NEOMIDEX EYE/EAR DROPS

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

• 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

• Historically used as a disinfectant
• Antiseptic
• Treatment of certain infections (now largely abandoned due to toxicity)

Dosage

Children: Specific dosing is not provided due to safety concerns and the potential for toxicity. Refer to appropriate clinical guidelines for dosing if applicable.

Adults: Specific dosing is not provided due to safety concerns and the potential for toxicity. Refer to appropriate clinical guidelines for dosing if applicable.

Mechanism of action

Mercuric compounds exert their effects primarily through the inhibition of sulfhydryl (thiol) groups in proteins and enzymes, leading to disruption of cellular functions. This interaction can affect various biochemical pathways, including those involved in cellular respiration and metabolism.

Pharmacodynamics

The pharmacodynamics of mercuric compounds is characterized by their ability to bind to cellular proteins, leading to alterations in enzymatic activity and disruption of cellular homeostasis. The toxic effects manifest in various organ systems, particularly the kidneys, nervous system, and gastrointestinal tract. Symptoms of mercury toxicity include tremors, memory loss, neuromuscular effects, and renal impairment.

Pharmacokinetics

Mercuric compounds are poorly absorbed from the gastrointestinal tract, but once absorbed, they can distribute widely throughout the body, accumulating in the kidneys, liver, and brain. The half-life of mercury in the body is prolonged, ranging from weeks to months, depending on the compound and individual factors. Excretion primarily occurs via the kidneys, with a small amount eliminated through feces and exhalation.

Contra-indications

• Hypersensitivity to mercuric compounds
• Severe renal impairment
• Active gastrointestinal disease

Adverse effects

• Nephrotoxicity
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Neurological effects (tremors, mood changes, cognitive impairment)
• Dermatitis
• Allergic reactions
• Hematological effects (anemia, leukopenia)

Interactions

• May interact with other nephrotoxic agents, increasing the risk of kidney damage
• Chelating agents like dimercaprol may be used in cases of poisoning but should be used cautiously

Precautions

• Use with caution in patients with pre-existing renal disease
• Monitor renal function regularly during treatment
• Avoid exposure in occupational settings due to potential for toxicity

Pregnancy

Mercuric compounds are contraindicated during pregnancy due to potential fetal toxicity and teratogenic effects.

Breast-feeding

Mercuric compounds should be avoided during breastfeeding due to the risk of excretion in breast milk and potential harm to the nursing infant.

Storage

Store in a tightly closed container, protected from light, at room temperature, away from moisture and incompatible substances.

Formulations

• Mercuric chloride
• Mercuric iodide
• Mercuric sulfide

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

Indications

• Pain relief
• Inflammation reduction
• Fever reduction
• Various therapeutic applications depending on specific phenyl-containing compounds

Dosage

Children: Refer to BNF for Children for dosage recommendations.

Adults: Refer to specific phenyl-containing compound for dosage recommendations.

Mechanism of action

Compounds containing the phenyl group often act by modulating neurotransmitter pathways, inhibiting cyclooxygenase enzymes, or interacting with various receptor sites, depending on the specific drug structure. For example, phenyl-containing analgesics may work by blocking the synthesis of prostaglandins, thus reducing pain and inflammation.

Pharmacodynamics

The pharmacodynamics of phenyl-containing compounds vary widely based on the specific drug, but many exhibit effects such as analgesia, anti-inflammatory activity, or antipyretic properties. The phenyl group can enhance lipophilicity, allowing for better absorption and distribution in the body.

Pharmacokinetics

The pharmacokinetics of phenyl-containing compounds are dependent on their chemical structure. Generally, these compounds have varied absorption rates, metabolism predominantly through hepatic pathways, and excretion primarily via renal mechanisms. The presence of the phenyl group can influence the half-life and bioavailability of the drug.

Pregnancy

Safety during pregnancy is not established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether phenyl is excreted in human milk. Caution should be exercised when administered to a nursing mother.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Nutritional supplementation
• Metabolic disorders
• Potential use in energy metabolism enhancement

Dosage

Children: Refer to the BNF for Children for appropriate dosing information as it may vary based on indication and formulation.

Adults: Refer to specific clinical guidelines or consult the BNF for appropriate dosing information as it may vary based on indication and formulation.

Mechanism of action

Phenylpropionate is primarily involved in metabolic processes. It may exert its effects through modulation of fatty acid metabolism and energy homeostasis. Specific pathways include the involvement in β-oxidation and potential interactions with peroxisome proliferator-activated receptors (PPARs), which regulate gene expression related to lipid metabolism.

Pharmacodynamics

Phenylpropionate exhibits properties that can influence lipid metabolism and energy utilization within the body. Its effects on fatty acid oxidation can lead to alterations in energy expenditure. The pharmacodynamic profile is characterized by its ability to impact metabolic pathways, although detailed receptor interactions remain less defined.

Pharmacokinetics

The pharmacokinetic properties of phenylpropionate, including absorption, distribution, metabolism, and excretion, have not been extensively documented in the available literature. As a carboxylic acid derivative, it is likely absorbed through the gastrointestinal tract, metabolized primarily in the liver, and excreted via the kidneys. Further studies would be needed to define specific parameters such as half-life and bioavailability.

Pregnancy

There is insufficient data on the safety of phenylpropionate in pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution should be exercised when phenylpropionate is administered to a nursing mother. The effects on the breastfeeding infant are not well studied.

Storage

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

Indications

• Pneumonia caused by multidrug-resistant gram-negative bacteria
• Septicemia caused by gram-negative bacteria
• Urinary tract infections caused by resistant organisms
• Skin infections caused by resistant gram-negative bacteria

Dosage

Children: Refer to BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to local guidelines or BNF for specific dosing recommendations based on the type and severity of infection.

Mechanism of action

Polymyxin exerts its antibacterial effect by disrupting the integrity of the bacterial cell membrane. It binds to the lipopolysaccharides and phospholipids in the outer membrane of gram-negative bacteria, leading to increased permeability and eventual cell lysis.

Pharmacodynamics

Polymyxin has a bactericidal effect against susceptible gram-negative organisms. Its action is concentration-dependent, with higher concentrations leading to a more significant bactericidal effect. Resistance can occur through modifications in the bacterial cell membrane components that reduce drug binding.

Pharmacokinetics

Polymyxin is poorly absorbed from the gastrointestinal tract and is typically administered parenterally (intravenously or intramuscularly) for systemic infections. It has a volume of distribution that suggests extensive tissue penetration but is primarily eliminated by the kidneys. Half-life varies based on renal function, and dose adjustments may be necessary in patients with renal impairment.

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Allergic reactions
• Respiratory distress
• Nausea
• Vomiting

Interactions

• Increased nephrotoxicity when used with other nephrotoxic agents such as aminoglycosides or cisplatin
• Potential for respiratory depression with neuromuscular blocking agents

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Consider the risk of neurotoxicity, especially with prolonged use

Pregnancy

Polymyxin is classified as category C. Its safety during pregnancy has not been established, thus it should only be used if clearly needed.

Breast-feeding

It is not known if polymyxin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Protect from freezing.

Formulations

• Polymyxin B sulfate injection
• Polymyxin E (colistin) inhalation solution
• Topical formulations

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.