3D KIT H. PYLORI KIT

Indications

• Bacterial infections
• Urinary tract infections
• Sinusitis
• Uncomplicated community-acquired pneumonia
• Salmonellosis
• Oral infections
• Lyme disease (under expert supervision)
• Acute exacerbation of bronchiectasis
• Anthrax (treatment and post-exposure prophylaxis)

Dosage

Children: 1 month–11 years: 30 mg/kg 3 times a day for 21 days; children 1–4 years: 250 mg 3 times a day; children 5–11 years: 500 mg 3 times a day.

Adults: 500 mg 3 times a day; increased if necessary up to 1 g 3 times a day in severe infections.

Mechanism of action

Amoxicillin works by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, interfering with the transpeptidation process necessary for cell wall integrity.

Pharmacodynamics

Amoxicillin exhibits bactericidal activity against susceptible bacteria. Its action is time-dependent, meaning that its effectiveness is related to the duration of time that the drug concentration remains above the minimum inhibitory concentration (MIC) for the target pathogen.

Pharmacokinetics

Amoxicillin is well absorbed from the gastrointestinal tract, with peak plasma concentrations achieved within 1-2 hours after oral administration. It is widely distributed in body tissues and fluids, and it is excreted primarily via the kidneys. The elimination half-life is approximately 1 hour, and renal impairment may necessitate dosage adjustments.

Adverse effects

• Skin rash
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Allergic reactions (including anaphylaxis)
• Superinfection (due to resistant organisms)

Interactions

• Allopurinol (increases risk of skin rash)

Precautions

• History of penicillin allergy
• Renal impairment (reduce dose)
• Use with caution in patients with mononucleosis

Pregnancy

Use only if clearly needed; no adequate studies in pregnant women.

Breast-feeding

Amoxicillin is excreted in breast milk; use with caution.

Storage

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

Formulations

• Phenoxymethylpenicillin 250mg/5ml oral solution
• Phenoxymethylpenicillin 250 mg tablets

Indications

• Bacterial infections
• Acute exacerbation of chronic obstructive pulmonary disease
• Community-acquired pneumonia
• Hospital-acquired pneumonia
• Urinary tract infections
• Complicated urinary tract infections
• Prostatitis
• Chronic pulmonary infections due to Pseudomonas aeruginosa
• Helicobacter pylori eradication (in combination with other drugs)

Dosage

Adults: 500 mg once daily for 5-14 days depending on the infection type and severity; for intravenous infusion, 500 mg to be given over at least 60 minutes.

Mechanism of action

Levofloxacin exerts its antimicrobial activity through the inhibition of two key bacterial enzymes: DNA gyrase and topoisomerase IV. DNA gyrase introduces negative supercoils into DNA during replication, while topoisomerase IV is essential for unlinking newly replicated chromosomes, allowing cell division. By inhibiting these enzymes, levofloxacin blocks DNA replication, resulting in cell death.

Pharmacodynamics

Levofloxacin is bactericidal and inhibits bacterial DNA replication. It has a longer duration of action than many other antibiotics, allowing for less frequent dosing. The drug may cause QTc-interval prolongation, necessitating caution in patients with risk factors for this condition. Levofloxacin shows in vitro activity against various bacterial pathogens, and while resistance can develop, it typically arises from mutations in target enzymes or drug efflux mechanisms.

Pharmacokinetics

Levofloxacin is well absorbed following oral administration, with peak plasma concentrations occurring within 1-2 hours. It has a volume of distribution of approximately 100 L and is approximately 30-40% protein bound. The drug is primarily excreted unchanged in the urine, with a half-life of about 6-8 hours, allowing for once or twice daily dosing.

Contra-indications

• Hypersensitivity to levofloxacin or other fluoroquinolones
• History of tendon disorders related to fluoroquinolone use
• Patients with a history of myasthenia gravis

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• QT interval prolongation
• Tendon rupture
• Clostridioides difficile-associated diarrhea
• Nephritis tubulointerstitial

Interactions

• Concurrent use with other drugs that prolong the QT interval
• Antacids, sucralfate, metal cations (e.g. magnesium, aluminum, calcium) can reduce absorption
• NSAIDs may increase the risk of CNS stimulation
• Warfarin may have increased anticoagulant effects

Precautions

• Use cautiously in patients with a history of seizures or CNS disorders
• Monitor for signs of tendon damage
• Consider risks in patients with electrolyte disturbances
• Use with caution in patients with renal impairment

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises caution; levofloxacin may be excreted in breast milk.

