-
What are the macrolides/ Ketolides?
Name them.
- - They are protein synthesis inhibitors
- Erythromycin
- Telithromycin
- Azithromycin
- Clarithromycin
-
What is some of the Pharmacology of The Macrolides?
Extretion?
Note: What can prolong their efficacy?
- -Concentrates in respiratory secretions (So, can be used to treat URT infections, pharyngitis, sinusitis, pneumonia)
- -Azithromycin is concentrated in *phagocytic cells and other tissues
- -Hepatic metabolism and excretion, some urinary extretion (Azithromycin)
* Efficacy can be prolonged by their concentrations in secretions.
-
What is the Mechanism of action of the macrolides?
- -Bind to 50 S subunit of bacterial ribosome
- -Prevents ribosomal translocation down m-RNA
- -Generally Bacteriostatic
-
What is bacteriostatic mean?
preventing bacteria from growing and multiplying but possibly not killing them
-
What are some mechanisms of Resistance to Macrolides?
- -Plasmid mediated alteration (by a methylase
- encoded by the erm beta gene) of receptor on ribosome – high level resistance {eg Strep pneumo}
- -Production of inactivating enzymes
- -Decrease in permeability of bacterial organism into the antimicrobial agent.
- -Increased efflux
(mediated by mefA gene) - low level resistance
-
What are the Levels of Pneumococcal resistance of the Macrolides and others?
- Penicillin V - 15%
- Erythromycin - 35% (not a good one)
- Augmentin - 8% (good)
- Cefpodoxime - 20%
- Azythromycin - 35% (not a good one)
-
Why are macrolides good for pneumococcal infections?
What is the drug of choice for otitus media?
-becaue they concentrat in the Respiratory secretions
- Augmentin- due to resistance pneumococi
-
What is the spectrum of Macrolides?
- Sensitive gram positive organisms; not enterococcus
- Some anaerobes
- Salmonella (Typhoid fever)*
- Legionnaire’s disease *
- Mycoplasma *
- Chlamydia
- Bordetella pertussis *
- Campylobacter *
- Atypical Mycobacteria *
-
What is the Drug of Choice for:
Salmonella Typhoid fever infection?
Bordetella Pertussis (Whooping Cough)?
MAI?
Atypical TB?
- Azythromycin
- Clarithromycin or Erythromycin
- Clarithromycin
- Clarithromycin
-
What are the Clinical Uses for the Macrolides?
When are they Contraindicated? except which?
Penicillin substitute for respiratory bacterial infections
Atypical pneumonia; Whooping cough (Clarithromycin)
MAI (Seen in AIDS) (Clarithromycin)
Resistant Salmonella (Azythromycin)
Contraindicated in pregnancy (except Azithromycin)
-
What is the Clinical use and the Spectrum of Telithromycin?
Where is it metabolized?
- Metabolized in the liver – half by CYP 450
- and half by CYP 349
PCN resistant pneumococci, H. flu, M. catarrhalis, and atypicals: B. pertussis, mycoplasma, legionella, chlamydia
-
What is the Toxcitity of Telithromycin?
- Blurred Vision
- GI disturbances
- Prolonged QT Interval
- Exacerbation of Myasthenia gravis
- Multiple drug interactions
-
What other drug is similar to microlides due to some cross resistance?
- - Clindamycin----- a Protein Synthesis Inhibitor
- -A Lincosamide Antibiotic - static
- -Good oral absorption (90%) and tissue
- penetration (not cns,eye)
- - Resistance is usually due to bacterial increased efflux
-
Clindamycin – Spectrum and Toxicity
- -Excellent drug for gram positive infections (including Staph aureus (even MRSA!!!!)
- -Excellent activity against anaerobes
- Lincosamides like Clindamycin destroy the
- normal intestinal flora, which allows C. difficile to grow & secrete its toxin, causing a bloody
- diarrhea
- -DOC to treat C. difficile overgrowth is Metronidazole then Vancomycin
-
What is Synercid?
How is it metabolized?
-A Streptogramin combination (quinupristin/dalfopristin 30:70)
-Metabolized and excreted by the liver. Only for IV use T1/2 1 to 3 hours
-
What is Synercid's Mechanism of action/ resistance?
Mechanism of Action
-Binds to 50 S subunit (unique sites)
- -Prevents ribosome from translocating down the mRNA and prevents protein synthesis at the elongation step
- -Bacteriocidal- Actually kills bacteria
Mechanism of Resistance
- -Mediated by usual three mechanisms
- -Resistance develops quite rapidly
-
What is the Spectrum of Synercid?
What is its toxicity?
- -Staph aureus and epidermidis
- -Strep pyogenes and aglacia
- -Some enterococci
- -Only treats Gram + Organisms
- Toxicity $$
- Precludes widespread use: drug interactions,
- phlebitis 40%, jaundice 30%, arthralgia
- and myalgia 20%
-
What is Linzolid?
What is it used to treat?
Where is it metabolized? better penetration where?
- -An Oxazolidione
- Available in oral and intravenous formulations
- Used to treat Vancomycin resistant microorganisms
- -Metabolized in liver; excreted by kidney
- -Better penetration into lung (pneumonia) than Vancomycin
-
What is Linzolids Mechanism of Action/Resistance?
- Mechanism of Action
- -Binds to 50 S subunit (unique site)
- -Inhibits initiation complex and translocation of tRNA
- -Generally Bacteriostatic
- Mechanismof Resistance
- -Decreased affinity of antimicrobial agent to bacterial target site
-
What is Linzolides Spectrum and Toxicity?
- All aerobic gram positive organisms especially resistant staph, strep and enterococci
- Toxicity
- -Thrombocytopenia and neutropenia (reversable
- bone marrow suppression)
- -weak MAO inhibitor
-
What are some Antimicrobials to avoid in pregnancy?
( SAFE Moms Take Really Good Care)
- Sulfonamides – Kernicterus
- Aminoglycosides – Ototoxicity
- Fluoroquinolones – Cartilage damage
- Erythromycin – Acute cholestatic hepatitis in mom &
- Clarithromycin – embryotoxic
- Metronidazole – mutagenasis
- Tetracyclines – discolored teeth,
- inhibition of bone growth
- Ribavirin (antiviral) – teratogenic
- Griseofulvin (antifungal) – teratogenic
- Chloramphenicol – “grey baby”
-
Mechanisms of Protein Synthesis Inhibition.
Which drugs use Formation of initiation complex?
Which drugs use Amino Acid incorporation?
Which drugs use Formation of peptide bond?
Which drugs use Translocation?
-Aminoglycosides (30 S) and Linezolide (50 S)
-Tetracyclines (30 S) and Dalfopristin/Quinupristin (50 S)
- -Chloramphenicol (50 S)
- -Macrolides (50 S) and Clindamycin (50 S)
-
What are the DOC for?
Chancroid?
Meningitis of New born?
Meningitis of Neonate?
Anerobes?
Pseudomonas?
Syphilis?
- -erythromycin or azithromycin (bascially pick a macrolide as the ans choice)
- -cefotaxime
- -ceftriaxone
- -cefotetan
- -ceftazidime
- -Penicillin G
-
What is the DOC for:
UTIs?
Whooping cough?
Legionella/Poniac fever?
Salmonella Typhi?
Borrelia?
Liver abscesses or Cholecystitis?
- -TMP/Sulfa drugs (next would be ciproflox)
- -macrolides
- -erythromycin
- -Azithromycin; ciproflox; ceftriaxone
- -ceftriaxone (for later stages);
- -Cefotaxime
|
|
