protein synthesis inhibitors

Question 1

T or F

- tetracycline/glycylcyclines have bacteriostatic effect

Answer 1

True

Question 2

T or F

- aminofgycosides are bacteriocidal

Answer 2

True

Question 3

• group of antibiotics represented by naturally occurring streptomycin, gentamicin, tobramycin, neomycin and semisynthetic analogues amikacin and netilimicin

Answer 3

aminoglycosides

Question 4

• structure of aminoglycosides

Answer 4

• amino sugars glycosidically linked to core aminocyclitol

Question 5

• aminoglycosides w the broadest spectrum of coverage due to 2-hydroxy-4-amino butyl group resisting deactivating enzymes

Answer 5

• amikacin

Question 6

• strong bases
• hydrophilic
• excist as polycations at physiological pH and poorly absorbed orally
• incompatible when mixed w beta lactams

Answer 6

aminoglyosides

Question 7

aminoglycosides nomenclature:

- Streptomyces ending in ‘mycin’

Answer 7

• streptomycin
• tobramycin
• neomycin

Question 8

aminoglycosides nomenclature:

- micromonospora ending in ‘micin’

Answer 8

• gentamicin

- netilmicin

Question 9

3 main effects of aminoglycosides

Answer 9

1. interference w initiation (ribosome is fixed to mRNA AUG start codon)
2. premature termination (error recognition of mRNA misreads)
3. incorporation of incorrect aa into proteins

Question 10

aminoglycosides blocked by….

Answer 10

• low oxygen, low pH, elevated Ca or Mg, or an increase in osmolarity

Question 11

• mostly active against aerobic gram neg bacilli

- not useful for anaerobes and poor activity against atypicals

Answer 11

aminioglycosides

Question 12

gentamicin antibiotic map

Answer 12

• all of these are gram negs
• Proteus mirabilis
• E.coli
• klebsiella pneumonia
• serratia
• enterbacter spp
• psuedomonas

Question 13

ADME of aminiglycosides

Answer 13

• poor oral bioavailability must be given IV or IM, some nebulizer forms such as tobra for CF
• distribute primarily in plasma and tissue interstitial fluid space
• poor distribution to human cells besides renal
• low CSF penetration
• don’t use in pregnant patients
• excreted primarily renally and metabolism is minimal
• monitor blood levels and half life is approx. 2-3 hrs

Question 14

adverse rxn to aminoglycosides

Answer 14

• serious side ffets so limit use to important infections
• ototoxicity
• nephrotoxicity (usually reversible)
• neuromuscular paralysis (rare) but don’t use w succinyl choline

Question 15

natural occurring tetracyclines

Answer 15

• tetracyclines

- chlorteteracycline

Question 16

semisynthetic tetracyclines

Answer 16

• doxycycline

- minocycline

Question 17

which generation of tetracyclines is this?

• unstable in acidic enviorments
• undergo 2 diff rxn:
  1. acid promotes epimerization
  2. acid induced dehydration w the loss of C6-OH group results in anhydritetracycline (nephrotoxic)

Answer 17

1st gen

Question 18

which generation of tetracyclines is this?

• do not have C6-OH group and thus more stable at acidic pH
• food containing divalent and trivalent metal ions (Ca, Mg, Al) interact w tetracycline and forms insoluble complexes
• this causes poor absorption of ions and tetracyclines and causes tooth staining in kids

Answer 18

2nd gen

Question 19

MOA of tetracyclines

Answer 19

• enter bacterial cells via passive diffusion though porins and by active transport across inner membrane
• bind to 30S subunit of bacterial ribosome and inhibit protein synthesis by preventing access of aminoacyl tRNA to the acceptor site of the mRNA ribosome complex

Question 20

• broad spectrum antibiotics
• active against gram pos including MRSA aswell as gram neg excluding Psuedomonas, although typically not used for Enterococus, Psuedomonas, or UTI (E.coli)
• can be useful against atypicals such as Rickettsia, Mycoplasma pneumonia, chlamydia, spirochetes(lyme disease/syphillus), vibrio cholera, anthrax, leprosy

Answer 20

tetracyclines

Question 21

ADME of tetracyclines

Answer 21

• GI absorption varies but oral absorption is impaired by ingestion of divalent and trivalent cations

Question 22

diff in tetracyclines and minoyclines

Answer 22

• tetracyclines eliminated primarily unchanged in urine
• minocycline undergoes hepatic metabolism
• doxycycline preferred in renally compromised bc eliminated via bile
• tetracycline half life is 6-12 hrs
• minocycline is 16-20 hours

Question 23

adverse effects of tetracyclines

Answer 23

• GI discomfort
• dermatologic issues such as pigment changes and photosensitivity
• bony structures and teeth issues
• renal toxicity
• don’t use in pregnancy

Question 24

• semisynthetic analog of minocycline
• IV infused
• highly hydrophobic
• broad spectrum coverage and sensitive to tetracycline resistant strains due to C9 glycoamidio side chain
• ## inhibits protein synthesis by binding 30S subunit

Answer 24

glycylcycline (Tigecycline)

Question 25

when are glycylcyclines (Tigecycline) indicated

Answer 25

• only in complicated SSTI and serious intra-abdominal infections

Question 26

antibiotic map coverage of Tigecycline

Answer 26

• all but psuedomonas

Question 27

ADME and Pk of tigecycline

Answer 27

• IV route
• large Vd
  extensively distributed in the body
• eliminated mainly via bile into feces
• dose adjust for HEPATIC diseases

Question 28

adverse effects of tigecyline

Answer 28

• Black box warning to reserve for serious conditions due to higher mortality risk
• discoloration of teeth don’t use in pregnancy or children