Aminoglycoside Antibiotics

Pharmacology

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05:02
Aminoglycoside Antibiotics
Hys8gznvsdsw6o61oc2p 180317 s1 usman muhammad introduction
09:04
Introduction
Sigz4l0zszcgi5qwg1yp 180317 s2 usman muhammad pharmacokinetics
07:55
Pharmacokinetics
Aibdiwqs82s1gpanagca 180317 s3 usman muhammad mechanism of action
06:01
Mechanism of Action
F5wrohtar76uyr8rpufk 180317 s4 usman muhammad side effects and contraindications
07:41
Side Effects and Contraindications
Vbi70sxes5g07y0j8qw2 180317 s5 usman muhammad interactions and antibacterial resistance
07:22
Interactions and Antibacterial Resistance

Lecture´s Description

Aminoglycoside Antibiotics are explained in this sqadia.com Lecture. First section of the lecture explains the Introduction and second lecture is designed for Pharmacokinetics. Mechanism of Action is explained in third section. Section four explains the Side Effects and Contraindications and section five is allocated for Interactions and Antibacterial Resistance.  

Introduction

Antibiotics are drugs that are used in the treatment or prevention of bacterial infections. Strictly speaking, antibiotics are natural substances produced by micro-organisms as opposed to semi-synthetic or synthetic antibiotics. Antibiotics form part of a wider range of antimicrobial agents, a group which also includes antifungals, antivirals, antiprotozoals and disinfectants. This group is also known as chemotherapeutic agents. The aminoglycoside group includes gentamicin, tobramycin, amikacin, netilmicin (not available in the U.S.), kanamycin, streptomycin, paromomycin, and neomycin. These drugs are used primarily to treat infections caused by aerobic gram-negative bacteria; streptomycin is an important agent for the treatment of tuberculosis, and paromomycin is used orally for intestinal amebiasis and in the management of hepatic coma.

Pharmacokinetics

The aminoglycosides are highly polar cations and therefore are very poorly absorbed from the GI tract. Less than 1% of a dose is absorbed after either oral or rectal administration. The drugs are not inactivated in the intestine and are eliminated quantitatively in the feces. Because of their polar nature, the aminoglycosides do not penetrate into most cells, the CNS, or the eye. Except for streptomycin, there is negligible binding of aminoglycosides to plasma albumin. Metabolism of the aminoglycosides does not occur in the host. The aminoglycosides are excreted almost entirely by glomerular filtration, and urine concentrations of 50-200 μg/mL are achieved.

Mechanism of Action

The aminoglycoside antibiotics are rapidly bactericidal. Bacterial killing is concentration dependent: The higher the concentration, the greater is the rate at which bacteria are killed. A post-antibiotic effect, that is, residual bactericidal activity persisting after the serum concentration has fallen below the minimum inhibitory concentration (MIC), also is characteristic of aminoglycoside antibiotics. Once inside the cell, aminoglycosides bind to polysomes. Aminoglycosides and β-lactams are synergistic and nearly always used in combination with a ß-lactam to extend coverage to possibly gram-positive microbes.

Side Effects and Contraindications

All aminoglycosides have the potential to produce reversible and irreversible vestibular, cochlear, and renal toxicity. These side effects complicate the use of these compounds and make their proper administration difficult. Retention of the aminoglycosides by the proximal tubular cells disrupts calcium-mediated transport processes, and this results in kidney damage ranging from mild, reversible renal impairment to severe, acute tubular necrosis, which can be irreversible. Vestibular and auditory dysfunction can follow the administration of any of the aminoglycosides, and ototoxicity may become a dose-limiting adverse effect. Aminoglycoside induced ototoxicity results in irreversible, bilateral high-frequency hearing loss and temporary vestibular hypofunction.

Interactions and Antibacterial Resistance

There are three principal mechanisms for the development of resistance: Synthesis of plasmid mediated bacterial transferase enzymes that can inactivate aminoglycosides. Mutation/deletion of porin channels resulting in decreased transport of aminoglycoside into the bacterial cytosol. By deletion or alteration of the receptor protein on 30S (Target) ribosomal unit because of mutations. Attachment of drug with 30S ribosomal unit is thus prevented. The role of aminoglycosides in the treatment of bacterial infections has diminished steadily as alternative drugs have become available. The aminoglycosides are narrow-spectrum agents, with their activity limited mainly to gram-negative aerobes.

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