UBROLEXIN

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

Indications

• Cancer (various types)
• Rheumatoid arthritis
• Multiple sclerosis
• Inflammatory bowel disease
• Psoriasis
• Hypercholesterolemia
• Infectious diseases (e.g., COVID-19)

Dosage

Children: Refer to the BNF for Children for paediatric dosing information, as it varies based on the specific monoclonal antibody and the condition being treated.

Adults: Refer to the specific monoclonal antibody product information for adult dosage, as it varies based on indication and specific agent used.

Mechanism of action

Monoclonal antibodies work by binding to specific proteins on the surface of cells. This binding can block the activity of certain proteins, mark cells for destruction by the immune system, or deliver cytotoxic agents directly to target cells. The mechanism of action varies depending on the specific monoclonal antibody but often involves modulation of immune response, inhibition of cell proliferation, and induction of apoptotic pathways.

Pharmacodynamics

The pharmacodynamics of monoclonal antibodies is primarily characterized by their specificity and affinity for targeted antigens. This leads to a variety of effects, including neutralization of pathogens, blockade of receptor-ligand interactions, and antibody-dependent cellular cytotoxicity. The clinical effects depend on the disease being treated and the specific antibody's action, such as inducing tumor regression in cancer or reducing inflammation in autoimmune diseases.

Pharmacokinetics

Monoclonal antibodies typically have a long half-life, allowing for less frequent dosing. They are generally administered intravenously or subcutaneously, with absorption and distribution influenced by the antibody's size and charge. The elimination occurs primarily through proteolytic degradation and intracellular recycling. Factors such as patient-specific variables, including immunogenicity and the presence of antibodies against the monoclonal antibody, can impact pharmacokinetics.

Interactions

• abatacept+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anakinra+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anthracyclines+monoclonalantibodies: Severe (increases risk of cardiotoxicity)
• filgotinib+monoclonalantibodies: Severe (increases risk of immunosuppression)
• monoclonalantibodies+fingolimod: Severe (increases risk of generalised infection (possibly life-threatening))
• normal immunoglobulin+monoclonalantibodies: Severe (affects effects)
• monoclonalantibodies+ozanimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+siponimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+vemurafenib: Severe (increases risk of hepatotoxicity)
• monoclonalantibodies+aminophylline: Moderate (decreases exposure)

Dosage

Children: Refer to established pharmacological guidelines and literature for specific dosing recommendations, as these can vary based on the clinical context and specific monosulphate compound in question.

Adults: Refer to established pharmacological guidelines and literature for specific dosing recommendations, as these can vary based on the clinical context and specific monosulphate compound in question.

Mechanism of action

Monosulphate compounds typically function by donating a sulfonate group to other molecules, facilitating various biochemical reactions. This mechanism is essential in the formation of sulfated metabolites which can enhance the solubility and excretion of drugs and toxins, thereby influencing their pharmacokinetics.

Pharmacodynamics

The pharmacodynamics of monosulphate compounds are closely linked to their ability to modify the activity of enzymes and receptors through sulfonation. This modification can result in altered drug activity, efficacy, and bioavailability. The impact on pharmacological effects can vary widely depending on the specific substrate and biological context.

Pharmacokinetics

Monosulphate compounds exhibit variable pharmacokinetic profiles based on their chemical structure and the specific biological pathways they engage. Generally, these compounds may undergo absorption in the gastrointestinal tract, followed by hepatic metabolism where they can be conjugated or transformed into active or inactive metabolites. Excretion typically occurs via renal pathways, although specifics can vary widely.

Pregnancy

Monosulphate should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. It is important to consult a healthcare provider for assessment.

Breast-feeding

Caution is advised when administering monosulphate during breastfeeding, as the effects on the infant are not fully understood. Consultation with a healthcare provider is recommended.

Storage

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

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.