Npsc521P Lecture 15 Protein Synthesis Inhibts

Front 1

1. List the three members of the tetracyclines described below.

Back 1

a. Tetracycline
b. Minocycline (Minocin)
c. Doxycycline (Vibramycin; Periostat)

Front 2

2. List the three members of the macrolide antibiotics described below.

Back 2

a. Azithromycin (z-pac; Zithromax)
b. Clarithromycin (Biaxin)
c. Erythromycin ethyl succinate (EES)

Front 3

3. For clindamycin, tetracyclines, macrolides describe the mechanisms and characteristics.

Back 3

a. Clindamycin
1. Mechanisms = reversibly binds to the 50 S subunit of bacterial ribosomes to inhibit peptide bond formation and protein synthesis. Binds at similar sites as the erythromycins and chloramphenicol.
2. Characteristics - Antibacterial activity –aerobes and anaerobes = S, aureus, viridans streptococci; more active than erythromycin or clarithromycin against anaerobic bacteria. Not very effective against gram neg.
3. Important agent in dentistry = Clindamycin (surgeons love it)

b. Tetracyclines
1. Mechanism = inhibits protein synthesis by binding with the 30S subunit blocking tRNA function and protein production
2. Characteristics = broad spectrum -effective against both gram-positive and gram-negative organisms and infections due to Mycoplasma, Chlamydia and Rickettsia. Active against periodontal AA and GI tract H. pylori
 Low dose doxycycline inhibits collagenase in vitro and has been shown to inhibit collagenase in gingival crevicular fluid in adults with periodontitis (PERIOSTAT)
 In dentistry is used in 3 ways:
o Periodontitis (oral)
o Direct pocket drop gel (tetradox)
o Use subantimicrobial dose to inhibit collagenase (PERIOSTAT)

Macrolides
1. Mechanism = huge molecule that binds reversibly to the 50 S ribosomal subunit which inhibits the translocation step wherein a newly synthesized peptidyl tRNA molecule moves from acceptor site on the ribosome to the peptidyl (or donor) site. The macrolides do not inhibit peptide bond formation directly.
2. Characteristics - Antibacterial activity- relatively narrow spectrum = Erythromycin most effective against gm positive cocci and bacilli; Clarithromycin is slightly more potent against erythromycin-sensitive strains of streptococci and staph.; Azithromycin (very unique antibiotic, very few side effects and only takes one pill a day) is generally less active than erythromycin against gm-positive organisms and is more active against H. influenzae and Campylobacter spp. Azithromycin very active against M catarrhalis, Chlamydia spp., M. pneumoniae, Fusobacterium spp., and N. gonorrhoeae. Uses = susceptible bacterial infections, pharyngitis/tonsillitis, sinusitis, otitis media, pneumoniae, chlamydia, others

Front 4

4. Describe the mechanism of antibacterial action of linezolide (Zyvox).

Back 4

a. Inhibits bacterial protein synthesis by binding to bacterial 23S ribosome RNA of the 50S subunit (70S??). Binding to the 23S inhibits the ribosomal assembly step of protein synthesis early on. There is no cross resistance with the other protein inhibitors.
b. Useful as optional drug if patients didn’t respond to clindamycin but never used as 1st choice drug for fear of resistance

Front 5

5. For metronidazole (Flagyl), describe its mechanism and characteristics.

Back 5

a. Mechanism = Antiparasitic; Antimicrobial. Its selective toxicity to protozoa and anaerobic bacteria derives from their energy metabolism which differs from aerobic cells. A single electron transfer from electron-transport components of the anaerobic pathogen forms a REACTIVE NITRO RADICAL within the metronidazole molecule. This radical targets the DNA of the pathogen cell and is toxic to the cell. Oxygen inhibits metronidazole-induced cytotoxicity because it competes for the electrons.
b. Characteristics = Active against anaerobic cocci, anaerobic gram-negative bacilli, including Bacteroides and anaerobic spore-forming gram-positive bacilli. Aerobic bacteria are resistant. Active against anaerobic protozoa parasites including trichomonas (T. vaginalis). Has a disulfiram effect which is enhanced by alcohol. Risk of a severe reaction from metronidazole-alcohol combination is low.

Front 6

6. Describe the mechanism of action of vancomycin.

Back 6

a. Mech = inhibits the synthesis of the cell wall in sensitive bacteria by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units thus preventing peptidoglycan synthesis

Front 7

7. What is Atridox, Arestin and Periostat and describe their use in dentistry.

Back 7

a. Periostat: a.k.a. doxycycline (subantimicrobial)
i. Use: Treatment of periodontitis associated with presence of Actinobacillus actinomycetemcomitans. Periostat is indicated for use as an adjunct to scaling and root planning to promote attachment level gain and to reduce pocket depth in adult periodontis (systemic levels are sub-inhibitory against bacteria)
ii. Low dose submicrobial form of doxycycline, used as collagenase inhibitor to restore periodontal tissues
b. Atridox: doxycycline Hyclate (Periodontal)  pocket drop gel
i. Use: Treatment of chronic adult periodontitis for gain in clinical attachment, reduction in probing depth, and reduction in bleeding upon probing. Used exclusively in dental applications.
c. Arestin: Minocycline Hydrochloride (Periodontal)  pocket drop gel
i. Use: Adjunct to scaling and root planning procedures for reduction of pocket depth in patiens with adult periodontitis. May be used as part of a periodontal maintenance program which include good oral hygiene, scaling, and root planning.

Front 8

8. List the adverse effects caused by tetracyclines.

Back 8

a. Superinfection dominated by Candida albicans – so called yeast infection – of oral cavity and/or vagina
b. Discoloration of the teeth and enamel hypoplasia (young children)
c. Can cause photosensitivity – reddening of the skin when exposed to sunlight

Front 9

9. List the drug interactions with the tetracyclines.

Back 9

a. Antacids containing CA++, Al+++, Mg ++ decrease tetracycline absorption from the GI tract because the metals bind to the tetracycline molecule to produce a large chelated molecule that is not easily taken up into the blood stream.
b. Tetracylines may decrease the effectiveness of penicillins (including pencillin VK, amoxicillin, ampicillin and other penicillins) in the ability of penicillins to eradicate an infection. Penicillin is a bactericidal agent requiring active, dividing bacteria to be effective. Tetracyclines are bacteriostatic agents, and, as such, reduce the activity of the bacteria thus reducing the ability of the penicillin to affect it. Only bacteriostatic that interacts with penicillin