Aminoglycosides are a class of antibiotics that were first discovered in 1944 and are produced by actinomycetes bacteria. They work by interfering with bacterial protein synthesis and are bactericidal. They are narrow spectrum and primarily effective against gram-negative bacteria. Common examples include streptomycin, neomycin, kanamycin, and gentamicin. While effective antibiotics, aminoglycosides have the drawbacks of nephrotoxicity, ototoxicity, and rapid development of bacterial resistance. Their use requires monitoring of dosages and risks.

1. Aminoglycoside
Prepared by:
Ahmed Kamal Abdel Aziz Mohamed

2. Aminoglycoside
• Streptomycin – 1944
• Actinomycetes – Streptomyces griseus
• Used to treat aerobic Gram –ve bacteria
• Interfere with protein synthesis
• Bactericidal
• Resemble each other in mode of action,
pharmacokinetic, therapeutic and toxic
properties.

3. Points of concern,
• Chemistry
• Antimicrobial activity
• Mode of action
• Common features
• Routes of administration
• Preparations
• Clinical use
• Maximum Daily Dose
• Contraindications
• Use During Pregnancy and Breastfeeding
• Adverse Effects
• Risk factors

4. Chemistry
• Streptomycin family – Streptomycin & dihydro-
streptomycin

5. Chemistry
• Neomycin family – Neomycin, Framycetin,
Paromomycin

6. Chemistry
• Kanamycin family – Kanamycin, Tobramycin,
Amikacin

7. Chemistry
• Gentamicin family – Gentamicin, Sisomicin,
Netilmicin

8. Points of concern,
• Chemistry
• Antimicrobial activity
• Mode of action
• Common features
• Routes of administration
• Preparations
• Clinical use
• Maximum Daily Dose
• Contraindications
• Use During Pregnancy and Breastfeeding
• Adverse Effects
• Risk factors

9. Antimicrobial activity
• Narrow spectrum antibiotics
• Gram –ve bacilli
• Enterobacteriaceae – E.coli, Proteus, Klebsiella,
Shigella
• Pseudomonas aeruginosa, Yersinia pestis,
Pasturella tularensis
• Haemophilus and Neisseria
• Mycobacterium tuberculosis
• MIC – 0.25 to 130 μg/ml

10. Mode of Action
• Rapidly bactericidal
• Inhibit protein synthesis
• Bacterial killing conc. dependent
• Residual bactericidal activity
• Act inside the cell
• Misreading and premature termination of
mRNA at ribosome
• Primary site of action is 30s ribosome subunit
• Resulting abnormal proteins are fatal to
microbes

11. Points of concern,
• Chemistry
• Antimicrobial activity
• Mode of action
• Common features
• Routes of administration
• Preparations
• Clinical use
• Maximum Daily Dose
• Contraindications
• Use During Pregnancy and Breastfeeding
• Adverse Effects
• Risk factors

12. Common features
• Poorly absorbed from GIT
• Distribution extra cellular
• CSF and Eye penetration is poor
• High conc. in renal cortex → nephrotoxicity; & In
endolymph & perilymph of inner ear → ototoxicity
• Excreted rapidly by glomerular filtration
• Bacterial resistance develops rapidly and cross-
resistance exists
• Highly active against Gram –ve bacilli inactive
against anaerobes
• Synergistic with penicillin or cephalosporin

13. Routes of administration
• Since they are not absorbed from the gut, they are
administered intravenously and intramuscularly.
• Some are used in topical preparations for wounds.
• Oral administration can be used for gut
decontamination (e.g., in hepatic encephalopathy).
• Tobramycin may be administered in a nebulized
form.

14. Preparations
• Streptomycin sulphate injection
• Kanamycin sulphate injection
• Neomycin sulphate cap
• Gentamicin sulphate injection
• Tobramycin injection
• Amikacin injection
• Netilmicin injection
• Paromomycin cap
• Framycetin ointment, cream or solution

15. Clinical uses
• Gram –ve bacillary infection – septicaemia, pelvic &
abdominal sepsis
• Bacterial endocarditis – enterococcal, streptococcal
or staphylococcal injection of heart valves
• Pneumonias, Tuberculosis
• Tularemia
• Plague, Brucellosis
• Topical – Neomycin, Framycetin.
• Infections of conjunctiva or external ear
• To sterilize the bowel of patients who receive
immunosuppressive therapy, before surgery & in
hepatic coma

16. Points of concern,
• Chemistry
• Antimicrobial activity
• Mode of action
• Common features
• Routes of administration
• Preparations
• Clinical use
• Maximum Daily Dose
• Contraindications
• Use During Pregnancy and Breastfeeding
• Adverse Effects
• Risk factors

17. Maximum Daily Dose
• For Amikacin, Kanamycin and Streptomycin is
15 mg/ kg
• For Gentamicin and Tobramycin is 5.5 mg/kg
• Netilmicin is 6.5 mg/ kg

18. Contraindications
• Aminoglycosides are contraindicated in patients
who are allergic to them.

19. Use During Pregnancy and
Breastfeeding
• Aminoglycosides are in pregnancy category D
(there is evidence of human risk, but clinical
benefits may outweigh risk).
• Aminoglycosides enter breast milk but are not
well absorbed orally.
• Thus, they are considered compatible with use
during breastfeeding.

