AVIR CREAM BP

Indications

• Adrenocortical insufficiency
• Inflammatory bowel disease
• Severe acute asthma
• Acute hypersensitivity reactions
• Congenital adrenal hyperplasia
• Replacement therapy in adrenal insufficiency

Dosage

Children: For children aged 1-5 months: Initially 25 mg 3 times a day, adjusted according to response. For children aged 6 months-5 years: Initially 50 mg 3 times a day, adjusted according to response. For children aged 6-11 years: Initially 100 mg 3 times a day, adjusted

Adults: 100-500 mg 3-4 times a day or when required. For replacement in adrenocortical insufficiency, 20-30 mg once daily, adjusted according to response.

Mechanism of action

Hydrocortisone binds to the glucocorticoid receptor, leading to decreased vasodilation and permeability of capillaries, inhibition of leukocyte migration to inflammation sites, and changes in gene expression that promote anti-inflammatory pathways. It inhibits phospholipase A2, NF-kappa B, and other inflammatory transcription factors, stabilizing leukocyte lysosomal membranes and reducing the release of destructive enzymes. High doses can raise sodium levels and decrease potassium levels through mineralocorticoid receptor activity.

Pharmacodynamics

Hydrocortisone's pharmacodynamic profile includes the inhibition of various inflammatory mediators and the promotion of anti-inflammatory cytokines. Its effects are dose-dependent, with lower doses providing anti-inflammatory benefits, while higher doses exhibit immunosuppressive effects. It has a wide therapeutic index and moderate duration of action.

Pharmacokinetics

Hydrocortisone is metabolized primarily in the liver, with its effects lasting for several hours to days. The onset of action varies with the route of administration, being more rapid when given intravenously. Its half-life is influenced by factors such as dose and administration route, and it is excreted through urine as metabolites.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to hydrocortisone or any excipients

Adverse effects

• Increased risk of infections
• Hyperglycemia
• Hypertension
• Fluid retention and edema
• Gastrointestinal disturbances
• Mood changes
• Osteoporosis
• Peptic ulcer disease
• Cushing's syndrome with long-term use

Interactions

• Mitotane: Moderate decrease in hydrocortisone exposure
• Rifampicin: Moderate decrease in hydrocortisone exposure
• Cobicistat: Unknown effect, potential increase in hydrocortisone exposure
• Idelalisib: Unknown effect, potential increase in hydrocortisone exposure
• Clarithromycin: Unknown effect, potential increase in hydrocortisone exposure

Precautions

• Use with caution in patients with diabetes
• Monitor for signs of infection during therapy
• Consider dose adjustment in patients with hepatic impairment
• Gradual withdrawal is recommended to avoid adrenal insufficiency after prolonged therapy

Pregnancy

Hydrocortisone is categorized as category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Hydrocortisone is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Injectable form (sodium succinate)
• Modified-release tablets
• Immediate-release tablets

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

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. Following topical application, corticosteroids produce anti-inflammatory, antipruritic, and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor. Corticosteroids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Corticosteroids, especially the fluorinated corticosteroids, have antimitotic activity on cutaneous fibroblasts and the epidermis. /Corticosteroids/ Reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited following the intravenous administration of hydrocortisone. This is associated with a parallel decrease in intranuclear NFkappaB, known to modulate inflammatory responses including ROS generation. Plasma levels of interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine produced by TH2 cells, are also increased after hydrocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47(phox) subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and plasma IL-10 levels /were investigated/. p47(phox) subunit protein levels in MNC showed a progressive decrease after hydrocortisone administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a nadir between 2 and 4 hours, and returned to a baseline level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and reverted to the baseline levels at 24 hours. In conclusion, p47(phox) subunit suppression may contribute to the inhibition of ROS generation in MNC after hydrocortisone administration. This suppression occurs in parallel with the suppression of NFkappaB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NFkappaB and an increase in IL-10 may cause the inhibitory modulation on p47(phox) subunit and ROS generation by MNC following hydrocortisone and other glucocorticoids.

Pharmacodynamics

Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes. Hydrocortisone has a wide therapeutic index and a moderate duration of action. Patients should stop taking the medication if irritation or sensitization occurs.

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.