needed. The tablets are scored so that they may be broken to allow for easier titration of dose. Do not exceed 4 sustained-released capsules or tablets per 24 hours.
(Hyoscyamine Drops): 1 to 2 milliliters (0.125 to 0.25 milligram) every 4 hours or as needed; do not exceed 12 milliliters/24 hours.
(Hyoscyamine Elixir): 5 to 10 milliliters (0.125 to 0.25 milligram) every 4 hours or as needed – do not exceed 60 ml/24 hours. Hypermotility of the lower urinary tract: 1 to 2 tablets (0.15 to 0.3 mg) 4 times daily or fewer if possible.
[Supplied: 0.125 mg/5 ml elixir; 0.375 mg extended release cap/Tablet; 0.5 mg/ml solution for injection; 0.125 mg SL Tab]
| Librax (clininium 2.5 mg + chlordiazepoxide 5 mg):
Adjunct treatment of peptic ulcer; treatment of IBS:
1-2 capsules 3-4 times/day (before meals and at bedtime).
| Mechanism of Action
Irritable bowel syndrome with constipation and chronic idiopathic constipation are both lower gastrointestinal dysmotility disorders. Clinical investigations have shown that both motor and sensory functions of the gut appear to be altered in patients suffering from irritable bowel syndrome (IBS), while in patients with chronic idiopathic constipation, reduced intestinal motility is the predominant cause of the condition. Both the enteric nervous system, which acts to integrate and process information in the gut, and 5-hydroxytryptamine (5-HT, serotonin) are thought to represent key elements in the etiology of both IBS and idiopathic constipation. Approximately 95% of serotonin is found throughout the gastrointestinal tract, primarily stored in enterochromaffin cells but also in enteric nerves acting as a neurotransmitter. Serotonin has been shown to be involved in regulating motility, visceral sensitivity and intestinal secretion. Investigations suggest an important role of serotonin Type-4 (5-HT4) receptors in the maintenance of gastrointestinal functions in humans. 5-HT4 receptor mRNA has been found throughout the human gastrointestinal tract.
Tegaserod is a 5-HT4 receptor partial agonist that binds with high affinity at human 5-HT4 receptors, whereas it has no appreciable affinity for 5-HT3 or dopamine receptors. It has moderate affinity for 5-HT1 receptors. Tegaserod, by acting as an agonist at neuronal 5-HT4 receptors, triggers the release of further neurotransmitters such as calcitonin gene-related peptide from sensory neurons. The activation of 5-HT4 receptors in the gastrointestinal tract stimulates the peristaltic reflex and intestinal secretion, as well as inhibits visceral sensitivity. In vivo studies showed that tegaserod enhanced basal motor activity and normalized impaired motility throughout the gastrointestinal tract. In addition, studies demonstrated that tegaserod moderated visceral sensitivity during colorectal distension in animals.
Chronic Idiopathic Constipation: Zelnorm® (tegaserod maleate) is indicated for the treatment of patients less than 65 years of age with chronic idiopathic constipation. The effectiveness of Zelnorm in patients 65 years or older with chronic idiopathic constipation has not been established (see Geriatric Use). The efficacy of Zelnorm for the treatment of IBS with constipation or chronic idiopathic constipation has not been studied beyond 12 weeks.
DOSAGE AND ADMINISTRATION:
Chronic Idiopathic Constipation: The recommended dosage of Zelnorm is 6 mg taken twice daily orally before meals. Physicians and patients should periodically assess the need for continued therapy.
Supplied: [2, 6mg tablets]
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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