20. Adverse Effects
All aminoglycosides cause
• Renal toxicity (often reversible)
• Vestibular and auditory toxicity (often
irreversible)
• Prolongation of effects of neuromuscular
blockers
• Symptoms and signs of vestibular damage are
vertigo, nausea, vomiting, nystagmus, and
ataxia.

21. Risk factors
 for renal, vestibular, and auditory toxicity are
• Frequent or very high doses
• Very high blood levels of the drug
• Long duration of therapy (particularly > 3 days)
• Older age
• A preexisting renal disorder
• Coadministration of :
vancomycin Some Trade Names
VANCOCIN
cyclosporine Some Trade Names :
1. NEORAL
2. SANDIMMUNE
amphotericin B Some Trade Names :
1. ABELCET
2. AMBISOME
3. AMPHOCIN
4. AMPHOTEC
 For auditory toxicity, preexisting hearing problems and coadministration of
loop diuretics
 For renal toxicity, coadministration of contrast agents

22. Points of concern,
• Chemistry
• Antimicrobial activity
• Mode of action
• Common features
• Routes of administration
• Preparations
• Clinical use
• Maximum Daily Dose
• Contraindications
• Use During Pregnancy and Breastfeeding
• Adverse Effects
• Risk factors

23. References
• ^ MeSH Aminoglycosides ^ Massachusetts Institute of Technology (February 26, 2008).
"Bacterial 'battle for survival' leads to new antibiotic". Press release.
http://web.mit.edu/newsoffice/2008/antibiotics-0226.html. Retrieved December 1, 2010. ^ a b
Pharmamotion --> Protein synthesis inhibitors: aminoglycosides mechanism of action animation.
Classification of agents Posted by Flavio Guzmán on 12/08/08[self-published source?] ^ Shakil, Shazi; Khan, Rosina;
Zarrilli, Raffaele; Khan, Asad U. (2007). "Aminoglycosides versus bacteria – a description of the action,
resistance mechanism, and nosocomial battleground". Journal of Biomedical Science 15 (1): 5–14.
doi:10.1007/s11373-007-9194-y. PMID 17657587. ^ Levison, Matthew E. (July 2009). "Aminoglycosides:
Bacteria and Antibacterial Drugs". Merck Manual Professional.
http://www.merck.com/mmpe/sec14/ch170/ch170b.html. ^ "Aminoglycosides".
http://www.aic.cuhk.edu.hk/web8/aminoglycosides.htm. ^ Champney, W. S. (2001). "Bacterial Ribosomal
Subunit Synthesis A Novel Antibiotic Target". Current Drug Targets - Infectious Disorders 1 (1): 19–36.
doi:10.2174/1568005013343281. PMID 12455231. ^ Lorian, Victor (1996). Antibiotics in Laboratory
Medicine. Williams & Wilkins Press. pp. 589–90. ISBN 0-683-05169-5. ^ Feero, W. Gregory; Guttmacher,
Alan E.; Dietz, Harry C. (2010). "New Therapeutic Approaches to Mendelian Disorders". New England
Journal of Medicine 363 (9): 852–63. doi:10.1056/NEJMra0907180. PMID 20818846. ^ Wilschanski,
Michael; Yahav, Yaacov; Yaacov, Yasmin; Blau, Hannah; Bentur, Lea; Rivlin, Joseph; Aviram, Micha; Bdolah-
Abram, Tali et al. (2003). "Gentamicin-Induced Correction of CFTR Function in Patients with Cystic Fibrosis
andCFTRStop Mutations". New England Journal of Medicine 349 (15): 1433–41.
doi:10.1056/NEJMoa022170. PMID 14534336. ^ Falagas, Matthew E; Grammatikos, Alexandros P;
Michalopoulos, Argyris (2008). "Potential of old-generation antibiotics to address current need for new
antibiotics". Expert Review of Anti-infective Therapy 6 (5): 593–600. doi:10.1586/14787210.6.5.593.
PMID 18847400. ^ Durante-Mangoni, Emanuele; Grammatikos, Alexandros; Utili, Riccardo; Falagas,
Matthew E. (2009). "Do we still need the aminoglycosides?". International Journal of Antimicrobial Agents
33 (3): 201–5. doi:10.1016/j.ijantimicag.2008.09.001. PMID 18976888.