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Gentamycin: Uses, MOA, Dosage, Side effects

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Gentamicin is an aminoglycoside antibiotic that is usually used in combination to treat severe systemic infections that are due to sensitive Gram-negative and other organisms.

They include biliary tract infections, brucellosis, endometritis, gastroenteritis, cystic fibrosis as well as prophylaxis of surgical infections and the treatment of immunocompromised patients in intensive care.

Like other aminoglycosides, gentamicin synergizes with penicillins in killing Streptococcus faecalis in endocarditis.

Gentamicin sometimes can be used alone but usually in combination with other antibiotics such as penicillins or cephalosporins

Gentamicin is often used synergistically in combination with a-lactam antibiotics or vancomycin for serious infections that require broad coverage.

Aminoglycosides induce the binding of “wrong” t-RNA-AA complexes, resulting in the synthesis of false proteins. Aminoglycosides are bactericidal.

Aminoglycoside antibiotics consist of glycoside-linked amino-sugars. They contain numerous hydroxyl groups and amino groups that can bind protons. Hence, these compounds are highly polar, poorly membrane permeable, and not absorbed enterally.

Aminoglycosides gain access to the bacterial interior by the use of bacterial transport systems. In the kidney, they enter the cells of the proximal tubules via an uptake system for oligopeptides.

 

Mechanism of action of gentamicin

 

Aminoglycosides passively diffuse via porin channels through the outer membrane of gram-negative aerobic bacteria. Transport across the inner membrane requires active uptake that is dependent on electron transport (gram-negative aerobes only), the so-called energy-dependent phase I transport.

Inside the cell, these agents interact with receptor proteins on the 30S ribosomal subunit. This “freezes” the initiation complex and leads to a buildup of monosomes; it also causes translation errors.

Like other aminoglycosides, gentamicin works by irreversibly binds to 30s subunits of bacterial ribosomes blocking recognition step in the protein synthesis and causes growth inhibition.

Route of administration

Gentamicin injection is administered intramuscularly. Intravenous administration should only be reserved for special cases.

Pharmacokinetics

Gentamycin is poorly absorbed from the gut and is given by intramuscular or intravenous injection.

It is poorly protein-bound (30%) and excreted renally.

This presumably reflects a post-antibiotic effect whereby bacterial growth is inhibited following clearance of the drug.

In patients with renal dysfunction, dose reduction and/or an increased dose interval is required.

Cerebrospinal fluid (CSF) penetration is poor.

Indications

Gentamycin is indicated for the following conditions when caused by susceptible organisms;

Urinary tract infections. Not indicated for uncomplicated UTI,

Systemic infections eg septicemia, peritonitis,

Bone and soft tissue infections eg osteomyelitis, wound and soft tissue infections,

Infected burns

Infections of upper respiratory tract eg pneumonia.

Topical gentamicin eye drops are used to treat eye infections.

Contraindications

Gentamicin is contraindicated in patients with allergies to it.

Aminoglycosides should be avoided in patients with myasthenia gravis, pregnancy, and lactation.

Administration and dosage

Gentamycin is usually administered intramuscularly every 8 hours to provide a total daily dose of 3-5 mg of gentamycin per kilogram body weight.

It may be given intravenously slowly over 3 minutes in similar doses to those used intramuscularly

Known symptoms of overdosage and its treatment

Gentamycin serum levels in excess of 12ug/ml may result in ototoxicity in patients with renal impairment. This is reversible if timeously observed and the dose is suitably adjusted.

In the event of overdosage or toxic reactions, peritoneal dialysis or hemodialysis will aid in the removal of gentamycin from the blood.

Side effects of gentamicin

These are important and are related to the duration of therapy and trough plasma concentrations.

They are more frequent in the elderly and in renal impairment. Therapeutic monitoring is performed by measuring plasma concentrations before dosing (trough) and at ‘peak’ levels

Tubular cells are susceptible to damage (nephrotoxicity, mostly reversible).

In the inner ear, sensory cells of the vestibular apparatus and Corti’s organ may be injured. Eighth nerve damage is potentially catastrophic and is often irreversible.

Acute tubular necrosis and renal failure are usually reversible if diagnosed promptly and the drug stopped or the dose reduced.

Aminoglycosides have a narrow therapeutic index; it may be necessary to monitor serum concentrations and individualize the dose.

At high doses, these agents produce a curare-like neuromuscular blockade with respiratory paralysis. Calcium gluconate and neostigmine are antidotes. Exacerbation of myasthenia gravis is predictable in patients with this disease.

The aminoglycosides can produce irreversible, cumulative ototoxicity affecting both the cochlea and the vestibular system. The incidence and relative toxicity with different aminoglycosides is a matter of some dispute but netilmicin is probably less cocleotoxic that gentamycin and tobramycin and amikacin more so and netilmicin also exhibits less vestibular toxicity than gentamicin, tobramycin or amikacin while streptomycin produces a high incidence of vestibular damage.

Vestibular damage is more common than hearing loss in patients receiving gentamycin.

Nephrotoxicity,

Hypomagnesia om prolonged use,

Antibiotic-associated colitis,

Stomatitis, nausea, and vomiting.

Precautions

Gentamicin is contraindicated in patients with a known history of allergy to it, and probably in those allergic to other aminoglycosides.

Great care is required in patients with myasthenia gravis, parkinsonism and other conditions characterized by muscular weakness.

Topical application of gentamycin os contraindicated in patients with known or suspected perforation of the eardrum.

The use of aminoglycosides during pregnancy may damage the 8th cranial nerve of the fetus.

Avoid use with potent diuretics, nephrotoxic or neurotoxic drugs.

Use with caution in premature infants and neonates because of renal immaturity and the resulting prolongation of serum half-life of the drug

Drug interactions

Nephrotoxic drugs including other aminoglycosides,

Vancomycin, some cephalosporins, cicloplastin, cisplatin, fludarabine.

Ototoxic drugs ie acrylic acid

Furosemide increases the risk of aminoglycoside toxicity.

Gentamycin and other aminoglycosides enhance neuromuscular blockade of nondepolarizing neuromuscular antagonists.

Resistance

Resistance generally results from bacterial enzymes that inactivate the drugs. The resistance contained on plasmids is transmitted by conjugation.


Post References

  • Harpers textbook of basic and clinical pharmacology

  • Revised on: 2021-07-10 02:20:07