AMINOGLYCOSIDES- mechanism of action, uses, adverse effects

AMINOGLYCOSIDES- mechanism of action, uses, adverse effects

1. AMINOGLYCOSIDES

2. THEY INCLUDE- STREPTOMYCIN GENTAMICIN TOBRAMYCIN AMIKACIN KANAMYCIN SISOMICIN NEOMYCIN FRAMYCETIN NETILMICIN

3. COMMON PROPERTIES- They are highly polar compounds. Hence poorly absorbed from GIT. Administered by parenteral route for systemic effect. Mainly distributed into ECF and poorly penetrate into the CSF. Not metabolised in the body. Excreted unchanged in urine.

4. 5. Have bactericidal action against gram-negative aerobes and are more active at alkaline pH. 6. Exhibit ototoxicity, nephrotoxicity and neuromuscular blocking effects. 7. Exhibit cross-resistance among them. 8. Anerobes are resistant to aminoglycosides. 9. Exhibit synergism when combined with beta- lactam antibiotics.

5. MECHAMISM OF ACTION- They are bactericidal agents. They act by binding to ribosomes, inhibit bacterial protein synthesis and affect permeability of cell membrane.

6. AMINOGYCOSIDES EXHIBIT- Concentration dependent killing effect. Post antibiotic effect.

7. DOSING Multiple-daily dosing regimen: the total daily dose is administered in two or three equally divided doses. Once-daily dosing regimen: Preferred Given as a single injection Dose adjustment is done according to body weight and creatinine clearance

8. ADVERSE EFFECTS OTOTOXICITY: M anifest as tinntus and deafness, headache, dizziness, nausea, vomiting, vertigo, nystagmus and ataxia. Elderly patients are more prone to ototoxicity. Use during pregnancy may cause ototoxicity in fetus .

9. Nephrotoxicity : Usually reversible. Incidence is highest with neomycin and least with streptomycin. Risk factors: elderly patients, pre-existing renal disease and concurrent use of other nephrotoxic drugs such as amphotericin B, vancomycin , cisplatin , cyclosporine, etc.

10. Neuromuscular blocking effect: Aminoglycosides inhibit the release of acetylcholine from the motor nerve. Myasthenic patients are more susceptible and hence these drugs should be avoided in them. Hypersensitivity reactions: Skin rashes Drug fever Eosinophilia

11. STREPTOMYCIN First aminoglycoside discovered. USES: Tuberculosis Plague Brucellosis

12. GENTAMICIN Most commonly because of its- Low cost Reliable activity against most gram-negative bacilli.

13. Uses of Gentamicin- 1. Aerobic gram-negative bacillary infections: Upper UTI with pyelonephritis Pneumonia Meningitis Osteomyelitis Infected burns AGs are often used in combination with penicillin/cephalosporin

14. Bacterial endocarditis due to S. viridans and Enterococcus: Penicillin G + gentamicin for S. viridans . Ampicillin + gentamicin for Enterococcus. Vancomycin + gentamicin for Enterococcus Gentamicin and ampicillin combination is also used for treatment of endocarditis in high risk patients before surgical procedures.

15. 3. Plague Brucellosis Topically for gram-negative skin, eye and ear infections. Gentamicin should not be mixed with other drugs in the syringe or i.v. infusion bottle as they may result in precipitation or inactivation of drugs.

16. NEOMYCIN H ighly nephrotoxic. Never used for systemic effect.

17. Uses of neomycin Used topically for- Infections of the skin and mucous membrane: Ulcers, wounds and burns. Infections of the eye and external ear: used in combination with bacitracin or polymyxin B.

18. Used orally (for local action) Neomycin sulphate: in combination with erythromycin, is useful for preparation of the bowel before abdominal surgery. Hepatic encephalopathy: on oral administration reduces the blood ammonia level by destroying the colonic bacteria. It is highly toxic, and hence it has been replaced by oral lactulose.

19. FRAMYCETIN (SOFRAMYCIN) Used topically for skin,eye and ear infections due to gram-negative bacteria.

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