Aminoglycosides Flashcards
(38 cards)
What are aminoglycosides❓
Antibiotics that contain amino sugars in glycosidic linkage
What are the properties of aminoglycosides❓
They are:
Polar cations
Not adequately absorbed after oral administration
Inadequate conc found in CSF
Relatively rapidly excreted
List some examples of aminoglycosides
Gentamicin Tobramycin Amikacin Netilmicin Kanamycin Streptomycin Neomycin
What are aminoglycosides used in treating❓
Primarily gram-negative bacterial infections
How could antimicrobial resistance be brought about❓
Aminoglycoside in the periplasmic space may be altered by microbial enzymes that phosphorylate adenylate or aceytylate specific hydroxyl or amino groups
Altered aminglycosides:
🚫bind effectively to ribosomes
🚫interfere with protein synthesis
Plasmids play a role in spread of resistance to other antibiotics
What are the limitations of aminoglycosides❓
Which aminoglycosides impact auditory function more❓
Which aminoglycosides have predominant vestibular effects❓
- Ototoxicity (*older patients are more susceptible)
Nephrotoxicity
Dysfunction of optic nerve
Peripheral neuritis
Neuromuscular blockade (⬆️dose of intraperitoneal/pericardial instillations) - Amikacin
Kanamycin
Neomycin - Streptomycin
Gentamicin
*Tobramycin affect both equally
Streptomycin was first isolated from which organism❓
In what year❓
Streptomyces griseus
1943
Gentamycin and netilmicin are from species of which organism❓
Actinomycete micromonospora
Describe the chemistry of aminoglycosides
- Hexose or aminocyclitol nucleus (usually in the center)
- H/A Nucleus is either streptidine (streptomycin) or 2-deoxystreptocine (all other aminoglycosides)
- 2/more aminosugars joined by a glycosidic linkage to the nucleus
What is the mode of transport of aminoglycosides❓
Transport/Phase 1/Energy Dependent state:
Diffusion through aqueous channel formed by porin proteins in the outer membrane of gram-negative bacteria
⬇️
Periplasmic space
⬇️
Generation of energy (membrane potential) to drive permeation of aminoglycosides into inner membrane
⬇️EDPhase2
Aminoglycosides bind to polysomes
⬇️
Inhibit the synthesis of proteins
Describe the mode of action of aminoglycosides
Rapidly bactericidal
Disrupt normal cycle of ribosomal function
Interfere w 1st step of protein synthesis
Cause accumulation of abnormal initiation complexes/streptomycin monosomes
Cause misreading of genetic code of mRNA template to produce incorrect proteins
⬇️translation of mRNA
What are the inhibitors of aminoglycoside transport in bacteria❓
How is relevant in practice❓
1. Divalent cations eg Ca2+ Hyperosmolality ⬇️pH Anaerobic environment
*impair the ability of bacteria to maintain membrane potential required for the transport of aminoglycosides
- Antimicrobial activity is markedly ⬇️ in anaerobic conditions or hyperosmotic acidic urine eg liver abscess
The intracellular site of action of the aminoglycosides is the _____ribosomal subunit
What does it comprise❓
What is the relevance of this❓
30s
50s (other A. apart from streptomycin)
21proteins
A single 165 molecule of RNA
Alteration of at least 3 of these proteins affect the action of streptomycin
What are the factors that could be responsible for antimicrobial resistance to aminoglycosides?
Inactivation of the drug by bacterial enzymes
Failure of permeation of antibiotics
⬇️affinity of the drug for bacterial ribosome
Oxygen-deprived infections
The antibacterial activity of aminoglycosides is mainly against gram negative bacilli
True or false
True
Action against gram positive bacteria is limited
Gentamicin and tobramycin are active invitro against >95% strains of staphylococcus aureus
True or false
Should they be administered alone❓
True
No
What are sensitive microorganisms❓
Microorganisms inhibited by peak conc. of antibiotics that can be achieved clinically in plasma but that are not associated with ⬆️toxicity
4-8❓/ml for gentamicin, tobramycin and netilmicin
8-16 ❓/ml for amikacin and kanamycin
Which aminoglycosides have retained their activity against nosocomial infections❓
Why❓
Amikacin
Netilmicin
Resistance to aminoglycoside metabolizing enzymes
What can cause a ⬇️absorption of aminoglycosides❓
Absorption of Neomycin is not altered in the presence of inflammatory bowel disease. True or false
Bacilliary dysentery
True
What could cause an accumulation of aminoglycosides❓
Renal impairment
Instillation into body cavities with serosal surfaces
Topical application to large wounds or cutaneous ulcers
A rapid absorption of aminoglycoside should be expected with what form of administration at what time intervals❓
IM/SC injection:
Peak plasma conc. -30-90min
IV injection:
Peak plasma conc -30min
Describe the distribution of aminoglycosides
What is the volume of distribution❓
- Excluded from most cells, CNS and the eye due to polarity
⬇️conc. in secretions and tissues
⬆️conc. in renal cortex (Nephrotoxicity)
⬆️conc in endolymph, perilymph of inner ear (Ototoxicity)
2.
25% of body weight, approx. the volume of ECF
Inflammation could ⬆️ the penetration of aminoglycosides into peritoneal and pericardial cavities
True or false
True
How would you administer aminoglycosides to an adult with gram negative bacillary meningitis❓
Intrathecal ad
OR
Intraventricular ad.
*Not needful in neonates who have immature BBB
