Protein Synthesis inhibitors Flashcards
Bacterial protein synthesis inhibitors sites of action:
Places of mechanism of action at different stages of protein synthesis:
Macrolides
They disturb the protein synthesis at what level of ________ step of translation, by binding to a different site of the 50S subunit to block **translocation of peptydil tRNA from acceptor site to donor site and peptide bond formation to stop translation.
elongation
Macrolides
How can resistance to macrolides occur?
What are two bateria that tend to alter the 50S (target) to prevent binding of macrolides?
In what bacteria are macrolides targers of MDR efflux transporters that prevent drug-target interaction?
Binds 50S ribosomal subunit - selectively toxic with no binding to human 60S ribosome
- Blocks translocation of peptidyl tRNA from acceptor to donor site on ribosome –> prevents peptide elongation
- *Bacteriostatic
How does it enter bacteria?
Not actively transported - enters by passive diffusion
-Weak base that is more active at alkaline pH
Macrolides pharmacokinetics
Which macrolide should be taken on an empty stomach?
For which macrolided does food does NOT matter?
Absorption varies depending salt form for what macrolide?
Which erythromycin is more bioavailable in children than ethylsuccinate?
Macrolide distribution in the body
Which two macrolided accumulate in macrophages and in certain tissues such as lungs, tonsils, cervix, and sputum?
In terms of elimination, which one is metabolized by the liver and excreted in bile?
Which one is not metabolized and goes through biliary excretion and tends to accumulate in the tissues, which means it only requires a daily dose?
Which one is renally eliminated?
Macrolides spectrum: clinical uses
For gram-positive cocci _____ are effective.
For gram-negative cocci (such as moraxella catharralis) ____ are effective.
For diptheria (gram-positive rod) use ______.
Gram-negative bacilli:
For H. Influenza use _____ and ______.
For H. pylori use _______.
For bordella pertussis ( whooping cough) you can use ALL.
For *legionella (community acquired pneumonia) and C. jejuni use _______.
For chlamidya use ______.
For mycoplasma pneumonia you can use ALL.
Questions:
Questions:
Macrolides adverse reactions:
Clarithromycin and erythromycin metabolites can inhibit what?
Macrolides sample questions:
Tetracyclines
Mechanism of Action: Bacteriostatic inhibition of bacterial protein synthesis.
Specific binding to 30S ribosome (reversible) prevents access of aminoacyl tRNA to site on mRNA-ribosome complex **blocking addition of amino acids to peptide chain.
Some selective toxicity because mammalian cells have an active efflux mechanism preventing intracellular accumulation of drugs and lack an active transport for moving drug into cell.
Resistance occurs due to:
(1) changes in proteins that transport drug into cell or membrane insertion of proteins that actively transport tetracycline out of cell (plasmid can code for multiple drug resistance [TCNs / CHLOR / SULF / AG / MAC]).
(2) ribosome protection by producing proteins that block tetracycline binding. *Tigecycline* NOT affected by these mechanisms.
Tetracyclines pharmacokinetics:
Which one is best if given in an empty stomach?
What happens if tetracyclines get retained in the GI track? Why is this bad?
What cations prevent absorption of tetracyclines?
Tetracyclines elimination
Which one is eliminated through the urine?
Which ones are concentrated in the liver and excreted in the bile?
What is the spectrum/clinical use of tetracyclines?
What two tetracyclines are used for MSSA-MRSA (gram-positive cocci)_________.
Tetracycline is used for __________ (gram-negative rods).
Tetracyclines spectrum:
For anaerobes such as P. acnes you use________.
For the rest you use:______
Sample questions:
- A 5-year-old kindergarten student presents with headache, fever, and cough of 2 days duration. Sputum is scant and nonpurulent and a Gram stain reveals many white cells but no organisms. Since this patient appears to have atypical (mycoplasmal) pneumonia, you should initiate treatment with:
A.Azithromycin (Zithromax)
B.Doxycycline (should not be given to kids under 5 years of age o women in their later half-pregnancy)
C.Cephalexin (Keflex, a 1st generation cephalosporin)
D.Chloramphenicol
E.Any of the above
Tetracyclines adverse reactions
Tetracyclines adverse reactons
- Doxycycline is:
A.Bactericidal (bacteriostatic)
B.Excreted mainly in the urine (no, by liver excretion to bile, tetracycline is excreted by urine)
C.Eliminated rapidly and is dosed 4 times a day
D.More effective than tetracycline against H. pylori (false, tetracycline is more effective against H. pylori)
E.Recommended therapy for community-acquired pneumonia
Tetracyclines questions:
Clindamycin
Is it well absorbed orally?
Penetrates most tissues well, specially_____.
It metabolized by the liver, so there is no need for adjustment in ______ conditions.
Is it excreted into breast milk?
Mechanism of action:
Binds to 50S ribosome –> prevents translocation of peptidyl tRNA (ECN binding site) –> prevents peptide bond formation.
**Bacteriostatic - but can be bactericidal against certain organisms at higher concentrations.
Clindamycin spectrum:
Clindamycin adverse reactions:
Aminoglycosides
Mechanism of action:
In order to be transported into bacteria, it requires________. Thus, it is not effective against_________.
Aminoglycosides
11.Regarding the mechanism of action of aminoglycosides, the drugs:
A.Are bacteriostatic
B.Bind irreversibly to the 30S ribosomal subunit
C.Cause misreading of the code on the mRNA template
D.Inhibit peptidyl transferase
E.Cause breakup of polysomes
Aminoglycosides:
Are they absorbed orally?
What allows rapid and complete absorption of aminoglycosides?
Their distribution is limited to ______.
Where does it selectively accumulates?
- Highly polar cationic compounds that are NOT significantly absorbed after oral administration.
- Rapid and complete absorption after IM (intramuscular injection) administration giving peak plasma concentrations in 30-90 minutes
Distribution in body limited to extracellular fluid
- Not concentrated in mammalian cells
- Binding to plasma proteins varies (0-30%).
Largely excluded from CNS (20% of Cp levels if meninges inflamed)
*Selectively accumulates in the renal cortex and inner ear predisposing these organs to toxicity.
Aminoglycosides
For gram-negative rods such as pseudomonas and E.Coli you use_________.
For presurgery bowel sterilzation and wound infection you use___________.
For gram positive cocci such as enterococci you use_______.
For gram-positive cocci such as mycobacterium tuberculosis you use________.
Aminoglycosides adverse reactions:
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