Mechanism of Action
As a synthetic opioid receptor agonist, Loperamide selectively binds to opioid receptors in the intestinal wall. The drug inhibits the release of acetylcholine and prostaglandins, leading to a decrease in propulsive gastrointestinal motility, increased transit time of luminal contents, and elevated anal sphincter tone.
A crucial pharmacokinetic factor is its resistance to crossing the blood-brain barrier (BBB). The ATP-dependent transport protein P-glycoprotein acts as an efflux pump, actively pumping drug molecules out of brain tissue and back into the vascular bed. This completely prevents the development of central opioid effects (euphoria, respiratory depression).
Pharmacological Effects
The primary pharmacological effect is a potent antidiarrheal action, similar to that of codeine, but achieved exclusively through peripheral mechanisms. The drug decreases intestinal motility, increases water and electrolyte absorption, and helps normalize stool consistency in diarrhea of various etiologies.
Indications for Use
The primary indication is the symptomatic management of acute and chronic diarrhea. The drug is used as part of combination therapy to rapidly reduce stool frequency and liquidity when it is necessary to limit the motor activity of the gastrointestinal tract.
Side Effects and Drug Interactions
Tolerability in therapeutic doses is favorable, with adverse reactions occurring rarely (in 1–10% of patients). Potential side effects include headache, nausea, constipation, and dizziness.
Drug interactions with P-glycoprotein inhibitors (e.g., verapamil, quinidine) are extremely dangerous. Blockade of this transport protein removes the brain's barrier protection: loperamide readily crosses the BBB, which carries the risk of severe central nervous system adverse reactions. Additionally, drug absorption is reduced when co-administered with antacids, calcium salts, and prokinetics (metoclopramide).
Administration Guidelines
The drug is available as 2 mg tablets and capsules. According to reference data, the standard initial single dose is 2–4 mg orally, while the maximum daily dose (MDD) is limited to 16 mg. The drug does not cause tolerance or drug dependence when used within therapeutic dosages.