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Antibiotics for Aminoglycosides


Antibiotics and Aminoglycosides - Aminoglycosides Antibiotics Side Effects - Use of Aminoglycosides
Aminoglycoside Antibiotics

Aminoglycosides (a-mee-noe-GLYE-koe-sides ) are used to treat serious bacterial infections. They work by killing bacteria or preventing their growth.

Aminoglycosides are given by injection to treat serious bacterial infections in many different parts of the body. In addition, some aminoglycosides may be given by irrigation (applying a solution of the medicine to the skin or mucous membranes or washing out a body cavity) or by inhalation into the lungs. Streptomycin may also be given for tuberculosis (TB). These medicines may be given with 1 or more other medicines for bacterial infections, or they may be given alone. Aminoglycosides may also be used for other conditions as determined by your doctor. However, aminoglycosides will not work for colds, flu, or other virus infections.

Aminoglycosides given by injection are usually used for serious bacterial infections for which other medicines may not work. However, aminoglycosides may also cause some serious side effects, including damage to your hearing, sense of balance, and kidneys. These side effects may be more likely to occur in elderly patients and newborn infants. You and your doctor should talk about the good these medicines may do as well as the risks of receiving them.

Aminoglycosides

  • 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
  • Aminoglycosides Uses


    Chemistry

  • Streptomycin family – Streptomycin & dihydro-streptomycin
  • Neomycin family – Neomycin, Framycetin, Paromomycin
  • Kanamycin family – Kanamycin, Tobramycin, Amikacin
  • Gentamicin family – Gentamicin, Sisomicin, Netilmicin
  • 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
  • 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
  • Bacterial resistance

  • Very poor GIT absorption
  • Rapid IM absorption
  • Peak plasma conc. 30 to 90 minutes
  • Poor penetration in Eye, CNS
  • High conc. in renal cortex & inner ear
  • PPB negligible
  • Excretion in glomerular filtration
  • 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
  • Adverse effects

    All aminoglycosides can produce nephrotoxicity & ototoxicity.

    OTOTOXICITY – Both vestibular and auditory damage, causing loss of hearing, vertigo & tinnitus, due to auditory nerve damage

  • Early signs of vestibular toxicity – motion related headache, dizziness or nausea
  • Serious ototoxicity can occur with ear drops
  • Risk of toxicity depends upon high dose, long duration, inefficient renal clearance and dehydration
  • Streptomycin, Gentamicin – Vestibular dysfunction
  • Amikacin, Kanamycin – Auditory dysfunction
  • NEPHROTOXICITY - Reversible renal impairment occurs in who receive drugs for more than 10 days due to accumulation and high retention in proximal tubular cells

  • Mild proteinuria and appearance of hyaline and granular casts
  • GFR
  • Acute tubular necrosis (Rare)
  • Risk factors – Low B.P., Loop diuretics and advanced age
  • Neuromuscular blockade – Intrapleural and intraperitoneal administration produces neuromuscular blockade & apnea (resp. arrest)

  • May aggravate or reveal myasthenia gravis or cause transient myasthenic syndrome
  • Blockade antagonized by neostigmine
  • Rashes
  • Haematological abnormalities
  • Bleeding
  • Superinfection
  • 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
  • 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
  • Streptomycin

  • Combination of chemotherapy of tuberculosis
  • Plague
  • Brucellosis
  • Tularemia
  • Streptococcal endocarditis- combined with Penicillin-G
  • ADRs: - Optic nerve dysfunction

  • Peripheral neuritis
  • Perioral paraesthessia
  • Gentamicin

  • Useful bactericidal for serious G -ve bacillary infection
  • First choice Aminoglycosides due to low cost, reliable activity and long experience of use
  • Tobramycin, amikacin and interchangeably
  • Used in infected burns, otitis externa, acute pyelonephritis
  • Trough plasma drugs conc. > 2µg / ml - toxic
  • U.T.I
  • Pneumonia
  • Meningitis
  • Endocarditis
  • Peritonitis
  • Intraabdominal and pelvic infection and septic states caused by sensitive bacteria,
  • pseudomonas, entrobacter, klebsiella
  • Skin, eye and ear infection
  • Tobramycin

  • Pseudomonas infections
  • Bacteremia
  • Osteomyelitis
  • Pneumonia
  • Tobramycin + Piperacillin
  • Tobramycin + Ceftzidime
  • Ophthalmic ointment & solution
  • Amikacin

  • Broadest antibacterial spectrum
  • Similar to gentamicin and tobramycin in therapeutic uses
  • Resistant to Aminoglycosides inactivating enzymes
  • Preferred in serious nosocomial G -ve bacillary infection in hospitals where Tobramycin & Gentamicin have developed resistance
  • Effective against M. tuberculosis & atypical mycobacteria in AIDS patients
  • Netilmicin

  • Serious aerobic G-ve bacillary infections due to enterobacteriacaea
  • Effective against Gentamicin resistant except entrococci pathogens
  • Neomycin

  • Broad spectrum antibiotics
  • Orally used intestinal antiseptic before colonic surgery
  • Suppression of intestinal flora in hepatic coma
  • Topically used in skin, eye and ear infection combined with other antibiotics like bacitracin or polymyxin-B to widen antibacterial spectrum and to prevent emergence of resistant strains
  • Neomycin and polymyxin B used for bladder irrigation in solution containing 40mg neomycin and 2 lac units of polymyxin-B per ml.
  • 1 ml added to 1 liter of 0.9% sodium chloride solution and is used for continuous irrigation of bladder in order to prevent bacteremia and bacteriurea associated with use of indwelling catheters at the rate of 1000 ml/day.
  • Neomycin cream, ointment alone and combination with other antibiotics and corticosteroids.
  • Used in burns, wounds, ulcers
  • Kanamycin

  • Reserve drug for Tuberculosis-combined with other antitubercular drugs
  • Most toxic
  • Orally used in therapy of hepatic coma.
  • Alogrithm for Dose Reduction of Aminoglycosides Based on Calculated Creatinine Clearance

    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
  • Cochlear Toxicity

  • High pitched tinnitus - first symptom
  • Auditory impairment after a few days if drug continues
  • Tinnitus persists upto 2 weeks after discontinuation
  • Sound perception lost first outside conversational range
  • Individual may be unaware of impairment
  • Detected on audiometric examination
  • Loss of hearing may progress
  • VESTIBULAR- Toxicity

  • Moderately intense headache lasting 1 to 2 days
  • Onset of labyrinthine dysfunction
  • Acute stage: Nausea, vomiting and difficulty in equilibrium persists for 1 to 2 weeks
  • Upright vertigo
  • Difficulty in sitting and standing
  • Eye focusing and reading difficult
  • Acute stage followed by chronic labyrinthine dysfunction:- ataxia, difficulty in sudden movements persists for 2 months
  • Later on symptom appear only on closing eyes
  • Recovery in 12 to 18 months
  • Permanent residual damage may occur
  • EARLY DISCONTINUATION OF DRUG PREVENTS DAMAGE AND PERMIT RECOVERY
  • Nephrotoxicity

  • Reversible renal damage in 8% to 26% patients
  • Renal proximal tubular cells accumulate and retain drug
  • Mild proteinuria, appearance of casts, hyaline or granular
  • Proximal tubular cells have regenerative capacity
  • Neomycin highly toxic- systemic administration contraindicated
  • Reduced excretion predisposed to ototoxicity
  • Monitor plasma drug conc. in prolonged and high dose therapy
  • Source - Dept. of Pharmacology, GMC Amritsar

    Antibiotics Dictionary

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