XSONE N

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

• Seborrhoeic dermatitis
• Dandruff
• Scalp psoriasis
• Bacterial infections affecting the scalp

Dosage

Children: For children, apply 3 times a week for 1 week, then apply twice weekly as needed. Refer to BNF for Children for further details.

Adults: Apply to the affected area as directed, typically 1-3 times weekly depending on the condition being treated. Refer to specific product guidelines for detailed dosing.

Mechanism of action

Benzalkonium chloride exerts its antimicrobial effect by disrupting the cell membrane of microorganisms, leading to leakage of cellular contents and ultimately cell death. This is facilitated by its cationic nature, which allows it to bind to negatively charged bacterial surfaces.

Pharmacodynamics

Benzalkonium chloride demonstrates rapid bactericidal activity, with effectiveness observed against gram-positive and gram-negative bacteria, fungi, and some viruses. Its antiseptic properties may be enhanced in the presence of moisture and are typically influenced by the concentration of the solution used.

Pharmacokinetics

Benzalkonium chloride is poorly absorbed through the skin. After topical application, it remains primarily at the site of application, where it exerts localized effects. Systemic absorption is minimal, and it is primarily eliminated through the skin and urine. However, specific pharmacokinetic data may vary based on formulation and application site.

Pregnancy

Benzalkonium chloride should be used with caution during pregnancy. Refer to specific guidelines or consult a healthcare professional.

Breast-feeding

Benzalkonium chloride should be used with caution while breastfeeding. Refer to specific guidelines or consult a healthcare professional.

Storage

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

Formulations

• Shampoo
• Soap or detergent
• Topical solution

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

• Disinfection of surfaces
• Antiseptic for skin
• Preservative in pharmaceuticals
• Treatment of minor cuts and abrasions

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in pediatric populations.

Adults: Refer to the BNF for specific formulations and concentrations as doses may vary based on the application and preparation.

Mechanism of action

The bactericidal action of benzalkonium chloride is believed to result from the disruption of intermolecular interactions, which leads to the dissociation of cellular membrane lipid bilayers in bacteria. This disruption compromises cellular permeability, causing leakage of vital cellular contents. Moreover, the agent can deactivate important molecular complexes such as enzymes that regulate various respiratory and metabolic activities within the cells. Cationic surfactants like benzalkonium chloride can thus effectively disrupt critical intermolecular interactions and tertiary structures in biochemical systems, impairing bacterial function.

Pharmacodynamics

Benzalkonium chloride is classified as a biocidal agent with a relatively long duration of action. It exhibits a spectrum of activity against various microorganisms, including bacteria, certain viruses, fungi, and protozoa; however, it is ineffective against bacterial spores. The agent tends to demonstrate greater efficacy against gram-positive bacteria compared to gram-negative ones. The mode of action can be bacteriostatic (preventing growth) or bactericidal (killing bacteria), depending on its concentration. The activity of benzalkonium chloride is generally stable across different pH levels but is enhanced at elevated temperatures and with extended exposure.

Pharmacokinetics

The pharmacokinetic properties of benzalkonium chloride, including absorption, distribution, metabolism, and excretion, are not fully characterized. Its topical application limits systemic exposure, and it primarily exerts localized effects at the site of application. The duration of action and efficacy may be influenced by the formulation and concentration used.

Pregnancy

Benzalkonium chloride is generally considered safe for use during pregnancy when applied topically, but systemic absorption should be minimized. Always consult a healthcare provider for use during pregnancy.

Breast-feeding

Benzalkonium chloride is considered safe for topical application during breastfeeding, but care should be taken to avoid exposure to the infant. Consultation with a healthcare provider is recommended.

Storage

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

Formulations

• Topical solution
• Disinfectant wipes
• Liquid antiseptics

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Anxiety disorders
• Nausea and vomiting
• Allergic conditions
• Preoperative sedation
• Pruritus

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations based on age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the indication and patient characteristics.

Mechanism of action

Hydroxyzine works by antagonizing the H1 histamine receptors, leading to a reduction in the effects of histamine in the body. This action helps alleviate symptoms of allergic reactions and promotes sedation. Additionally, it may exert effects on serotonin and adrenergic receptors, which could contribute to its anxiolytic properties. Hydroxyzine is also involved in various metabolic pathways, including selenium metabolism and the degradation of reactive oxygen species.

Pharmacodynamics

The pharmacodynamic effects of hydroxyzine include sedation, anxiolysis, and reduction of allergic symptoms. Its sedative effects can make it useful in managing anxiety and inducing sleep, while its antihistaminic properties help to relieve symptoms such as itching and rashes associated with allergic reactions. The onset of action is typically within 15 to 30 minutes when taken orally, with peak effects occurring within 1 to 2 hours.

Pharmacokinetics

Hydroxyzine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 hours after oral administration. It is extensively metabolized in the liver, with metabolites, including cetirizine, possessing their own therapeutic effects. Hydroxyzine has a half-life of approximately 20 hours, allowing for once or twice daily dosing. It is primarily excreted in the urine, with less than 1% of the unchanged drug found in urine.

