Гидрохлорид Лоперамид

Химические свойства

White Solid

Использование

Loperamide hydrochloride is a Ca2+ channel protein inhibitor and MOR activator.

Показания

Loperamide hydrochloride (Imodium) structurally resembles both haloperidol and meperidine. In equal doses, loperamide protects against diarrhea longer than does diphenoxylate. It reduces the daily fecal volume and decreases intestinal fluid and electrolyte loss. Loperamide produces rapid and sustained inhibition of the peristaltic reflex through depression of longitudinal and circular muscle activity.The drug also possesses antisecretory activity, presumably through an effect on intestinal opioid receptors.

Определение

ChEBI: A hydrochloride obtained by combining loperamide with one equivalent of hydrochloric acid. Used for treatment of diarrhoea resulting from gastroenteritis or inflammatory bowel disease.

Общее описание

Loperamide is an antidiarrheal agent used in controlling acute nonspecific diarrhea and chronic diarrhea associated with inflammatory bowel diseases.

Биологическая активность

High affinity μ -opioid receptor agonist with peripheral selectivity (K i values are 2, 48 and 1156 nM for μ -, δ - and κ -opioid receptors respectively). Antidiarrhoeal and antihyperalgesic agent. Also a Ca 2+ channel blocker; at low micromolar concentrations it blocks broad spectrum neuronal HVA Ca 2+ channels and at higher concentrations it reduces Ca 2+ flux through NMDA receptor operated channels.

Механизм действия

Loperamide also is a potent inhibitor of intestinal CYP3A4, increasing the intestinal absorption of other CYP3A4 substrates. The clinically significant drug interactions of loperamide with coadministered CYP3A4 and CYP2C8 substrates or inhibitors would be limited, however, because of its two metabolic pathways.

Фармакокине?тика

Loperamide is marketed as capsules (2 mg) and liquid (1 mg/5 mL) preparations. The recommended dose is 4 mg initially and an additional 2 mg following each diarrheal stool. The dose should not exceed 16 mg/day. It is too lipophilic to dissolve in water for an intravenous dosage form, a property that limits its abuse potential. The compound is highly lipophilic and undergoes slow dissolution, thus limiting the bioavailability of the agent to approximately 40% of the dose. Its low oral bioavailability also can be attributed to first-pass metabolism by both CYP2C8 and CYP3A4 to its primary N-demethyl metabolite. Peak plasma levels are reached in approximately 5 hours, with an elimination half-life of approximately 11 hours. Approximately 1% of the dose is excreted into the urine unchanged.

Клиническое использование

Loperamide is effective against a wide range of secretory stimuli and can be used in the control and symptomatic relief of acute diarrhea that is not secondary to bacterial infection.

Побочные эффекты

Adverse effects associated with its use include abdominal pain and distention, constipation, dry mouth, hypersensitivity, and nausea and vomiting.