Protein Synthesis Inhibtors

Question 1

What are the two families of 30 S inhibitors

(list bacteriostatic or bacteriocidal)

Answer 1

Aminoglycosides (cidal irreversibly bind)

Tetracyclines (bacteriostatic reversibly bind)

Question 2

What are the four families of 50S inhibitors

(list bacteriostatic or bacteriocidal)

Answer 2

Macrolides (bacteriostatic)

Clindamycin (bacteriostatic)

Chloramphenicol (bacteriostatic)

Quinupristin-Dalfopristin

Question 3

List 5 Aminoglycoside drugs

Answer 3

Tobramycin

Amikacin

Neomycin

Gentamicin

Streptomycin

Question 4

aminoglycosides are more effective aginst what than any other antibioitc class

why then are they not always used for that?

Answer 4

Gram negative aerobes

often times are more toxic then alternatives so are saved for serious infections resistant to those less toxic drugs

Question 5

Aminoglycosides are only effective against ____ class when combined with ____

Answer 5

Few gram pos organisms

when combined with CWSI’s

Question 6

What group of organisms are aminoglycosides not effective against and why

Answer 6

anaerobes

because they requrie oxygen dependent transport process to enter the cell

Question 7

what is the chemistry of aminoglycosides and what does that mean about their absorption

Answer 7

they are amino sugars meaining they are extensively ionized in acidic fluids

This means poor bioavailability when administered orally so

must be given parenterally for systemic infections

Can be good orally for gi infections (because trapped in gi)

Can be used topically for skin mucous membranes and ocular tissues

Question 8

What drug are aminoglycosides used in combo with and why

Answer 8

CWSI

allows the ag to enter the bacteria and synergistically allows more activity against both gram postive and gram negative

Question 9

What is the main route and time of elimination of aminoglycosides

Answer 9

Glomerular filtration primarily

Half life 2-3 hours

Question 10

Which aminoglycosides can be used in a TB infection

Answer 10

Streptomycin and Amikacin

Question 11

Which populations would need to avoid Aminoglycosides

Answer 11

Pregnant women (pregnancy category D drug)

Individuals with low creatinine clearance

Question 12

What is the mechanism by which drugs become resistant to Aminoglycosides

Answer 12

Bacterial acetylase, adenylase, and phophorylase enyzmes

(degrade the aminoglycoside and prevent its binding to its site)

(could also decrease drug accumulation through porin mutation)
(could also alter target site to decrease the binding to the 30S ribosome)

Question 13

Which aminoglycoside is more resistant to bacterial resistance mechanism

Answer 13

Amikacin

( it is protected at more sites than gentamicin and tobramicin)

Question 14

List 4 major adverse effects of aminoglycosides

Answer 14

1. Nephrotoxicity
   
   • causes tubular necrosis by accumlating in renal cortical cells
   • usually reversible
2. Ototoxicity
   
   • accumulates in peri/endolymph of the ear when AG levels are elevated, can be irreversible
3. Levels must be adjusted/monitored closely to prevent toxicity
   
   • single daily dosing
4. Toxicity increased in combo w/ other nephrotoxic or ototoxic agents

Question 15

define the mechanism of action of the aminoglycosides and the tetracyclines

Answer 15

Aminoflycosides: bind to the initiations site of the 30s and prevent formation of the initiation complex

Tetracyclines: inhibits the binding of tRNA to the A site of the 30S ribosome

Question 16

how are tetracyclines absorption affected and how are they distributed

Answer 16

• Absorption affected by Food
  
  • Tetracyclines: all foods decreas absorption
  • Doxy and Minocycline: food DOES NOT decrease absorption
• Absorption Decreased by polyvalent Cations (dairy, calcium, iron, antacids)
• Distirbution: well distributed but does not cross BBB (except Minocycline)

Question 17

How are teetracyclines eliminated

Answer 17

Tetra and Mino: Renal and Biliary

Doxy: Biliary

Question 18

what are the main adverse effects of tetracyclines (6)

Answer 18

• Concentrates in growing teeth and bones (contra in kids less than 8 and pregnant women-category D0
• Allergi Reactions
• Dermatologic (phtosensitivity-accum in skin hyperpigmentation with minocycline)
• Hepatotoxicity (fatty liver- high incidence in pregnancy)
• Ototoxicity (minocycline)
• GI issues
  
  • GI upset N/V/D (less for mino and doxy
  • GI flora
    
    • superinfecctions and drug drug interactions
• May make oral contraceptives less effective

Question 19

what are the main mechanisms of resistance against tetracyclines

Answer 19

Decreased Drug accumulation

Altered Target site

Enzymatic drug inactivation

Important resistant organism: Psuedomonas

Question 20

what are 2 main similarities and 2 main differences between the tetracyclines

Answer 20

• Similarities
  
  • antimicrobial spectrum
  • all bind divalent and trivalent cations so their avialability is dec with food containing cations
• Differances
  
  • oral bioavailability
    
    • 70% tetracycilnes (10 hr half life)
    • >90% doxy and mino (15 and 19 respectively)
  • intensity of adverse effects
    
    • tetra has most effect on teeth and bone
    • doxy has most photottoxicity
    • mino has most ototoxicity (and is only one to cross bbb)

Question 21

what are the similarities and differences between tigecycline and tetracyclines

Answer 21

similar

Chemistry and pharmacokinetics to tetracyclines

differences

parenteral only

longer half life (27-42 hours)

biliary excretioon

Binds with affinity 5x that of tets (though to same region of the 30S

NO OTOTOXicity