Aminoglycosides department of pharmacology

Aminoglycosides department of pharmacology.

1. AMINOGLYCOSIDES

2. COMMON PROPERTIES:
1.Water soluble, Used as sulfate salts.
2.Ionize in solution not absorbed orally
3.Excreted unchanged in urine by glomerular filtration.
4.Bactericidal
5.Aerobic Gram Negative organisms
6.Narrow margin of safety.
7.Never used alone, combined with B Lactum
&Vancomycin
8.Exhibit Ototoxicity and nephrotoxicity.
9.Measured by creatinine clearance.
10.Dose reduction in Renal insufficiency &elderly Patients.

3. CLASSIFICATION
streptomyces
•streptomycin
•Neomycin
•Kanamycin
•Tobramycin
Micromonospora
•Amikacin
•Gentamicin
•Sisomicin
•Netilmicin

4. MECHANISM OF DRUG ACTION
1.Misreading of Mrna

2 Interfere with protein synthesis.
3 Causes Break up polysomes to Monosomes

5. MECHANISM OF RESISTANCE:
•Inactivation of drug by enzymes
•Impaired entry into cell.
•Mutation.

6. PHARMACOKINETICS AND ONCE DAILY
DOSAGE.
Streptomycin
•Poorly absorbed in GIT
•is highly ionised distributed only extracellularly.
•Low conc attained in synovial ,pleural ,peritoneal
fluids .Not metabolized , excreted unchanged in
urine by G.F.
•IM, IV
•CONCENTRATION DEPENDANT KILLING
•POST ANTIBIOTIC EFFECT
•.LOWEST NEPHROTOXICITY
•T1/2 2 – 3 Hrs.

7. ADVERSE EFFECTS
Vestibular toxicity ---
Vertigo ,ataxia
Ototoxicity
Cochlear---Tinnitus ,Hearing loss
Vestibular / cochlear sensory cells and hairs undergoes
permanent destruction.
Hypersensivity reactions ,rashes ,fever contact
dermatitis

8. Toxicity in Renal cortex
Totally reversible
Neuromuscular Blockade
Reduce ach release from Motar (N) endings
Neomycin

Streptomycin

9. MOST OTOTOXIC
•Kanamycin
•Amikacin
•Neomycin
MOST VESTIBULOTOXIC
•Streptomycin
•Gentamicin
NEPHROTOXICITY:
•Gentamicin
•Tobramycin
•Neomycin

10. PRECAUTIONS AND INTERACTIONS:
•Pregnancy
•Avoid with other ototoxic drugs.
•Avoid with other nephrotoxic drugs.
•Avoid Mixing with pencillin in same syringe.

11. INDIVIDUAL DRUGS:
STREPTOMYCIN:
•Obtained from streptomyces griseus
•Inhibits H. Ducrey, Brucella, Y. Pestis,
Tularensis, Nocardia.
•Not Metabolized T1/2 – 2-4 HRS
•Lowest nephrotoxicity
•Used-TB, SABE, Plague, Tularemia

12. GENTAMICIN:
•Obtained –micromonaspora
•more potent-T1/2 2-4 hrs
•broader spectrum of action. Psuedomonas, proteus, E.Coli,
Klebsiella.
•More Nephrotoxic.
•Very valuable in critically
ill pts(RTI,With ventilators ,post op pts ICU s).
• USED: SABE, Meningitis in G.N Bacilli ,Burns, UTI, Lung
Abscesses.Mostly combined with B Lactums
•CHEAPEST .

13. KANAMYCIN
•Lacks activity against pseudomonas
Oto toxic
•More
Nephrotoxic
Rarely Used –most toxic.
TOBRA MYCIN:
2 – 4 times More potent against pseudomonas and
proteus
Reserve to gentamicin(INTERCHANGABLE)
Less toxic than gentamicin .
Available as spray in RTI.

14. AMIKACIN:
•Semi synthetic derivative of kanamycin
•Resistance to bacterial inactivating enzymes
•Reserve drug
•Wide spectrum of activity .
•Effective in T.B

15. SISOMICIN:
More potent on pseudomonas
Interchangeable with gentamicin.
Combined with Pencillin .
NETILMICIN:
Broader spectrum than gentamicin
Resistant to inactivating enzymes
Effective in gentamicin resistant strain
Less ototoxic
Preferable in critically ill Patients

16. NEOMYCIN:
•Not used systemically – toxicity
Gram +ve
•Wide spectrum
Gram –ve
Topical : Mixed infections topically(combined with
polymixin bacitracin)
Oral 1) Preparation of bowel before surgery,
2) hepatic coma (Suppresses NH
3

production.
FRAMYCETIN:
Toxic for systemic administration.
 Topical