Genticyn Hc

Uses

Gentamicin & Hydrocortisone ear drops is used for the treatment of chronic suppurative otitis media, otitis externa and as prophylactic treatment of otitis externa following trauma. Gentamicin & Hydrocortisone ear drops is also used for post-operative local use in surgery to infected mastoid cavities.

Gentamicin & Hydrocortisone cream is used for redness, itching, and swelling of the skin

Genticyn Hc is also used to associated treatment for these conditions: Bacterial Conjunctivitis, Bacterial Infections, Bacterial Peritonitis, Bacterial dacryocystitis, Blepharoconjunctivitis, Central Nervous System Infections, Conjunctivitis allergic, Corneal infection, Dermatitis infected, Ecthyma, Eczematous dermatitis infected, Folliculitis, Furunculosis, Gram-negative enteric bacilli neonatal sepsis, Impetigo contagious, Inflammation, Keratitis bacterial, Keratoconjunctivitis, Meibomianitis, Meningitis, Bacterial, Ocular Inflammation, Pustular Psoriasis (PP), Pustular acne, Pyoderma Gangrenosum, Seborrheic Dermatitis, Septicemia gram-negative, Skin Infections, Skin Infections, Bacterial, Skin and Subcutaneous Tissue Bacterial Infections, Sycosis barbae, Bacterial blepharitis, Bacterial corneal ulcers, Bacterial dermatoses, Complicated Bacterial Urinary Tract Infections, Complicated Respiratory tract infection bacterial, Corticosteroid-responsive dermatoses, Ocular bacterial infections, Severe Endocarditis enterococcal, Severe Infection Pseudomonas aeruginosa, Severe Staphylococcal infectionAcute, Inflammatory Superficial Cutaneous Lesions caused by susceptible bacteria, Adrenal cortical hypofunctions, Anal Fissures, Anal inflammation, Androgenital syndrome, Conjunctivitis, Conjunctivitis allergic, Corneal Inflammation, Dermatitis infected, Diaper Dermatitis, Eczema infected, Episcleritis, Hemorrhoids, Iridocyclitis, Iritis, Ocular Inflammation, Ocular Irritation, Postoperative pain, Proctitis, Pruritus, Pruritus Ani, Radiation Induced Proctitis, Rheumatoid Arthritis, Scleritis, Skin Infections, Skin Irritation, Superficial ocular bacterial infections caused by susceptible bacteria, Thyroiditis, Ulcerative Colitis, Anal eczema, Bacterial blepharitis, Corneal clouding, Corticosteroid responsive Dermatosis of the anal region, Corticosteroid-responsive dermatoses, Cryptitis, Localized uninfected hemorrhoids, Mild Anal Fissures, Pruritus associated with bowel movements, Skin and skin-structure infections caused by susceptible bacteria, Postoperative Eye Care

How Genticyn Hc works

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.[A233320] 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.[A232324, A232329] 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.[A232329, A232339] Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation.[A232344] Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.

Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.

Dosage

Genticyn Hc dosage

Ear Drops-

For Middle Ear Infection: Instill 2-4 drops in the affected ear three to four times a day and at night, or more frequently if required. The suspension should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness, which may result from the instillation of a cold suspension. The patient should lie with the affected ear upward, and then the drops should be instilled. The tragus should then be pumped 5 times by pushing inward to facilitate penetration of the drops into the middle ear. This position should be maintained for two minutes. Repeat, if necessary, for the opposite ear. Discard unused portion after therapy is completed. For Ear

Canal Infection: Instill 2-4 drops in the affected ear three to four times a day and at night, or more frequently if required. The suspension should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness, which may result from the instillation of a cold suspension. The patient should lie with the affected ear upward, and then the drops should be instilled. This position should be maintained for two minutes to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear. Discard unused portion after therapy is completed.

Cream-

For redness, itching, and swelling of the skin: Apply to the affected area of the skin two or three times per day.

Ear Drops need to shake well immediately before use.

