Scribd Logo
Upload

Welcome to Scribd!

  • 37 views

    Aminoglycosides: Jagir R. Patel Asst Prof Dept. Pharmacology Anand Pharmacy College

    Uploaded by

    Jagir
    This document summarizes information about aminoglycoside antibiotics presented by Jagir R. Patel from the Department of Pharmacology at Anand Pharmacy College. It discusses the classification, mechanisms of action, mechanisms of resistance, dosing regimens, toxicity, and examples of common aminoglycoside antibiotics like streptomycin, gentamicin, neomycin, and tobramycin. The key mechanisms of action involve binding to the bacterial ribosome to inhibit protein synthesis and cause bacterial cell death. Toxicities include ototoxicity and nephrotoxicity.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd

    Aminoglycosides: Jagir R. Patel Asst Prof Dept. Pharmacology Anand Pharmacy College

    Uploaded by

    Jagir
    37 views24 pages
    This document summarizes information about aminoglycoside antibiotics presented by Jagir R. Patel from the Department of Pharmacology at Anand Pharmacy College. It discusses the classification, mechanisms of action, mechanisms of resistance, dosing regimens, toxicity, and examples of common aminoglycoside antibiotics like streptomycin, gentamicin, neomycin, and tobramycin. The key mechanisms of action involve binding to the bacterial ribosome to inhibit protein synthesis and cause bacterial cell death. Toxicities include ototoxicity and nephrotoxicity.

    Original Title

    Aminoglycosides.pptx

    Copyright

    © © All Rights Reserved

    Available Formats

    PPTX, PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    This document summarizes information about aminoglycoside antibiotics presented by Jagir R. Patel from the Department of Pharmacology at Anand Pharmacy College. It discusses the classification, mechanisms of action, mechanisms of resistance, dosing regimens, toxicity, and examples of common aminoglycoside antibiotics like streptomycin, gentamicin, neomycin, and tobramycin. The key mechanisms of action involve binding to the bacterial ribosome to inhibit protein synthesis and cause bacterial cell death. Toxicities include ototoxicity and nephrotoxicity.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    37 views24 pages

    Aminoglycosides: Jagir R. Patel Asst Prof Dept. Pharmacology Anand Pharmacy College

    Uploaded by

    Jagir
    This document summarizes information about aminoglycoside antibiotics presented by Jagir R. Patel from the Department of Pharmacology at Anand Pharmacy College. It discusses the classification, mechanisms of action, mechanisms of resistance, dosing regimens, toxicity, and examples of common aminoglycoside antibiotics like streptomycin, gentamicin, neomycin, and tobramycin. The key mechanisms of action involve binding to the bacterial ribosome to inhibit protein synthesis and cause bacterial cell death. Toxicities include ototoxicity and nephrotoxicity.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 24

    Aminoglycosides

    Jagir R. Patel
    Asst Prof Dept. Pharmacology
    Anand pharmacy college

    Jagir R. Patel, Asst Prof, Dept. Pharmacology, APC


    Aminoglycosides
     Aminoglycosides that are derived from bacteria of
    the Streptomyces genus are named with the suffix mycin, whereas
    those that are derived from Micromonospora are named with the
    suffix micin

    • Streptomycin, Neomycin,
    Gentamycin, Soframycin,
    Streptomyces
    Tobramycin
    mycin • Poromycin, Kanamycin

    Micromonospor • Gentamicin, Netlimicin,


    a
    micin
    verdamicin, Sisomicin
    Jagir R. Patel, Asst Prof, Dept.
    Pharmacology, APC
    Antimicrobial spectrum

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Mechanism of transportation of aminoglycosides into
    bacterial cell

    Transport of aminoglycosides into bacteria


    through porin channels

    Oxygen dependent process, anaerobes are


    more resistant when oxygen supply is deficient

    Penetration is also favored by high pH. i.e.


    more active in alkaline medium

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    MOA
    Aminoglycosides bind to 30s ribosomal subunit. And also to 50s-30s junction

    Inhibition of Protein synthesis by Misreading of Codon

    Premature termination of protein synthesis, or insertion of wrong amino acids into


    growing peptides chain

    Formation of defective proteins

    Incorporation of defective proteins into bacterial cell membrane

    Altered permeability and disruption of cell membrane

    Jagir R. Patel, Asst Prof, Dept.


