AminoglycosidesMD. ATIQUR RAHMAN

Objectives

Aminoglycosides

Classification of Aminoglycosides

Pharmacokinetics

Mechanism of Action Aminoglycosides

Adverse Effects

Clinical uses

What is Aminoglycosides

Aminoglycosides are a group of bactericidal antibiotics, which act by inhibiting bacterial protein synthesis.

Classification of Aminoglycosides

Aminoglycosides

mycin (Streptomyces)

Streptomycin

Kanamycin

Neomycin

Hygromycin B · Spectinomycin

Paromomycin

micin (Micromonospora)

Amikacin

Gentamicin

Verdamicin

Astromicin

Pharmacokinetics

Structurally related amino sugars attached by glycosidic linkages

Polar compounds

Not absorbed orally

Given intramuscularly or intravenously for systemic effects

Limited tissue penetration

Do not readily cross the blood-brain barrier

Plasma levels are affected by changes in renal function

Pharmacokinetics

Major mode of excretion

Glomerular filtration

Excretion is directly proportional to creatinine clearance

With normal renal function, elimination half-life is 2-3 h

Dosage adjustment must be made in renal insufficiency to avoid

toxic accumulation

Monitoring plasma levels is needed for safe and effective dosage

selection and adjustment

Pharmacokinetics

For traditional dosing regimens

2 or 3 times daily

Peak serum levels

Measured at 30-60 minutes after administration

Trough serum levels

Measured just before the next dose

Mechanism of Action

Interferes with bacterial protein synthesis by binding to the 30S

ribosomal subunit. An oxygen-dependent transport system is

necessary for aminoglycosides to reach their target site;the transport system is inhibited by divalent cations (Ca++,

Mg++), low pH, anaerobiasis, and hyperosmolarity.

Rapidly bactericidal.

Concentration-dependent bactericidal activity, which means that

the rate and extent of bacterial killing increases as drug

concentrations increase.

Post-antibiotic effect (ie): continued killing of bacteria despiteantibiotic levels below the MIC of the organism.

Mechanism of Action in image

Fig: 1 Fig: 2 Fig: 3

Fig: 4 Fig: 5 Fig: 6

Mechanism of Action in image

Fig: 7 Fig: 8 Fig: 9

Adverse Effects

Nephrotoxicity

A wide variation in the incidence.

Usually reversible. Increase in serum creatinine and BUN.

Otoxicity

Cochlear and vestibular.

Bilateral and permanent.

Neuromuscular blockade

Low incidence.

Enhanced by concomitant administration of neuromuscular blocking drugs and anesthetics, patients with hypocalcemia or miastenia gravis or when the i.p or rapid i.v injection are used.

Other adverse effects

Hypersensitivity reactions, superinfection, CNS effects and GI disturbances.

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

Summery

Reference

http://www.slideshare.net/blue89/aminoglycoside?qid=b5a38d77-

faaf-48f5-8d80-ebe4624bb73b&v=default&b=&from_search=4

http://pharmacologycorner.com/protein-synthesis-inhibitors-aminoglycosides-mechanism-of-action-animation-classification-of-

agents/

http://www.merckmanuals.com/professional/infectious_diseases/ba

cteria_and_antibacterial_drugs/aminoglycosides.html

http://www.slideshare.net/sijo28/45aminoglycosides?qid=b5a38d77-

faaf-48f5-8d80-ebe4624bb73b&v=default&b=&from_search=6

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