Tetracycline/Glycicycline (Anti-Biotics) Flashcards
(38 cards)
Name the 4 tetracyclines and 1 glycicyclines
Tetracycline, Doxycycline, Minocycline, Demeclocycline, and Tigecycline.
Although TCN’s are generally given orally and have good absorption, which can be administered via IV?
Doxy, Mino, and Tigecyclines. Note tigecycline is ONLY IV, not oral.
What can mess with the absorption of all TCN’s? (4 things)
Alkaline pH, dairy products, divalent/trivalent cations, and antacids. These things can chelate the drug forming poorly soluble complexes.
Which of the TCN’s are impaired by food?
Tetra and Demeclocyclines.
What is the consequence of increasing the concentration of TCNs? What’s the consequence of this?
The higher the dose the higher the unabsorbed fraction, i.e unchanged drug. The TCN’s then remain in the gut lumen and modify the intestinal flora. –> Increased risk of c. diff.
What’s interesting about the Vd of TCN’s?
Seem to get into almost all fluids including CSF, urine, prostate, enamel of unerupted teeth, bone and regular teeth. Thus, avoid in children and preggo, it crosses the placenta and enters breask milk.
In terms of CSF absorption, which of the TCN’s have the best activity?
Mino > Doxy > TCN.
In addition to the general Vd, minocycline is also found to concentrate where?
In tears and in saliva.
Which 3 TCNs undergo mostly renal (some biliary) elimination, is mostly unchanged and undergo enterohepatic cycling?
TCN, mino and demeclo.
How is Doxy and mino excreted? TCN?
Doxy: Mostly biliary some renal, enterohepatic cycling of unchanged drug. Mino: Extensive hepatic metabolism to inactive metabolites. TCN: Largely excreted unchanged in bile and urine.
Which TCN has no renal excretion?
Minocycline.
Which 3 TCN’s require no adjustments for renally impaired?
Doxy, Mino, Tigecyclines.
Which TCN have the shortest and longest half lives?
TCN has shortest ~9 hrs, Tigecycline has longest ~ 40 hrs.
How do TCNs enter Gram + and Gram - bacteria?
Gram + through some energy dependent mech not known yet, gram neg it diffuses through the porins and gets transported across cell membranes via some energy dependent mech.
Site of action of TCN’s and their general MOA?
Site of action is the 30S subunit of ribosomes, where they block the A site and thus preventing the tRNA from binding there and prevents amino acids from being added.
Name the 3 Atypical bacteria?
Mycoplasma pneumoniae, Legionella and Chlamydia, the latter 2 are obligate intracellular organisms and the first one is so tiny that it lacks a cell wall. As a result a lot of ABX lacks activity against them.
List the activity of TCNs.
Good against atypicals, some spirochetes (like Triponema and Borellia), gram +, including caMRSA, gram neg, Rickettsia, C. Burnetti, Plasmodia spp.
Which TCN in particular is very useful against rocky mountain spotted fever? What causes this?
Doxycycline, and Rickettsia causes this.
If TCN’s have such broad activity how come its really only used for limited things?
It has widespread resistance making their value limited.
Activity of Tigecycline?
Generally TCN activity + some stuff that developed resistance to TCN, such as MRSA, Multidrug resistant strep pneumo, other strep, Vancomycin resistant enterococci (VRE), ESBL producing gram neg, anarobics including baceroides fragilis.
To what (and why) are staph resistant to?
Due to efflux pump TetK, resistant to TCN, but not to doxy, mino or tige
Which bacteria have the Tet(AE) efflux pump and what does this make them resistant to?
Gram neg have these and it makes them resistant to older TCN’s but not to tigecycline.
What two organisms are intrinsically resistant to all TCN’s and tigecyclines, and why?
Proteus and P. aeruginosa, because of multidrug efflux pumps.
What are ribosomal protection proteins? What can overcome this?
Proteins some gram + and - have that make binding to the ribosomes by the drug difficult due to modifications. Due to the chemistry of tigecycline, it can overcome the ribosomal protection and avoid some of the efflux pumps.
