Ecodex G Cream

Indications

• Vaginal candidiasis
• Vulval candidiasis
• Superficial fungal infections

Dosage

Children: Refer to BNF for Children for appropriate dosing information.

Adults: For vaginal candidiasis, 1 pessary or 5 g of cream should be applied intravaginally at night for at least 14 days, with the course possibly repeated if necessary. For vulval candidiasis, apply cream 2-3 times a day to the affected area for the same duration.

Mechanism of action

Econazole nitrate exerts its antifungal effects by inhibiting the enzyme lanosterol 14-alpha-demethylase, which is crucial for the conversion of lanosterol to ergosterol in the fungal cell membrane. This disruption in ergosterol synthesis compromises the structural integrity of the fungal cell membrane, leading to increased permeability, cell lysis, and ultimately, cell death.

Pharmacodynamics

Econazole exhibits broad-spectrum antifungal activity against various fungi, including Candida species and dermatophytes. It is effective in treating superficial fungal infections due to its ability to penetrate the skin and mucosal tissues. The drug's effectiveness is enhanced when used consistently over the recommended treatment duration, which is typically at least 14 days for most infections.

Pharmacokinetics

Econazole is primarily administered topically, leading to minimal systemic absorption. When applied to the skin or vaginal mucosa, it achieves localized concentrations sufficient for antifungal activity. The pharmacokinetics of econazole indicate a high degree of binding to skin and mucosal tissues, allowing for sustained release and prolonged antifungal action. The elimination half-life is not well defined due to its local application and limited systemic exposure.

Contra-indications

• Hypersensitivity to econazole nitrate or any of the excipients
• Pregnancy, particularly during the first trimester

Adverse effects

• Skin reactions
• Vaginal burning
• Angioedema

Interactions

• May damage latex condoms and diaphragms

Precautions

• Use with caution in patients with a history of hypersensitivity reactions
• Monitor for skin reactions
• Avoid use during the first trimester of pregnancy

Pregnancy

Oral antifungal treatments should be avoided during pregnancy. Pregnant women may need a longer duration of treatment, usually about 7 days, to clear the infection.

Breast-feeding

Limited data available, but caution is advised as econazole may be excreted in breast milk.

Storage

Store below 25 degrees Celsius. Keep the container tightly closed and protect from light.

Formulations

• Econazole nitrate 10 mg per 1 gram cream
• Econazole nitrate vaginal pessaries

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Nasal polyps

Dosage

Children: For children aged 5 to 12 years with asthma, the usual inhaled dose is 50 to 200 micrograms twice daily. For allergic rhinitis, refer to the BNF for Children

Adults: For asthma, the usual dose of inhaled beclomethasone is 100 to 400 micrograms twice daily, adjusted based on clinical response. For allergic rhinitis, 200 to 400 micrograms as a nasal spray may be administered once daily.

Mechanism of action

Beclomethasone acts by binding to glucocorticoid receptors in the cytoplasm of target cells. This complex translocates to the nucleus, where it influences gene transcription, leading to the downregulation of pro-inflammatory cytokines and the upregulation of anti-inflammatory proteins. This mechanism results in decreased inflammation, mucus production, and airway hyper-responsiveness.

Pharmacodynamics

The anti-inflammatory effects of beclomethasone are attributed to its ability to inhibit the release of inflammatory mediators, including leukotrienes and prostaglandins. It also reduces the recruitment of inflammatory cells to the site of inflammation. The onset of action for inhaled beclomethasone may take several hours to days, with maximum benefits typically observed after continuous use.

Pharmacokinetics

Beclomethasone is well-absorbed following inhalation, with a significant portion undergoing first-pass metabolism in the liver, thereby reducing systemic exposure. Its half-life is approximately 2.5 hours, but the duration of action may extend due to the drug's accumulation in lung tissue. The elimination of beclomethasone is primarily hepatic, with metabolites excreted in urine and feces.

Contra-indications

• Hypersensitivity to beclomethasone or any of its components
• Untreated systemic fungal infections

Adverse effects

• Cushing's syndrome
• Adrenal suppression
• Osteoporosis
• Growth retardation in children
• Skin thinning
• Increased risk of infections
• Oral candidiasis

Interactions

• CYP3A4 inhibitors may increase systemic exposure to beclomethasone
• Vaccines (live) may have reduced efficacy

Precautions

• Use with caution in patients with active or quiescent tuberculosis
• Monitor for signs of adrenal insufficiency
• Consider risks in patients with diabetes mellitus
• Use with caution in patients with hypertension

Pregnancy

Beclomethasone is classified as category C. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Beclomethasone is excreted in breast milk, caution should be exercised when administering to nursing women.

