G-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
• Community-acquired pneumonia
• Skin infections
• Prophylaxis for certain infections

Dosage

Adults: 500 mg once daily for

Mechanism of action

Clarithromycin is metabolized to 14-OH clarithromycin, which is active. It penetrates bacterial cell walls and reversibly binds to domain V of the 23S ribosomal RNA of the 50S ribosomal subunit, blocking the translocation of aminoacyl-tRNA and inhibiting polypeptide synthesis. It may be bactericidal in high concentrations against susceptible organisms, particularly Streptococcus pyogenes, S. pneumoniae, Haemophilus influenzae, and Chlamydia trachomatis. Additionally, clarithromycin inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein.

Pharmacodynamics

Clarithromycin exhibits a broad spectrum of activity against numerous gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes. It also shows activity against gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis, as well as against various anaerobic bacteria, mycobacteria, and other organisms like Mycoplasma, Ureaplasma, and Chlamydia. While typically bacteriostatic, it can sometimes demonstrate bactericidal properties depending on the concentration and the organism.

Pharmacokinetics

Clarithromycin is well absorbed after oral administration, with its bioavailability enhanced by food. It is extensively metabolized in the liver, primarily via CYP3A4, leading to active metabolites. The drug has a half-life of approximately 3 to 4 hours, but its active metabolite, 14-OH clarithromycin, has a longer half-life, contributing to its prolonged activity. Renal impairment can significantly affect its clearance, necessitating dosage adjustments in patients with reduced renal function.

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Dysgeusia
• Headache
• Rash
• Liver enzyme elevations
• QT prolongation

Interactions

• Clarithromycin + acalabrutinib: Severe (increases exposure)
• Clarithromycin + antiarrhythmics: Severe (increases exposure)
• Clarithromycin + dronedarone: Severe (increases exposure)
• Clarithromycin + non-sedating antihistamines: Severe (increases exposure)
• Clarithromycin + mizolastine: Severe (increases exposure)
• Clarithromycin + lurasidone: Severe (increases exposure)
• Clarithromycin + quetiapine: Severe (increases exposure)
• Clarithromycin + avapritinib: Severe (increases exposure)
• Clarithromycin + benzodiazepines: Severe (increases exposure)
• Clarithromycin + alprazolam: Severe (increases exposure)

Precautions

• Caution in hepatic impairment
• Use with caution in renal impairment
• Monitor for signs of QT prolongation
• Consider alternative therapy in patients with history of arrhythmias
• Use with caution in patients with myasthenia gravis due to potential exacerbation

Pregnancy

Manufacturers advise use only if adequate alternatives are not available.

Breast-feeding

Present in milk; use only if no suitable alternatives.

Storage

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

Formulations

• Oral suspension 200 mg/5 mL
• Capsules 250 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

Clarithromycin is first metabolized to 14-OH clarithromycin, which is active and works synergistically with its parent compound. Like other macrolides, it then penetrates bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump. Clarithromycin usually is bacteriostatic, although it may be bactericidal in high concentrations or against highly susceptible organisms. Bactericidal activity has been observed against Streptococcus pyogenes, S. pneumoniae, Haemophilus influenzae, and Chlamydia trachomatis. Clarithromycin inhibits protein synthesis in susceptible organisms by penetrating the cell wall and binding to 50S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. The site of action of clarithromycin appears to be the same as that of erythromycin, clindamycin, lincomycin, and chloramphenicol.

Pharmacodynamics

Clarithromycin is a macrolide antibiotic whose spectrum of activity includes many gram-positive (<i>Staphylococcus aureus, S. pneumoniae, and S. pyogenes</i>) and gram-negative aerobic bacteria (<i>Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis</i>), many anaerobic bacteria, some mycobacteria, and some other organisms including <i>Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma</i>, and <i>Borrelia</i>. Other aerobic bacteria that clarithromycin has activity against include <i>C. pneumoniae and M. pneumoniae</i>. Clarithromycin has an in-vitro activity that is similar or greater than that of erythromycin against erythromycin-susceptible organisms. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration.