Protein Synth. Inhibiting antibiotics

Question 1

Macrolides

Answer 1

Suffix: “thromycin” Erythromycin, Clarithromycin, Azithromycin

Question 2

Macrolide mechanism of action

Answer 2

Inhibition of protein synthesis by binding 50S ribosomal subunit, blocking translocation of peptidyl tRNA from acceptor spot to peptidyl site.
Passive diffusion into cells. Weak base, more active at basic pH.
Bacteriostatic at non-toxic dose (generally)
Selective toxicity b/c drug won’t bind mammalian 60S

Question 3

Macrolide pharmacokinetics

Answer 3

Abs:
Erythromycin: enteric coating to avoid destruction in stomach
Azithromycin: take w/o food (higher pH)
Clarithromycin: food doesn’t matter
Distribution:
wide, except CSF and brain. traverses placenta

Question 4

Macrolide excretion

Answer 4

Erythromycin: Liver metab., excreted in bile. Avoid in liver disease.
Clarithromycin: hepatic metabolism to active compound, renal excretion
Azithromycin: NOT METABOLIZED. High tissue penetratio/binding –> once daily dosing

Question 5

Tetracyclines

Answer 5

Tetracycline, Doxycycline, Minocycline

Question 6

Tetracycline mechanism of action

Answer 6

Actively transported into bacterial cell. Reversibly bind 30S ribosomal subunit. Blocks aminoacyl tRNA site. Resistance change in active transport proteins/production of proteins that block drug binding

Question 7

Tetracycline pharmakokinetics

Answer 7

Best given on empty stomach. Abs. is impaired by dairy products, and a variety of metal ions that complex w/ drug to form insoluble salts.
Tetracycline is short acting, doxy & mino are longer acting

Question 8

Clindamycin

Answer 8

Binds 50S, blocking peptide synthesis. Bacteriostatic. Penetrates bone especially well.
Danger of C. diff superinfection/ pseudomembranous colitis, but not more-so than broad spectrum

Question 9

Aminoglycosides

Answer 9

Hexose ring with various amino sugars attached via glycosidic bonds. Highly water soluble, so enter ECF readily but require active transport into cells

Question 10

Aminoglycoside mechanism of action

Answer 10

Binds 30S, preventing initiation of translation, breakup of polysomes, misreading of mRNA.
Requires active transport, so O2 is required–not effective against anaerobes.

Question 11

Aminoglycoside resistance

Answer 11

plasmid-mediated transfer of the means to impair drug binding with ribosome

Question 12

Aminoglycoside pharmacokinetics & dosing

Answer 12

Highly polar, anionic, so oral is not effective.
Rapid absorption with IM.
Excluded from CNS and eye, but accumulates in inner ear and renal cortex, leading to selective toxicity in those areas.
Concentration-dependent killing, and post-antibiotic effect, so given once daily.

Question 13

Aminoglycoside toxicity

Answer 13

Highly individual kinetics, so close patient monitoring necessary.
Often irreversible CN VIII damage (hearing and inner ear)
Reversible renal toxicity

Question 14

Chloramphenicol

Answer 14

First synthetic AB of significance. Highly lipophilic.

Question 15

Chloramphenicol mechanism of action

Answer 15

Reversible binding to 50S to block peptidyl transferase. Bacteriostatic.
Also inhibits mammalian bone marrow mitochondrial protein synth @ 70S, reducing selective toxicity

Question 16

Chloramphenicol kinetics

Answer 16

Rapid GI abs. widely distributed to tissue and fluid, including CNS and CSF.
Fetal/neonate liver cannot conjugate, leading to toxicity, so avoid in preganat/breast feeding mothers.
Toxicity: Bone marrow, Gray Baby Syndrome