Protein Synthesis Inhibitors Flashcards
What are the 8 basic categories of Protein Synthesis Inhibitors?
- Initiation (Aminoglycosides, Linezolid)
- Elongation 1 (Tetracyclines, Streptogramins)
- Elongation 2 (Chloramphenicol)
- Elongation 3 (Macrolides/Ketolides, Clindamycin)
- Gylcylcyclines
What class of drug binds to the 30S subunit and prevents INITIATION of the whole peptide?
- Aminoglycosides
- A ‘intitiates’ alphabet and the protein inhibitors
Aminoglycosides prevent ______-tRNA from binding to the ________ site on the 30S subunit.
- Methionine-tRNA (start codon=AUG)
- P SITE is the site of initiation (contrast with ‘A site’ where incoming Aminoacyl-tRNAs arrive)
What drug binds the 50S subunit towards the 30S face and prevents the two from hooking up (thus prevents intiation)?
Linezolid
The two classes of drug that screw with INITIATION of bacterial protein synthesis are?
-Aminoglycosides and Linezolid
What class of drug binds at the 30S subunit and prevents the FIRST STEP IN ELONGATION of the bacterial peptide?
-Tetracyclines
Tetracyclines prevent ___________ from binding to the __________ site on the 30S subunit.
- incoming Aminoacyl-tRNAs
- A SITE
What drugs bind to the 50S subunit and prevent the enzyme Peptidyl Transferase?
-Chloramphenicol
_________ prevents the enzyme that adds a single new amino acid to the growing peptide chain.
-Chloramphenicol
What drugs bind the 50S subunit and prevent the last step in peptide elongation (translocation)?
-Macrolides and Clindamycin
Macrolides+Clindamycin prevent the process of ____________, which involves the ribosome advancing 3 base pairs towards the 3’ end of the bacterial mRNA.
-translocation
What is the only protein synthesis inhibitor that is bacteriostatic PLUS bacteriocidal?
- Aminoglycosides
- they can cause misreading of mRNA (frameshift-like effect)
Aminoglycosides are to Linezolid as Tetracyclines are to _______________?
Dalfopristin/Quinupristin (streptogramins)
What subunit is a common site of binding of drugs to combat VRSA and VRE?
- 50S subunit
- seen in Linezolid and Dalfopristin/Quinupristin
How are aminoglycosides taken up into the bacteria, and what implications does this have on spectrum of action?
- REQUIRES O2 dependent uptake
- therefore, NOT effective vs ANEROBES
What 3 aminoglycosides are used often in combo with other drugs?
-TAG (Tobramycin, Amikacin, Gentamicin)
What aminoglycoside is topical, therefore is often used in bowel sx?
-Neomycin
What aminoglycoside is used often in TB, and is DOC for bubonic plague and Tularemia?
-Streptomycin
Describe the 4 big time toxicities associated with Aminoglycosides.
- Nephrotoxicity (ATN of the PCT)
- Ototoxicity
- Teratogenic
- Neuromuscular blockade (decr Ach, like botox!)
What component of a triple antibiotic ointment (Neosporin) will most likely cause contact dermatitis?
- Neomycin
- (polymyxin and bacitraicin do not)
The primary mechanism of resistance to Aminoglycosides is?
-production of conjugating enzymes (aka transferase enzymes) that chemically modify the drug
Tetracylines are broad spectrum drugs, but what specific infections should we remember for Doxycycline in particular?
- DOC for Rickettsia infections (RMSF)
- DOC for Spirochetes (Lyme)
- Mycoplasma, Chlamydia
- big in Brucella, Treponema, and Vibrio too
Demeclocycline is a tetracycline that should only be thought about for?
- SIADH treatment!
- blocks V2R on the collecting duct
What are some common causes of SIADH?
- lesion to posterior pituitary
- small cell CA of lung (paraneoplastic)
