POSITON OINTMENT

Indications

• Oral candidiasis
• Perioral fungal infections
• Oropharyngeal candidiasis

Dosage

Children: 100,000 units by mouth 4 times a day, usually for 7 days, continued for 48 hours after lesions have resolved.

Adults: 100,000 units by mouth 4 times a day, usually for 7 days, continued for 48 hours after lesions have resolved.

Mechanism of action

Nystatin is a channel-forming ionophore that binds to ergosterol, a sterol found in fungal cell membranes, creating membrane-spanning pores. This disrupts the membrane's integrity, resulting in the leakage of intracellular components and loss of electrochemical gradients essential for cell function, leading to cell death.

Pharmacodynamics

Nystatin exhibits both fungistatic and fungicidal activity against a wide range of yeasts and yeast-like fungi, particularly _Candida albicans_. Resistance is minimal with _Candida albicans_ but may develop in other _Candida_ species. It is ineffective against bacteria, protozoa, or viruses and has significant systemic toxicity, limiting its use to topical and oral applications.

Pharmacokinetics

Nystatin is poorly absorbed from the gastrointestinal tract, which allows it to exert its effects locally within the gut and oral cavity. Because of its limited systemic absorption, it is primarily used for local treatment of fungal infections. The drug is not metabolized systemically and is excreted unchanged in the feces.

Contra-indications

• Infants with impaired swallowing
• Acute porphyrias

Adverse effects

• Abdominal distress
• Angioedema
• Diarrhoea
• Face oedema
• Nausea
• Sensitisation
• Skin reactions
• Stevens-Johnson syndrome
• Vomiting

Precautions

• Caution in patients with acute porphyrias
• Use with care in patients with a history of hypersensitivity to nystatin or other polyene antifungals

Pregnancy

Nystatin is generally considered safe in pregnancy; however, it should be used only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Nystatin is excreted in breast milk but is considered safe for use during breastfeeding as it is poorly absorbed systemically.

Storage

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

Formulations

• Nystatin oral suspension 100,000 units/ml
• Nystatin tablets
• Nystatin capsules

Indications

• Bacterial eye infections (e.g., conjunctivitis)
• Hepatic coma adjunctive therapy
• Infections caused by susceptible aerobic gram-positive and gram-negative bacteria

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines for adults based on the condition being treated.

Mechanism of action

Neomycin binds irreversibly to the 30S ribosomal subunit of susceptible bacteria, leading to misreading of mRNA and incorrect amino acid incorporation into proteins. This disrupts the translational machinery necessary for protein synthesis, resulting in the production of nonfunctional or toxic peptides and ultimately causing bacterial cell death. Additionally, neomycin inhibits nuclear translocation of angiogenin in endothelial cells, affecting angiogenesis.

Pharmacodynamics

Neomycin demonstrates bactericidal activity by inhibiting protein synthesis in bacteria, which suppresses their growth and survival. It is particularly effective against aerobic bacteria and has been shown to be active against various strains of Escherichia coli and the Klebsiella-Enterobacter group. The duration of its bactericidal activity can last from 48 to 72 hours following oral administration.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract when taken orally, which is beneficial for its intended use in treating intestinal infections and hepatic coma. It is primarily excreted unchanged in the urine. Its pharmacokinetic profile allows for effective local action in the gut while minimizing systemic exposure, reducing the risk of nephrotoxicity and ototoxicity commonly associated with aminoglycosides.

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Allergic reactions
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Neuromuscular blockade

Interactions

• Increased risk of nephrotoxicity when used with other nephrotoxic agents (e.g., cisplatin, vancomycin)
• Potentially enhanced neuromuscular blockade when used with muscle relaxants

Precautions

• Monitor renal function during treatment due to the risk of nephrotoxicity
• Use with caution in patients with pre-existing renal impairment
• Consider potential ototoxic effects, especially in patients with existing hearing impairment

Pregnancy

Neomycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown adverse effects.

Breast-feeding

Use with caution during breastfeeding as neomycin is excreted in breast milk, and the effects on the nursing infant are unknown.

Storage

Store in a cool, dry place away from light. Ensure that it is kept out of reach of children.

Formulations

• Topical ointment
• Powder for oral suspension
• Eye drops

Indications

• Asthma
• Allergic rhinitis
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Dermatitis
• Psoriasis
• Inflammatory bowel disease

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on condition and formulation.

Adults: Refer to BNF for specific dosing recommendations based on condition and formulation.

Mechanism of action

Triamcinolone inhibits phospholipase A2 on cell membranes, preventing the breakdown of lysosomal membranes of leukocytes. This action reduces the formation of arachidonic acid, leading to decreased expression of cyclooxygenase and lipoxygenase, which inhibits the synthesis of prostaglandins and leukotrienes. Additionally, triamcinolone inhibits nuclear factor kappa-B, reducing pro-inflammatory signals such as interleukin-6 and interleukin-8. It interacts with specific intracellular receptor proteins to alter the expression of corticosteroid-responsive genes, leading to the synthesis of proteins like lipocortin that further inhibit inflammatory pathways.

