Wk 4 - Protein Synthesis Inhibitors

Question 1

Linezolid

Answer 1

• Bacteriostatic
• Inhibits protein synthesis by binding 23SrRNA (on 50S subunit) and PREVENTING FORMATION OF THE INITIATION COMPLEX

Spectrum of activity:
GRAM +
Can treat MRSA and vancomycin resistant enterococci

Resistance:
∆ 23S subunit

Adverse effects:

• Bone marrow suppression
• hallucinations
• Increased HR/agitation/nausea
• Can lead to Serotonin Syndrome if taken with SSRI

Question 2

Aminoglycosides: what are they?

Answer 2

Tobramicin

Amikacin

Neomycin

Gentamicin

Streptomycin

TANGS

Question 3

Aminoglycosides

Tobramicin, amikacin, neomycin, gentamicin, streptomycin

Answer 3

• Bactericidal
• Prevents formation of initiation complex: causes misreading of mRNA to induce early termination

Spectrum of activity:
Gram (-) aerobic
… because it’s so narrow it’s usually used in combo

Resistance:
- Inactivated through acetylation/phosphorylation/adenylation

Adverse effects:

• Nephrotoxicity
• Ototoxicity (vestibular/auditory dysfunction)
• DON’T TAKE DURING PREGNANCY!

Question 4

Tetracyclines: what are they?

Answer 4

“Too Many Drugs!”

Tetracycline
Minocycline
Doxycycline

Question 5

Tetracyclines:

Tetracycline, Minocycline, Doxycycline

Answer 5

• Bacteriostatic
• Bind 30S rRNA subunit and prevent ATTACHMENT OF AMINOACYL TRNA DURING INITIATION

Spectrum: broad but resistance sucks

Resistance:

• Efflux pumps
• ∆ ribosomal target

Adverse effects:

• DON’T HAVE ANY METALS… form chelates and decreases gut absorption
• GI irritation and photosensitivity
• BAD FOR KIDS: discoloration of teeth/bone growth inhibition
• DON’T TAKE DURING PREGNANCY!

Question 6

Chloramphenicol

Answer 6

• Bacteriostatic
• Bind 50S subunit and prevents peptide bond formation (peptidyltransferase can’t associate with amino acid subunit)

Activity: extended but bad side effects

Resistance:
Acetyltransferase modifies drug so it can’t bind to the ribosome

Adverse effects:
VERY TOXIC
- Bone marrow depression
- Aplastic anemia
- Gray Baby Syndrome: Infants don’t have UDP-glucuronyl transferase and they have decreased renal function
—– can’t metabolize chloramphenicol so it accumulates in system –> CV and respiratory collapse :(

Question 7

What drug leads to gray baby syndrome?

Answer 7

Chloramphenicol

Question 8

What drugs cause bone marrow depression?

Answer 8

Chloramphenicol

Linezolid

Question 9

What drugs target the 30S subunit?

Answer 9

Aminglycosides (TANGS)

Tetracyclines (Too Many Drugs)

Question 10

Which drugs target 50S subunit?

Answer 10

Chloramphenicol
Clindamycin
Linezolid
Streptogramins (Quinupristin/dalfopristin)
Macrolides (ACE)

Question 11

Macrolides: what are they?

Answer 11

Azithromycin
Clarithromycin
Erythromycin

ACE!

Question 12

Macrolides: Azithromycin, Clarithromycin, Erythromycin

Answer 12

• Bacteriostatic
• Bind 50S subunit (23S rRNA) and inhibit translocation)

Spectrum:

• Broad for respiratory
• Chlamydia
• Mycoplasma pneumonia — azithromycin

Resistance:

• Methylate 23S rRNA binding site
• Efflux pumps
• Hydrolyze via esterases

Adverse effects

• GI issues
• Hepatic failure
• Prolonged QT interval
• DON’T TAKE CLARITHROMYCIN DURING PREGNANCY

… Inhibit CYP450 enzymes so check with other medications

Question 13

Which drugs have resistant bacteria that methylate the 23S rRNA binding site?

Answer 13

Macrolides
Clindamycin
Streptogramins (quinupristin/dalfopristin)

Question 14

Clindamycin

Answer 14

• Bacteriostatic
• Binds 50S rRNA and blocks translocation

Spectrum:

• Gram + (aerobic and anaerobic)
• Treats acne!

Resistance:

• Mutate ribosome
• Methylate rRNA – cross resistance with macrocodes and streptogramins
• Adenylation

Adverse effects

• Hypersensitivity
• GI issues
• C. diff superinfection

Question 15

Streptogramins: what are they?

Answer 15

Quinupristin and dalfopristin

Question 16

Streptogramins:

Quinupristin and dalfopristin

Answer 16

• Bacteriostatic alone
• Bactericidal combined
• Bind 50S subunit and inhibit translocation

Spectrum of activity
- Use sparingly! Only if you have drug resistance to multiple G+ bacteria

Resistance

• Methylate 23S rRNA
• Inactivating enzymes
• Efflux pumps
• Cross resistance with macrolides and clindamycin

Adverse effects:

• Joint pain
• Muscle pain
• Inhibits CYP450 enzyme – check with other drugs

Question 17

What happens when a drug induces disulfiram reaction?

Answer 17

• Blocks processing of ethanol because it inhibits acetaldehyde dehydrogenase
• Causes toxic acetaldehyde to build up

2ND GENERATION CEPHALOSPORINS AND METRONIDAZOLE DO THIS

Question 18

Which drugs shouldn’t be used with newborns?

Answer 18

Chloramphenicol

Sulfonamides (NA inhibitor)

Question 19

Which drugs shouldn’t be used with children?

Answer 19

Tetracyclines

Fluoroquinolones (NA inhibitor)

Question 20

Which drugs shouldn’t be used in pregnancy?

Answer 20

Tetracycline
Aminoglycosides (TANGS)
Clarithromycin (a macrolide)
Fluoroquinolones (NA inhibitor)
Chloramphenicol
Sulfonamides (NA inhibitor)

Question 21

Which drugs shouldn’t be used in elderly populations?

Answer 21

Aminoglycosides (TANGS)
Fluoroquinolones (NA inhibitor)
Adjust doses for beta lactams (depending on renal function)