Storage

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

Formulations

• 500 mg tablet for oral use
• Solution for intravenous infusion
• Nebuliser solution
• Eye drops

Indications

• Gastric ulcer
• Duodenal ulcer
• Gastro-oesophageal reflux disease (GERD)
• Functional dyspepsia
• NSAID-associated peptic ulcer disease
• Zollinger-Ellison syndrome

Dosage

Adults: Initially 20 mg once daily for 4 to 8 weeks for GERD. For gastric and duodenal ulcers, the initial dose is 20 mg daily for 4 to 8 weeks. For NSAID-associated peptic ulcer disease, the recommended dose is 20 mg once daily for 4 to 8 weeks. Dose adjustments may be necessary in hepatic impairment, with a maximum dose of 20 mg daily

Mechanism of action

Rabeprazole sodium acts by irreversibly binding to and inhibiting the H+/K+ ATPase enzyme system (proton pump) in the gastric epithelium. This action leads to a decrease in gastric acid secretion, both basal and stimulated. The inhibition is dose-dependent and can last for 24 hours or longer, which helps in healing peptic ulcers and alleviating symptoms of acid-related disorders.

Pharmacodynamics

Rabeprazole sodium effectively suppresses gastric acid secretion, providing symptomatic relief and promoting mucosal healing in conditions associated with excessive gastric acidity. It demonstrates a rapid onset of action, with peak plasma concentrations occurring approximately 3-4 hours after administration. The drug's effects on gastric acid secretion can lead to increased gastric pH and improved healing of ulcerative lesions.

Pharmacokinetics

Rabeprazole sodium is rapidly absorbed after oral administration, with bioavailability of approximately 52% due to first-pass metabolism. The drug is extensively metabolized in the liver, primarily via the cytochrome P450 system. Its elimination half-life ranges from 1 to 2 hours, and it is excreted primarily through urine as metabolites. Food does not significantly affect its absorption.

Adverse effects

• Asthenia
• Angioedema
• Electrolyte imbalance
• Muscle spasms
• Hyperlipidaemia
• Weight change

Precautions

• Manufacturer advises caution in severe hepatic impairment, monitor liver function and discontinue if deterioration occurs.

Pregnancy

Manufacturer advises to avoid unless potential benefit outweighs risk-fetotoxic in animals.

Breast-feeding

Specialist sources indicate that the amount in milk is small and not known to be harmful.

Storage

Store below 25 degrees Celsius. Protect from light and moisture.

Formulations

• Gastro-resistant tablet
• Powder for solution for injection

Indications

• Gastroesophageal reflux disease (GERD)
• Peptic ulcers
• Zollinger-Ellison syndrome
• Prevention of gastric ulcers associated with NSAID use

Dosage

Adults: Refer to BNF for specific dosing recommendations based on condition being treated.

Mechanism of action

Rabeprazole inhibits gastric acid secretion by irreversibly binding to the hydrogen-potassium ATPase enzyme system (H+, K+-ATPase) located at the parietal cell surface. This action blocks the final step in the gastric acid secretion process, leading to a reduction in hydrogen ion transport into the gastric lumen. Rabeprazole is activated in the acidic environment of the stomach, transforming into an active sulfenamide which exerts its inhibitory effects.

Pharmacodynamics

By preventing the production of gastric acid, rabeprazole alleviates symptoms associated with excessive acid secretion, such as heartburn and esophagitis. It is particularly effective in treating gastroesophageal reflux disease (GERD) and peptic ulcers, as well as in combination with antibiotics for the eradication of Helicobacter pylori. Furthermore, rabeprazole is utilized in managing conditions like Zollinger-Ellison syndrome, where there is an overproduction of gastric acid.

Pharmacokinetics

Rabeprazole is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver through the cytochrome P450 system, primarily via CYP2C19 and CYP3A4 isoenzymes. The elimination half-life of rabeprazole ranges from 1 to 2 hours. The drug is excreted mainly in the urine as metabolites, with minimal unchanged drug present. Food intake can affect the absorption but not the overall efficacy of the drug.

