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Name some Ribosomal Antibiotics groups
Name some Aminoglycosides
What are the Aminoglycosides mechanism of action?
Binds to 30 S subunit
of Bacterial Ribosome
- Bacteriocidal Inhibitors of Protein Synthesis
- -Blocks formation of initiation complex
- -Causes misreading of mRNA template - cidal
- -Inhibits translocation
- -Prevents polysome formation
- -Blocks subunit association
How do bacterial microbes deveplope resistnance??
- -Plasmid mediated formation of inactivating
- enzymes – group transferases
- -Inhibition of drug penetration into bacterial
- -Decrease affinity of 30 S subunit target site
- for antimicrobial agent
What is the Spectrum of Aminoglycosides?
- E coli
What are the clinical uses of Aminoglycosides?
Commonly used in combination with other drugs
Synergistic with Cell Wall Active drugs
Serious gram negative infections in hospitalized patients
Empirically for Neonatal infections
Second line against mycobacterial infections
- -Significant renal toxicity – acute tubular
- necrosis, reversible and dose related
- -Ototoxicity – auditory and vestibular may be irreversible, but is dose related
- -Not approved for use in pregnancy
- -Neuromuscular blockade
-Follow drug levels in host
Name the Tetracyclines
When are Tetracyclines antagonistic?
Antagonistic when used in combination with Beta lactam antibiotics
- -Tetracycline is excreted in urine, Doxycycline in feces
- - Tetracycline < Minocycline (8-18 hours)
What is the mechanism of Action/resistance of Tetracyclines?
- Mechanism of Action (Bacteriostatic)
- -Binds reversibly to 30 S subunit of bacterial ribosome - static
- -Inhibits attachment of aminoacyl-tRNA
- Mechanism of Resistance
- -Plasmid mediated facilitated efflux of
- drug from the bacterial organism
- -Decreased entry into the bacterial organism
What is the spectrum of Tetracyclines?
- -Gram Positive Staph and Strep *
- -Gram Negative Enterics *
- -Anaerobes *
- -Atypical agents – Mycoplasma, Chlamydia, Chancroid, Rickettsia,Borrelia, Entamoeba
What are some Clinical uses of Tetracyclines ?
- -Subacute Bronchitis due to H. influenzae and Strep pneumonia
- -Atypical pneumonia
- -STD’s; Prostatitis (Doxycycline)
- -Rocky Mountain Spotted Fever
- -Lyme Disease
What are the Toxicities of Tetracyclines?
- -GI – nausea, abdominal pain, diarrhea
- -Fetal and childhood effects on bones and teeth –
- -Hepatic necrosis (especially Doxy) may be fatal
- -Renal – renal tubular acidosis
- -CNS – Headache, Vestibular – dose dependent, Pseudotumor cebri
- -Jarisch - Herxheimer reaction
What is Tigecycline?
what is its mechanism?
A glycylcycline derivative of minocycline for iv use only.
High affinity binding to the 30 S unit of the ribosome which blocks amino-acyl tRNA binding
What is the pharmacology of Tigecycline?
What is its spectrum?
- It is Bacteriostatic.
- MRSA, MRSE, VRE,
- resistant pneumococci and enterococci.
- Acinetobacter and other gram negative
- aerobes and anaerobes, some mycobacteria, and mycoplasma, NOT pseudomonas
Synergistic with Rifampin
Skin and skin structure infections
Not approved for children
What is the Toxicity of Tigecycline?
- Cross hypersensitivity to tetracyclines
- Nausea and vomiting $
- Headache and pseudotumor cebri $
- Possible bone and tooth discoloration $
- Transaminase elevation
What is Chloramphenicol?
What is its Mechanism of action?
- Unique antimicrobial, only one in its class,
- rarely used due its feared toxicity
- -Binds 50 S subunit of bacterial ribosome
- -Inhibits peptidyl transferase
-inhibits Cytochrome p450
What is the Mechanism of resistance of Chloramphenicol?
- Plasmid mediated production of antibiotic
- inactivating enzyme $
- Reduced permeability of bacterial organism to
What its the Spectrum of Chloramphenicols?
Not Staphylococci, not pseudomonas
H. influenzae, Neisseria meningitides, Salmonella
What is the Clinical use of Chloramphenicols?
- Toxicity has almost completely truncated its use in the U.S. except for specific indications in which it is the drug of last choice:
- Brain Abscess
- Typhoid fever
- Rocky Mountain Spotted Fever
What is the Toxicity of Chloramphenicols?
Idiosyncratic Aplastic anemia, irreversible 1/40,000 $$$
Dose related Aplastic anemia
Gray baby syndrome – inability to conjugate chloramphenicol because of immaturity/decreased levels of glucuronosyl transferase $$$