30S Protein Synthesis Inhibitors - Fitzpatrick

Question 1

2 groups of 30S inhibitors

Answer 1

Aminoglycosides

Tetracyclines

Question 2

Most commonly used Aminoglycoside

What organisms? Especially if they…

Answer 2

Gentamicin

Gram (-) aerobes (E. coli, Enterobacter, Serratia, Klebsiella, Tularemia)
- Especially those resistant to other safer antimicrobials

Question 3

Tobramycin - clinical use

Answer 3

Pseudomonas

Question 4

Amikacin - clinical use

Answer 4

Gentamicin-resistant organisms

Question 5

Brucellosis - clinical treatment

Answer 5

Gentamicin + doxycycline

Question 6

Tularemia - clinical treatment

Answer 6

Gentamicin

Question 7

Yersinia pestis (plague) - clinical treatment

Answer 7

Streptomycin + doxycycline

Question 8

Pseudomonas - clinical treatment

Answer 8

Tobramycin + Piperacillin/Ticarcillin

Question 9

Klebsiella - clinical treatment

Answer 9

Gentamycin + Piperacillin/Ticarcillin

Question 10

While Gram (-) is typically the indication for Aminoglycosides, they may also be used synergistically with what else for what Gram (+) diseases?

Answer 10

W/ beta-lactams for Strep/Enterococcal endocarditis

Question 11

Why are Aminoglycosides good for Gram (-) infections?

Answer 11

Highly polar, water-soluble structure allows for good passage through PORINS in outer membrane of Gram (-)

Question 12

Why are Aminoglycosides good for Gram (-) AEROBES only?

Answer 12

Enters Gram (-) aerobes through an O2-dependent channel in the INNER membrane. Anaerobes don’t have this channel, thus they are resistant to Aminoglycosides

Question 13

Are Aminoglycosides bacteriostatic or bacteriocidal? Explain.

Answer 13

Bacteriocidal - cause ribosome (via 30S subunit) to mis-read the mRNA and add a wrong amino acid, resulting in deficient proteins and DEATH

Question 14

How might you be resistant to Aminoglycosides? (4)

Answer 14

• Depletion/deficit of porins (multi-drug resistance)
• Anaerobes or anaerobic environment
• Enzymatic alteration of drug (acetyl, phosphoryl., adenyl)
• 30S ribosome mutation

Question 15

Examples of anaerobic bacteria resistant to Aminoglycosides

Answer 15

• Clostridia
• Actinomyces
• Bacteroides
• C. diff.
• Fusobacteria

Question 16

Aminoglycosides, if given too much, will accumulate in which 2 places?

Thus, what are 2 adverse effects of aminoglycosides?

Answer 16

• Kidney —> nephrotoxicity

- Perilymph (ear) —> ototoxicity

Question 17

How to prevent adverse effects of Aminoglycosides?

Answer 17

Dose such that serum levels reach zero by the end of each day, thus preventing the development of a new steady state level that is GREATER THAN zero

Question 18

How are Aminoglycosides excreted?

Answer 18

100% via kidneys (b/c so polar)

Question 19

Who is a contraindication for Aminoglycoside use?

Answer 19

Perinatal or fetuses (hearing loss)

Question 20

What is the 3rd adverse effect of Aminoglycosides besides nephrotoxicity and ototoxicity?

What condition may be a contraindication then?

Answer 20

Neuromuscular blockade (nAChRs)

Myasthenia gravis

Question 21

Treatment for Aminoglycoside-induced neuromuscular blockade

Answer 21

Neostigmine or ventilator

Question 22

Tetracyclines - drugs (5)

Answer 22

• Tetracycline
• Minocycline
• Doxycycline
• Tigecycline

Question 23

Most commonly used Tetracycline

Answer 23

Doxycycline

Question 24

Characteristics of Doxycycline to remember (3)

Answer 24

• Highly potent
• PARENTERAL
• Good w/ renal impairment

Question 25

Minocycline - best for what?

Answer 25

Meningococcal CARRIER STATE (CNS)

Question 26

Tigecycline - best for what?

Answer 26

MRSA

Question 27

Clinical indications for Doxycycline (6)

Answer 27

- MYCOPLASMA PNEUMONIA (important in this section) - Rickettsia (RMSF, Q fever, Typhus) - Borrelia (Lyme disease) - Chlamydia (STD) - Psittacosis pneumonia - Vibrio (Cholera)

Question 28

Tetracyclines are used together with Aminoglycosides for which infections? (3)

Answer 28

- Brucellosis (cows) - Gentamycin + Doxycycline - Tularemia (rabbits) - Gentamycin or Tetracycline - Plague (rats) - Streptomycin + Doxycycline

Question 29

How is MoA of Tetracyclines different from Aminoglycosides?

Answer 29

- Bacteriostatic - Bind to 30S and prevent tRNA binding to mRNA - Inhibits RATE of protein synthesis

Question 30

2 mechanisms of resistance to Tetracyclines

Answer 30

- EFFLUX PUMPS (pump drug out of bacteria) | - Ribosome mutation (inhibits 30S binding to drug)

Question 31

Adverse effects of Tetracyclines

Answer 31

- Accumulate and stain in calcified tissues (bone, teeth) - Fatty liver (in pregnancy) --> hepatitis - GI superinfections (after eliminated gut microflora)

Question 32

A patient is on a Tetracycline for a gram (-) infection of some kind. What should NOT be taken w/ these drugs?

Answer 32

Calcium supplements or Antacids containing Ca++/Mg++ Tetracyclines chelate Ca/Mg --> stain teeth and bone

Question 33

A pregnant woman needs an antibiotic for a gram (-) infection, and the doctor suggests a Tetracycline. Is this a good choice? Why or why not?

Answer 33

NO - in pregnancy, the Tetracyclines alter metabolism in the mitochondria of the liver, INCREASING lipid production, causing FATTY LIVER --> fatal hepatitis

Question 34

A patient in on a Tetracycline for an abnormal pneumonia. Later, they develop severe pain in the gut and black stool. Explain.

Answer 34

Tetracyclines kill commensal enteric bacteria --> Clostridium difficile thrives --> PSEUDOMEMBRANOUS COLITIS

Question 35

Tigecycline has additional activity against which organisms? (NOT ON EXAM)

Answer 35

MRSA, VRE