by ajith covas mannuthy

1. TOXICITY OF AMINOGLYCOSIDE ANTIBIOTICS

2. INTRODUCTION
• Group of natural and semisynthetic antibiotics.
• Amino sugar + aminocyclitol via glycoside bond.
• Streptomycin – 1st discovered – 1944 – Waksman &
co-workers from Streptomyces griseus ( actinobacterium )
• Amikacin – 1st semi synthetic – from Kanamycin
• Bactericidal drug – Inhibit protein synthesis –
Formation of aberrant proteins – streptomycin (bind
with 30S subunit) – others (bind with 50S subunit) –
Bacteria more permeable – leakage – cell death

3. • Excellent water solubility – Poor lipid soluble.
• Nephrotoxicity – due to increased no: of amino groups
Eg :- Neomycin – 6 amino group – more toxic
Streptomycin – 3 amino group – less toxic
• They are not absorbed from the gut. So I/m or I/v
• Uses : Local & Systemic infection – Mainly Gram –ve
• In Vet practice, Neomycin – toxic – so topical only
Gentamicin – Broad spectrum antibiotic

4. I. NEPHROTOXICITY
• Excessive accumulation in PCT cells ( 40 – 50 times
than in blood )
• Basic polycation, attract to membrane phospholipids
• High Phosphatidyl inositol content – PCT &
Cochlea
• Pinocytosis – sequestrate in lysosomes –interact with
organelles - cell death – cell necrosis
• Inhibit phospholipidases, ATPases - reduced PG
synthesis – direct effect on GFR.

5. • Toxicity reversible initially- renewable PCT cells
• Manifestations : Enzymes of brush border in
urine, proteinuria, casts, low GFR etc..
• Reduced antibiotic clearance – lead to ototoxicity
• Later stages - polyuria – loss of response to ADH
• Neomycin – 6 amino group – more toxic
DihydroStreptomycin – 3 amino group – less toxic

6. II. OTOTOXICITY
• Both Vestibular & auditory dysfunction
• Accumulate in perilymph & endolymph
• Ototoxicity – irreversible – Non renewable cells
• Cochlear damage – Hearing loss (high frequency
sound first) – loss of hair cells in Organ of Corti
• Vestibular damage – Affect balance of body –
Nystagmus, incoordination, vertigo, head
tilt, ataxia, loss of righting reflex etc...

7. • Vestibulotoxicity – Streptomycin > Gentamicin
• Ototoxicity – Neomycin > Kanamycin & Amikacin
• Cats are more susceptible than dogs.
• Renal dysfunction increase ototoxicity

8. III NEUROMUSCULAR BLOCKAGE
• Interfere Acetyl Choline release from motor nerve
ending – antagonism of Calcium ( exocytosis )
• Decrease sensitivity of post synaptic membrane
• Toxicity only when administer along with
neuromuscular blocking agent & general anesthetic
• Muscular weakness, apnea, respiratory arrest
• Neomycin & Streptomycin high side effect

9. IV OTHER EFFECTS
• Less allergic reactions
• Peripheral neuritis & optic nerve damage
• Intestinal malabsorption syndrome
• Diarrhea, Flattening of intestinal villi etc…

10. DRUG INTERACTIONS
• Loop diuretics or Osmotic diuretics => Enhanced
nephrotoxicity & ototoxicity
• Inhalant anesthetics or neuromuscular blocking
agents => respiratory paralysis
• Halothane => Cardiovascular depression
• Cephalosporin => additive nephrotoxicity
• Carbenicillin or Ticarcillin => inactivate

11. CONTRAINDICATIONS & PRECAUTIONS
• In hypersensitive animals, Animals with renal
diseases, Neonatal & Geriatrics - dose rate
reduced & treatment interval increased.
• Not recommended in pregnants – adverse effect
on foetus

12. TREATMENT
• Infusion of neurotropic factor , neurotropin 3 (NT-3)
in membraneous labrynth
• Dialysis
• Administration of carbenicillin or ticarcillin (12-
20g/day) to complex with aminoglycosides
• Ca salts or neostigmine given I/v, to treat
neuromuscular blockage
• Avoiding concurrent use of nephrotoxic drugs