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Tetracycline Structure-Activity Relationship
Substitutions 5, 6, 7, 9 can be varied or removed w/o loss of activity
stereochemistry at position 4 is crucial
stereo chemistry at 5a is necessary
aromatization of ring C greatly reduces activity
Tetracyclines form complexes with metal ions and decreases absoption:
Fe2+, Fe3+, Ca2+, Zn2+, Al3+, Mg2+
Chelation of Ca2+
causes problems in developing teeth of pediatrics
Tetracyclines should be avoided
in kids < or equal to 8
Tetracycline MoA
bind to 16s rRNA of 30s ribosomal subunit 
interfere with binding of amoniacyl tRNA to acceptor site
Tetracyclines are bacterio______
Tetracycline absoption
doxycicline well absorbed
Tetracycline distribution
all tissues, concentrated in reticuloendothelial cells of spleen, bone, liver
Tetracycline excretion
renal, fecal
Dose adjustment for
Tetracycline Adverse effects
GI: N, V, D,
Candida and/or C. diff overgrowth
minocycline can cause vestibular toxicity
avoid use in pregrant beyond 1st trimester
Tetracycline drug interactions
multivalent cations
retinoids (increase intracrannial pressure, tetracycliens also increase pressure)
Tetracycline Resistance
tetM (translation)
tetK (energy driven efflux pump)
Tigecycline not affected by resistance of
tetM, tetK
Tigecyline used for
gram (+)  (MSSA, MRSE, Staph. epidermis, strept. pneumoniae, Vancomycin resistant enterocaucus
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