SK CREAM (Each 30g contains Betamethane Dipropionate/ Clotrimazole/ Gentamycin Sulfur)

Indications

• Vaginal candidiasis
• Vulval candidiasis
• Superficial fungal infections
• Otitis externa (as part of combination therapy)

Dosage

Adults: For vaginal candidiasis, 1 pessary of 500 mg can be inserted at night. Alternatively, for treatment with 1% cream, apply 2–3 times a day to the affected area for at least 14 days. For recurrent vulvovaginal candidiasis

Mechanism of action

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. It inhibits ergosterol biosynthesis, which is essential for maintaining the integrity of fungal cell membranes. The inhibition of lanosterol 14-demethylase (CYP51) is a key mechanism behind its antifungal properties, leading to decreased ergosterol synthesis and resulting in cell membrane dysfunction. Clotrimazole also affects calcium homeostasis by inhibiting sarcoplasmic reticulum Ca2+-ATPase and blocking calcium-dependent potassium channels, contributing to its overall pharmacological effects.

Pharmacodynamics

Clotrimazole is considered a broad-spectrum antifungal that alters the permeability of fungal cell membranes, leading to inhibition of growth in pathogenic yeasts. At lower concentrations, it exhibits fungistatic properties, while at higher concentrations, it may be fungicidal against certain strains like Candida albicans. However, resistance to clotrimazole has become more common in recent years, limiting its efficacy in some populations.

Pharmacokinetics

Clotrimazole is primarily applied topically, and its absorption varies depending on the formulation and site of application. Following topical administration, systemic absorption is minimal, thereby reducing the risk of systemic side effects. The drug is metabolized in the liver and excreted via urine and feces. The pharmacokinetics may differ based on the dosing regimen and specific formulation used.

Contra-indications

• Hypersensitivity to clotrimazole or any excipients in the formulation
• Not recommended if trying to conceive due to potential damage to latex condoms and diaphragms

Adverse effects

• Skin reactions
• Vaginal burning
• Angioedema

Interactions

• Clotrimazole may increase the exposure of lomitapide, though the specific nature of this interaction is unknown

Precautions

• Avoid use in pregnancy without medical advice
• Use caution in patients with a history of hypersensitivity reactions

Pregnancy

Clotrimazole should be used during pregnancy only if clearly needed. Oral antifungal treatments should be avoided.

Breast-feeding

Clotrimazole is excreted in breast milk; caution is advised when used in breastfeeding mothers.

Storage

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

Formulations

• Clotrimazole 1% cream
• Clotrimazole 2% cream
• Clotrimazole 500 mg vaginal pessaries
• Clotrimazole 10% vaginal cream
• Clotrimazole 1% solution (ear drops)

Indications

• Allergic reactions
• Asthma exacerbations
• Rheumatoid arthritis
• Psoriasis
• Eczema
• Inflammatory bowel disease
• Cerebral edema
• Hormonal disorders

Dosage

Children: Refer to BNF for Children for appropriate dosing recommendations based on the child's age, weight, and specific condition.

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

Mechanism of action

Betamethasone exerts its effects by binding to the glucocorticoid receptor, which modulates the expression of various genes involved in the inflammatory response. This leads to a decrease in the synthesis of pro-inflammatory cytokines, inhibition of leukocyte infiltration at the site of inflammation, and suppression of the immune response.

Pharmacodynamics

The pharmacodynamic effects of betamethasone include reduction of inflammation, suppression of the immune system, and alteration of the metabolism of carbohydrates, proteins, and fats. The drug has potent anti-inflammatory effects, much stronger than those of cortisol, and is effective in managing conditions that require rapid control of inflammation.

Pharmacokinetics

Betamethasone is well absorbed when administered orally, intramuscularly, or topically. It has a half-life that varies depending on the route of administration, with intramuscular injections having a prolonged effect. The drug is metabolized in the liver, and its metabolites are excreted primarily in urine. Betamethasone's bioavailability and clearance can be affected by factors such as age, liver function, and concurrent medications.

Adverse effects

• Increased risk of infection
• Hyperglycemia
• Weight gain
• Hypertension
• Osteoporosis
• Gastrointestinal disturbances
• Mood changes
• Skin thinning
• Cushing's syndrome

Interactions

• Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal side effects
• Antidiabetic medications may require dosage adjustment due to potential hyperglycemia
• Anticoagulants may have altered effects in patients receiving glucocorticoids

Precautions

• Use with caution in patients with a history of diabetes mellitus or hypertension
• Monitor for signs of infection
• Gradual tapering is advised to avoid adrenal insufficiency after long-term use
• Consider potential effects on growth in pediatric patients

Pregnancy

Betamethasone is classified as a Category C drug. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Betamethasone is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical cream
• Topical ointment
• Oral tablet
• Injectable solution

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

Indications

• Acne vulgaris
• Seborrheic dermatitis
• Scabies
• Tinea infections

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines tailored for pediatric patients.

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

Mechanism of action

Topically applied sulfur exhibits mild antifungal and antibacterial activity. It is suggested that sulfur forms hydrogen sulfide and/or polythionic acid, which may exert germicidal effects. The antifungal activity is largely attributed to its keratolytic action, leading to the shedding of fungal spores and hyphae within the stratum corneum. It has shown potent inhibitory effects against some streptococci and moderate effects against Staphylococcus aureus, while showing no activity against gram-negative bacteria. Its antibacterial action may result from the inactivation of sulfhydryl groups in bacterial enzyme systems. Additionally, sulfur is toxic to the parasitic arthropod Sarcoptes scabiei, further supporting its use in treating scabies.

