VE-HEAL SPRAY

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

Indications

• Complicated urinary tract infections
• Pneumonia caused by multidrug-resistant Gram-negative bacteria
• Sepsis due to resistant organisms
• Infections in burn patients

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing, as it varies based on the age, weight, and condition of the child.

Adults: Refer to appropriate clinical guidelines for adult dosing, as it varies based on the type and severity of infection.

Mechanism of action

Polymyxins exert their antibacterial effects through disruption of the bacterial cell membrane. They bind to the lipopolysaccharide (LPS) and phospholipids in the outer membrane of Gram-negative bacteria, leading to increased permeability and eventual cell death.

Pharmacodynamics

The pharmacodynamics of polymyxins involves concentration-dependent killing, where higher concentrations lead to more rapid bacterial death. The drug's effectiveness is influenced by the susceptibility of the bacteria and the site of infection, with synergy observed when used in combination with other antibiotics.

Pharmacokinetics

Polymyxins are poorly absorbed from the gastrointestinal tract, which limits their use to parenteral administration for systemic infections. They are distributed widely in body tissues and fluids, including lungs and kidneys. Elimination primarily occurs through renal excretion, and dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to polymyxins
• Renal impairment
• Neuromuscular disorders

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Allergic reactions
• Diarrhea
• Nausea

Interactions

• Increased risk of nephrotoxicity when used with other nephrotoxic agents such as aminoglycosides, vancomycin, or amphotericin B
• Potential antagonism with other antibiotics

Precautions

• Monitor renal function during therapy
• Caution in patients with pre-existing conditions affecting renal function
• Use with caution in patients with neuromuscular disorders

Pregnancy

Polymyxin is classified as a Category C drug. The benefits must be weighed against potential risks.

Breast-feeding

Use with caution as it is not known if polymyxin is excreted in human milk.

Storage

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

Formulations

• Polymyxin B sulfate - injection
• Colistimethate sodium - injection

Indications

• Topical treatment of minor skin infections
• Prevention of infection in minor cuts and abrasions
• Ophthalmic infections caused by susceptible bacteria

Dosage

Children: Refer to specific product guidelines for appropriate dosing in children based on age and weight.

Adults: Refer to specific product guidelines for topical application. Systemic use is generally reserved for severe infections and should be done under strict medical supervision.

Mechanism of action

Bacitracin exerts its antibacterial effect by inhibiting bacterial cell wall synthesis. It interferes with the dephosphorylation of bactoprenol, a lipid carrier molecule that plays a critical role in the transport of peptidoglycan precursors across the bacterial membrane. This disruption hinders the formation of the cell wall, leading to cell lysis and death.

Pharmacodynamics

Bacitracin is predominantly active against gram-positive bacteria. Its bactericidal action is attributed to its ability to disrupt the integrity of the bacterial cell wall. The drug's effect is concentration-dependent, meaning that higher concentrations can lead to more pronounced antibacterial activity. Resistance to bacitracin is relatively rare but can occur through mutations that alter the target sites.

Pharmacokinetics

Bacitracin is poorly absorbed from the gastrointestinal tract and is primarily used topically. When applied to the skin or mucous membranes, it acts locally with minimal systemic absorption. In cases of systemic use, such as intravenous administration for severe infections, bacitracin is excreted primarily by the kidneys. The pharmacokinetic profile varies depending on the route of administration, with topical applications generally resulting in lower systemic levels.

Contra-indications

• Hypersensitivity to bacitracin or any component of the formulation
• Use in individuals with a history of severe allergic reactions to antibiotics

Adverse effects

• Local irritation at the site of application
• Allergic reactions including rash and urticaria
• Nephrotoxicity with systemic use, especially with prolonged therapy
• Neurotoxicity if used in large amounts or in patients with renal impairment

Interactions

• Increased risk of nephrotoxicity when used with other nephrotoxic agents such as aminoglycosides
• Potential interaction with other topical agents that may alter skin permeability or enhance absorption

Precautions

• Use with caution in patients with renal impairment
• Avoid application on large areas of broken skin or over extensive burns
• Not for ophthalmic use unless specifically formulated for that purpose

Pregnancy

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

Breast-feeding

Bacitracin is excreted in breast milk in small amounts. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Topical solution
• Powder for solution

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.