aminogly a

8/13/2019 Aminogly A

1/38

AMINOGLYCOSIDES

The different members of this group

share many properties in common.


2/38


3/38

AMINOGLYCOSIDES

Streptomycin

Gentamicin

Tobramycin

Amikacin

Netilmicin

Kanamycin

Neomycin


4/38

AMINOGLYCOSIDES

Amino sugars linked

through glycosidic

bonds.

Polycations: This is

in part responsible

for many of their

sharedpharmacokinetic

properties


5/38

ANTIBACTERIAL

ACTIVITY

Primarily active against aerobic gram negative

bacteria.

Active against many staphylococci and certain

Mycobacteria.

Anaerobic bacteria are not susceptible.


6/38

SENSITIVITY AND

RESISTANCE


7/38

AMINOGLYCOSIDE

TRANSPORT

Transport across the cell membrane is by

active transport.

Antimicrobial activity is reduced in an

anaerobic environment and at low pH.


8/38

RESISTANCE

Cross-resistance occurs to varying degrees withthe different aminoglycosides.

Amikaciin


9/38

ABSORPTION AND

DISTRIBUTION

Oral bioavailability is low.

Once daily dosing (postantibiotic effect).

Distribution into most body tissues

including the CNS is low.


10/38

EXCRETION

Rapidly and almost entirely excreted by

glomerular filtration (proportional to

creatinine clearance).

Accumulation occurs with impaired renal

function.


11/38


12/38


13/38

THERAPEUTIC USES

Severe , complicated infections.

Often combined with -lactams.


14/38

STREPTOMYCIN

Bacterial endocarditis (combined with a

penicillin or vancomycin).

Tuberculosis.


15/38

Gentamicin, Tobramycin,

Netilmicin and Amikacin

Similar in clinical indications and range

of activity.

Gentamicin is often preferred but

resistance may limit its use.


16/38

THERAPEUTIC USES

Serious gram negative infections

especially those due to Pseudomonas,

Enterobacter, Klebsiella, Serratia etc.

UTIs, bacteremia, meningitis, infectedburns, pneumonia, osteomyelitis, ear

infections etc.


17/38

THERAPEUTIC USES

Severe Pseudomonasinfections are best

treated with one of these 4 AGs plus an

antipseudomonal penicillin orcephalosporin.

Gentamicin combined with a penicillin isoften used to treat bacterial endocarditis.


18/38

THERAPEUTIC USES

Tobramycin is often used in pseudomonal

infections.

Amikacin is used as the preferred agent

in hospitals.

Netilmicin- may be useful in resistant

infections.


19/38

DRUG INTERACTIONS

Antipseudomonal penicillins inactivateaminoglycosides.

Ethacrynic acid and other loop diuretics.

Nephrotoxic agents.

Neuromuscular blocking agents.


20/38


21/38

Inhibit protein synthesis by binding tothe 30S ribosomal subunit

Pharmacokinetics-Poorly absorbed

from the GI tract, Dont get into the

CNS very well, Rapidly excreted by

kidney

Toxicity-Ototoxicity, Nephrotoxicity,Neuromuscular blockade

SHARED PROPERTIES OF THE AMINOGLYCOSIDES


22/38

Streptomycin T.B., Endocarditis

Gentamicin Endocarditis, gram negative

infections, Pseudomonas

Tobramycin Gram negative infections,

Pseudomonas

Amikacin Reserve drug for gram negative-

infections

THERAPEUTIC USES OF THE AMINOGLYCOSIDES


23/38


24/38

50S

5

5

3

5 3AUG

5 3AUG

30S

3

AUG

X

Blocks initiation

Premature termination

Wrong amino acid is

incorporated

+ aminoglycosidemRNA translation

Effects of Aminoglycosides

Mature protein

Growing polypeptide

m nog ycos es on rote n ynt es s


25/38

30S

m nog ycos es on rote n ynt es s

50S

5 3Blocks initiation

35

Premature termination

5 3AUG

mRNA translation

+

Amino

Glycoside

35

Incorporation of wrong amino acid

X

Mature Protein

Growing Polypeptide


26/38

MECHANISM OF ACTION

Exact mechanism of cell death is

unknown.

Postantibiotic effect.


27/38

RESISTANCE

Alterations in ribosomal proteins.

Decreased permeability to the antibiotic.


28/38


29/38

TOXICITY

Ototoxicity (Vestibular and Auditory).

Nephrotoxicity.

Neuromuscular Blockade.


30/38


31/38

OTOTOXICITY

The most serious toxic effect

(uncommon, irreversible and

cumulative).

Caused by all the aminoglycosides


32/38


33/38

OTOTOXICITY

Several factors increase the risk.

Careful monitoring is important.


34/38


35/38


36/38

NEPHROTOXICITY

Several factors may increase the risk.

Reversible and usually mild.

Reduced excretion can lead to ototoxicity.


37/38

NEUROMUSCULAR

BLOCKADE

Rare but potentially serious.

Occurs at high concentrations ofaminoglycosides or in patients with anunderlying risk factor.

Acute neuromuscular blockade,respiratory paralysis and death canoccur.


38/38

ACh

ACh

ACh

ACh

AChACh

ACh

Ac + Ch

chol ineacetyltransferase

high affi nityuptake

vesicle

receptorACh esterase

ACh

tdh

Acety lCoA + Ch

TDH

7/90

Amino

Glycosides

aminogly a

Documents