Pharmacodynamics

Sulfur's pharmacodynamic effects are mainly due to its ability to promote keratolysis, allowing for the removal of dead skin cells and facilitating the treatment of acne and other skin conditions. Its antibacterial properties help reduce bacterial load on the skin, which is essential for preventing infection and controlling acne lesions. The exact mechanisms for its action in acne treatment are not fully elucidated but involve a combination of these effects.

Pharmacokinetics

When applied topically, sulfur is minimally absorbed systemically, which limits potential systemic side effects. Its local effects are prominent as it acts directly on the affected skin areas. The keratolytic action occurs relatively quickly, while the antimicrobial effects may vary based on the microbial strain and concentration used.

Adverse effects

• Skin irritation
• Dryness
• Redness
• Peeling
• Allergic reactions

Precautions

• Use with caution in patients with sensitive skin
• Avoid contact with eyes and mucous membranes

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution while breastfeeding, as it is not known whether sulfur is excreted in human milk.

Storage

Store in a cool, dry place away from light.

Formulations

• Topical cream
• Topical lotion
• Topical ointment

Mechanism of action

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane,. Because ergosterol directly promotes the growth of fungal cells in a hormone‐like fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth. Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as _CYP51_) is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca2+‐ATPase, depletion of intracellular calcium, and blocking of calcium‐dependent potassium channels and voltage‐dependent calcium channels. The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities. Clotrimazole exerts its antifungal activity by altering cell membrane permeability, apparently by binding with phospholipids in the fungal cell membrane. In contrast to polyene antibiotics (eg, amphotericin B), the action of clotrimazole is less dependent on the sterol content of the cell membrane. As a result of alteration of permeability, the cell membrane is unable to function as a selective barrier, and potassium and other cellular constituents are lost.

Pharmacodynamics

Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidal _in vitro_ against Candida albicans and other species of the genus Candida at higher concentrations. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations. Clotrimazole is generally considered to be a fungistatic, and not a fungicidal drug, although this contrast is not absolute, as clotrimazole shows fungicidal properties at higher concentrations.

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/

Mechanism of action

Topically applied sulfur has mild antifungal and antibacterial activity. It has been suggested that when applied topically to the skin, sulfur forms hydrogen sulfide and/or polythionic acid, which may exert germicidal activity. In vitro studies indicate that sulfur has little if any fungistatic or fungicidal activity. Therefore, sulfur's antifungal activity probably results largely from its keratolytic action, causing shedding of fungal spores and hyphae embedded within the stratum corneum. In vitro, sulfur has been shown to have some antibacterial activity; the drug has a potent inhibitory effect against some streptococci, a moderate inhibitory effect against Staphylococcus aureus, and no activity against gram-negative bacteria. It has been suggested that the drug's antibacterial activity may partly result from inactivation of sulfhydryl groups contained in bacterial enzyme systems, since the antibacterial effect of the drug has reportedly been neutralized by addition of cysteine and other sulfhydryl-containing compounds to the culture medium. Topically applied sulfur is reportedly toxic to the parasitic arthropod Sarcoptes scabiei. The exact mechanism(s) of action of "sulfur" in the treatment of acne is not fully understood but is presumed to involve the drug's keratolytic and antibacterial effects. Although some studies indicate that "sulfur" may also be comedogenic, other studies have been unable to substantiate this effect and the drug generally is considered effective in the topical treatment of acne. The aim of this research was to analyze the effects and the modes of action of elemental sulfur (S(0)) in bioluminescence and respiration of Vibrio fischeri cells and the enzymes crude luciferase, pure catalase, and alcohol dehydrogenase (ADH). Metallic copper removed sulfur and reduced the toxicity of acetone extracts of sediment samples analyzed in the bioluminescence test. The sulfur inhibition of cell bioluminescence was noncompetitive with decanal, the luciferase substrate; reversible, with maximum toxicity after 15 min (EC50 = 11.8 ug/L); and almost totally recovered after 2 hr. In vitro preincubation of crude luciferase extract with sulfur (0.28 ppm) weakly inhibited bioluminescence at 5 min, but at 30 min the inhibition reached 60%. Increasing the concentration of sulfur in the parts per million concentration range in vitro decreased bioluminescence, which was not constant, but depended on exposure time, and no dead-end/total inhibition was observed. The redox state of enzymes in the in vitro system significantly affected inhibition. Hydrogen peroxide restored fully and the reducing agent dithiothreitol, itself toxic, restored only partially luciferase activity in the presence of sulfur. Sulfur (5.5 ppm) slightly inhibited ADH and catalase, and dithiothreitol enhanced sulfur inhibition. High sulfur concentrations (2.2 ppm) inhibited the bioluminescence and enhanced the respiration rate of V. fischeri cells. Elemental sulfur data were interpreted to show that sulfur acted on at least a few V. fischeri cell sites: reversibly modifying luciferase at sites sensitive to/protected by oxidative and reducing agents and by affecting electron transport processes, resulting in enhanced oxygen consumption. Sulfur together with an enzyme reducing agent inhibited the oxidoreductive enzymes ADH and catalase, which have /thiol/ groups, metal ion cofactors, or heme, respectively, in their active centers. Sulfur must be converted to pentathionic acid (H2S5O6) in order to exert germicidal action. Presumably oxidation of sulfur to pentathionic acid is accomplished by certain microorganisms or by epidermal cells when element is applied to skin. Sulfur possesses a keratolytic property, which may be the basis for the therapeutic action of the element in certain cutaneous disorders unassociated with infection.