ATC Group: A06A Laxatives

Alvimopan is a selective antagonist of the cloned human μ-opioid receptor with a Ki of 0.4 nM (0.2 ng/mL) and no measurable opioid-agonist effects in standard pharmacologic assays. The dissociation of [³H]-alvimopan from the human μ-opioid receptor is slower than that of other opioid ligands, consistent with its higher affinity for the receptor. At concentrations of 1 to 10 µM, alvimopan demonstrated no activity at any of over 70 non-opioid receptors, enzymes, and ion channels.

Bisacodyl is a locally acting laxative from the diphenylmethane derivatives group having a dual action. As a contact laxative, for which also antiresorptive hydragogue effects have been described, bisacodyl stimulates after hydrolysis in the large intestine, the mucosa of both the large intestine and of the rectum. Stimulation of the mucosa of the large intestine results in colonic peristalsis with promotion of accumulation of water, and consequently electrolytes, in the colonic lumen. This results in a stimulation of defecation, reduction of transit time and softening of the stool. Stimulation of the rectum causes increased motility and a feeling of rectal fullness. The rectal effect may help to restore the “call to stool” although its clinical relevance remains to be established.

Castor oil is a vegetable oil pressed from the seeds of the castor bean, Ricinus communis. Castor oil is used medicinally as a laxative and as an excipient.

Danthron, a natural product, was originally extracted from the roots and rhizome of Polygonaceae plant. Danthron is a reddish, synthetic anthraquinone derivative. Danthron has been widely used as a laxative.

Docusate is an anionic wetting agent, which acts as a faecal softener by lowering the surface tension and allowing penetration of accumulated hard dry faeces by water and salts. Docusate sodium also possesses stimulant activity.

Glycerol has uses as a hyperosmotic, osmotic diuretic, and ophthalmic agent. It may be used as an eye drop in the treatment of glaucoma to reduce intraocular pressure, as a solution or suppository for short-term treatment of constipation, to evacuate the bowel prior to a colonoscopy, and in some ocular surgeries. It may be given intravenously to reduce pressure inside the brain and used externally on the skin as a moisturizer.

Ispaghula is particularly rich in alimentary fibres and mucilages. Ispaghula is capable of absorbing up to 40 times its own weight in water. Gut motility and transit rate can be modified by ispaghula through mechanical stimulation of the gut wall as a result of the increase in intestinal bulk by water and the decrease in viscosity of the luminal contents.

Lactitol is a sugar alcohol used as a replacement bulk sweetener for low calorie foods with approximately 40% of the sweetness of sugar. Lactitol also promotes colon health as a prebiotic. Lactitol is a laxative and is used to prevent or treat constipation.

Lactulose is a synthetic disaccharide which is metabolised by gastro-intestinal bacterial flora to low molecular weight acids (chiefly lactic and acetic acids). There is no endogenous metabolising enzyme in the human gut. Its mode of action in constipation is as an osmotic agent producing soft stools.

Linaclotide is a Guanylate Cyclase-C receptor agonist (GCCA) with visceral analgesic and secretory activities. Through its action at GC-C, linaclotide has been shown to reduce visceral pain and increase GI transit in animal models and increase colonic transit in humans.

Lubiprostone is a locally acting chloride channel activator that enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium concentrations in the serum. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby facilitating the passage of stool and alleviating symptoms associated with chronic idiopathic constipation (CIC).

High molecular weight (4000) macrogols are long linear polymers which retain water molecules by means of hydrogen bonds. When administered by the oral route, they lead to an increase in volume of intestinal fluids.

Magnesium carbonate, MgCO3 (archaic name magnesia alba), is an inorganic salt. The most common magnesium carbonate forms are the anhydrous salt called magnesite (MgCO3) and the di, tri, and pentahydrates known as barringtonite (MgCO3·2 H2O), nesquehonite (MgCO3·3 H2O), and lansfordite (MgCO3·5 H2O), respectively. The primary use of magnesium carbonate is the production of magnesium oxide by calcining.

Magnesium oxide (MgO), or magnesia, is an empirical formula of MgO and consists of a lattice of Mg2+ ions and O2− ions held together by ionic bonding.

Magnesium sulfate is a saline purgative. It can be employed locally in various inflammatory conditions, due to its osmotic action.

Mannitol is a naturally occurring sugar alcohol used clinically primarily for its osmotic diuretic properties.

Methylcellulose is a chemical compound derived from cellulose. Methylcellulose is used to treat constipation. It is classified as a bulk forming laxative. Methylcellulose is a hydrophilic colloid which absorbs water causing it to swell to a soft gel of uniform consistency. It works by increasing the amount of stool present which improves intestinal contractions.

Methylnaltrexone bromide is a selective antagonist of opioid binding at the mu-receptor. As a quaternary amine, the ability of methylnaltrexone bromide to cross the blood-brain barrier is restricted. This allows methylnaltrexone bromide to function as a peripherally acting mu-opioid antagonist in tissues such as the gastrointestinal tract, without impacting opioid-mediated analgesic effects on the central nervous system.

Naldemedine is an antagonist of opioid binding at the mu-, delta-, and kappa-opioid receptors. Naldemedine functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids without reversing the central nervous system (CNS)-mediated opioid effects.

Naloxegol is a PEGylated derivative of the mu-opioid receptor antagonist naloxone. PEGylation reduces naloxegol’s passive permeability and also renders the compound a substrate for the P-glycoprotein transporter. Naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in the gastrointestinal tract, thereby decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system.

Plecanatide is a structural analog of human uroguanylin, and similarly to uroguanylin, plecanatide functions as a guanylate cyclase-C (GC-C) agonist. Both plecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP).

Prucalopride is a dihydrobenzofurancarboxamide with gastrointestinal prokinetic activities. Prucalopride is a selective, high affinity serotonin (5-HT₄) receptor agonist, which is likely to explain its prokinetic effects.

The sugar moiety of the sennosides is removed by bacteria in the large intestine releasing the active anthrone fraction. This stimulates peristalsis via the submucosal and myenteric nerve plexuses.

Sodium picosulfate is a locally acting laxative from the triarylmethane group, which after bacterial cleavage in the colon, has a dual-action with stimulation of the mucosa of both the large intestine and of the rectum.

Sodium Sulfate Anhydrous is the anhydrous, sodium salt form of sulfuric acid. Sodium sulfate anhydrous disassociates in water to provide sodium ions and sulfate ions. Sodium ion is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Sodium sulfate anhydrous is an electrolyte replenisher and is used in isosmotic solutions so that administration does not disturb normal electrolyte balance and does not lead to absorption or excretion of water and ions.

Tegaserod is an agonist of serotonin type-4 (5-HT₄) receptors that stimulates the peristaltic reflex and intestinal secretion, inhibits visceral sensitivity, enhances basal motor activity, and normalizes impaired motility throughout the gastrointestinal tract.