Pharmacodynamics

Triamcinolone exhibits significant anti-inflammatory effects through multiple mechanisms, including suppression of immune cell migration and modulation of inflammatory mediator production. Its effects can lead to reduced edema, erythema, and pain associated with inflammatory processes. The drug’s action is mediated by its ability to influence gene expression in target tissues, resulting in a broad range of effects on the immune response and inflammation.

Pharmacokinetics

Triamcinolone is well absorbed following parenteral administration, with peak plasma concentrations typically observed within a few hours. It has a relatively long half-life, which allows for sustained therapeutic effects. The drug is metabolized primarily in the liver and excreted via the kidneys. Its pharmacokinetic profile may vary depending on the route of administration and the specific formulation used.

Interactions

• mitotane+triamcinolone: Moderate (decreases exposure)
• rifampicin+triamcinolone: Moderate (decreases exposure)
• cobicistat+triamcinolone: Unknown (increases exposure)
• idelalisib+triamcinolone: Unknown (increases exposure)
• clarithromycin+triamcinolone: Unknown (increases exposure)

Pregnancy

Corticosteroids, including triamcinolone, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. They may cause fetal harm, particularly when used in high doses or for prolonged periods in the second and third trimesters.

Breast-feeding

Triamcinolone is excreted in human milk, and caution should be exercised when administering to nursing mothers. The benefits of breastfeeding should be weighed against the potential risk of adverse effects on the infant.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Mechanism of action

Nystatin is a channel-forming ionophore, meaning it exerts its therapeutic effect via formation of a membrane-spanning pore in the fungal plasma membrane. The formation of this pore results in a change in membrane permeability that allows for leakage of intracellular contents and the subsequent disruption of electrochemical gradients necessary for proper cell function. Selectivity for fungal cells over mammalian cells is due to nystatin’s greater binding affinity for ergosterol, a key sterol found in fungal cell walls, as opposed to its mammalian counterpart, cholesterol. Nystatin exerts its antifungal activity by binding to sterols in the fungal cell membrane. The drug is not active against organisms (e.g., bacteria) that do not contain sterols in their cell membrane. As a result of this binding, the membrane is no longer able to function as a selective barrier, and potassium and other cellular constituents are lost. ... /Antimicrobial/ agents that act directly on the cell membrane of the microorganism, affecting permeability and leading to leakage of intracellular compounds; these include ... the polyene antifungal agents nystatin ... which bind to cell-wall sterols ...

Pharmacodynamics

Nystatin is an antifungal that is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi. It exerts its antifungal effects via disruption of the fungal cell membrane. Resistance to nystatin is minimal in _Candida albicans_, but tends to develop in other species of _Candida_. Nystatin carries no significant activity against bacteria, protozoa, or viruses. It carries significant systemic toxicity and is currently unavailable in a formula appropriate for systemic use - its efficacy is currently restricted, therefore, to topical, oral, and gastrointestinal 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.

Mechanism of action

Corticosteroids like triamcinolone inhibit phospholipase A2 on cell membranes, preventing the breakdown of lysosomal membranes of leukocytes, which in turn prevent the formation of arachidonic acid, which decrease expression of cyclooxygenase and lipoxygenase, inhibiting synthesis of prostaglandins and leukotrienes. Anti-inflammatory activity occurs via reversal of vascular dilation and reducing permeability, which prevents macrophage and leukocyte migration. Triamcinolone also inhibits nuclear factor kappa-B, which decreases the production of pro-inflammatory signals such as interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. 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)/ The potent anti-inflammatory action may be due to an inhibition of the secretion of growth factors, endothelial activating and other cytokines from lymphocytes, eosinophils, macrophages, fibroblasts, and mast cells. The results are decreased influx of inflammatory cells into the bronchial walls, due in part to inhibition of expression of adhesion molecules on the endothelium and in the tissue. Decreased activation and survival of eosinophils in the lung tissue and a reduction in numbers of mast cells are further effects. Corticosteroids may inhibit release of mediators from basophils and enzymes from macrophages. There is decreased permeability through vasoconstriction and direct inhibition of endothelial cell contradiction. Beta-adrenergic-receptor numbers may be increased, which results in an enhanced response to beta-adrenergic bronchodilators and reduced down-regulation of beta-receptors after prolonged beta-agonist exposure. Inhaled corticosteroids also inhibit mucus secretion in airways, possibly by a direct action on submucosal gland cells and an indirect inhibitory effect caused by the reduction in inflammatory mediators that stimulate mucus secretion. The amount and viscosity of sputum are reduced. /Corticosteroids (inhalation-local/

Pharmacodynamics

Triamcinolone is a corticosteroid with anti-inflammatory properties. These properties are used to treat inflammation in conditions that affect various organs and tissues. Triamcinolone should not be administered as an epidural injection.