    Bactericidal effect
    Pharmacology, APC
    Mechanism

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Mechanism of Resistance
     Bacterial resistance is due to

     Inactivation of drug by bacterial enzymes which phosphorylate,


    adenylate or acetylate the drug.

     Decreased entry of drug into bacterial cell due to alteration in pores of


    outer membrane of organism which becomes less permeable

     Decreased affinity for the Ribosomes due to mutation

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Aminoglycosides and its Bactericidal
    Effect
     A concentration –dependent killing: higher the
    plasma concentration more of the bacterial is killed
    rapidly

     A post antibiotic effect: bactericidal effect is


    present even when serum concentrations falls
    below MIC. Therefore once daily dose regimen is
    effective

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Dose Regimen
     Once daily dose regimen:
     total daily dose in single injection because higher plasma concentration
    is achieved in single dose
     It is safer then multiple dose regimen due to, the plasma concentration
    remains below threshold levels for toxicity for a longer period of time.

     Multiple dose regimen: the total daily dose is administered in 2 or 3


    equally divided doses.

     Single dose regimen is not preferred in bacterial endocarditis, children


    and patients with renal impairment.
     Dose adjustment of aminoglycosides is done accordingly to body
    weight and creatinine clearance

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Adverse effects of Aminoglycosides
     Ototoxicity:
     Vestibular and cochlear dysfunctions can occur due to cranial nerve
    damage.
     The drug concentration In endolymph of the inner ear which can lead to
    progressive damage to vestibular and cochlear hair cells.
     Results into: deafness, tinnitus
     Vestibular damage results into: nausea, vomiting, vertigo, ataxia

    Risk factors
    1. Elderly patients
    2. Repeated courses of aminoglycosides
    3. Persistent increase in plasma conc
    4. Patients with preexisting auditory impairment
    Jagir R. Patel, Asst Prof, Dept.
    Pharmacology, APC
    Cont..
     Nephrotoxicity
     The drug gets concentrated in renal cortex and produce reversible
    nephrotoxicity.
    Risk factor:
    1. Elderly patients
    2. Preexisting renal diseases

     Neuromuscular blocking effect;


    1. Aminoglycosides releases Ach from motor nerve, Leads to apnoea and
    muscular paralysis

     Hypersensitive reactions

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Major toxicity

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Cont.…

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Drug Interactions
     Aminoglycosides + vancomycin, monoclines, loop diuretics
    = increase ototoxicity

     Aminoglycosides + vancomycin, amphotericin, cisplatin,


    cyclosporine = increase nephrotoxity

     Aminoglycosides + Myasthenic patients = increase


    susceptibility for paralysis

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Streptomycin 1st aminoglycoside
     Given i.m., rapidly distributed don't cross BBB, and cross placental
    barrier, and excreted via urine

     Indications
     Tuberculosis
     Bacterial endocarditis
     Bacteraemia; Meningitis; Pneumonia ; Brucellosis; Urinary tract
    infections
     Plague
     Tularaemia

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Gentamycin
      Poorly absorbed from the GI tract. Rapidly absorbed (IM).
     Diffuses mainly into extracellular fluids; minimal penetration to ocular
    tissues; diffuses readily into the perilymph of the inner ear. Crosses
    the placenta and enters breast milk excreted via urine

     Urinary tract infections 160 mg/kg


     Superficial ophthalmic infections 0.3 % eye drops
     Otitis external 0.3%
     Skin infections 0.1%
     Generally used for infections caused by E.coli, Klebsiella,
    P.areuginosa