Adverse effects

• Headache
• Nausea
• Diarrhea
• Constipation
• Abdominal pain
• Rash
• Dizziness

Interactions

• apalutamide+rabeprazole: Unknown (decreases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for potential vitamin B12 deficiency with long-term use
• Consider risk of Clostridium difficile infection in patients with diarrhea

Pregnancy

Rabeprazole is classified as category B. Animal studies have shown no harm, but there are no well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

Rabeprazole is excreted in breast milk. Caution should be exercised when administered to a nursing mother.

Storage

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

Formulations

• Tablets: 20 mg

Mechanism of action

Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action. The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/ Amoxicillin is similar to penicillin in its bactericidal action against susceptible bacteria during the stage of active multiplication. It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.

Pharmacodynamics

Amoxicillin competitively inhibit penicillin binding proteins, leading to upregulation of autolytic enzymes and inhibition of cell wall synthesis. Amoxicillin has a long duration of action as it is usually given twice daily. Amoxicillin has a wide therapeutic range as mild overdoses are not associated with significant toxicity. Patients should be counselled regarding the risk of anaphylaxis, _Clostridium difficile_ infections, and bacterial resistance.

Mechanism of action

Levofloxacin, like other fluoroquinolone antibiotics, exerts its antimicrobial activity via the inhibition of two key bacterial enzymes: DNA gyrase and topoisomerase IV. Both targets are type II topoisomerases, but have unique functions within the bacterial cell. DNA gyrase is an enzyme found only in bacteria that introduces negative supercoils into DNA during replication - this helps to relieve torsional strain caused by the introduction of positive supercoils during replication, and these negative supercoils are essential for chromosome condensation and the promotion of transcription initiation. It is comprised of four subunits (two A subunits and two B subunits) of which the A subunits appear to be the target of fluoroquinolone antibiotics. Bacterial topoisomerase IV, in addition to contributing to the relaxation of positive supercoils, is essential at the terminal stages of DNA replication and functions to “unlink” newly replicated chromosomes to allow for the completion of cell division. Inhibition of these enzymes by levofloxacin likely occurs via complexation with the topoisomerase enzymes. The end result is a blockade of DNA replication, thus inhibiting cell division and resulting in cell death. Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP).

Pharmacodynamics

Levofloxacin is bactericidal and exerts its antimicrobial effects via inhibition of bacterial DNA replication. It has a relatively long duration of action in comparison with other antibiotics that allows for once or twice daily dosing. Levofloxacin is associated with QTc-interval prolongation and should be used with caution in patients with other risk factors for prolongation (e.g. hypokalemia, concomitant medications). Levofloxacin has demonstrated _in vitro_ activity against a number of aerobic gram-positive and gram-negative bacteria and may carry some activity against certain species of anaerobic bacteria and other pathogens such as _Chlamydia_ and _Legionella_. Resistance to levofloxacin may develop, and is generally due to mutations in DNA gyrase or topoisomerase IV, or via alterations to drug efflux. Cross-resistance may occur between levofloxacin and other fluoroquinolones, but is unlikely to develop between levofloxacin and other antibiotic classes (e.g. macrolides) due to significant differences in chemical structure and mechanism of action. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

Mechanism of action

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H⁺/K⁺ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds. Rabeprazole is a selective and irreversible proton pump inhibitor. Rabeprazole suppresses gastric acid secretion by specific inhibition of the hydrogen-potassium adenosine triphosphatase (H+, K+-ATPase) enzyme system found at the secretory surface of parietal cells. It inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen. Since the H+, K+-ATPase enzyme system is regarded as the acid (proton) pump of the gastric mucosa, rabeprazole is known as a gastric acid pump inhibitor. Rabeprazole does not have anticholinergic or histamine H2-receptor antagonist properties. Rabeprazole binds to hydrogen-potassium ATPase in gastric parietal cells; inactivation of this enzyme system (also known as the proton, hydrogen, or acid pump) blocks the final step in the secretion of hydrochloric acid secretion. The antisecretory effect is apparent within 1 hour following oral administration with the median inhibitory effect on 24-hour gastric acidity being 88% of maximal after the first dose.

Pharmacodynamics

Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H⁺, K⁺ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.