Tetracycline/Glycicycline (Anti-Biotics)

Question 1

Name the 4 tetracyclines and 1 glycicyclines

Answer 1

Tetracycline, Doxycycline, Minocycline, Demeclocycline, and Tigecycline.

Question 2

Although TCN’s are generally given orally and have good absorption, which can be administered via IV?

Answer 2

Doxy, Mino, and Tigecyclines. Note tigecycline is ONLY IV, not oral.

Question 3

What can mess with the absorption of all TCN’s? (4 things)

Answer 3

Alkaline pH, dairy products, divalent/trivalent cations, and antacids. These things can chelate the drug forming poorly soluble complexes.

Question 4

Which of the TCN’s are impaired by food?

Answer 4

Tetra and Demeclocyclines.

Question 5

What is the consequence of increasing the concentration of TCNs? What’s the consequence of this?

Answer 5

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.

Question 6

What’s interesting about the Vd of TCN’s?

Answer 6

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.

Question 7

In terms of CSF absorption, which of the TCN’s have the best activity?

Answer 7

Mino > Doxy > TCN.

Question 8

In addition to the general Vd, minocycline is also found to concentrate where?

Answer 8

In tears and in saliva.

Question 9

Which 3 TCNs undergo mostly renal (some biliary) elimination, is mostly unchanged and undergo enterohepatic cycling?

Answer 9

TCN, mino and demeclo.

Question 10

How is Doxy and mino excreted? TCN?

Answer 10

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.

Question 11

Which TCN has no renal excretion?

Answer 11

Minocycline.

Question 12

Which 3 TCN’s require no adjustments for renally impaired?

Answer 12

Doxy, Mino, Tigecyclines.

Question 13

Which TCN have the shortest and longest half lives?

Answer 13

TCN has shortest ~9 hrs, Tigecycline has longest ~ 40 hrs.

Question 14

How do TCNs enter Gram + and Gram - bacteria?

Answer 14

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.

Question 15

Site of action of TCN’s and their general MOA?

Answer 15

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.

Question 16

Name the 3 Atypical bacteria?

Answer 16

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.

Question 17

List the activity of TCNs.

Answer 17

Good against atypicals, some spirochetes (like Triponema and Borellia), gram +, including caMRSA, gram neg, Rickettsia, C. Burnetti, Plasmodia spp.

Question 18

Which TCN in particular is very useful against rocky mountain spotted fever? What causes this?

Answer 18

Doxycycline, and Rickettsia causes this.

Question 19

If TCN’s have such broad activity how come its really only used for limited things?

Answer 19

It has widespread resistance making their value limited.

Question 20

Activity of Tigecycline?

Answer 20

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.

Question 21

To what (and why) are staph resistant to?

Answer 21

Due to efflux pump TetK, resistant to TCN, but not to doxy, mino or tige

Question 22

Which bacteria have the Tet(AE) efflux pump and what does this make them resistant to?

Answer 22

Gram neg have these and it makes them resistant to older TCN’s but not to tigecycline.

Question 23

What two organisms are intrinsically resistant to all TCN’s and tigecyclines, and why?

Answer 23

Proteus and P. aeruginosa, because of multidrug efflux pumps.

Question 24

What are ribosomal protection proteins? What can overcome this?

Answer 24

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.

Question 25

Which TCN is most commonly used and why?

Answer 25

Doxycycline due to ease of administration and x1 daily dosing.

Question 26

Given the tons of resistance, what are the TCN’s really useful for?

Answer 26

First line tx for rickettsia, mycoplasma and chlamadia. Useful for caMRSA, acne, some GI issues, plasmodium spp, and some spirochetes.

Question 27

When would we use tigecyclines?

Answer 27

Complicated skin/skin structure infections like from MRSA and VRE, complicated intra-ab infection, community acquired pneumonia (but not VAP).

Question 28

What is VAP

Answer 28

Ventillator associated pneumonia, which tends to be caused by pseudomonas, thus we cannot use tigecyclines for these as they are resistant.

Question 29

What is the only practical use for Demecocycline and why?

Answer 29

Useful for SIADH, due to the inhibition of action of vasopressin on renal tubules.

Question 30

List the AE’s of TCN’s

Answer 30

Nausea/diarrhea/vomitting (can be severe), phototoxicity (can cause 2nd or 3rd degree burns), 2nd ary infections via C. diff and Candida, hepatic tox, renal tox: azotemia and fanconi syndrome, deposition in bone and teeth, HS rxns (rare).

Question 31

What are the less common TCN’s AE’s?

Answer 31

Pseudotumor cerebri, Thrombophlebitis (IV), tissue hyperpigmentation, thrombocytopenia, neutropenia.

Question 32

What are the 2 renal tox issues to be aware of for TCN’s?

Answer 32

Azotemia, due to the protein synthesis inhibition action, with normal people not a problem but might excerbate the issue in people already with azotemia. Also, fanconi syndrome: toxicity to renal tubules, occurs when the TCN’s go out of date and turn into a different compound.

Question 33

Unique AE’s of minocycline? Why is this given sometimes to teenagers?

Answer 33

It’s given to treat acne, and it can cause vestibular toxicities, as well as a blue-gray or brown skin pigmentation change.

Question 34

Unique AE of demecocycline?

Answer 34

Nephrogenic diabetes insipidus, however this effect can be used in advantage to treat pt’s with SIADH.

Question 35

Unique AE’s of Tigecyclines?

Answer 35

Pancreatitis, and there seems to be an increased mortality association in treating pt’s with tigecyclines for serious infections in comparison to other drugs.

Question 36

Preggo and TCN?

Answer 36

Contraindicated for both the mother (increased risk of hepatotox) and the fetus (teeth discoloration, mental retardation, bone stunting).

Question 37

TCN and peds?

Answer 37

Contraindicated in kids smaller than 8 years old, due to messing with the teeth and bone.

Question 38

DDI’s with TCN’s?

Answer 38

Antacids would decrease absorption as would anything else that have di or tri valent cations or bile resins (which work the same way). Warfarin (decreased flora would decrease vit K production and thus mess with warfarin activity), oral contraceptives (which needs intestinal flora to activate), diuretics (would increase BUN), Penicillins (would decrease efficacy of cell wall inhibitors).