Gentamicin

Mechanism of action and pharmacokinetics

By chemical structure, gentamicin is a polar hydrophilic compound: aminosugars are attached via glycosidic bonds to a cyclic alcohol (aminocyclitol). In nature, it is produced by actinomycetes of the genus Micromonospora (hence the suffix "-mycin").

The mechanism of action is associated with the inhibition of protein synthesis. The transport of the drug to the target (to the 30S ribosomal subunit) occurs in two stages: passive diffusion through the cell wall and active transport through the cytoplasmic membrane.

Pharmacokinetics:

• The average volume of distribution ($V_d$) is about 15 L. This anatomically corresponds to the extracellular fluid volume (the sum of blood plasma and interstitial fluid volumes).
• As a hydrophilic substance, gentamicin passes through the capillary endothelium, but does not cross cell membranes. Because of this, it does not enter cells and is completely ineffective in intracellular infections.
• It does not cross the blood-brain barrier (BBB), therefore it is not used for the treatment of bacterial meningitis.
• It is excreted by the kidneys unchanged. In case of impaired renal function, cumulation (accumulation) of the drug occurs, which sharply increases the risk of toxic effects.

Pharmacological effects and spectrum

Gentamicin is a potent antibiotic aimed at combating severe infections.

• It exhibits high efficacy against Gram-negative bacteria, primarily Pseudomonas aeruginosa (Pseudomonas aeruginosa).
• Effective in tularemia.
• Important difference from generation I: practically inactive against Mycobacterium tuberculosis (unlike Streptomycin and Kanamycin).

Indications for use

Systemic use (intramuscularly, intravenously): Prescribed for severe infections caused by Gram-negative bacteria resistant to other antibiotics:

• Sepsis and infective endocarditis.
• Severe pneumonia.
• Complicated abdominal and urogenital infections.
• Brucellosis (used in combination with first-line drugs — tetracyclines).

Local application:

• In surgery and dermatology: treatment of infected soft tissue wounds and burns (topically as a 0.1% ointment).
• In ophthalmology: bacterial eye infections such as blepharitis, keratitis, keratoconjunctivitis, and iridocyclitis (0.3% eye drops and 0.1% eye ointment are used).

Side effects and contraindications

The side effects of gentamicin can manifest even when using therapeutic doses and severely limit its use, up to exclusion from clinical practice.

• The main hazard, typical of the entire aminoglycoside group, is ototoxicity (hearing impairment).
• The risk of toxic effects increases manifold in systemic diseases of the excretory organs (renal failure) due to a decrease in the elimination rate and cumulation.
• Pathologies of the cardiovascular system and lungs can cause hemodynamic disturbances, which distort the pattern of drug distribution in the body.

Drug interactions

The cell walls of certain bacteria (e.g., enterococci) are poorly permeable to aminoglycosides during monotherapy. In such cases, a combination with $\beta$-lactam antibiotics is used.

This is a classic example of synergism (potentiation):

1. $\beta$-lactams disrupt bacterial cell wall synthesis.
2. Wall permeability increases.
3. The transport of gentamicin into the cell to the ribosomes is facilitated.

Examples: in enterococcal infection, gentamicin is combined with benzylpenicillin, and in klebsiella infection, with antipseudomonal penicillins.

Forms of release and prescriptions

The drug is available in several forms for systemic and local use. The dosage for i.m. and i.v. administration is calculated by body weight: 0.0004 g/kg.

• Powder in 0.08 g vials.
• Solution in 4% ampoules — 1–2 ml.
• 0.1% eye ointment — 10–15 g.
• 0.3% eye drops solution (1–2 drops are prescribed into the conjunctival sac).
• Ointment for cutaneous use 0.1%.

Example of a prescription for solution in ampoules: Rp.: Sol. Gentamycini sulfatis 4% - 2 ml D.t.d. N. 10 in ampull. S. Intramuscularly 2 ml 2 times a day.

Example of a prescription for eye drops: Rp.: Sol. Gentamycini sulfatis 0,3% - 5 ml D.S. 1-2 drops into the conjunctival sac 3 times a day.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Classification of aminoglycosides by generation (I, II, III) and their differences.
• Mechanisms of bacterial resistance development to aminoglycosides.
• Pharmacokinetic features of hydrophilic antibiotics and volume of distribution.
• Comparative characteristics of gentamicin, tobramycin, and amikacin.
• Principles of combination antibiotic therapy: synergism, additive effect, and antagonism.

Other topics in the «Drugs and Prescriptions» section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.