Interactions

• hydroxyzine+antiepileptics: Severe (increases risk of overheating and dehydration)
• hydroxyzine+zonisamide: Severe (increases risk of overheating and dehydration)
• hydroxychloroquine+penicillamine: Severe (increases risk of haematological toxicity)
• hydroxychloroquine+agalsidase alfa: Unknown (decreases effects)
• hydroxychloroquine+agalsidase beta: Unknown (decreases exposure)
• hydroxychloroquine+oral cholera vaccine: Unknown (decreases efficacy)
• live vaccines+hydroxy carbamide: Unknown (increases risk of generalised infection (possibly life-threatening))
• lanthanum+hydroxychloroquine: Unknown (decreases absorption)
• macrolides+hydroxychloroquine: Unknown (increases risk of serious cardiovascular adverse effects)
• hydroxychloroquine+remdesivir: Unknown (decreases effects)

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. Hydroxychloroquine is excreted in breast milk, and effects on the infant are unknown.

Storage

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

Formulations

• Tablets
• Oral solution

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

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

• Emulsifying agent in drug formulations
• Stabilizer for parenteral preparations
• Solubilizer for hydrophobic drug compounds
• Ingredient in topical formulations

Dosage

Children: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Adults: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Mechanism of action

Polysorbate functions primarily as an emulsifying agent. It reduces the surface tension between immiscible liquids, allowing them to mix more easily. This property is particularly useful in stabilizing emulsions and suspensions, facilitating the delivery of active pharmaceutical ingredients in various formulations.

Pharmacodynamics

Polysorbate does not exert pharmacological effects in the traditional sense, as it does not bind to specific receptors to elicit a physiological response. Instead, it plays a crucial role in modifying the physical properties of drug formulations, thereby enhancing drug delivery and absorption. Its ability to solubilize drugs enhances their bioavailability, particularly for poorly soluble compounds.

Pharmacokinetics

Polysorbate is generally considered to be non-toxic and is not absorbed to a significant extent when administered orally. It is metabolized by the liver and excreted primarily through the gastrointestinal tract. The pharmacokinetic profile may vary depending on the route of administration and the specific formulation in which it is used.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use cautiously in patients with known allergies to polysorbates or related compounds
• Monitor for allergic reactions in susceptible individuals

Pregnancy

Polysorbate is generally considered safe for use during pregnancy, but consult with a healthcare provider for specific cases.

Breast-feeding

Polysorbate is considered safe during breastfeeding, but consult with a healthcare provider for individual advice.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Polysorbate 20
• Polysorbate 80

Indications

• Hyperthyroidism
• Graves' disease
• Thyroid storm

Dosage

Children: Refer to the BNF

Adults: The usual initial dose of propylthiouracil in adults is 300 mg per day, divided into 3 doses. The maintenance dose is typically 100-150 mg per day, adjusted based on thyroid function tests.

Mechanism of action

Propylthiouracil acts by inhibiting the enzyme thyroid peroxidase, which is involved in the iodination of tyrosine residues in thyroglobulin, a precursor of thyroid hormones. By blocking this enzyme, PTU reduces the production of thyroxine (T4) and triiodothyronine (T3), leading to decreased thyroid hormone levels in circulation. Additionally, PTU inhibits the conversion of T4 to T3 in peripheral tissues, further contributing to its antithyroid effects.

Pharmacodynamics

The pharmacodynamic effects of propylthiouracil are primarily centered around its ability to lower thyroid hormone levels, which helps alleviate symptoms of hyperthyroidism such as increased heart rate, weight loss, and anxiety. The onset of action can vary, but therapeutic effects may be observed within several weeks of initiation. Monitoring thyroid function tests is essential to assess the efficacy and adjust dosing as needed.

Pharmacokinetics

Propylthiouracil is well absorbed from the gastrointestinal tract, though its bioavailability can be affected by factors such as food intake. The drug is extensively metabolized in the liver, and its elimination half-life averages around 1-2 hours. Most of the drug is excreted in urine as metabolites. It is important to note that due to its rapid metabolism, multiple daily doses may be required to maintain therapeutic levels.

Interactions

• propylthiouracil+metyrapone: Severe (decreases effects)

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

Although not entirely elucidated, the bactericidal action of benzalkonium chloride is believed to be due to the disruption of intermolecular interactions. Such disruption can cause the dissociation of cellular membrane lipid bilayers of bacteria, resulting in compromised cellular permeability control and the leakage of important cellular contents. Additionally, other important molecular complexes like enzymes which control the maintenance of a great range of respiratory and metabolic cellular activities, are also susceptible to such deactivation. Consequently, a variety of critical intermolecular interactions and tertiary structures in very highly specific biochemical systems that allow bacterial agents to function normally can be readily disrupted or deactivated by cationic surfactants like benzalkonium chloride..

Pharmacodynamics

Benzalkonium chloride solutions are generally categorized as biocidal agents with relative long durations of action. Their spectrum of activity has been demonstrated against bacteria, to some viruses, fungi, and protozoa, although bacterial spores are treated as being resistant to the agent. Additionally, the agent generally shows more activity against gram-positive than gram-negative bacteria. Finally, solutions of benzalkonium chloride are bacteriostatic or bactericidal based on their concentration. Bacteriostatic agents act to prevent further growth of bacterial organisms that are present while bactericidal agents function to kill bacteria that are present. In general, the activity of the agent is not largely affected by pH, but such activity does increase substantially at higher temperatures and prolonged exposure times.

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.