FML-NEO LIQUIFILM OPHTHALMIC SUSPENSION

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

• Local treatment of inflammatory eye conditions
• Short-term management of eye inflammation

Dosage

Children: For children aged 2–17 years, apply every 1 hour for 24–48 hours, then reduce to 2–4 times a day as needed.

Adults: Apply every 1 hour for 24–48 hours, then reduce to 2–4 times a day as needed.

Mechanism of action

Fluorometholone acts by inducing phospholipase A2 inhibitory proteins known as lipocortins, which control the biosynthesis of inflammatory mediators like prostaglandins and leukotrienes. These proteins inhibit the release of arachidonic acid from membrane phospholipids. The drug binds to cytosolic glucocorticoid receptors, forming a receptor-ligand complex that translocates into the nucleus to bind glucocorticoid response elements in target genes, leading to modulation of gene expression related to inflammation.

Pharmacodynamics

Fluorometholone inhibits the inflammatory response, affecting various processes such as edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, collagen deposition, and scar formation. This broad anti-inflammatory action helps in managing symptoms associated with ocular inflammation.

Pharmacokinetics

Fluorometholone is primarily administered topically as eye drops, which allows for localized action with limited systemic absorption. The pharmacokinetics of the drug in the eye involve rapid penetration into ocular tissues, with peak concentrations occurring shortly after administration. Due to its formulation, it is designed to minimize systemic exposure and side effects.

Adverse effects

• Eye discomfort
• Stinging
• Altered taste
• Visual impairment
• Cataract
• Eye disorders

Precautions

• Risk of central serous chorioretinopathy with local and systemic administration
• Consider the potential for increased intraocular pressure with prolonged use

Pregnancy

Fluorometholone should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is recommended.

Breast-feeding

There is no specific information on the excretion of fluorometholone in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Formulations

• Fluorometholone 0.1% eye drops (FML Liquifilm) - 5 ml or 10 ml bottles

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

There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Their primary target is the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes.

Pharmacodynamics

Corticosteroids such as fluorometholone inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.

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.