Aminoglycoside and spectinomycin, indications, contraindications, mechanism of action

1. Aminoglycosides
and
Spectinomycin
Yjnah D. Lim BMLS III-A
Riverside College Inc.

2. AMINOGLYCOSIDES

4. Streptomyces
• Gram-positive rods
• Resemble filamentous fungi
• Have unique ability to produce to produce bioactive
secondary metabolites such as antifungals, antivirals,
antitumoral, anti-hypertensives, and mainly antibiotics
and immunosuppressives.
• Streptomycin - 1st aminoglycoside; Streptomyces
griseus

5. Micromonospora
• Gentamicin is the aminoglycoside used most
often because of its low cost and reliable activity
against gram-negative aerobes.
• Micromonospora purpurea

6. Mnemonics Time
TANGS do NOT kill anaerobes.
• Aminoglycosides
• Tobramycin
• Amikacin
• Neomycin
• Gentamicin
• Streptomycin
• Adverse Effects
• Nephrotoxicity
• Ototoxicity
• Teratogen

7. Aminoglycosides
• Include: streptomycin, neomycin, kanamycin, amikacin,
gentamicin, tobramycin, sisomicin and netilmicin
• In vivo-effectiveness result from concentration-
dependent killing action.
• Capable of exerting post-antibiotic effect.
• “Once-daily” dosing: Numerous clinical studies
demonstrate that a single daily dose of aminoglycoside
is just as effective—and probably less toxic— than
multiple smaller doses.
• Elimination half-life of 2-3 hrs (normal renal function)

8. • Water soluble and more active in alkaline pH
• Poor oral absorption, poor GI absorption
• Given intramuscularly or intravenously for systemic
effect
• Do not easily cross the BBB
• Given together with Beta-lactams to decrease
adverse effects and increase bactericidal effect
• “Synergistic killing”

9. Mechanism of Action
Drug is actively
transported across the
cell membrane into the
cytoplasm by an oxygen-
dependent process.
Transmembrane
electrochemical
gradient supplies
energy for this process.
Transport is coupled
to a proton pump.
Aminoglycosides bind
to specific 30S-
subunit ribosomal
proteins.
Protein synthesis is inhibited in at
least 3 ways:
• Interference with the initiation
complex of peptide formation
• Misreading of mRNA
• Breakup of polysomes into
nonfunctional monosomes/
Inhibiting translocation

11. Amikacin is not inactivated by the
common enzymes that inactivate
gentamicin and tobramycin.

12. Indications
• Aminoglycosides are mostly used against
gram-negative aerobic enteric bacteria.
• In addition, some Mycobacteria, including the
bacteria Mycobacterium tuberculosis, are
susceptible to aminoglycosides.

13. • They are almost always used in combination with a
β-lactam antibiotic to extend coverage to include
potential gram-positive pathogens and to take
advantage of the synergism between these two
classes of drugs.
Example:
Aminoglycoside + Penicillin:
For pseudomonal, listerial and enterococcal
infections.

15. • Tobramycin: Intravenous; more active than
gentamicin versus Pseudomonas.
• Amikacin: Intravenous; resistant to many enzymes
that inactivate gentamicin and tobramycin
• Streptomycin: Intramuscular, widespread
resistance limits use to specific indications such as
tuberculosis and enterococcal endocarditis.
• Neomycin: Oral or topical, poor bioavailability;
used before bowel surgery to decrease aerobic
flora.

16. Contraindications
• In patients with mitochondrial diseases as
they may result in impaired mtDNA translation,
which can lead to irreversible hearing loss,
tinnitus, cardiac toxicity, and renal toxicity.
• During pregnancy to prevent ototoxicity in
fetus (teratogenic).

17. Adverse Effects
• Ototoxicity
Auditory or vestibular damage (or both) may occur with
any aminoglycoside and may be irreversible.
Ototoxic: Amikacin, Kanamycin and Neomycin
Vestibulotoxic: Gentamicin and Streptomycin
Netilmicin is the least ototoxic.
• Nephrotoxicity
Takes the form of acute tubular necrosis. This reversible
adverse effect is more common in elderly patients.
Neomycin is the most nephrotoxic drug, streptomycin is
the least one.

18. • Neuromuscular Blockade
Although rare, a curare-like block may occur at
high doses of aminoglycosides and may result
in respiratory paralysis.
Reversible by treatment of calcium gluconate
and neostigmine.
• Skin Reactions
Allergic reactions and contact dermatitis may
occur.
Neomycin

19. SPECTINOMYCIN

20. • Spectinomycin is an aminocyclitol
antibiotic that is structurally related
to aminoglycosides.
• Spectinomycin is rapidly absorbed
after intramuscular injection.

21. Mechanism of Action
Glucose-6-phosphate ,
which is reduced by
NADH to form a
ketone at C2
This ketone is then
formed into a primary
amine group through
PLP and glutamine
transamination
This process is
repeated again at
C4 to form a second
primary amine
Once these two amines are
present, the glucose ring is
ready to be methylated
through two S-adenosyl
methionine molecules
The glucose ring is
finally ready to be
converted into an
inositol ring through
inositol cyclase
This can then be
hydrolyzed to get rid of the
phosphate group, making
the inositol ring necessary
for spectinomycin

22. • Spectinomycin is an inhibitor of
protein synthesis in the bacterial cell.
• The site of action is the 30S ribosomal
subunit.
• It prevents elongation of polypeptide
chain at the translocation step.
• It is bactericidal in its action.

23. Indications
• Due to susceptible strains of Neisseria
gonorrhoeae:
• Used almost solely as an alternative treatment for
drug-resistant gonorrhea or gonorrhea in penicillin-
allergic patients.
• Male: acute gonorrheal urethritis and proctitis
• Female: acute gonorrheal cervicitis and proctitis

24. Contraindications
• Spectinomycin, sold under the tradename
Trobicin is contraindicated in patients
previously found hypersensitive to it.

25. Adverse Effects
• There is pain at the injection site
and, occasionally, fever and nausea.
• Gastrointestinal disturbance
• Hypersensitivity

26. Route of Administration
• Spectinomycin:
Intramuscular Injection