UNIVERSITY„OVIDIUS“ OF CONSTANTS

FARMACEUTICAL UNIVERSITY

AMINOGLYCOSIDES
ENGLISH LANGUAGE

STUDENTS
PROF. COROBAN COSTEL TANASE STEFAN CORINA
PINTOIU ANDREICA VALENTINA
ASISTENTA DE FARMACIE
ANUL II
CONSTANTA 2020
 CONTENTS
1. AMINOGLYCOSIDES – DEFINITION

2. THE ORIGIN OF AMINOGLOCOSIDES

3. AMINOGLYCOSIDES – CLASSIFICATION GENARATION I

4. AMINOGLYCOSIDES – CLASSIFICATION GENARATION II

5. AMINOGLYCOSIDES – CLASSIFICATION GENARATION III

6. REPRESENTATIVES OF AMINOGLYCOSES

7. MECHANISM OF ACTION OF AMINOGLYCOSIDES

8. AMINOGLYCOSIDES - ANTIBACTERIAL SPECTRUM

9. AMINOGLYCOSIDES - PHARMACOKINETICS

10. AMINOGLYCOSIDES - INDICATIONS

11. AMINOGLYCOSIDES - CONTRAINDICATIONS

12. AMINOGLYCOSIDES - ADVERSE EFFECTS

13. AMINOGLYCOSIDES - DOSES FOR ADULT AND CHILD USE

14. AMINOGLYCOSIDES - PHARMACOTOXICOLOGY

15. AMINOGLYCOSIDE RESISTANT

16. CAUSES OF AMINOGLYCOSIDE RESISTANCE

17. CONCLUSIONS

18. BIBLIOGRAPHY
AMINOGLYCOSIDES - DEFINITION

Aminoglycosides are antibiotics with action

on Gram-negative bacteria, which work through
inhibition of protein synthesis and containing in
their structure o amino group glycoside entity.
Aminoglycosides have bactericidal activity on
Gram-negative aerobic bacteria and anaerobic
bacilli, at species in which the phenomenon of
resistance to antibiotics.
Activity is lacking on Gram-positive bacteria and
Gram-negative anaerobic bacteria.
 THE ORIGIN OF AMINOGLOCOSIDES

Aminoglycosides are a group of antibiotics obtained in origin, from various

species of Streptomyces.
Depending on the species from which they were synthesized, there are 4
families:
 Streptomycin family, extracted from Streptomyces griseus, which is the
serial head of the aminoglycoside class, being the first discovered (in 1944).
 Neomycin family, extracted from Streptomyces fradiae;
 Kanamycin family, extracted from Streptomyces kanamyceticus;
 Gentamicin family, secreted by the actinomycete species Micromollospora,
isolated in 1969.
 • Generation I
 Streptomycin;
 Kanamycin;
 Neomycin;
AMINOGLYCOSIDES -  Paromomycin;
CLASSIFICATION  Spectinomycin;
Therapeutic use is limited:
 Streptomycin is used more in
tuberculosis;
 Spectinomycin in gonorrhea;
 Neomycin used exclusively locally.
AMINOGLYCOSIDES – CLASSIFICATION GENARATION II

• Generation II
 Gentamicin;
 Tobramycin;
 Spiromycin.
The spectrum includes gram + and
gram - and bacteria
 are used parenterally (injections)
in infections with these germs.
AMINOGLYCOSIDES – CLASSIFICATION
GENARATION III

• Generation III
 Amikacina;
 Dibekacin;
 Netilmycin;

 have a broad antibacterial spectrum

 bacterial resistance is installed more slowly
 lower systemic toxicity.
They are active on gram +, gram - bacteria,
inclusive on resistant germs.
REPRESENTATIVES OF
AMINOGLYCOSES

• Streptomycin;
• Gentamicin;
• Tobramycin;
• Amikacin;
• Kanamycin;
• Neomycin;
• Sisomycin;
• Netilmycine;
• Paromomycin;
• Spectinomycin;
• Framycetin;
• Isepamicin;
• Dibekamicin.
MECHANISM OF ACTION
OF AMINOGLYCOSIDES

