TERREXINE

Indications

• Bacterial infections due to sensitive Gram-positive and Gram-negative bacteria
• Skin infections
• Soft-tissue infections
• Uncomplicated urinary-tract infections
• Acute diverticulitis (in combination with metronidazole)
• Prophylaxis of recurrent urinary-tract infections

Dosage

Children: Child 1 month–11 years: 25 mg/kg 2–4 times a day (max. per dose 500 mg). Child

Adults: 250 mg every 6 hours, alternatively 500 mg every 8–12 hours; increased to 1–1.5 g every 6–8 hours for severe infections.

Mechanism of action

Cefalexin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins located in the bacterial cytoplasmic membrane. This action prevents the cross-linkage of peptidoglycan chains, which is essential for bacterial cell wall strength and rigidity. Consequently, this leads to cell lysis and death, particularly in rapidly dividing bacteria.

Pharmacodynamics

Cefalexin is bactericidal and exhibits activity primarily against Gram-positive bacteria. It is effective in treating superficial infections resulting from minor wounds or lacerations. By interfering with the cross-linking reaction between N-acetyl muramic acid and N-acetylglucosamine in the bacterial cell wall, cefalexin promotes cell lysis, making it a widely used antibiotic in clinical practice.

Pharmacokinetics

Cefalexin is well absorbed when taken orally, with peak plasma concentrations typically occurring within 1 hour of administration. It is widely distributed throughout body tissues and fluids, including bile, urine, and synovial fluid. The drug is primarily excreted unchanged in the urine, and its half-life is approximately 1 hour. Renal impairment may necessitate dosage adjustments.

Contra-indications

• Hypersensitivity to cephalosporins
• History of immediate hypersensitivity to penicillin and other beta-lactams

Adverse effects

• Abdominal pain
• Diarrhoea
• Dizziness
• Eosinophilia
• Headache
• Leucopenia
• Nausea
• Neutropenia
• Pseudomembranous enterocolitis
• Skin reactions
• Thrombocytopenia
• Vomiting
• Vulvovaginal candidiasis
• Anaphylactic reaction
• Angioedema
• Agranulocytosis
• Hemolytic anemia
• Tubulointerstitial nephritis
• Severe cutaneous adverse reactions (SCARs)

Interactions

• Probenecid may increase the serum concentration of cephalexin
• Antacids may decrease the absorption of cephalexin
• Other nephrotoxic drugs may increase the risk of kidney damage

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of superinfection during prolonged therapy
• Caution in patients with a history of gastrointestinal disease, particularly colitis

Pregnancy

Not known to be harmful.

Breast-feeding

Present in milk in low concentration, but generally considered appropriate to use.

Storage

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

Formulations

• Capsules: 250 mg, 500 mg
• Oral suspension: 125 mg/5 mL, 250 mg/5 mL

Indications

• Serious infections caused by aerobic Gram-negative bacteria
• Infections due to mycobacteria, including tuberculosis
• Endocarditis in conjunction with penicillin-related antibiotics

Dosage

Children: Refer to BNF for Children for specific dosing information, as it is determined by weight and age.

Adults: Refer to BNF for specific dosing information, as it varies based on the type and severity of the infection.

Mechanism of action

Kanamycin irreversibly binds to specific proteins and 16S rRNA of the 30S ribosomal subunit. This binding interferes with the decoding site, leading to misreading of mRNA, incorrect amino acid insertion into peptides, and disruption of polysomes into nonfunctional monosomes. This bactericidal action results in the inhibition of protein synthesis in susceptible microorganisms.

Pharmacodynamics

Kanamycin is effective primarily against aerobic Gram-negative bacteria and some mycobacteria, including those causing tuberculosis. It disrupts the integrity of the bacterial cell membrane and inhibits protein synthesis, rendering bacteria unable to grow and replicate. While it can be used for Gram-positive infections, other antibiotics are usually preferred due to their higher potency and lower toxicity.

Pharmacokinetics

Kanamycin is administered parenterally, as it is poorly absorbed from the gastrointestinal tract. It demonstrates a volume of distribution that is primarily extracellular. The drug is primarily eliminated by the kidneys through glomerular filtration, necessitating dose adjustments in patients with renal impairment. Kanamycin's half-life is approximately 2 to 3 hours in individuals with normal renal function.

Contra-indications

• Hypersensitivity to kanamycin or any aminoglycoside antibiotic
• Severe renal impairment
• Myasthenia gravis

Adverse effects

• Nephrotoxicity
• Ototoxicity (hearing loss, vestibular toxicity)
• Neuromuscular blockade
• Allergic reactions (skin rash, itching)
• Gastrointestinal disturbances (nausea, vomiting)

Interactions

• Other nephrotoxic drugs (e.g., cisplatin, vancomycin) may increase the risk of renal toxicity
• Neurotoxins may potentiate neuromuscular blockade
• Concurrent use with diuretics (e.g., furosemide) may enhance ototoxicity

Precautions

• Monitor renal function regularly during treatment
• Use with caution in patients with pre-existing hearing loss
• Adjust dosage in cases of renal impairment
• Ensure adequate hydration to minimize risk of nephrotoxicity

Pregnancy

Kanamycin is classified as category D. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Kanamycin is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Refrigeration may be required for some formulations.

Formulations

• Kanamycin sulfate injection
• Kanamycin oral solution

Mechanism of action

Cephalexin is a first generation cephalosporin antibiotic. Cephalosporins contain a beta lactam and dihydrothiazide. Unlike penicillins, cephalosprins are more resistant to the action of beta lactamase. Cephalexin inhibits bacterial cell wall synthesis, leading breakdown and eventualy cell death. CEPHALOTHIN & ITS CONGENERS INHIBIT BACTERIAL CELL-WALL SYNTHESIS IN MANNER SIMILAR TO THAT OF PENICILLIN. /CEPHALOSPORINS/ 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/ Bactericidal; action depends on ability to reach and bind penicillin-binding proteins located in bacterial cytoplasmic membranes; cephalosporins inhibit bacterial septum and cell wall synthesis, probably by acylation of membrane-bound transpeptidase enzymes. This prevents cross-linkage of peptidoglycan chains, which is necessary for bacterial cell wall strength and rigidity. Also, cell division and growth are inhibited, and lysis and elongation of susceptible bacteria frequently occur. Rapidly dividing bacteria are those most susceptible to the action of cephalosporins. /Cephalosporins/ CEPHALOSPORIN C IS VERY RESISTANT TO ACTION OF PENICILLINASE, FOR WHICH IT IS BOTH COMPETITIVE & NONCOMPETITIVE INHIBITOR, DEPENDING ON SUBSTRATE TESTED... /CEPHALOSPORINS/

Pharmacodynamics

Cephalexin (also called Cefalexin) is a first generation cephalosporin antibiotic. It is one of the most widely prescribed antibiotics, often used for the treatment of superficial infections that result as complications of minor wounds or lacerations. It is effective against most gram-positive bacteria through its inihibition of the cross linking reaction between N-acetyl muramicacid and N-acetylglucosamine in the cell wall, leading to cell lysis.

Mechanism of action

Aminoglycosides like kanamycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Kanamycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Kanamycin, an aminoglycoside, acts by inhibiting the synthesis of protein in susceptible microorganisms. It is bactericidal in vitro against Gram-negative bacteria and certain Gram-positive bacteria. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

Pharmacodynamics

Kanamycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.