FRAMYDEX EYE/EAR DROPS

Indications

• Bacterial infection in otitis externa

Dosage

Children: Apply 2–3 drops 4–5 times a day, including a dose at bedtime.

Adults: Apply 2–3 drops 4–5 times a day, including a dose at bedtime.

Mechanism of action

Framycetinsulfate exerts its antibacterial effect by inhibiting protein synthesis in bacteria. It binds to the 30S ribosomal subunit, causing misreading of mRNA and ultimately leading to the production of nonfunctional or toxic peptides. This action disrupts bacterial cell function and contributes to cell death.

Pharmacodynamics

Framycetinsulfate is effective against a range of gram-negative and some gram-positive bacteria. Its ability to penetrate bacterial cell walls and interfere with protein synthesis makes it a potent antibacterial agent. However, resistance can develop, particularly with prolonged use.

Pharmacokinetics

When applied topically, framycetinsulfate has limited systemic absorption. Its pharmacokinetic profile is characterized by minimal systemic exposure, which reduces the risk of systemic side effects. The drug is primarily excreted unchanged in urine. Local application leads to high concentrations at the site of infection, which is beneficial for treating localized infections like otitis externa.

Contra-indications

• Perforated tympanic membrane

Adverse effects

• Ototoxicity
• Local irritation
• Allergic reactions

Interactions

• Potential risk of ototoxicity may increase when used with other aminoglycosides

Precautions

• Avoid prolonged use
• Use with caution in patients with mitochondrial mutations

Pregnancy

Framycetin sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult product literature for detailed guidance.

Breast-feeding

Caution is advised when administering framycetin sulfate during breastfeeding. Consult product literature for detailed guidance.

Storage

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

Formulations

• Ear drops containing framycetin sulfate

Indications

• Suppression of inflammatory and allergic disorders
• Adjunctive treatment of suspected bacterial meningitis
• Reduction of peri- and neonatal morbidity and mortality in preterm birth
• Management of severe croup
• Congenital adrenal hyperplasia
• COVID-19 requiring supplemental oxygen

Dosage

Adults: For adults, the typical dosing varies by condition

Mechanism of action

Dexamethasone binds to the glucocorticoid receptor, leading to changes in gene expression that result in decreased inflammatory and immune responses. It inhibits phospholipase A2, reducing the formation of pro-inflammatory mediators, and promotes anti-inflammatory genes like interleukin-10. The drug also inhibits neutrophil apoptosis and demargination, contributing to its anti-inflammatory effects. Its glucocorticoid activity results in significant immunosuppression at higher doses.

Pharmacodynamics

Dexamethasone's pharmacodynamics involve the modulation of inflammatory responses through glucocorticoid receptor binding. It inhibits pro-inflammatory signals while promoting anti-inflammatory signals. The duration of action varies based on the administration route, and careful dosing is required to avoid suppression of the hypothalamic-pituitary-adrenal axis and increased infection risk. The drug has a wide therapeutic window, allowing for higher doses than the body's natural production.

Pharmacokinetics

Dexamethasone is well-absorbed after oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It is extensively metabolized in the liver, primarily through hepatic cytochrome P450 enzymes. The elimination half-life ranges from 3 to 4 hours, although it may be longer in certain populations. The drug is excreted mainly in urine as metabolites. The pharmacokinetics can be affected by factors such as liver function and co-administered medications.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to dexamethasone or any component of the formulation
• Active tuberculosis
• Cautious use in patients with peptic ulcer disease

Adverse effects

• Oedema
• Hypotension
• Increased susceptibility to infections
• Mood changes
• Cushing's syndrome
• Hyperglycemia
• Gastrointestinal perforation
• Osteoporosis
• Adrenal suppression

Interactions

• Severe interaction with avapritinib (decreases exposure)
• Moderate interaction with mitotane (decreases exposure)
• Moderate interaction with monoclonal antibodies (decreases exposure)
• Moderate interaction with tocilizumab (decreases exposure)
• Moderate interaction with aprepitant (increases exposure)
• Moderate interaction with netupitant (increases exposure)
• Moderate interaction with rifampicin (decreases exposure)
• Unknown interaction with cobicistat (increases exposure)
• Unknown interaction with caspofungin (decreases concentration)
• Unknown interaction with idelalisib (increases exposure)

Precautions

• Use with caution in patients with a history of tuberculosis
• Monitor for signs of infection due to immunosuppressive effects
• Consider dose adjustments in hepatic impairment
• Taper dosage to avoid withdrawal symptoms after prolonged use
• Monitor blood glucose levels in diabetic patients

Pregnancy

Dexamethasone is classified as a pregnancy category C drug. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dexamethasone is excreted in breast milk. Caution is advised when administering to breastfeeding women, and the risks versus benefits should be considered.

