Protein synthesis inhibitors
Aminoglycosides
MOA
polybasic amino groups linked
glycosidically to two or more aminosugar
Streptomycin was the first member
discovered
in 1944 by Waksman
Entry in steps in G- Difffusion through porins and crossing cytoplasmic membrane by carrier mediated energy dependent processes
Action
Penetration is favoured by high pH
cell wall synthesis inhibitors exhibit synergism
i.e. bacterial killing is supraadditive, e.g. in
enterococcal endocarditis.
~20 times more active in alkaline than in acidic medium.
streptomycin
binds to 30S ribosomes
cidal action due to secondary changes in the integrity of bacterial cell membrane
more permeable- leakage- cell death
Augumentation of Phase 2 entry of antibiotic
Resistance
Decreased efficiency of the aminoglycoside
transporting mechanism
Mutation decreasing the affinity
Inactivating enzymes by conjugation and transfer of plasmids.
DI
pregnancy due
to risk of foetal ototoxicity
concurrent use of other nephrotoxic drugs, e.g. NSAIDs, amphotericin B, vancomycin,cyclosporine and cisplatin
60 years age and
in those with kidney damage
ototoxic drugs like vancomycin, minocycline and frusemide
Do not mix aminoglycoside with any drug
in the same syringe/infusion
pk
highly ionized and are neither absorbed
nor destroyed in the g.i.t
injection site in muscles is rapid: peak
plasma levels are attained in 30–60 minutes
distributed only extracellularly
Low concentrations -serous fluids
higher concentrations
are present in endolymph and renal
cortex, Concentrations in CSF and
aqueous humour are nontherapeutic, crosses placenta
Not metabolized, Excreted unchanged in urine- GF
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Dosing
Dosing
subthreshold for
ototoxicity and nephrotoxicity
Gentamicin/tobramycin/sisomicin/netilmicin 3–5 mg/kg/day
concentration dependent
bactericidal action &post-antibiotic
effect
Streptomycin/kanamycin/amikacin 7.5–15 mg/kg/day
Toxicity
ototoxicity irreversible
vestibular S(most),T
cochlear A(most), K, Neo, T
nephrotoxicity
NM blockade
netil- least ototoxic
Neo(most) so topical
G(most), Tobra
S(least)
inhi of presynaptic Ach release and postsynaptic sensitivity decrease
Risk factrs- hypocalcemia, periotoneal administration, CI- MG
Resp. depression treat-iv calcium
Neo,S(most), T(least)
Uses
G,T,A against G- except salmonella
Synergistic with B lactams
S- Tb, plague,tularemia
A- 2nd line tb
Netil- serious infections
Neo& framycetin topical neo gut sterilisation in HE
Spectinomycin- PPNG & P allergic gonorrhea
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