Rilexine 200 LC

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

• Corticosteroid-responsive conditions
• Autoimmune diseases
• Inflammatory eye conditions
• Certain malignancies
• Chronic inflammatory disorders

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing recommendations based on age and weight.

Adults: Refer to the BNF for specific adult dosing guidelines based on the condition being treated. Doses may vary depending on the severity of the condition and the clinical response.

Mechanism of action

Prednisolone binds to the glucocorticoid receptor, resulting in altered gene expression that decreases vasodilation, capillary permeability, and leukocyte migration to sites of inflammation. It inhibits phospholipase A2, reducing the production of arachidonic acid derivatives, and suppresses pro-inflammatory transcription factors such as NF-Kappa B. This results in an anti-inflammatory effect at lower doses and immunosuppressive effects at higher doses.

Pharmacodynamics

Corticosteroids like prednisolone exert their effects by inhibiting pro-inflammatory signals and promoting anti-inflammatory signals through their action on the glucocorticoid receptor. Prednisolone has a relatively short half-life of 2.1 to 3.5 hours, and while it has a wide therapeutic window, long-term use can lead to hypothalamic-pituitary-adrenal axis suppression and increased infection risk.

Pharmacokinetics

Prednisolone is rapidly absorbed and has a short duration of action. Its pharmacokinetics involve extensive metabolism in the liver, primarily through hepatic enzymes, leading to various metabolites. The elimination half-life is approximately 2.1 to 3.5 hours, and it is primarily excreted in the urine. Chronic use can affect circadian rhythms and homeostasis.

Contra-indications

• Known allergy to prednisolone or any of its components
• Systemic fungal infections
• Active tuberculosis
• Untreated bacterial infections

Adverse effects

• Increased susceptibility to infections
• Gastrointestinal disturbances
• Fluid retention
• Hypertension
• Cushing's syndrome
• Osteoporosis
• Mood changes
• Hyperglycemia

Interactions

• Mitotane (Moderate - decreases exposure)
• Rifampicin (Moderate - decreases exposure)
• Cobicistat (Unknown - increases exposure)
• Idelalisib (Unknown - increases exposure)
• Clarithromycin (Unknown - increases exposure)

Precautions

• Monitor for signs of infection during therapy
• Use with caution in patients with a history of gastrointestinal ulcers
• Tapering of dosage may be necessary to avoid withdrawal symptoms
• Consider potential effects on growth in pediatric patients

Pregnancy

Prednisolone is classified as a Category C drug. It should only be used if the potential benefits justify the potential risk to the fetus.

Breast-feeding

Prednisolone is excreted in breast milk. Caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Tablets: 2 mg, 4 mg, 16 mg, 100 mg
• Suspension for injection
• Powder and solvent for solution for injection

Indications

• Bowel sterilization before surgery
• Hepatic coma
• Topical infections caused by susceptible organisms

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: By mouth: 1 g every 1 hour for 4 hours, then 1 g every 4 hours for 2–3 days. For hepatic coma: Up to 4 g daily in divided doses usually for 5–7 days.

Mechanism of action

Neomycin sulfate binds to the 30S ribosomal subunit of bacteria, leading to the misreading of mRNA and the inhibition of protein synthesis. This disrupts the production of essential proteins needed for bacterial growth and function, ultimately resulting in cell death.

Pharmacodynamics

Neomycin demonstrates bactericidal activity against susceptible bacteria. Its efficacy is enhanced in alkaline environments, which is why it is often used in combination with other agents for surgical prophylaxis. The drug is primarily effective against a range of gram-negative organisms, including Escherichia coli and Klebsiella species, but also has some activity against gram-positive organisms.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract, and its systemic absorption is minimal when administered orally. In cases of systemic use, such as intramuscular or intravenous administration, neomycin is distributed widely in the body but is primarily excreted unchanged in the urine. The elimination half-life varies but is generally around 2 to 3 hours in individuals with normal renal function. Monitoring of serum concentrations is essential to prevent toxicity, especially in patients with renal impairment.

