Aminoglycosides are a class of antibiotics that are commonly used to treat various bacterial infections. These antibiotics are primarily effective against Gram-negative bacteria and some Gram-positive bacteria. Here are some detailed notes on the pharmacology of aminoglycosides: 1. Mechanism of Action: Aminoglycosides inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit, causing misreading of mRNA and ultimately leading to the production of nonfunctional or toxic peptides. This bactericidal action disrupts bacterial growth and reproduction. 2. Spectrum of Activity: Aminoglycosides are particularly effective against Gram-negative bacteria, including Escherichia coli, Klebsiella, Pseudomonas, and Proteus species. They also have some activity against certain Gram-positive bacteria such as Staphylococcus and Streptococcus species. Aminoglycosides are often used in combination with other antibiotics to broaden their spectrum of activity. 3. Pharmacokinetics: Absorption: Aminoglycosides are poorly absorbed orally and are typically administered via intramuscular or intravenous routes. Distribution: They have limited tissue penetration, mainly staying in the extracellular space. They do not readily penetrate the central nervous system. Elimination: Aminoglycosides are primarily eliminated by the kidneys, and their elimination rate is directly proportional to the glomerular filtration rate (GFR). 4. Dosing and Administration: Aminoglycosides are usually given in divided doses to maintain therapeutic drug levels while minimizing toxicity. Therapeutic drug monitoring is essential to adjust dosing, as aminoglycosides have a narrow therapeutic index, meaning there is a small margin between therapeutic and toxic concentrations. 5. Adverse Effects: Nephrotoxicity: Aminoglycosides can cause kidney damage, especially if high levels persist in the bloodstream. Monitoring renal function is crucial during therapy. Ototoxicity: These antibiotics can damage the inner ear, leading to hearing loss and balance problems. Neuromuscular Blockade: High doses or prolonged use of aminoglycosides can result in muscle weakness and paralysis. Allergic Reactions: While rare, allergic reactions can occur, leading to rash, fever, and other symptoms. 6. Resistance: Resistance to aminoglycosides can develop through several mechanisms, including the production of modifying enzymes that inactivate the drug, reduced drug uptake, and alterations in the ribosomal target site. 7. Clinical Uses: Aminoglycosides are used for severe bacterial infections, especially when resistance is a concern. Common indications include complicated urinary tract infections, intra-abdominal infections, sepsis, and respiratory tract infections. They are also used as prophylaxis in surgical procedures and for empiric treatment of febrile neutropenia in cancer patients.

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Aminoglycosides
-Prajwal Waman Ghatol

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Introduction
Common Properties of Aminoglycosides
Classification
Mechanism Of Action
Dosing
Adverse Effects
Therapeutic Uses
Brief discussion of some aminoglycosides
What will we
learn?

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01.
02.
03.
These are a group or natural
and semisynthetic antibiotics
having polybasic amino groups
linked glycosidically to two or
more aminosugar residues.
Introduction
Streptomycin was the first
member discovered in 1944 by
Waksman and his colleagues.
Others were produced later,
and now aminoglycosides are a
sizable family.
All aminoglycosides are produced
by soil actinomycetes and have
many common properties which
we will discuss now.

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01.
They contain two or more aminosugars attached by
glycosidic linkage to hexose ring.
Common
Properties
of
Aminoglycosides
02.
03.
04.
05.
They are highly polar compounds, hence poorly absorbed
from the GI tract. They are administered by parenteral route
(i.m./i.v.) for systemic effect.
.
They are mainly distributed into extracellular fluid
and poorly penetrate into the CSF.
They are not metabolized in the body.
They are excreted unchanged in urine.

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06.
They have bactericidal action against gram-negative
aerobes and are more active
at alkaline pH.
Common
Properties
of
Aminoglycosides
07.
08.
09.
They exhibit partial cross-resistance among them.
Transport of aminoglycosides into the bacterial cell
requires oxygen; hence, anaerobes are resistant to
aminoglycosides.
They cause ototoxicity and nephrotoxicity.

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Classification

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Mechanism of Action

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Mechanisms of
Bacterial Resistance.
Bacterial resistance to aminoglycosides is due to
(i) inactivation of the drug by bacterial enzymes,
(ii) decreased entry of drug into bacterial cell and
(iii) decreased affinity of the drug for the ribosomes.

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DOSING
Aminoglycosides Exhibit
1. A concentration-dependent killing effect – higher the plasma
concentration, more of the bacteria killed rapidly.
2. . A postantibiotic effect – bactericidal effect is present even when
serum concentration falls below MIC. Therefore, once-daily dosing
regimen is effective.

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DOSING
1. Once-daily dosing regimen – total daily dose is given as a single injection. It
is preferred because it:
 Is as effective as multiple-dose regimen. Higher peak plasma concentration
is achieved following single dose.
 Is safer than multiple-dose regimen. The plasma trough concentration of
aminoglycosides remains below threshold levels for toxicity for a long
period of time.
 Is convenient.