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Neomycin
     It is highly nephrotoxic hence no systemic uses, only used topically
     Absorption: Poorly absorbed from the GI tract.
    Distribution: Low concentrations in intestinal wall and muscles.
    Metabolism: Undergoes minimal hepatic metabolism.
    Excretion: Via faeces

    Indications:
     Topically for skin and mucous membranes: ulcers, wounds, burns
     Infection in eye, and external ear in combination with bacitracin
     Preoperative intestinal antisepsis
     Hepatic encephalopathy

    Adv.: nephrotoxicity
    Jagir R. Patel, Asst Prof, Dept.
    Pharmacology, APC
    Soframycin/framycetin
     Framycetin is an aminoglyoside antibiotic which is the major
    component of neomycin.
     Susceptible organisms include many gram-negative bacteria (but not
    Pseudomonas) and many strains of Staphylococcus.
     Used topically in the treatment of skin, eye and ear infections often in
    combination with steroids and other antimicrobials.

     Indications 0.5%
     Posttraumatic or pre- and postoperative otitis externa
     Conjunctivitis, blepharitis and blepharoconjunctivitis
     Skin infections

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Amikacin
     Amongst other aminoglycosides, it has broad spectrum of activity for
    gram –ve organisms
     It is resistant to aminoglycoside inactivating enzymes

     P.K. Rapidly absorbed (IM) Detected in body tissues and fluids. Crosses
    the placenta but does not readily penetrate into CSF, substantial penetration
    of the blood-brain barrier, Excreted in urine,

    Indications 7-15mg/kg
    Uncomplicated urinary tract infections
    Severe Gram-negative nosocomial infections, and TB

    Major side effect: auditory function/ ototoxicity


    Jagir R. Patel, Asst Prof, Dept.
    Pharmacology, APC
    Tobramycin
     Superior to gentamycin against P.areuginosa
     Tobramycin interferes w/ bacterial protein synthesis by binding to 30S
    and 50S ribosomal subunits, resulting in a defective bacterial cell
    membrane.

     Indications
     Bone and joint infections; Gastrointestinal infections; Lower
    respiratory tract infections; Skin and soft tissue infections ; Central
    nervous system infections
    Mild to moderate urinary tract infections
     Ocular infections

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Paromomycin
     Paromomycin acts directly on amoeba.
     It has antibacterial activity against normal and pathogenic organisms in
    the GI tract and interferes w/ bacterial protein synthesis by binding to
    30S ribosomal subunits.
    Absorption: Poorly absorbed from the GI tract. Excreted via faces

     Indications
     Intestinal amoebiasis
     Giardiasis, vaginal trichomoniasis
     Hepatic encephalopathy

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Netlimicin
     Netlimicin, binds to 30S and to some extent to 50S ribosomal subunit of
    susceptible bacteria disrupting proteinsynthesis, thus rendering the
    bacterial cell membrane defective.
     They are resistant to aminoglycoside inactivating enzymes.

    Absorption: Rapidly and completely absorbed i.m. or i.v.
    Excretion: Via urine

     Indications: Urinary tract infections, Susceptible infections

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    General Properties
     They are highly polar compounds hence poorly absorbed from GIT,
    they are administered by parenteral route for systemic effect
     They are mainly distributed into extracellular fluid and poorly penetrate
    into CSF
     They are not metabolized in liver
     They are excreted unchanged in urine
     They have bactericidal action against gram-ve aerobes and are more
    active at alkaline pH.
     They cause ototoxicity and nephrotoxicity
     They exhibit partial cross resistance
     Transport of aminoglycosides into bacterial cells require oxygen, hence
    anaerobes are resistance to aminoglycosides

    Jagir R. Patel, Asst Prof, Dept.


    Pharmacology, APC
    Jagir R. Patel, Asst Prof, Dept.
    Pharmacology, APC

    You might also like