30s Protein Synthesis Inhibitors ic8

Question 1

What are the 3 classes of Protein Synthesis Inhibitors (30s)

Answer 1

Tetracyclines (TDM)
Tetracycline
Doxycycline
Minocycline

Tigecycline

Aminoglycosides (STANG)
Streptomycin
Tobramycin
Amikacin
Neomycin
Gentamicin

Question 2

MOA of Tetracyclines

Answer 2

Bind reversibly to the 30s subunit of ribosome, prevent binding of tRNA of the A site

Question 3

Administration of Tetracyclines and counselling points

Answer 3

Good oral F

Consume on empty stomach
Avoid administration with dairy products (Ca2+) or divalent, trivalent cations (Mg2+, Al3+)

Distributes to tissue containing calcium (stain teeth), can cross placental barrier

Do not give for pregnant, breastfeeding, children below 8

Question 4

General properties of Tetracyclines (spectrum, cannot cover)

Answer 4

Bacteriostatic antibiotic
(dont give with Beta lactams)

Broad spectrum, Gram (+) and Gram (-), Atypicals (MCL)

Cannot cover Pseudomonas

Question 5

Which Tetracycline can cover MRSA?

Answer 5

Doxycycline

Question 6

Counselling points for Tetracyclines and Tigecyclines (4 points)

Answer 6

Drug-Food interactions
Avoid dairy (Ca2+), Divalent or Trivalent cation

Drug-Drug interactions (FYI)
Other drugs w narrow TI eg.
Digoxin, Warfarin

Best taken on empty stomach
Gastric / Esophageal irritation
Take with a full glass of water
Do not take immediately before going to bed

Phototoxicity

Question 7

2 mechanisms of resistance to Tetracyclines

and how does Tigecycline overcome it?

Answer 7

1) Efflux pumps

2) Ribosomal protection
Bacteria produces protein which bind to ribosome, protecting it

Tigecycline overcomes this by binding to ribosomal stronger than the protein, kicking out the protein

Question 8

Spectrum of activity of Tigecycline vs Tetracyclines

Examples of resistant strains (4 points)

Answer 8

Tigecycline has similar coverage, but covers more resistant strains eg. Carbapenem resistant ESBL

Strains include
MRSA
Multidrug resistant Strep
VRE
ESBL Gram (-) bacteria, resistant to Carbapenems

Question 9

Administration of Tigecycline

Answer 9

Parenteral (unlike Tetracyclines)

Question 10

What is Tigecycline not active against?
hint: gram (-)

Answer 10

Pseudomonas

Question 11

Adverse effects of Tetracycline and Tigecycline (4 points)

Answer 11

1) Gastric discomfort
Esophageal irritation
Take on an empty stomach
Drink with a full glass of water, do not take immediately before going to bed

2) Calcified tissue
Bind to calcified tissue
Cause discolouration of teeth, stunt growth
Avoid in pregnancy, breastfeeding and children < 8yo

3) Phototoxicity
Dont go under sun
Wear enough sunscreen

4) Superinfection
Result of gut flora affected
Cause CDAD

Question 12

MOA of Aminoglycosides

Answer 12

Distort structure of ribosomes
Block Initiation complex at 30s
Misreading of codons
Inhibit translocation

Question 13

Why are Aminoglycosides only active against Aerobes?

Answer 13

Transport through inner membrane is an active transport process, requires energy and oxygen

Question 14

Characteristics of Aminoglycosides
(what kind of killing, spectrum of activity, administration, elimination)

Answer 14

Rapidly bactericidal
Concentration dependent killing
Gram (+) and (-)
Parenteral (except Neomycin out of necessity)
Renal

Question 15

What are Aminoglycosides typically used for?

Answer 15

Used against Aerobic Gram (-)
eg. E coli, Klebs, MDR (eg. Pseudomonas)

Empiric therapy for serious infections

Question 16

What can we combine Aminoglycosides with? Provide examples

What is the effect? (3 points)

Answer 16

Combine Aminoglycosides with Beta lactams (eg. 3rd, 4th gen Cephalosporins)

1) Expand empiric spectrum of activity
Beta lactam: Anaerobe coverage, Gram (+)
Aminoglycoside: Aerobe gram (-)

2) Provide synergistic bacterial killing
Beta lactam target cell wall, allows Aminoglycoside to penetrate bacteria

3) Prevent emergence of resistance

Question 17

Examples of Aminoglycosides

Which has the widest spectrum of activity?
Which is used orally?

Answer 17

Streptomycin
Tobramycin
Amikacin (widest SOA)
Neomycin (oral, not given parentally due to nephrotoxicity)
Gentamicin

Question 18

Adverse effects of Aminoglycosides (2 points)

Answer 18

Nephrotoxicity, Ototoxicity
Similar to Vancomycin
Avoid use in other nephrotoxic drugs eg. Amphotericin B, Vancomycin, NSAIDs

Neuromuscular paralysis
Dont use for Myasthenia gravis (autoimmune condition causing muscle weakness)

Question 19

6 NOs of Aminoglycosides

Answer 19

NO Protein synthesis

Aerobic Gram (-) Negative Organisms

NO pregnancy

NO oral (except Neomycin)

NO CSF penetration

Nephro and Oto toxicities

Question 20

3 resistance mechanisms to Aminoglycosides

Answer 20

Efflux pumps

Alter 30s ribosomal subunit, prevent Aminoglycoside attachment

Aminoglycoside inactivating enzymes