ITOKINE

Indications

• Functional dyspepsia
• Gastroesophageal reflux disease (GERD)
• Gastroparesis
• Postoperative ileus

Dosage

Children: For children, itopride should be used with caution, and specific dosing should be referred to in the BNF for Children due to the need for careful consideration of age, weight, and clinical condition.

Adults: The usual adult dose for itopride is 150 mg per day, divided into three doses of 50 mg each, taken before meals.

Mechanism of action

Itopride has anticholinesterase activity, which prevents the breakdown of acetylcholine (ACh) in the gastrointestinal tract. It also acts as a dopamine D2 receptor antagonist. By inhibiting AChE, it increases ACh levels, stimulating gastric smooth muscle contraction via M3 receptors. Additionally, by antagonizing D2 receptors, it diminishes the inhibitory effects of dopamine on ACh release, further promoting gastric motility and enhancing lower esophageal sphincter pressure.

Pharmacodynamics

The pharmacodynamic profile of itopride involves increased gastric motility and improved coordination between the stomach and duodenum. The inhibition of AChE leads to elevated ACh concentrations, which enhances smooth muscle contraction. The antagonism of D2 receptors supports this effect by removing the suppression on ACh release, leading to enhanced gastrointestinal activity, which is particularly beneficial in treating symptoms associated with dyspepsia and other motility disorders.

Pharmacokinetics

Itopride is well absorbed from the gastrointestinal tract, with a bioavailability that allows for effective therapeutic concentrations. It undergoes hepatic metabolism, primarily through conjugation and may have variable half-life depending on individual patient factors. The elimination route is primarily through urine, with metabolites being excreted. Its pharmacokinetic properties support its use as a prokinetic agent in managing gastric motility disorders.

Contra-indications

• Hypersensitivity to itopride or any of its components
• Gastrointestinal bleeding
• Mechanical obstruction of the gastrointestinal tract
• Severe renal impairment

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Dizziness
• Headache
• Somnolence
• Extrapyramidal symptoms

Interactions

• May enhance the effects of other prokinetic agents
• Anticholinergic drugs may reduce its efficacy
• May interact with dopaminergic agents

Precautions

• Use with caution in patients with a history of extrapyramidal symptoms
• Caution in patients with hepatic impairment
• Should be used cautiously in elderly patients

Pregnancy

There is insufficient data on the use of itopride during pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Itopride is excreted in breast milk. Caution should be exercised when administering it to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets (50 mg, 150 mg)
• Oral suspension

Mechanism of action

Itopride has anticholinesterase (AchE) activity as well as dopamine D2 receptor antagonistic activity. It is well established that M3 receptors exist on the smooth muscle layer throughout the gut and acetylcholine (ACh) released from enteric nerve endings stimulates the contraction of smooth muscle through M3 receptors. The enzyme AChE hydrolyses the released ACh, inactivates it and thus inhibits the gastric motility leading to various digestive disorders. Besides ACh, dopamine is present in significant amounts in the gastrointestinal tract and has several inhibitory effects on gastrointestinal motility, including reduction of lower esophageal sphincter and intragastric pressure. These effects appear to result from suppression of ACh release from the myenteric motor neurons and are mediated by the D2 subtype of dopamine receptors. Itopride, by virtue of its dopamine D2 receptor antagonism, removes the inhibitory effects on Ach release. It also inhibits the enzyme AchE which prevents the degradation of ACh. The net effect is an increase in ACh concentration, which in turn, promotes gastric motility, increases the lower esophageal sphincter pressure, accelerates gastric emptying and improves gastro-duodenal coordination. This dual mode of action of Itopride is unique and different from the actions of other prokinetic agents available in the market.