TRIGAST

Indications

• Gastric ulceration
• Duodenal ulceration
• Gastroesophageal reflux disease (GERD)
• NSAID-associated ulceration
• Prophylaxis of stress ulceration

Dosage

Children: Refer to the BNF for Children for specific paediatric

Adults: For gastric and duodenal ulceration: 400 mg twice daily, taken with breakfast and at bedtime. For NSAID-associated ulceration: 400 mg twice daily for 8 weeks. Prophylaxis of stress ulceration: 200-400 mg every 12 hours as needed.

Mechanism of action

Famotidine blocks the action of histamine on H2 receptors located on the basolateral membrane of gastric parietal cells. This inhibition leads to a decrease in intracellular cAMP levels, resulting in reduced activation of proton pumps that secrete gastric acid. By acting on these receptors, famotidine decreases both basal and stimulated gastric acid secretion.

Pharmacodynamics

Famotidine effectively reduces gastric acid production, suppresses acid concentration, and decreases pepsin content in gastric secretions. It inhibits both basal and nocturnal gastric acid secretion, as well as acid secretion induced by food, caffeine, insulin, and other stimulants. The onset of action occurs within one hour, with peak effects reached at 1-3 hours post-administration, and a duration of effect lasting approximately 10-12 hours.

Pharmacokinetics

Famotidine is absorbed orally, with peak plasma concentrations achieved within 1-3 hours. It undergoes minimal metabolism, and a small portion is metabolized via the hepatic cytochrome P450 system. The elimination half-life is approximately 2.5 to 3.5 hours, and it is primarily excreted unchanged in urine. Dose adjustments may be necessary in patients with renal impairment.

Adverse effects

• Anaphylactic reaction
• Aplastic anaemia
• Confusion
• Depression
• Erectile dysfunction
• Gynaecomastia
• Hallucination
• Hepatic disorders
• Leucopenia
• Nausea
• Tachycardia
• Agranulocytosis
• Alopecia
• Arthralgia
• Fever
• Galactorrhoea
• Pancytopenia
• Thrombocytopenia
• Vasculitis

Precautions

• Signs and symptoms of gastric cancer should be ruled out before treatment.
• Increased risk of confusion in hepatic impairment.
• Dose adjustments required in renal impairment.

Pregnancy

Famotidine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Significant amounts may be present in breast milk; avoid use if possible.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Tablets: 20 mg, 40 mg
• Oral suspension: 40 mg/5 ml

Mechanism of action

Carbonate ions participate in buffering reactions that help maintain pH homeostasis in biological systems. They can react with acids to form bicarbonate and carbon dioxide, thus neutralizing excess acidity in the body. This mechanism is crucial in processes such as respiration and metabolism.

Pharmacodynamics

As a buffer, carbonate helps to stabilize pH levels in different biological environments, preventing excessive acidity or alkalinity that could impair cellular functions. It is involved in the transport of carbon dioxide in the blood and plays a role in maintaining the acid-base equilibrium necessary for physiological processes.

Pharmacokinetics

Carbonate ions are readily absorbed in the gastrointestinal tract when ingested and can be found in various body fluids. They are involved in the bicarbonate buffering system, where they are converted to bicarbonate (HCO3-) and carbon dioxide (CO2) through reactions with acids. The kidneys regulate the levels of bicarbonate and carbonate in the body, excreting or reabsorbing them as needed to maintain homeostasis.

Pregnancy

There is no specific information available regarding the use of carbonate compounds during pregnancy. Consult a healthcare provider for advice.

Breast-feeding

There is no specific information available regarding the use of carbonate compounds while breastfeeding. Consult a healthcare provider for advice.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Mechanism of action

Histamine acts as a local hormone that stimulates the acid output by parietal cells via a paracrine mechanism. Neuroendocrine cells called enterochromaffin-like (ECL) cells lie close to the parietal cells and regulate the basal secretion of histamine. Histamine release is also promoted from stimulation by acetylcholine and gastrin, a peptide hormone. Gastrin (G) cells release gastrin, which works on CCK₂ receptors on ECL cells. This action promotes the release of histamine from ECL cells. Upon release, histamine acts on H₂ receptors expressed on the basolateral membrane of parietal cells, leading to increased intracellular cAMP levels and activated proton pumps on parietal cells. Proton pump releases more protons into the stomach, thereby increasing the secretion of acid. In conditions that are associated with acid hypersecretion such as ulcers, there is a loss of regulation of acid secretion. Famotidine works on H₂ receptors and blocks the actions of histamine. H2-receptor antagonists inhibit basal and nocturnal gastric acid secretion by competitive inhibition of the action of histamine at the histamine H2-receptors of the parietal cells. They also inhibit gastric acid secretion stimulated by food, betazole, pentagastrin, caffeine, insulin, and physiological vagal reflex. /Histamine H2-receptor antagonists/ Weak inhibitor of hepatic cytochrome p450 mixed function oxidase system. Famotidine is a competitive H2 receptor antagonist that inhibits basal, overnight, and pentagastrin-stimulated gastric acid secretion. Pharmacologically, it is three times more potent than ranitidine and 20 times more potent than cimetidine.

Pharmacodynamics

Famotidine decreases the production of gastric acid, suppresses acid concentration and pepsin content, and decreases the volume of gastric secretion. Famotidine inhibits both basal and nocturnal gastric acid secretion, as well as acid secretion stimulated by food, caffeine, insulin, and pentagastrin. Famotidine has a dose-dependent therapeutic action, with the highest dose having the most extended duration of action and the highest inhibitory effect on gastric acid secretion. Following oral administration, the onset of action is within one hour, and the peak effect is reached within 1-3 hours. The duration of effect is about 10-12 hours.