Side Effects

Allergic contact dermatitis, Transient irritation, burning, stinging, Increased redness, lacrimation

Toxicity

As with other aminoglycosides, nephrotoxicity and ototoxicity are associated with gentamicin. Signs of nephrotoxicity include an increase in plasma creatinine and urea, while signs of ototoxicity include issues with balance, nausea, tinnitus, and hearing loss. It is important to note that aminoglycoside-induced nephrotoxicity is typically reversible, while ototoxicity is more likely to be permanent. The risk of both toxicities increases with long-term gentamicin therapy. Gentamicin is considered to be more vestibulotoxic than cochleotoxic compared to other aminoglycosides. Unfortunately, gentamicin-related ototoxicity does not correlate with cumulative dosing, peak and trough levels, or dosing schedule. The unpredictability of ototoxicity supports close monitoring of the patient throughout treatment. In cases of toxicity or overdose, the medication should be discontinued immediately; hemodialysis may be initiated to lower gentamicin serum concentrations.

Side effects include inhibition of bone formation, suppression of calcium absorption and delayed wound healing

Precaution

Concurrent use of neuromuscular blocking agents; myasthenia gravis, parkinsonism; conditions predisposing to ototoxicity and nephrotoxicity; lactation. Monitor plasma concentrations of gentamicin in patients receiving high doses or prolonged courses, in infants, elderly, patients with renal impairment, cystic fibrosis or significant obesity. Monitor auditory and renal functions.

Interaction

Gentamicin: Additive effect with other neurotoxic and/or nephrotoxic drugs including cephalosporins, methicillin, amphotericin B, ciclosporin, cisplatin, potent diuretics (e.g. ethacrynic acid, furosemide) and neuromuscular blocking agents (e.g. succinylcholine, tubocurarine). May potentiate the effect of anticoagulants (e.g. warfarin, phenindione). May antagonise the effect of neostigmine and pyridostigmine. Increased risk of hypocalcaemia with bisphosphonates. Increased risk of neuromuscular blockade with botulinum toxin. Indometacin may increase the plasma concentration of gentamicin in neonates.

Hydrocortisone: Thiazides may enhance hyperglycaemia and hypokalaemia caused by corticosteroids. Increased incidence of peptic ulcer or Gl bleeding with concurrent NSAIDs admin. Response to anticoagulants altered. Dose of antidiabetics and antihypertensives needs to be increased. Decreases serum cone of salicylates and antimuscarinic agents. Ethanol may enhance gastric mucosal irritation. Reduced efficacy with concurrent use of carbamazepine, phenytoin, primidone, barbiturates and rifampicin. Mutual inhibition of metabolism between ciclosporin and corticosteroids increase plasma cone of both drugs. Enhanced effect in women taking oestrogens or oral contraceptives.

Elimination Route

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.

Half Life

One study assessing the pharmacokinetics of gentamicin in children and adults reported a mean half-life of 75 minutes after intravenous administration. The mean half-life associated with intramuscular administration was about 29 minutes longer. Fever and anemia may result in a shorter half-life although dose adjustments are not usually necessary. Severe burns are also associated with a shorter half-life and may result in lower gentamicin serum concentrations.

6-8 hours

Clearance

The renal clearance of gentamicin is comparable to individual creatinine clearance.

Elimination Route

Gentamicin is excreted primarily by the kidneys. In patients with normal renal function, 70% or more of an initial gentamicin dose can be recovered in the urine within 24 hours. Excretion of gentamicin is significantly reduced in patients with renal impairment.

Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

Pregnancy & Breastfeeding use

Pregnancy Category- C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Contraindication

History of hypersensitivity to aminoglycoside; pregnancy; hepatic impairment.

Acute Overdose

Acute overdosage is very unlikely to occur, however, in the case of chronic overdosage or misuse, the features of hypercorticism may appear and in this situation topical steroids should be discontinued

Storage Condition

To avoid contamination, do not touch the tip of the container to the eye, eyelid or any surface.

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

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