‣ Aminoglycosides irreversibly inhibit the synthesis of

bacterial proteins, having a bactericidal action.
‣ After diffusion through the outer membrane channels,
they are actively transported transmembrane through an
oxygen-dependent process.
‣ This active transport is inhibited in situations of low
intracellular pH or anaerobiosis and stimulated by
antibiotics that inhibit the formation of the bacterial wall,
such as penicillins, cephalosporins, Vancomycin.
‣ Aminoglycosides are rapidly bactericidal antibiotics, and
the combination with beta-lactams, fluoroquinolones, and
polypeptide antibiotics is synergistic.
 AMINOGLYCOSIDES - ANTIBACTERIAL SPECTRUM

a) active on:

• Staphylococci (including Staphylococcus • Pseudomonas aeruginosa;

aureus); • Francisella tularensis;
• Escherichia coli; • Mycobacterium tuberculosis;
• Klebsiella pneumoniae; • Vibrio cholerae;
• Salmonella spp; • Serratia marcenses;
• Shigella spp; • Enterobacter aerogenes;
• Yersinia pesti; • Listeria monocytogenes;
• Proteus spp; • Acinetobacter baumanii;
• Haemophilus influenzae; • Brucella melitensis, Brucella
abortus.
 b) inactive on:

• strictly anaerobic bacteria

(Clostridium spp, Bacteroidess
spp);
• Treponema pallidum;
• Streptococcus pneumoniae.

AMINOGLYCOSIDES -
ANTIBACTERIAL
SPECTRUM
AMINOGLYCOSIDES -
PHARMACOKINETICS

1) Route of administration for aminoglycosides:

• intramuscular or intravenous for systemic infections;

• intrarachidian for meningitis (except Neomycin);
• orally (Neomycin, Streptomycin) for intestinal infections,
reduction of intestinal flora before surgery or in hepato-
portal encephalopathy / acute liver failure;
• topically, on the skin and mucous membranes (Neomycin,
Gentamicin, Kanamycin, Tobramycin);
• aerosols, due to the fact that it concentrates very well in the
lungs.
 2) Distribution of aminoglycosides in the body:

AMINOGLYCOSIDES - • the level of aminoglycosides in the tissues is usually low, their

penetration into various body fluids is variable;
PHARMACOKINETICS
• the concentration in the cerebrospinal fluid is low;

• high concentrations are in the kidneys in the renal cortex and in

the ear in the endolymph and perilymph of the inner ear;
• crosses the feto-placental barrier and can accumulate in fetal
plasma and amniotic fluid;
• does not cross the intestinal and blood-brain barrier;
• are removed from the body by hemodialysis.
AMINOGLYCOSIDES -
INDICATIONS

of choice for empirical therapy of severe infections;

• tuberculoză: Streptomicina;
• osteomyelitis: Gentamicin;
• hepato-portal encephalopathy, preoperative preparation of colon surgery: Neomycin;
• chronic complicated urinary tract infections (uncomplicated urinary tract infections respond
well to Trimethoprim, Sulfamethoxazole, Ciprofloxacin);
• tularemia caused by Francisella tularensis: Streptomycin;
• gonococcal infections with penicillin-resistant strains: Spectinomycin;
• antiparasitic used against Entamoeba histolytica, Cryptosporidium spp and Leishmania spp:
Paromycin;
• pseudomonas aeruginosa: hospital nosocomial infections, especially in intensive care units,
septic arthritis in immunocompromised patients: Gentamicin, Tobramycin, Amikacin and
Netilmycin.
AMINOGLYCOSIDES
CONTRAINDICATIONS

• pregnancy;
• myasthenia gravis;
• in the perioperative period (in order not to interfere with curarizants, ie
neuromuscular blockers that relax and paralyze striated muscles
during surgery);
• ENT pathology and chronic kidney disease (use with caution) !!
AMINOGLYCOSIDES - ADVERSE EFFECTS