Adverse effects

• neurotoxicity
• ototoxicity
• nephrotoxicity
• allergic reactions
• skin rashes
• hearing loss

Interactions

• other nephrotoxic drugs
• loop diuretics
• neuromuscular blocking agents

Precautions

• monitor renal function
• use cautiously in patients with hearing impairment
• avoid concurrent use with other ototoxic medications
• ensure adequate hydration

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use caution; neomycin can be absorbed systemically and may affect the nursing infant.

Storage

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

Formulations

• oral tablets
• topical ointments
• injectable solutions

Indications

• Bacterial infections caused by aerobic organisms
• Topical treatment of skin infections

Mechanism of action

Neomycin binds to specific proteins and 16S rRNA within the 30S ribosomal subunit of susceptible bacteria. This binding interferes with the decoding site, causing misreading of mRNA and leading to the incorporation of incorrect amino acids into polypeptides. As a result, nonfunctional or toxic peptides are produced, and polysomes are disrupted into nonfunctional monosomes. Neomycin's bactericidal action is characterized by its ability to irreversibly bind to the 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

Pharmacodynamics

Neomycin is primarily active against aerobic bacteria and is not effective against fungi, viruses, or most anaerobic bacteria. It mediates its bactericidal effects by inhibiting protein synthesis, which suppresses bacterial growth and survival. Following oral administration, neomycin exhibits a duration of bactericidal activity lasting between 48 to 72 hours. It is particularly useful in treating infections caused by strains of E. coli and Klebsiella, and it also acts to reduce colonic bacterial populations in patients with hepatic coma.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract when taken orally, which limits its systemic availability and enhances its utility in targeting colonic bacteria. It is generally not used parenterally due to its potential for nephrotoxicity and ototoxicity. The duration of action following oral administration can last from 48 to 72 hours, and it is primarily excreted unchanged in the urine. Caution should be exercised when using neomycin in patients with renal impairment, as the risk of toxicity increases.

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Allergic reactions
• Diarrhea
• Nausea
• Vomiting

Interactions

• neomycin+digoxin: Unknown (decreases absorption)
• neomycin+sorafenib: Unknown (decreases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Evaluate hearing function in long-term use

Pregnancy

Neomycin is classified as category D; it should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Neomycin is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Eye drops
• Oral tablets

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

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels. Although altered homeostatic regulation, including disturbance of 24-h rhythms, is often observed in the patients undergoing glucocorticoid therapy, the mechanisms underlying the disturbance remains poorly understood. We report here that chronic treatment with a synthetic glucocorticoid, prednisolone, can cause alteration of circadian clock function at molecular level. Treatment of cultured hepatic cells (HepG2) with prednisolone induced expression of Period1 (Per1), and the prednisolone treatment also attenuated the serum-induced oscillations in the expression of Period2 (Per2), Rev-erbalpha, and Bmal1 mRNA in HepG2 cells. Because the attenuation of clock gene oscillations was blocked by pretreating the cells with a Per1 antisense phosphothioate oligodeoxynucleotide, the extensive expression of Per1 induced by prednisolone may have resulted in the reduced amplitude of other clock gene oscillations. Continuous administration of prednisolone into mice constitutively increased the Per1 mRNA levels in liver and skeletal muscle, which seems to attenuate the oscillation in the expressions of Per2, Rev-erbalpha, and Bmal1. However, a single daily administration of prednisolone at the time of day corresponding to acrophase of endogenous glucocorticoid levels had little effect on the rhythmic expression of clock genes. These results suggest a possible pharmacological action by prednisolone on the core circadian oscillation mechanism and indicate the possibility that the alteration of clock function induced by prednisolone can be avoided by optimizing the dosing schedule. Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisolone has a short duration of action as the half life is 2.1-3.5 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Mechanism of action

Framycetin binds to specific 30S-subunit proteins and 16S rRNA, 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. Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation. 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/ A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy. ... 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

Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria. Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms. Neomycin is active against both gram positive and gram negative organisms, including the major _E. coli_ species resident in the colon as well as the enteropathogenic forms of _E. coli_. It is also active against _Klebsiella_-_Enterobacter_ group. Resistant strains of _E. coli_, _Klebsiella_ and _Proteus spp_. may emerge from neomycin therapy. Neomycin has no antifungal activity and has some activity against some protozoa.