Storage

Store at room temperature (15-30 degrees Celsius), protect from light, and keep out of reach of children.

Formulations

• Tablet (6 mg)
• Solution for injection (3.3 mg/1 ml)
• Dexamethasone sodium phosphate solution for injection (6.6 mg/2 ml)

Indications

• Bacterial conjunctivitis
• Other bacterial eye infections

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Framycetin binds to specific proteins within the 30S ribosomal subunit and to 16S rRNA, specifically targeting four nucleotides of the rRNA and a single amino acid of protein S12. This binding interferes with the decoding site near nucleotide 1400 in 16S rRNA, leading to misreading of mRNA. Consequently, incorrect amino acids are incorporated into the polypeptide chains, resulting in nonfunctional or toxic peptides and the disintegration of polysomes into nonfunctional monosomes. This mechanism ultimately leads to the bactericidal effect characteristic of aminoglycoside antibiotics.

Pharmacodynamics

Framycetin effectively treats bacterial infections by inhibiting protein synthesis in susceptible bacteria. It primarily targets aerobic bacteria and is not effective against anaerobic bacteria or non-bacterial pathogens. The drug has a bactericidal effect, suppressing the growth and survival of bacteria, which is critical in treating infections such as conjunctivitis and other bacterial eye conditions.

Pharmacokinetics

Framycetin's pharmacokinetic profile, including absorption, distribution, metabolism, and excretion specifics, is not extensively detailed in the provided data. However, as with other aminoglycosides, it is generally understood that these drugs can have significant renal excretion and may require monitoring in patients with renal impairment. The duration of activity can extend from 48 to 72 hours following administration.

Adverse effects

• Ocular irritation
• Allergic reactions
• Contact dermatitis
• Local discomfort

Precautions

• Use with caution in patients with known hypersensitivity to aminoglycosides
• Avoid prolonged use to minimize the risk of developing antibiotic resistance
• Monitor for signs of local irritation or sensitivity

Pregnancy

Framycetin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider for guidance.

Breast-feeding

Framycetin may be excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Eye drops
• Ointment
• Cream

Indications

• Topical treatment of localized skin infections
• Ophthalmic infections
• Ear infections
• Bacterial conjunctivitis

Dosage

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

Adults: For topical use, apply a thin layer to the affected area 1 to 3 times daily or as directed by a healthcare professional.

Mechanism of action

Gramicidin exerts its antibacterial effect by disrupting the bacterial cell membrane. It forms channels in the membrane, leading to increased permeability and subsequent loss of essential intracellular components, which ultimately results in cell death. This mechanism is particularly effective against gram-positive bacteria.

Pharmacodynamics

The pharmacodynamics of gramicidin involves its interaction with the bacterial cell membrane, causing leakage of ions and small molecules, which is detrimental to bacterial survival. The drug's potency is influenced by its concentration and the susceptibility of the bacteria involved. Gramicidin shows bactericidal activity, meaning it kills bacteria rather than merely inhibiting their growth.

Pharmacokinetics

Gramicidin is primarily administered topically, and its systemic absorption is minimal, which limits its use to localized infections. Due to its polypeptide structure, it is not well absorbed through the gastrointestinal tract. The elimination half-life of gramicidin is not well defined due to its topical use and limited systemic exposure. Localized application ensures high concentrations at the site of infection with minimal side effects.

Adverse effects

• Local irritation
• Allergic reactions

Precautions

• Use with caution in patients with a history of hypersensitivity to gramicidin or other antibiotics
• Should not be used in large areas of the body or on broken skin

Pregnancy

Gramicidin is not recommended during pregnancy unless clearly needed.

Breast-feeding

It is not known whether gramicidin is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light.

Formulations

• Topical solution
• Ointment
• Eye drops

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. Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA, and stimulate transcription of mRNA and subsequent protein synthesis of enzymes ultimately responsible for anti-inflammatory effects of topical application of corticosteroids to the eye. In high concentrations which may be achieved after topical application, corticosteroids may exert direct membrane effects. Corticosteroids decrease cellular and fibrinous exudation and tissue infiltration, inhibit fibroblastic and collagen-forming activity, retard epithelial regeneration, diminish postinflammatory neovascularization and reduce toward normal levels the excessive permeability of inflamed capillaries. /Corticosteroids (Otic)/ 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/ Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocttes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids. The overall actions of topical corticosteroids are catabolic. /Corticosteroids (topical)/

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Dexamethasone's duration of action varies depending on the route. Corticosteroids have a wide therapeutic window as patients may 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.