Subclass Mechanism of

action
Mechanism of
resistance
Pharmacokinetic Effect Antimicrobial
spectrum:
AMINOGLYCOSIDE
- More toxic than
most a/b but
important for
treatment of aerobic
gram neg bact,
mycobacteria,
protozoan.
- mycin suffix
derived from
Streptomyces
- micin suffix
derived from
Micromonospora
-Streptomycin widely
used. Least toxic, least
active against gram neg
bacilli. Restricted for
treatment of
tuberculosis.
- spectinomycin is an
aminocyclitol a/b related
to aminoglycoside
-lack of amino sugars
and glycosidic bonds
- not available in US
-Spectinomycin active in
vitri against many gram
+ve and gram ve
-Solely as alternative
treatment for drug
resistant gonorrhea or
gonorrhea in penicillin
resistat allergic
-strains of gonococci
may be resistant but no
cross resistance with
other drug used in
gonorrhea

Bactericidal
Overall process
Transport of
aminoglycoside
s through
bacterial cell
wall and
cytoplasmic
membrane
- Penetrate
(passive diff)
through porin
channel of gram
ve or water
filled areas of
peptidoglycan of
gram +ve
- Bind to transport
molecule ->
actively
transported to
cytoplasm
- Drug transporter
complex moved
across
cytoplasmic
(potential
gradient) and
transport is
coupled to a
proton pump.
- Low
extracellular pH
and anaerobic
inhibit transport
- Transport
enhanced by cell
wall active drugs
like penicillin,
vancomycin
(synergism)
Binding to
ribosomal site
->inhibit
protein
synthesis
- Bind to 30S
subunits
- 3 ways:
-interference
with the
initiation
complex of
peptide
- production of
transferase
enzyme
- enzyme
inactivates by
adenylylation,
acetylation,
phosphorylation
Impaired entry
into cell
- Genotypic
Result from
mutation,
deletion of
porin protein
- Phenotypic
O2
dependent
transport
not
functional
- Receptor on
30S deleted or
altered by
mutation
- poly cation and
highly polar
- not absorbed in
GIT
- Penetrate
vitreous humour
of eye, most
secretion of body
fluids, although
HC attained in
joint, pleural fluid
- given IM or IV
- neomycin for
topical infection
of skin, eyes, ears
- occasionally
given orally to
sterilize bowel
prior intestinal
surgery
- paromomycin
given orally for
parasitic infection
-do not cross BBB
- may cross
placenta
- HC accumulate
in renal cortex and
perilymph of
inner ear
- metabolism do
not occur in host,
rapidly excreted
in urine, virtually
entirely by
glomerular
filtration in
kidney
Therapeutic index
is narrow and
toxicity can be
serious
-renal fx must be
assessed,
monitoring of
plasma
concentration
- spectinomycin is
rapidly absorbed
after IM
- serious, dose
related toxic
effect
- ototoxicity
-nephrotoxicity
- neomycin,
kanamycin,
amikacin most
ototoxic
- streptomycin,
gentamicin most
vestibulotoxic
- neomycin,
tobramycin,
gentamicin most
nephrotoxic
-spectinomycin
nephrotoxicity
and anemia
observed rarely

- Broad
spectrum a/b
- Effective
against gram
ve and
some gram
+ve
- Widely used
against gram
ve enteric
organism
and in sepsis
- Low activity
against
anaerobes,
streptococci,
pneumococc
i
- Given with
penicillin in
infection by
streptococci,
Listeria sp.,
P.
aeruginosa
- Gentamicin
most
commonly
used
- Tobramycin
preferred for
P.
aeroginosa
infection
- Amikacin
widest
antimicrob
spectrum
- Amikacin +
netilmicin
effective
against
organism
resistant to
gentamicin
and
tobramycin
-
formation
-misreading of
mRNA, cause
incorporation of
incorrect amino
acids into
peptide
-breakup of
polysomes into
nunfunctional
monosomes