CUSI GENTADEXA EYE/EAR DROPS

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

• Nasal congestion
• Sinus congestion
• Allergic rhinitis
• Common cold symptoms

Dosage

Children: Refer to product-specific guidelines as dosing may vary by formulation and intended use.

Adults: Refer to product-specific guidelines as dosing may vary by formulation and intended use.

Mechanism of action

Phosphatetetryzoline is a selective alpha-adrenergic agonist. It binds to alpha-1 adrenergic receptors on the smooth muscle of blood vessels in the nasal mucosa, causing vasoconstriction. This action decreases blood flow to the nasal tissues, resulting in reduced edema and congestion. The sympathomimetic effect leads to a quick reduction in nasal swelling and promotes easier breathing.

Pharmacodynamics

The pharmacodynamics of phosphatetetryzoline involve its action as a vasoconstrictor, which leads to decreased nasal resistance and improved airflow. The onset of action is typically rapid, providing relief within minutes of administration. The duration of effect can vary based on the formulation and route of administration, but it generally provides symptomatic relief for several hours.

Pharmacokinetics

Phosphatetetryzoline is administered topically, which limits systemic absorption and reduces potential systemic side effects. The onset of action is immediate due to its direct application to the nasal mucosa. The drug is metabolized in the liver, and its metabolites are excreted primarily in the urine. The half-life may vary, but due to its local application, significant systemic exposure is minimized.

Adverse effects

• Local irritation
• Burning sensation
• Redness
• Increased lacrimation

Precautions

• Use with caution in patients with cardiovascular disease
• Consider potential for rebound congestion with prolonged use
• Not recommended for use in individuals with angle-closure glaucoma

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Safety during breastfeeding has not been established. Caution is advised.

Storage

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

Formulations

• Ophthalmic solution
• Nasal spray

Indications

• Allergic conditions
• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Inflammatory bowel disease
• Autoimmune disorders
• Certain cancers
• Adrenal insufficiency

Dosage

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

Adults: Refer to specific guidelines or the BNF for appropriate dosing.

Mechanism of action

Sulphatedexamethasone exerts its effects by binding to the glucocorticoid receptor, leading to the modulation of gene expression. This results in decreased production of pro-inflammatory cytokines, inhibition of leukocyte infiltration at the site of inflammation, and suppression of inflammatory mediators. Additionally, glucocorticoids influence various metabolic pathways, including glucose metabolism and protein synthesis.

Pharmacodynamics

The pharmacodynamic effects of sulphatedexamethasone include potent anti-inflammatory activity, reduction of edema, and modulation of immune responses. It has a high affinity for the glucocorticoid receptor, which contributes to its efficacy in treating conditions such as allergies, autoimmune disorders, and certain types of cancer. The drug also has effects on carbohydrate metabolism, promoting gluconeogenesis and affecting insulin sensitivity.

Pharmacokinetics

Sulphatedexamethasone is well absorbed when administered orally, with peak plasma concentrations typically occurring within one to two hours. It is extensively metabolized in the liver, primarily through the cytochrome P450 enzyme system. The drug has a relatively long half-life, allowing for once-daily dosing in many cases. It is excreted primarily in the urine as metabolites, with a small percentage excreted unchanged.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to dexamethasone or any component of the formulation
• Administration of live vaccines in immunocompromised patients

Adverse effects

• Increased risk of infections
• Gastrointestinal disturbances, including peptic ulcers
• Weight gain and fluid retention
• Mood changes, including euphoria or depression
• Osteoporosis with long-term use
• Hypertension
• Hyperglycemia, potentially leading to diabetes mellitus

Interactions

• Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal side effects
• Anticoagulants may have altered effects
• Effects of antidiabetic medications may be reduced
• Live vaccines may be less effective or contraindicated

Precautions

• Use with caution in patients with pre-existing infections
• Monitor for signs of adrenal suppression with long-term use
• Gradual withdrawal is recommended after prolonged therapy to avoid adrenal crisis
• Caution in patients with hypertension, diabetes, or peptic ulcer disease

Pregnancy

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

Breast-feeding

Caution is advised when administering to breastfeeding mothers, as dexamethasone is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Oral tablets
• Injectable solutions
• Topical preparations

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/