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DOSING
2. Multiple-daily dosing regimen – the total daily dose is administered in
two or three equally divided doses.
Once-daily dosing regimen is not preferred in bacterial endocarditis,
children and patients with renal impairment. Dose adjustment of
aminoglycosides is done according to body weight and creatinine
clearance.

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Adverse Effects
1. OTOTOXICITY: Vestibular and cochlear dysfunctions can occur
due to VIII cranial nerve damage. Aminoglycosides get
concentrated in the perilymph and endolymph of the inner ear
which can lead to progressive damage to vestibular and cochlear
hair cells.
The important risk factors for ototoxicity are the following:
(a) Elderly patients
(b) Repeated courses of aminoglycosides
(c) Persistently increased concentration of the drug in plasma
(d) Patients with pre existing auditory impairment
(e) Concurrent use of other ototoxic drugs, such as vancomycin, minocycline and
loop diuretics

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Adverse Effects
2. Nephrotoxicity: Aminoglycosides get concentrated in renal cortex
and produce nephrotoxicity, which is usually reversible on
discontinuation of the drug. The incidence of nephrotoxicity is
highest with neomycin and least with streptomycin.
3. Neuromuscular blocking effect: Apnoea and muscular paralysis
have been reported. It may be reversed by administration of
calcium salt. Aminoglycosides inhibit release of acetylcholine from
motor nerve. Myasthenic patients are more susceptible to
neuromuscular blocking effect of these drugs; hence, they should
be avoided.

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Adverse Effects
4. HYPERSENSITIVITY REACTIONS are rare; occasionally skin
rashes, drug fever and eosinophilia can occur. Cross-sensitivity
between aminoglycosides may occur.
5. Use of aminoglycosides during pregnancy may cause ototoxicity
in fetus.

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Brief discussion of some aminoglycosides
STREPTOMYCIN
Streptomycin was the first aminoglycoside discovered in 1944.
The common properties, mechanism of action and adverse effects are explained above.
Uses. Streptomycin is one of the first-line drugs for TB and is used in combination with other
antitubercular drugs. The other uses include tularemia, plague and brucellosis.
GENTAMICIN
It is the most commonly used aminoglycoside antibiotic for aerobic gram-negative bacillary
infections due to E. coli, Klebsiella, Proteus, Enterobacter and P. aeruginosa. It is also
effective against gram-positive infections – enterococci, S.viridans and staphylococci but
not M. tuberculosis. It is available for parenteral and topical administration.

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Brief discussion of some aminoglycosides

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Brief discussion of some aminoglycosides

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Brief discussion of some aminoglycosides

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Therapeutic uses Gentamicin and other
aminoglycosides
Among aminoglycosides, gentamicin is the most commonly used because it
is cheap and effective against most of the aerobic gram-negative bacilli.
1. Severe aerobic gram-negative bacillary infections :-
• Urinary tract infection with pyelonephritis
• Pneumonia
• Meningitis
• Osteomyelitis
• Septicaemia
• Peritonitis
• Infected burns
Due to
Pseudomonas,
Klebsiella, E. coli,
Proteus, etc.

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Therapeutic uses Gentamicin and other
aminoglycosides
■ Gentamicin, tobramycin, amikacin and netilmicin are effective against P.
aeruginosa.
■ Amikacin and netilmicin are used for treatment of serious nosocomial
infections due to gram-negative bacilli.
■ Aminoglycosides are often used in combination with penicillins/third-
generation cephalosporins in these conditions.

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Therapeutic Uses
2. Bacterial endocarditis due to S.viridans and Enterococcus: Gentamicin is
used in combination with a penicillin or vancomycin. Combination broadens
the spectrum of activity, produces synergistic effect and decreases
emergence of resistance.
■ Penicillin G " gentamicin for S.viridans.
■ Ampicillin " gentamicin for Enterococcus.
■ Vancomycin " gentamicin for Enterococcus (patients allergic to B-lactam
antibiotics).
■ Gentamicin and ampicillin combination is also used for the prophylaxis of
endocarditis in high-risk patients before surgical procedures.

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Therapeutic Uses
3. TB: Streptomycin, kanamycin and amikacin are used in the treatment of TB.
4. OTHER GRAM-NEGATIVE INFECTIONS
■ Plague: Streptomycin/gentamicin is used intramuscularly.
■ Brucellosis: Streptomycin/gentamicin is used in combination with
doxycycline.
■ Tularaemia: Streptomycin or gentamicin is the drug of choice. FQs and
tetracyclines are also effective.
5. Gentamicin, tobramycin, neomycin, sisomicin, framycetin, etc., are used
topically for gram-negative skin, eye and ear infections.

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Thank you!