Tetracyclines and tetracycline analogs

Question 1

MOA

Answer 1

Tetracyclines and tetracycline analogs inhibit bacterial protein synthesis by reversibly binding to the 30S ribosome, blocking binding of amino-acyl tRNA to the acceptor (A) site on the mRNA-ribosomal complex. This prevents the addition of amino acid residues to the elongating peptide chain and inhibits protein synthesis.

Question 2

MOR

Answer 2

1.Decreased accumulation of tetracycline within the bacteria due to either altered permeability or the presence of tetracycline-specific efflux pumps.

2.Decreased access of the tetracycline to the ribosome due to the presence of ribosomal protection proteins.

3.Enzymatic inactivation of the tetracycline.

Question 3

Drugs in class

Answer 3

Tetracyclines:Tetracycline, Doxycycline, Minocycline

Tetracycline analogs: Tigecycline , Eravacycline ,
Omadacycline

Question 4

Spectrum of activity
Gram positive aerobes

Answer 4

Gram-Positive Aerobes – minocycline and doxycycline most active

Some Group and Viridans Streptococcus
Streptococcus pneumoniae (PSSP, doxycycline  85% susceptible)
Some Enterococcus spp.
Some Staphylococcus aureus (primarily MSSA, 80% susceptible)
Bacillus, Listeria, Nocardia

Question 5

Spectrum of activity
Gram negative

Answer 5

2. Gram-Negative Aerobes –were initially useful for Gram-negative aerobes, but many Enterobacteriaceae are relatively resistant

Haemophilus influenzae (90% susceptible)
Haemophilus ducreyi (chancroid)
Campylobacter jejuni
Helicobacter pylori
Acinetobacter baumannii (minocycline IV)

Question 6

Spectrum of activity
Atypical

Answer 6

Legionella pneumophila, Chlamydophila pneumoniae and psittaci;

Question 7

Spectrum of activity for Tigecycline, eravacycline and omadacycline

Answer 7

1. Gram-Positive Aerobes
   Group streptococci
   Viridans streptococci
   Enterococcus faecalis (VSE and some VRE)
   Staphylococcus aureus (MSSA and MRSA)
   Listeria monocytogenes

2.Gram-Negative Aerobes
Acinetobacter baumannii (omadacycline MICs higher)
Aeromonas hydrophila
Citrobacter freundii and koseri
Enterobacter cloacae and aerogenes
E. coli
Klebsiella pneumoniae and oxytoca
Serratia marcescens
Stenotrophomonas maltophilia (omadacycline MICs higher)

Question 8

Pharmacology

Answer 8

Bacteriostatic

Question 9

Absorption

Answer 9

tigecycline and eravacycline are only available IV; doxycycline, minocycline, omadacyline are available IV and PO, tetracycline is only available PO

Absorption of the oral tetracyclines and omadacycline is impaired by the concurrent ingestion of dairy products, aluminum hydroxide gels, calcium, magnesium, iron, zinc, and bismuth subsalicylate due to chelation with divalent or trivalent cations.

Question 10

Distribution

Answer 10

Tetracyclines and tetracycline analogs are widely distributed into body tissues and fluids (prostatic, seminal fluids)

only small amounts diffuse into CSF - not good

Question 11

Elimination

Answer 11

tetracycline is excreted unchanged in kidney - dose adjustment needed

Doxycycline and minocycline are excreted mainly by nonrenal routes, and do not require dosage adjustment in renal insufficiency

Tetracycline analogs are mainly eliminated by biliary/fecal excretion of unchanged drug and its metabolites no dose adjustment needed in renal insufficiency

Question 12

Adverse effects

Answer 12

1. GI - N/V/D
2. Dermatologic - Photosensitivity
3. Pregnancy category D - dont use during prego or lactation as well as for kids <8 as it can cause permanent discoloration of adult teeth (grey/blue color)

Question 13

Drug interactions

Answer 13

Oral tetracyclines and omadacycline interact with divalent and trivalent cations

Absorption of the oral tetracyclines and omadacycline is impaired by the concurrent ingestion of dairy products, aluminum hydroxide gels, calcium, magnesium, iron, zinc, and bismuth subsalicylate due to chelation with divalent or trivalent cations.