Protein Synthesis Inhibitors

Question 1

Why are PCNs/cephalosporins not an effective therapy for mycoplasma pneumoniae?

Answer 1

because it lacks a peptioglycan cell wall. PCNs/cephalosporins are inhibitors of peptidoglycan cell wall synthesis

Question 2

What is the difference between bacterial and mammalian ribosomes?

Answer 2

the bacterial ribosome is smaller (70S) than the mammalian ribosome (80S), It’s made of 50S and 30S subunits instead of 60S and 40S that’s in humans. Mammalian cells don’t have peptidoglycan cell walls

Question 3

What general classes and specific antibiotics are classified as protein synthesis inhibitors?

Answer 3

tetracyclines, macrolides, chloramphenicol, clindamycin

Question 4

What is the MOA of tetracyclines?

Answer 4

Binds to 30S subunit of the bacterial ribosome and blocks access of the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site

Question 5

What is the antibacterial spectrum tetracyclines cover?

Answer 5

Broad spectrum antibiotics, active against many gram positive and gram negative organisms including anaerobes

Question 6

When should you not use a tetracycline?

Answer 6

not used when suspecting s. aureus because the majority of penicillinase producing staph are also insensitive to tetracyclines

Question 7

Describe the pharmacokinetics of tetracyclines

Answer 7

adequately but incompletely absorbed after oral ingestion. Taking with dairy decreases absorption (less of a problem with doxycycline). All tetracyclines cross placental barrier and concentrate in fetal bones and dentition

Question 8

Describe the elimination of tetracycline

Answer 8

processed in liver, released in the bile and reabsorbed in the intestine to enter urine via glomerular filtration. doxycycline’s metabolite is excreted into from the bile into the feces so it can be used in renally compromised patients.

Question 9

What are adverse effects of tetracyclines?

Answer 9

Deposition in the bone and primary dentition occurs in growing children causing discoloration and hypoplasia of the teeth and stunting of growth. take w/foods other than dairy to avoid GI upset

Question 10

What are CI of tetracyclines?

Answer 10

pregnant/breastfeeding, children <8yrs, use doxy for impaired renal fxn, caution if impaired liver fxn and w/lupus

Question 11

How are tetracyclines used clinically as treatment?

Answer 11

Useful in STIs, atypical pneumonia, exacerbations of chronic bronchitis, acne vulgaris, and for sinusitis and acute prostatitis. Usually doxy 100mg BID.

Question 12

What conditions are each tetracycline the drug of choice for?

Answer 12

Doxycycline: mycoplasma pneumoniae, chlamydiae, rickettsiae (Rocky Mountain Spotted Fever), and Lyme Disease. Minocycline: acne vulgaris. Demeclocycline: Sudden Innappropriate Antidiuretic Hormone

Question 13

What is the MOA of macrolides?

Answer 13

Bind irreversibly to a site on the 50S subunit of the bacterial ribosome

Question 14

What are the antibacterial spectrums for each macrolide?

Answer 14

Erythromycin: used in patients allergic to the PCNs, chlamydial species, mycoplasma pneumoniae, and legionella. Clarithromycin (Biaxin) also effective against H. influenzae. Azithromycin (Zithromax) is less active against streptococci and staphylococci than erythomycin, but more active against H. influenzae and M. catarrhalis, urethritis caused by Chlamydia trachomatis

Question 15

When are macrolides an ineffective choice of treatment?

Answer 15

Most strains of staph in hospital are resistant to erythromycin. Clarithromycin and azithromycin show cross resistance with erythromycin

Question 16

Describe the pharmacokinetics of macrolides

Answer 16

Erythromycin base destroyed by gastric acid so enteric coated tablet is required. Clarithromycin and Azithromycin are stable to stomach acid and readily absorbed. Widely distributed in tissues except for CSF

Question 17

How are each of the macrolides metabolized?

Answer 17

Erythromycin is a cytochrome P450 drug. Clarithromycin metabolized by liver and may also interfere with other drugs. Azithromycin is NOT a P450 drug and tends to have very few interactions with other medications

Question 18

How are each of the macrolides excreted?

Answer 18

Erythromycin and azithromycin are concentrated in the bile. Clarithromycin and its metabolites are eliminated by the kidney and liver. dosage should be adjusted in patients with compromised renal function

Question 19

What are adverse effects of macrolides?

Answer 19

diarrhea especially a problem with erythromycin.
transient deafness has been associated with erythromycin at high dosages. Prolonged QT wave w/ erythromycin & Clarithromycin (rare) could lead to severe arrhythmias

Question 20

Why is azithromycin easier to use than the other macrolides?

Answer 20

fewer adverse effects and drug interactions. Don’t have to worry as much about dosage adjustments for renally/hepatically compromised patients. Long half life so only have to take once a day (good for peds) for 3-5 days

Question 21

For what diseases do macrolides tend to be the drug of choice?

Answer 21

chlamydial species (single 1gm dose). good coverage of typical and atypical pneumonias. good for chronic bronchitis associated w/COPD. 1st line alternative therapy for group A streptococcal pharyngitis (strep throat)

Question 22

What is the most important consideration of using chloramphenicol?

Answer 22

because of its high toxicity, its use is restricted to life-threatening infections when there are no alternatives

Question 23

What is the mechanism of action of chloramphenicol?

Answer 23

Binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction

Question 24

What is the antimicrobial spectrum of chloramphenicol?

Answer 24

Very broad including excellent activity against anaerobes, gram positve/negative species. Not effective against Pseudomonas or Chlamydiae

Question 25

What are the pharmacokinetics of chloramphenicol?

Answer 25

Completely absorbed orally and readily enters CSF

Question 26

What are adverse effects of chloramphenicol?

Answer 26

Hemolytic Anemia, Aplastic Anemia (which is usually fatal, occurs independent of dose and may occur after therapy has ceased!) Gray Baby Syndrome – because of interference with human mitochondrial ribosomes, can lead to poor feeding, depressed breathing, cardiovascular collapse, cyanosis, and death

Question 27

What microbed is always resistant to clindamycin?

Answer 27

Clostridium difficile

Question 28

What are common medications that work well against anaerobes?

Answer 28

clindamycin or metronidazole (Flagyl)