aminoglycosides Flashcards
Some drugs and aminoglycosides
• As the plasma level is increased above the MIC, the drug kills an increasing proportion of bacteria at a more rapid rate
conc dependent
Any antibiotic, including penicillins and cephalosporins
• Directly related to time above MIC
• Independent of concentration once the MIC is reached
TIME DEPENDENT
Structurally related amino sugars attached by glycosidic linkages
aminoglycosides
are aminoglycosides polar or not
polar
RoA of aminoglycosides
Given intramuscularly or intravenously for systemic effects
Are aminoglycosides absorbed orally?
no
tissue penetration of aminoglycosides (full partial limited)
Limited
Does it readily cross the blood-brain barrier
no
Major mode of excretion
•
Glomerular filtration
Excretion is directly proportional to —- clearance
creatinine
With normal renal function, elimination half-life is
2-3 h
Peak serum levels
Measured at
30-60 minutes after administration
Trough serum levels
Measured when
just before the next dose
MoA of AG
Bactericidal (irreversible) inhibitors of protein synthesis
Penetration of bacterial cell wall is partly dependent on ___________
O2-dependent active transport
Transport is enhanced by ________
cell wall synthesis inhibitors
Bind to _____ AND Interfere with protein synthesis
30S ribosomal unit
ag interfere with protein synthesis by
- Block formation of initiation complex
- Cause misreading of the code on the mRNA template
- Inhibit translocation
MECHANISMS OF RESISTANCE
Failure to penetrate into the cell
Plasmid-mediated formation of inactivating enzymes
• Primary mechanism of resistance
Plasmid-mediated formation of inactivating enzymes
•
Catalyze the acetylation of amine functions
Transfer of phosphoryl or adenyl groups to the O2 atoms of hydroxyl groups on the aminoglycoside
Group transferases
transferases produced by enzyme can inactivate
- Amikacin
- Gentamicin
- Tobramycin
- Not streptomycin
- Netilmicin is less susceptible and is active against more strains of organisms
for Serious infections caused by aerobic gram (-) bacteria • E. coli Enterobacter • Klebsiella Proteus • Providencia Pseudomonas • Serratia
GENTAMICIN, TOBRAMYCIN, and AMIKACIN
Tuberculosis
Plague
Tularemia
Multi-drug-resistant (MDR) strains of M. tb resistant to streptomycin maybe susceptible to amikacin
STREPTOMYCIN
Used topically
Locally
• In the GIT
• Eliminate bacterial flora
NEOMYCIN
Reserved for serious infections resistant to other aminoglycosides
NETILMICIN
Aminocylitol related to aminoglycosides
Back-up drug
Intramuscular as single dose for gonorrhea
SPECTINOMYCIN
A. OTOTOXICITY
Auditory or vestibular damage (or both) maybe irreversible or reversible?
IRREVERSIBLE
DRUGS RESPONSIBLE FOR
• Auditory impairment
Amikacin and kanamycin
DRUGS RESPONSIBLE FOR
Vestibular dysfunction
Gentamicin and tobramycin
OTOTOXICITY Risk is proportionate to the
• High if dosage is not modified in renal dysfunction
plasma levels
Increased with the use of loop diuretics
Contraindicated in pregnancy
OTOTOXICITY Risk
RESPONSIBLE FOR
• Allergic skin reactions like contact dermatitis
Neomycin
C.
Rare
Curare-like block may occur at high doses
NEUROMUSCULAR BLOCKADE
is neuromuscular blockade reversible or irre
reversible
neuromuscular blockade causes
respiratory paralysis
treatment of neuromuscular blockade
Calcium
Neostigmine
treatment of neuromuscular blockade requires
Ventilatory support
nephrotoxicity more common in (2)
Patients concurrently receiving • Amphotericin B • Cephalosporins • Vancomycin Elderly
is nephrotoxicity reversible or irre
rever
Most nephrotoxic drugs
Gentamicin and tobramycin
nephrotoxicity is in the form of
acute tubular necrosis
