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A.E. of aminoglycosides
nephrotoxicity and ototoxicity
- BACTERIOCIDAL
Semi-synthetic aminoglycoside
- amikacin and netilmicin
MOA of aminoglycosides:
1. interfere with initiation of protein synthesis --> resulting in accumulation of abnormal initiation complex.
2. Misreading of the mRNA template--> incorrect amino acids to be incorporated into growing polypeptide chain.
3. They induce breakup of polysomes into non-functional monosomes.
Resistance to aminoglycosides most important:
1. Drug inactivation by enzymes
2. decrease permeation, changes in receptor protein of the binding sites.
Drug inactivation enzymes are
acetylases
adenylases
phosphorylases
AMIKACIN
LEAST LIKELY TO THESE INACTIVATING ENZYMES because of protective side chains.
Decrease permeation:
Decreased uptake via changes in membrane characteristics or transport mechanisms
Streptomycin:
- changes in receptor protein of the binding sites --> single step mutation in E.coli
Aminoglycosides
- VERY POOR ORAL ABSORPTIONwH
Where is the highest concentration of aminoglycosides?
- renal cortex
- endolymph
- perilymph of the inner ear.
MAJOR A.E. OF AMINOGLYCOSIDES:
- accumulation of drug in fetal plasma and amniotic fluid (STREPTOMYCIN and TOBRAMYCIN) causes hearing loss in children for pregnant pt.
Excretion for AMINOGLYCOSIDES via:
glomerular filtration
aminoglycosides a.e.
1. Nephrotoxic: reversible: neomycin > streptomycin
- promimal tubular necrosis
+ increased BUN
+ serum Cr
+ Presence of protein or tubular cells in the urine.
Nephrotoxic agents + aminoglycosides are what that cause NEPHROTOXICITY
- amphotericin B
- Vanco
- Furosemide
- Cisplatin
- Cyclosporine
- Cephalothin
Ototoxicity in relationship with aminoglycosides:
- irreversible due to BOTH vestibular and auditory dysfunction
- potentiated by loop
Neuromuscular blockade
- highest with neomycin after administration with intrapleural and intraperitoneal adm.
- affect Ca entry
Treatment of neuromuscular blockade:
- Calcium gluconate/Cholinesterase inhibitors.
- Higher incidence in myasthenia gravis patients.
Streptomycin is causes:
1. Dysfunction of the optic nerve
2. Scotomas
3. Peripheral Neuritis
4. Paresthesia
What does aminoglycosides cover:
aerobic gm (-) rods.