• nephrotoxicity due to acute tubular necrosis - which is potentially reversible after

discontinuation of therapy and is accelerated by the simultaneous administration
of loop diuretics (Furosemide);
• ototoxicity hearing loss and deafness (due to cochlear toxicity), vertigo,
nystagmus (due to vestibular lesions);
• neuro-muscular paralysis is rare, but with lethal potential (respiratory paralysis,
respiratory arrest); occurs after intrapleural or intraperitoneal administration of
high doses of aminoglycosides; the effect is reversible if promptly administered
Neostigmine or calcium gluconate;
• contact dermatitis;
• pain at the injection site.
 AMINOGLYCOSIDES - DOSES
FOR ADULT AND CHILD USE

Aminoglycoside Doses in adults Doses in children

STREPTOMYCIN
0.5 - 1 g / day (24 h) 30 - 50 mg / kg body weight / day
GENTAMICIN 3 mg / kg body weight / day (8, 12, 24 h) 2 - 4 mg / kg body weight /

KANAMYCIN 15 mg / kg body weight / day (12 h) 15 mg / kg body weight / day

AMIKACIN 15 mg / kg body weight / day (12 - 24 h) 15 mg / kg body weight / day

TOBRAMYCIN
3 - 5 mg / kg body weight / day (8, 12, 24 h) 3 mg / kg body weight / day

ISEPAMICIN _
15 mg / kg body weight / day (24 h)

NETILMYCINE
4 - 7 mg / kg body weight / day (8, 12, 24 h) 6 - 9 mg / kg body weight / day

SISOMYCIN
3 mg / kg body weight / day (8, 12, 24 h) 3 - 5 mg / kg body weight / day

DIBEKACIN _
3 mg / kg body weight / day (12 - 24 h)
AMINOGLYCOSIDES
PHARMACOTOXICOLOGY

1. Ototoxicity - causes irreversible deafness.

 Aminoglycosides cause the destruction of sensory cells and degeneration of the acoustic nerve. Lesions can be cochlear and vestibular (cochlea = the
part of the inner ear intended for hearing;
vestibule - is the organ of balance)
 Cochlear lesions are manifested by:
- tinnitus (tinnitus = noises or earaches);
- the feeling of clogged ears;
- deafness.
 Vestibular lesions are manifested by:
- balance disorders (due to irreversible toxic damage to the pair VIII a cranial nerves);
- headache;
- nausea;
- vomiting;
- nystagmus (involuntary and jerky movements of the horizontal eyes or vertical).
AMINOGLYCOSIDES
PHARMACOTOXICOL
OGY
2. Nephrotoxicity
occurs due to accumulation
aminoglycosides in the renal parenchyma.
 AMINOGLYCOSIDE RESISTANT

• Bacteria are considered resistant when

their development is not stopped by the
maximum concentration of antibiotic
tolerated by the host organism. Bacterial
species that normally respond to a drug in
chronic, long-term treatment can develop
resistance.
• Many bacteria have adapted through
mutations, and have developed more
virulent strains, many of which are
resistant to multiple antibiotics.
 The mechanisms by which bacteria develop
resistance are:

 decreased drug uptake when the oxygen-

CAUSES OF dependent transport system for aminoglycosides
AMINOGLYCOSIDE is absent;
RESISTANCE  mutations in the ribosomes, which change the
binding site of aminoglycosides, so implicitly the
binding to the 30S subunit of ribosomes will be
compromised;
 synthesis of enzymes that modify and inactivate
aminoglycosides, such as phospho-transferase,
acetyl-transferase, nucleotidyl-transferase.
 The main causes of antibiotic
resistance:

 free access to antibiotics;

 unjustified administration of
antibiotics;
 the absence of guidelines for the
use of antibiotics - specific to each
region;
 the increase in the number of
invasive procedures (in which
antibiotics are administered for
prophylactic purposes) and in-
hospital infections with bacteria
whose strains are increasingly
CONCLUSIONS aggressive and resistant to
standard antibiotic.
BIBLIOGRAPHY

1. Stroescu, V., Bazele farmacologice ale practicii medicale, Ed. Medicalå, Bucuresti, 2001
2. Dr. Raghu Prasada, Assistant Professor, Dept.of Pharmacology Ssims & RC
3. Cristea, Aurelia, N., Farmacie Clinica, Vol II, Editura Medicala, Bucuresti, 2017
 Thank you
for your attention!