framycetin, dexamethasone, and gramicidin

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action:  

framycetin belongs to the class of antibiotics known as aminoglycosides. It inhibits bacterial protein synthesis by binding to the bacterial ribosome, specifically the 30S subunit. This binding prevents the proper formation of the bacterial protein chain, inhibiting bacterial growth. 

gramicidin is a peptide antibiotic that disrupts bacterial cell membranes. It forms channels within the bacterial membrane, leading to the leakage of ions and other molecules. This disruption of the bacterial membrane integrity ultimately results in cell death. 

dexamethasone belongs to the class of corticosteroids, which are synthetic hormones with potent anti-inflammatory and immunosuppressive effects. It acts by binding to glucocorticoid receptors in the cytoplasm of target cells. This receptor-ligand complex enters the nucleus and modulates gene expression, resulting in various anti-inflammatory and immunosuppressive actions.  

Spectrum of Activity: 

framycetin has a broad-spectrum activity against many Gram-positive and Gram-negative bacteria. It is commonly used in topical preparations to treat and prevent bacterial skin infections.  

gramicidin primarily acts against Gram-positive bacteria. It is often used with other antibiotics or as an ingredient in topical preparations for its bactericidal properties. gramicidin is not effective against Gram-negative bacteria due to the presence of an outer membrane, which limits its access to the bacterial cell. 

dexamethasone is primarily used for its systemic effects rather than its direct antimicrobial activity. It is a broad-spectrum anti-inflammatory medication often prescribed to reduce inflammation and suppress immune responses in various conditions. While it can help alleviate symptoms associated with inflammation caused by infection, it does not directly target or kill bacteria or other microorganisms. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Burning sensation in eyes 

Increased intraocular pressure 

Hypersensitivity reaction 

Corneal perforation 

Stinging of eyes 

Post-marketing reports 

Pruritus 

Cushing’s syndrome  

Blurred vision 

Decreased visual acuity 

Adrenocortical insufficiency 

Type IV hypersensitivity reaction 

Cataract 

Dermatitis 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Allergy or Hypersensitivity: The combined formulation should not be used if an individual has a known allergy or hypersensitivity to any components. 
• Viral Infections: The combined formulation is primarily indicated for bacterial infections and is ineffective against viral infections. It should not be used in cases where the infection is caused solely by a viral pathogen.  
• Fungal Infections: Similarly, the combined formulation is ineffective against fungal infections. If the infection is suspected to be fungal, alternative antifungal treatment should be considered. 
• Tuberculosis (TB) Infection: dexamethasone, a formulation component, is contraindicated in active tuberculosis infections.  
• Ocular Herpes Simplex Infection: dexamethasone, when used topically, can potentially exacerbate or prolong the course of certain viral infections, including ocular herpes simplex infections.  
• Corneal Ulcers: The combined formulation may be contraindicated in individuals with corneal ulcers or suspected perforations of the cornea. corticosteroids in the presence of corneal ulcers can delay healing and potentially exacerbate the condition. 

Caution: 

• Allergic Reactions: Individuals may react to any components in the combined formulation, including framycetin, gramicidin, or dexamethasone.  
• Superinfection: Prolonged or excessive use of antibiotic-containing ear or eye drops, such as those containing framycetin and gramicidin, can lead to the development of superinfections.  
• Delayed Wound Healing: dexamethasone, a corticosteroid, has anti-inflammatory and immunosuppressive effects. While these properties can be beneficial in reducing inflammation, they can also delay wound healing. 
• Adverse Effects of dexamethasone: dexamethasone can have potential adverse effects when used topically or systemically.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

These three components provide a multi-faceted approach to treating ear and eye conditions. framycetin and gramicidin work synergistically to target and eliminate bacterial pathogens, while dexamethasone helps to reduce inflammation, alleviate symptoms, and support the healing process.  

Pharmacodynamics:  

• Antibacterial Activity: framycetin and gramicidin work synergistically to kill susceptible bacteria, targeting Gram-positive and Gram-negative strains. 
• Anti-Inflammatory Activity: dexamethasone reduces inflammation, swelling, and discomfort associated with infections. 
• Symptom Relief: The combination relieves bacterial infections and associated inflammation in conditions like otitis externa and conjunctivitis. 

Pharmacokinetics: 

Absorption 

When applied topically in ear or eye drops, framycetin is minimally absorbed systemically. It primarily acts locally at the site of application. 

gramicidin is minimally absorbed systemically when applied topically as ear or eye drops. Its action is mainly localized at the site of the application. 

dexamethasone can be absorbed systemically when applied topically as ear or eye drops. However, the extent of absorption depends on factors such as the formulation and the integrity of the local barriers.  

Distribution 

After absorption, framycetin remains localized chiefly at the administration site, exerting its antibacterial effects. After absorption, gramicidin remains primarily localized at the site of administration, where it exerts its antimicrobial effects against Gram-positive bacteria. 

Once absorbed, dexamethasone is distributed throughout the body via the bloodstream. It can reach target tissues and exert its anti-inflammatory and immunosuppressive effects. 

Metabolism 

framycetin undergoes minimal metabolism in the body. It is primarily excreted unchanged. gramicidin is a peptide and is not metabolized in the body. dexamethasone undergoes extensive metabolism in the liver by various enzymes, primarily through the CYP3A4 pathway. 

Elimination and Excretion 

The elimination of framycetin occurs primarily via renal excretion. It is excreted unchanged in the urine. The excretion of gramicidin occurs primarily through renal excretion without significant biotransformation. Metabolized dexamethasone and its metabolites are excreted via the kidneys, primarily as conjugated metabolites in the urine. 

Adminstartion

Administration: 

Ophthalmic 

Gently pull down the lower eyelid to create a small pouch. Hold the dropper close to the eye but avoid touching the dropper tip to any surface. Squeeze the prescribed number of drops into the lower eyelid pouch. Be careful not to blink or squeeze the eye excessively during administration. 

Otic 

Gently pull the earlobe of the affected ear backward and upward to straighten the ear canal. Hold the dropper close to the ear canal entrance but avoid touching the dropper tip to any surface or the ear itself. Squeeze the recommended number of drops into the ear canal. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: framycetin, dexamethasone, and gramicidin 

Why do we use framycetin, dexamethasone, and gramicidin? 

The combined formulation of framycetin, gramicidin, and dexamethasone is commonly used in ear and eye drops for various indications.  

• Otitis Externa: Otitis externa, also known as swimmer’s ear, is an infection or inflammation of the outer ear canal. The combined formulation can treat bacterial otitis externa by providing antibacterial activity (framycetin and gramicidin) and reducing inflammation and symptoms (dexamethasone). 
• Conjunctivitis: Conjunctivitis, also known as pink eye, is an inflammation of the conjunctiva (the clear tissue covering the eye’s white part). The combined formulation can treat bacterial conjunctivitis by providing antibacterial activity (framycetin and gramicidin) and reducing inflammation and associated symptoms (dexamethasone). 
• Blepharitis: Blepharitis is an inflammation of the eyelids, usually caused by bacterial infection. The combined formulation can treat bacterial blepharitis by providing antibacterial activity (framycetin and gramicidin) and reducing inflammation and discomfort (dexamethasone).