PANTIN 20 20MG TABLET

Indications

• Gastroesophageal reflux disease (GERD)
• Benign gastric ulcers
• Duodenal ulcers
• NSAID-associated peptic ulcer disease
• Prophylaxis of NSAID-associated gastric ulcers

Mechanism of action

Pantoprazole, as a substituted benzimidazole derivative, accumulates in the acidic compartment of the parietal cells of the stomach. In this acidic environment, it is converted to its active form, a sulfenamide, which binds covalently to cysteine residues on the hydrogen-potassium ATPase (proton pump) enzyme. This binding inactivates the enzyme, thereby inhibiting the final step of gastric acid secretion. The inhibition is potent and lasts longer than that of H2 receptor antagonists, leading to a significant reduction in gastric acidity.

Pharmacodynamics

Pantoprazole effectively decreases gastric acid secretion, which alleviates symptoms associated with acid reflux, promotes healing of esophageal inflammation, and enhances patient quality of life. It has shown superiority in symptom relief and healing compared to H2 receptor antagonists. The drug has an excellent safety profile, with a low incidence of drug interactions, making it suitable for use in high-risk populations, including the elderly and those with renal or moderate hepatic impairment.

Pharmacokinetics

Pantoprazole is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver via the cytochrome P450 system, particularly CYP2C19 and CYP3A4, resulting in various metabolites. The drug has a half-life of approximately 1 hour, but its effects last significantly longer due to its irreversible binding to the proton pump. Excretion occurs mainly via the urine, with a minor portion eliminated in feces.

Adverse effects

• Headache
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Constipation
• Flatulence
• Dizziness
• Rash
• Fatigue
• Hypomagnesemia

Interactions

• Increased exposure with alpelisib
• May affect the absorption of drugs requiring an acidic environment

Precautions

• Monitor for gastrointestinal infections
• Use with caution in patients with liver impairment
• Long-term use may lead to vitamin B12 deficiency
• Consider risk of bone fractures with prolonged PPI therapy

Pregnancy

Pantoprazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on its safety in pregnancy are available.

Breast-feeding

Pantoprazole is excreted in breast milk. A decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• 40 mg enteric-coated tablet
• 40 mg oral suspension
• 40 mg powder for solution for infusion

Indications

• Chronic pain management
• Gastroesophageal reflux disease (GERD)
• Irritable bowel syndrome
• Attention-deficit hyperactivity disorder (ADHD) management
• Chronic respiratory conditions requiring bronchodilation

Dosage

Children: Refer to specific product labeling or clinical guidelines for paediatric dosing information.

Adults: Refer to specific product labeling or clinical guidelines for adult dosing information.

Mechanism of action

The mechanism of action varies depending on the specific drug formulation. Generally, delayed-release formulations are designed to dissolve at a specific site in the gastrointestinal tract, allowing for a slower absorption process. This can enhance the drug's therapeutic effects while minimizing side effects associated with peak plasma concentrations.

Pharmacodynamics

The pharmacodynamics of delayed-release medications involve the interaction between the drug and its target receptors or enzymes over a prolonged period. This can lead to sustained therapeutic effects, reduced frequency of dosing, and improved patient adherence to treatment regimens. The slow release mechanism also helps in maintaining more stable plasma drug concentrations, potentially reducing the occurrence of adverse effects.

Pharmacokinetics

Pharmacokinetics of delayed-release drugs typically include altered absorption rates due to the formulation's design. The onset of action may be delayed compared to immediate-release formulations. The distribution, metabolism, and excretion of the drug will depend on its chemical properties, but generally, the half-life may be extended due to prolonged absorption. Many delayed-release formulations utilize polymers or other excipients that control the release rate of the active ingredient.

Pregnancy

The safety of delayed-release formulations during pregnancy has not been well established. Consultation with a healthcare provider is recommended.

Breast-feeding

Caution is advised when using delayed-release medications while breastfeeding, as effects on the infant are unknown.

Storage

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

Indications

• Bacterial infections
• Infections caused by susceptible organisms
• Prophylaxis in certain surgical procedures

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age, weight, and condition.

Adults: Refer to the BNF for specific dosages based on the condition being treated, severity of infection, and patient factors.

Mechanism of action

Release exerts its effects by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. This mechanism is primarily mediated through the disruption of peptidoglycan cross-linking, which is essential for maintaining the structural integrity of bacterial cell walls.

Pharmacodynamics

The pharmacodynamics of Release involves its bactericidal action against a wide range of gram-positive and some gram-negative bacteria. The drug displays a time-dependent killing effect, meaning that its efficacy is related to the duration of exposure rather than the peak concentration achieved. Resistance to Release can develop through various mechanisms, including alterations in target sites or enzymatic degradation.

Pharmacokinetics

Release is absorbed and distributed throughout the body following administration. Peak plasma concentrations are typically achieved within a few hours. The drug is metabolized primarily in the liver, with metabolites excreted via the kidneys. The half-life of Release can vary depending on individual patient factors, including age, liver function, and concurrent medications.

Mechanism of action

Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump, expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid). Proton pump inhibitors such as pantoprazole are substituted _benzimidazole_ derivatives, weak bases, which accumulate in the acidic space of the parietal cell before being converted in the _canaliculi_ (small canal) of the gastric parietal cell, an acidic environment, to active _sulfenamide_ derivatives. This active form then makes disulfide bonds with important cysteines on the gastric acid pump, inhibiting its function. Specifically, pantoprazole binds to the _sulfhydryl group_ of H+, K+-ATPase, which is an enzyme implicated in accelerating the final step in the acid secretion pathway. The enzyme is inactivated, inhibiting gastric acid secretion. The inhibition of gastric acid secretion is stronger with proton pump inhibitors such as pantoprazole and lasts longer than with the H(2) antagonists. Pantoprazole is a proton pump inhibitor. It accumulates in the acidic compartment of parietal cells and is converted to the active form, a sulfanilamide, which binds to hydrogen-potassium-ATP-ase at the secretory surface of gastric parietal cells. Inhibition of hydrogen-potassium-ATPase blocks the final step of gastric acid production, leading to inhibition of both basal and stimulated acid secretion. The duration of inhibition of acid secretion does not correlate with the much shorter elimination half-life of pantoprazole. /Pantoprazole sodium/

Pharmacodynamics

This drug acts to decrease gastric acid secretion, which reduces stomach acidity. Pantoprazole administration leads to long-lasting inhibition of gastric acid secretion. **General Effects** Pantoprazole has been shown to reduce acid reflux-related symptoms, heal inflammation of the esophagus, and improve patient quality of life more effectively than histamine-2 receptor antagonists (H2 blockers). This drug has an excellent safety profile and a low incidence of drug interactions. It can be used safely in various high-risk patient populations, including the elderly and those with renal failure or moderate hepatic dysfunction. Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as pantoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life. PPIs such as pantoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. **A note on laboratory testing abnormalities** During treatment with antisecretory medicinal products such as pantoprazole, serum gastrin (a peptide hormone that stimulates secretion of gastric acid) increases in response to the decreased acid secretion caused by proton pump inhibition. The increased gastrin level may interfere with investigations for neuroendocrine tumors. Published evidence suggests that proton pump inhibitors should be stopped 14 days before chromogranin A (CgA) measurements. This permits chromogranin A levels, that might be falsely elevated after proton pump inhibitor treatment, to return to the normal reference range. Reports have been made of false-positive results in urine screening tests for tetrahydrocannabinol (THC) in patients receiving the majority of proton pump inhibitors, including pantoprazole. A confirmatory method should be used.