Storage

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

Formulations

• Inhalation aerosol
• Nasal spray
• Topical cream
• Topical lotion

Indications

• Tinea pedis (athlete's foot)
• Tinea cruris (jock itch)
• Tinea corporis (ringworm)
• Candidiasis (yeast infections)
• Dermatophyte infections

Dosage

Children: For children, refer to the BNF for Children for appropriate dosing information.

Adults: Apply to the affected area once daily for 2 to 4 weeks, depending on the specific infection being treated.

Mechanism of action

Econazole interacts with 14-alpha demethylase, a cytochrome P-450 enzyme necessary for converting lanosterol to ergosterol. Inhibition of ergosterol synthesis results in increased cellular permeability and leakage of cellular contents. Additionally, econazole may inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

Pharmacodynamics

Econazole is an antifungal agent related to other azoles such as fluconazole, ketoconazole, itraconazole, and clotrimazole. It prevents fungal organisms from producing vital substances required for their growth and function, making it effective only against fungal infections.

Pregnancy

Econazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Econazole may be excreted in human breast milk, use caution when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Topical cream
• Topical solution
• Vaginal cream

Indications

• Severe infections caused by Gram-negative bacteria
• Urinary tract infections
• Bacteremia
• Sepsis
• Pneumonia
• Intra-abdominal infections
• Skin and soft tissue infections

Dosage

Adults: The usual dosage for adults is 3 to 5 mg/kg/day divided into 3 doses, given intravenously or intramuscularly. Adjustments should be made based on renal function and severity of infection.

Mechanism of action

Gentamicin acts by binding to the bacterial 30S ribosomal subunit, leading to misreading of mRNA and subsequent production of nonfunctional or toxic peptides. This disrupts protein synthesis and leads to bacterial cell death. The drug enters bacterial cells in a three-phase process: first, ionic binding occurs with the cell membrane, increasing permeability. Second, energy-dependent transport allows the drug to access its intracellular target. Third, concentration-dependent killing is observed as gentamicin accumulates within the cell, amplifying its effects on protein synthesis and membrane integrity.

Pharmacodynamics

Gentamicin exhibits concentration-dependent bactericidal activity, meaning that its efficacy increases with higher concentrations. The pharmacodynamic properties highlight the rapid and delayed bactericidal effects, with membrane disruption occurring immediately followed by impaired protein synthesis. The drug's action is particularly effective against aerobic Gram-negative bacteria, while its effectiveness is significantly reduced in anaerobic conditions.

Pharmacokinetics

Gentamicin is poorly absorbed from the gastrointestinal tract; thus, it is typically administered intravenously or intramuscularly. It has a volume of distribution that reflects extensive tissue penetration, particularly in renal and gastrointestinal tissues. The elimination half-life ranges from 2 to 3 hours in healthy individuals, but it can be prolonged in patients with renal impairment. The drug is primarily eliminated by renal excretion, with dosage adjustments required in cases of renal dysfunction.

Contra-indications

• Hypersensitivity to gentamicin or other aminoglycosides
• Severe renal impairment
• Myasthenia gravis

Adverse effects

• Nephrotoxicity
• Ototoxicity (hearing loss, balance disorders)
• Neuromuscular blockade
• Allergic reactions (rash, pruritus)
• Peripheral neuropathy

Interactions

• Increased risk of nephrotoxicity with other nephrotoxic agents (e.g., cisplatin, vancomycin)
• Increased risk of ototoxicity with loop diuretics (e.g., furosemide)
• Synergistic effects with beta-lactam antibiotics

Precautions

• Monitor renal function during treatment
• Use caution in patients with pre-existing hearing loss
• Adjust dosage in patients with renal impairment
• Consider potential drug interactions

Pregnancy

Gentamicin should be used during pregnancy only if clearly needed, due to potential risk of fetal harm.

Breast-feeding

Gentamicin is excreted in breast milk, but is generally considered safe. Monitor for possible effects on the infant.

Storage

Store in a cool, dry place, away from light. Do not refrigerate or freeze.

Formulations

• Injection (solution for injection)
• Topical ointment
• Eye drops

Mechanism of action

Econazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Econazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

Pharmacodynamics

Econazole is an antifungal medication related to fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox), and clotrimazole (Lotrimin, Mycelex). Econazole prevents fungal organisms from producing vital substances required for growth and function. This medication is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections.

Mechanism of action

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. 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/ ... 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/