AMINOGLYCOSIDES

INTRODUCTION TO AMINOGLYCOSIDES

• The term aminoglycoside is derived from the chemical structure of these compounds, which are made up of amino groups (―NH2) attached to glycosides  (derivatives of sugar)
• The first aminoglycoside, the antibiotic streptomycin, was discovered in 1944 isolated the compound from Streptomyces grieus, a strain of soil bacteria by American biochemists Selman Waksman, Albert schatz, and Elizabeth Bugie.

DEFINITION OF AMINOGLYCOSIDES

• Aminoglycosides are composed of amino and sugar molecule in their structure which are potent broad spectrum bactericidal antibiotics  that act by binding the 30S ribosome, thereby inhibiting bacterial protein synthesis. Spectinomycin is a bacteriostatic antibiotic chemically related to the aminoglycosides.

CLASSIFICATION OF AMINOGLYCOSIDES

• Systemic Aminoglycosides: These are drugs that are Administered  through parenterally either as an  Intravenous or Intra-muscular Regimen
  • Examples Include:
    • Streptomycin : Inj. 1gm IM/IV
    • Gentamicin: Inj. 10mg/ 40mg IM/IV,  Aerosol 250mg IN
    • Kanamycin: Inj. 75mg/2ml, 500mg/2ml, 1mg/3ml IV
    • Amikacin: Inj. 50mg/ml, 250mg/ml IV
    • Sisomicin: Inj. 3mg IV/IM
    • Tobramycin: Inj. 10mg/ml, 40mg/ml  IM/IV
    • Netilimicin: Inj. 4-6mg IM/IV
• Topical Aminoglycosides: Topical gentamicin comes as a cream  and an ointment to apply to the skin or  as ear &eye drops. Topical agents are  applied at the same times every day.
  • Examples Include:
    • Neomycin
    • Framycetin

MECHANISM OF ACTION OF AMINOGLYCOSIDES

Initially they penetrate bacterial cell wall, to reach peri plasmic space  through porin channels (passive diffusion)

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Further transport across cytoplasmic membrane takes place by active  transport by proton pump; an oxygen dependent process

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Bind 30S ribosomal subunits and interfere the initiation complex

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Induce misreading of genetic code on mRNA  B

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Breakup of polysomes into monosomes

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  Destruction of bacteria

INDICATIONS FOR AMINOGLYCOSIDES

• Primarily against Gram Negative aerobic bacilli
  • Proteus, pseudomonas
  • E.coli, Enterobacter
  • Klebsiella
  • Shigella
• Also Indicated for few Gram positive cocci:
  • staphylococcus aureus, streptococcus viridians

Clinical Uses

• Gram Negative bacillary infection – Septicaemia, pelvic & abdominal sepsis
• Bacterial endocarditis – Enterococcal,  streptococcal  or  staphylococcal  infection  of  heart valves
• Pneumonias, Tuberculosis
• Tularaemia
• Plague, Brucellosis
• Topical- - Neomycin, Framycetin
• Infections of conjunctiva or external ear
• To sterilize the bowel of patients who receive immunosuppressive therapy, before surgery & in hepatic coma.

PHARMACOKINETICS OF AMINOGLYCOSIDES

• Aminoglycosides are poorly absorbed orally
• well absorbed from the peritoneum, pleural cavity, joints, and from denuded skin.
• Aminoglycosides are distributed well into extracellular fluid except for vitreous humor, cerebrospinal fluid, respiratory secretions, and bile (particularly in patients with biliary obstruction).
• Intraventricular injection is required to treat endophthalmitis.
• Intraventricular injection is often required to reach intraventricular cerebrospinal fluid levels high enough to treat meningitis.
• Aminoglycosides are excreted by glomerular filtration and have a serum half-life of 2 to 3 hours; the half-life increases exponentially as the glomerular filtration rate falls (e.g. in renal insufficiency, in  older people).
• So, dose adjustment is needed in renal insufficiency & older People.

PRECAUTIONS & CONTRAAINDICATIONS OF AMINOGLYCOSIDES

• Pregnancy: fetal ototoxicity
• With other ototoxic drugs: furosemide, minocycline
• With nephrotoxic drugs: vancomycin ,cisplatin
• Elderly patients over 65 years of age
• History of allergic to sulfites (often found in certain wines and dried fruits)
• Those with kidney disease
• Cautious use of muscle relaxants.

TOXICITY & SIDEEFFECTS OF AMINOGLYCOSIDES

Ototoxicity:

• Vestibular damage
• Cochlear damage

Nephrotoxicity:

• Renal Insufficiency
• Decreased creatinine clearance

Neuromuscular blockade:

• Paralysis
• Altered sensorium

Hypersensitivity reactions:

• Skin Rash

Ototoxicity

• Impairment of VIII cranial nerve function
• May be irreversible
• Cochlear damage –Hearing loss and tinnitus –More with neomycin , amikacin and kanamycin
• Vestibular damage
• –Vertigo, ataxia, loss of balance –More with Streptomycin, gentamycin
• Tobramycin has both types of toxicity
• Netilmicin claimed to have low ototoxicity.

Nephrotoxicity

• Gentamicin, amikacin and tobramycin are more toxic than streptomycin.
• Responsible for 10-15% of all renal failure Cases.
• Reversible if drug promptly discontinued
• Decreased renal clearance/excretion of antibiotic poses high risk for ototoxicity.

Neuromuscular blockade

• Causes Neuromuscular junction blockade by –Displacing Calcium from Neuromuscular junction –By  blocking post synaptic Neuromuscular receptors  –Inhibiting Ach release from motor nerve
• Neomycin & streptomycin: more propensity
• Tobramycin Poses risk of Myasthenic weakness by these drugs.

Guidelines to adjust Dose in Renal insufficiency

NURSING RESPONSIBILITY IN ADMINSIETRING AMINOGLYCOSIDES

• Monitor the neurological status of the patient
• Monitor vital signs regularly
• Perform Audiometry tests & monitor the hearing acuity
• Monitor the renal Function and creatinine clearance test once every 3 days after administration of the drug
• Monitor the client continuously for any signs of adverse reactions like Skin rash, hypersensitivity etc.
• Monitor muscular function and activity
• Maintain Intake Output Chart
• Do not administer the drugs with other antibiotics like vancomycin & cisplatin to prevent toxicity
• Do not mix with any other drug in same syringe
• Evaluate therapeutic response: Treatment of Infections.