pharmaceuticals

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.