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Inhibition of Protein Synthesis (Casey)
A compilation of Kaplan + lecture notes. (Casey)
40
Pharmacology
Graduate
11/01/2012

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Cards

Term
[image]
Definition

1. 50 large ribosomal unit joins with 30s ribosomal unit

2. Initiation- tRNA goes onto P site with a Met group attached

3. Amino acid incorporation- tRNA w/ specific AA sits onto the A-site

4. Elongation: Petide bond forms via peptidyl transferase between AA groups

5. A site tRNA moves over to P site to move over for another tRNA to repeat the process

6. Termination

Term
[image]
Definition
  1. Aminoglycosides (30s), Oxazoladinones (linezolid) (50s): blocks initiation complex
  2. Tetracyclines/glycylcycline (30s), dalfopristin/quinupristin (50s): blocks AA incorporation
  3. Cloramphenicol (50s): blocks peptide bond formation
  4. Macrolides/Clindamycin (lincosamides) (50s), type B streptogramins, ketolide: blocks elongation

 

Term
What is the difference between human and bacterial translation ribosomal units?
Definition

Bacteria: 70s

Humans: 80s

Term
Which group of drugs inhibit the 30s ribosomal units?
Definition

A=Aminoglycosides

T= Tetracyclines

Term
Are protein synthesis inhibitors bacteriostatic or bacteriocidal?
Definition
Bacteriostatic except aminoglycosides
Term
Right off the bat, what does the name "aminoglycosides" tell you?
Definition
Seeing -"glycosides" tells you it's made up of sugar--> water soluble--> polar--> goes through kidney--> probably has kidney toxicities
Term
What are the 50s inhibitors?
Definition

Chloramphenicol, clindamycin

Erythromycin

Lincomycin

Linezolid

Term

"Buy AT 30, CCELL (sell) at 50" 

 

What does this mean?

Definition

30s inhibitors:

Aminoglycosides

Tetracyclines


50s inhibitors:

Chloramphenicol, Clindamycin

Erythromycin

Lincomycin

Linezolid

 

Term
What are examples of aminoglycosides?
Definition

"Mean" GNATS can NOT kill anaerobes

Gentamicin

Neomycin

Amikacin

Tobramycin

Streptomycin

Term
What is the mechanism of action for aminoglycosides?
Definition

Blocks initiation of complex, causes misreading of codes upon tRNA trying to come in and bind to subunit and f***s it up

 

Requires O2 for uptake

Term
Aminoglycosides are best used on which organisms?
Definition

G- aerobic rods

Used in conjnction w/ cell wall inhibitors (β-lactams)

 Neomycin for bowel surgery

Also for enterococci & P. aeruginosa

 

 

 

Term
[image]
Definition
Memorize it
Term
What are the toxicities of aminoglycosides?
Definition

"Mean" GNATS canNOT kill anaerobes

Nephrotoicity (esp. w/ cephalosporins)

Ototoxicity (especially w/ loop diuretics)

Teratogen 

 

Neuromuscular blockade, blocks acetylcholine release

Term

What is the most common drug associated w/ contact dermatitis?

What other agents can you find in neomycin/sporin?

Definition

Neomycin (neosporin)

Can find polymixin and bacitracin

 

*Boards love this question*

Term
A patient comes in with decreased acetylcholine release leading to muscle paralysis, dry eyes, etc., what should you be thinking about?
Definition

Botulism toxin or aminoglycoside SE

If botulin is not one of the answers, then look for a -mycin drug :)

Also a common board question

Term
What is the MOA of tetracyclines?
Definition
Bind to 30S and prevent attachment of aminoacyl tRNA; limited CNS penetration
Term
What can tetracyclines be used to treat?
Definition

Broad spectrum, but good with atypical bacteria like H. pylori, M. pneumonia, vibrio,

Rickettsia (typhus/spotted fever), Lyme disease, Chlamydia


Term
What are some examples of tetracyclines?
Definition
  • doxacycline
  • minocycline
  • democlocycline (Blocks ADH receptors, use for SIADH)
Term
What are the side effects/toxicities of tetracycline?
Definition
  • Tooth enamel dysplasia (discoloration)
  • Dec bone growth in children
  • Phototoxicity
  • GI distress
  • Vestibular dysfunction
  • DO NOT give to children or pregnant women
Term
What is the resistance that some bacteria have to aminoglycosides?
Definition
  • Production of conjugating enzymes (transferase)
  • Inactivate drugs by acetylation (of own ribosomes to prevent recognition by drug), phosphorylation, or adenylation
Term
What do you know about cloramphenicol just by looking at its name?
Definition
Anytime you have -phen or phen sounding in a name, it means it is lipid soluble and can probably cross the BBB.  Ex: acetominophen
Term
What is the MOA of cloramphenicol
Definition
  • Blocks transpeptidation, 50s inhibitor
Term
What is cloramphenicol usually used for?
Definition
  • Meningitis (H. influenzae, N. miningitidis, S. pneumoniae)
  • Conservative in states, used a lot still in developing countries
Term
What are the toxicities of cloramphenicol?
Definition
  • Bone marrow suppression
  • "Gray baby"-> toxicity+lack UDP glucuronyl transferase= kernicterus
  • Anemia (dose dependent
  • aplastic anemia (dose independent)
Term

What is the MOA of macrolides?

 

Definition

Blocks translocation:

Binds to 23S rRNA of 50s ribosomal subunit

Term
What are some examples of marcolides?
Definition
  • Erythromycin
  • Azithromycin
  • Clarithromycin
Term
What can macrolides be used for?
Definition
  • Atypical pneumonias (mycoplasma, chlamydia, legionella)
  • URIs
  • STDs
  • G+ cocci
  • Neisseria
Term
What do macrolides have to do with cytochrome P450?
Definition
Macrolides block CY P450 EXCEPT azithromycin
Term
What are the side effects/toxicities of macrolides?
Definition
  • Prolonged QT interval (esp erythromycin)
  • GI discomfort (most common cause of noncompliance) by stimulating motilin
  • Reversible deafness (ototoxic)
  • Acute cholestatic hepatitis
  • eosinophilia, skin rashes
  • increases serum conc. of theophyllines
Term
What is the MOA of clindamycin?
Definition
Blocks peptide bond formation at 50S ribosomal subunit
Term
What can clindamycin be used for?
Definition

Anaerobic infections (G+, S. aureus: osteomyelitis)

in aspiration pneumonia/lung abscesses 

 

"Treats anaerobes above the diaphragm vs. metronidazole anaerobic infections below diaphragm"

Term
What are the toxicities of clindamycin?
Definition
  • Pseudomembranous colitis (C. dif)
  • fever
  • diarrhea
Term
What do you want to treat C. Dif infection with?
Definition
  1. metronidazole
  2. Vancomycin
Term
What is another name for Linezolid?
Definition
oxazoladinones
Term
What is the MOA of linezolid?
Definition
Blocks formation of initiation complex by messing with 50s ribosomal subunit
Term
What is linezolid used for?
Definition

VRSA/VRE

drug resistant pneumococci

Term
What are the side effects of linezolid?
Definition
supress bone marrow
Term
Is clindamycin an aminoglycoside?
Definition
No, this is an exception.  Don't let the mycin fool you. They have different MOAs. 
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