Protein Synthesis Inhibitors

Question 1

Aminoglycosides

Answer 1

30S subunit interference
GNATS
Gentamycin (topical, IV, IM)
Neomycin (topical, PO)
Amikacin (IV, IM)
Tobramycin (topical, IV, IM, Nebulized)
Streptomycin
Active transport across cell membrane into cytoplasm by an oxygen dependent process
Bactericidal due to irreversible binding to 30S and formation of aberrant proteins (interferes with initiation complex, prevents proofreading, block movement of ribosome)
Aerobic gram- including Pseudomonas

Question 2

Aminoglycoside toxicity

Answer 2

High concentrations accumulate in renal cortex, endolymph, perilymph of inner ear
Nephrotoxic, ototoxic
Neuromuscular blockade: usually with direct intraperitoneal or intrapleural application of large dose

Prolonged high trough levels

Question 3

Tetracyclines

Answer 3

Tetracycline (PO) and Doxycycline (IV/PO)
Bacteriostatic
Passive diffusion and energy dependent protein mechanism
Reversible bind 30S subunit blocking access to tRNA to mRNA at acceptor site
MRSA

Question 4

Tetracycline kinetics

Answer 4

Incompletely absorbed PO
Worse if taken with dairy, Mg, Al antacids, and Fe preparations due to formation of nonabsorbable chelates
Concentrates in tissue with high Ca content (bad in pregnancy and crosses placenta)
Metabolized in liver

Question 5

Tetracyclines adverse effects

Answer 5

Photosensitivity
Chelation (readily bound to Ca deposited in newly formed bone or teeth in young children)
Gastric discomfort (take with food)
Nephrotoxicity (renal tubular acidosis due to out of date meds)

Question 6

Tigecycline

Answer 6

Reversibly binds 30S ribosome interfering with tRNA binding
Bacteriostatic
MRSA, Acinetobacter, gram - (NOT Pseudomonas, Proteus, Providencia)
Rapid distribution (not for bacteremia)

Question 7

Macrolides

Answer 7

Azithromycin (IV, PO), Clarithromycin (PO), Erythromycin (IV, PO, topical)
Bacteriostatic
Binds irreversibly to 50S subunit
Transpeptidation prevented by blocking polypeptide exit tunnel
tRNA dissociated from ribosome
Taken up by leukocytes and delivered to site of infection
Gram + and -, intracellulars, H pylori
Community acquired PNA, URIs, acute otitis media

Question 8

Macrolide kinetics

Answer 8

Potential for drug interactions via CYP3A4
Erythromycin and Clarithromycin inhibit cytochrome P450
Azitromycin does not

Question 9

Macrolide adverse side effects

Answer 9

Agonists at motilin receptor: profound diarrhea, cramping
Ototoxicity
Phlebitic
Hepatotoxic
Metallic taste - Clarithromycin
Erythromycin, Clarithromycin: prolonged QT interval

Question 10

Chloramphenicol

Answer 10

Binds reversibly to 50S subunit and inhibitspeptide bond formation
Broad spectrum
TOXIC: gray baby syndrome (babies lack glucuronidine transferase, chloramphenicol accumulates and affects mitochondria, leads to acidosis, gray color, death), anemia, aplastic anemia, drug interactions

Question 11

Clindamycin

Answer 11

Binds 50S preventing translocation
Gram + and some -, anaerobes NOT C. diff, CA-MRSA
anaerobic infections (above the belt)
Hepatically cleared
High risk of C diff

Question 12

Linezolid

Answer 12

Binds to 50S to prevent formation of 70S initiation complex
Gram + including MRSA, VRE, Listeria
Bacteriostatic
Bacteriocidal against strep and clostridium perfringens
MRSA and VRE
Adverse effects: ha, thrombocytopenia, irreversible peripheral neuropathy and optic neuritis > 28 days
Inhibits monoamine oxidase activity, can precipitate serotonin syndrome in patients taking SSRIs