Bacterial Protein Synthesis Agents

Question 1

Tetracycline

Answer 1

Tetracyclines
Characteristics:
- Bacteriostatic
- Target Gram Positive and Gram Negative

MOA:
- Bind reversibly to 16S subunit of 30S ribosomal subunit
–> Inhibits translation
- Taken up by susceptible organisms through active transport to inhibit protein synthesis

AE:
- Staining of teeth and Dental Hypoplasia
- Bone Deformities
- Expired Tetracycline becomes very toxic
–> Becomes Anhydride Tetracycline (Nephrotoxic)

• Contraindicated in pregnant women, nursing mothers, and children

Question 2

Aminoglycosides

Answer 2

Ex. Gentamicin, Streptomycin

Characteristics:
- Bacteriostatic/Bactericidal
- Target Gram-Negative
- Need oxygen to get inside bacteria

MOA:
- Bind irreversibly to 30S ribosomal subunit and inhibit protein synthesis
- As cationic molecules they create pores in the outer membrane causing leakage of cell contents and allowing more antibiotics to get in

AE:
- Ototoxicity
- Nephrotoxicity
- Rare Neuromuscular Block (Causes paralysis)

Question 3

Macrolides

Answer 3

Ex. Erythromycin

Characteristics:
- Bacteriostatic
- Penicillin alternative
MOA:
- Binds 23S rRNA on 50S subunit to inhibit peptidyl transferase thus, blocks transfer of amino acid onto growing peptide chain

AE:
- Cholestatic Jaundice
- Inhibits CYP 450 (Erythromycin, Clairthromycin)

Question 4

Chloramphenicol

Answer 4

Characteristics:
- Bacteriostatic
- Targets Gram-negative and Gram-Positive bacteria
- Treats serious meningitis when penicillin can not be used

MOA:
Binds to 23S rRNA molecules on the 50S subunit inhibiting peptidyl transferase
- Blocks transfer of amino acids onto growing peptide chain

AE:
- Pancytopenia
- Grey Baby Syndrome

Question 5

Oxazolidinone

Answer 5

Ex. Linezolid
Characteristics:
- Bacteriostatic
- Targets Gram-positive and resistant bacteria (MRSA)

MOA:
- Binds to 70S subunit to antagonize N-formylmethinoyl-tRNAand inhibit protein synthesis
- Weak MAO inhibitor
- 100% Oral Bioavailability

AE:
- Thrombocytopenia
- Serotonin Syndrome
- Hyperlactatemia

Question 6

Fusidic Acid

Answer 6

Characteristics:
- Bacteriostatic
- Steroid Antibiotic
- Targets Gram-positive

MOA:
- Interferes with translation to inhibit protein synthesis

AE:
- Jaundice

Question 7

Streptogramins

Answer 7

Ex. Quinupristin/Dalfopristin
Characteristics:
- Bacteriostatic
- Targets Gram-positive
- Cyclic Peptide
- Combination antibiotic where Dalfopristin promotes binding of Quinupristin

MOA:
- Binds to 50S subunit on bacterial ribosome to inhibit protein synthesis

AE:
- Arthralgia (Joint aches)
- Myalgia (Muscle aches)

Question 8

Clindamycin

Answer 8

Lincosamide
Characteristics:
- Bacteriostatic

MOA:
- Binds to 23S on the 50S ribosomal subunit to inhibit peptidyl transferase
- Prevents transfer of amino acids on growing peptide chain

AE:
- Lethal Pseudomembranous Colitis

Question 9

Quinolones

Answer 9

Ex. Nalidixic Acid, Ciprofloxacin

Characteristics:
- Bactericidal
- Targets both Gram-positive and Gram-negative
- Very stable, can survive in the environment leading to bacteria resistance

Gram Positive MOA:
- Inhibits topoisomerase II (Bacterial DNA gyrase)
- Prevents negative supercoiling of DNA by DNA gyrase
–> Needed to allow transcription/replication

Gram Negative MOA:
Inhibits topoisomerase IV
- Prevents topoisomerase IV mediated decatenation (unlinking) of daughter DNA molecules

AE:
- Arthropathy
- Convulsions (Exacerbated If used with theophylline)