Tetracyclines

What is the tetracycline of choice in patients with renal failure?

*Doxycycline*. The glucoronide of doxycycline is very water-soluble and is not readily reabsorbed by the intestine and is excreted into the feces (i.e. not eliminated via glomerular filtration). *Tigecycline* also does not accumulate in pts with reduced renal function.

What organism is incredible resistant to tetracyclines?

*Streptococcus pyogenes*. Penicillinase-producing staphylococci are resistant to tetracyclines, but may be susceptible to tigecycline.

Tigecycline

- Same spectrum as doxycycline but has *extra G+ activity* against tetracycline-resistant organisms - Glycylglycine derivative of minocycline - IV only - MRSA - *MRSE (methicillin-resistant S. epidermidis)* - VISA - VRSA - VREcium - Pen-resistant S. pneumoniae (pneumococci) - *Bacteroides*(G-) - Used for complicated skin/soft tissue infections, intra-abdominal infections and community-acquired pneumonia

What are other microbes treated by doxycycline (not DOC or 1st line)?

- T. palidum (syphilis) - Leptospira (Weil's disease/leptospirosis) when the pt. is allergic to penicillin - F. tularensis (tularemia) - Y. pestis (plague) - Pasteurella (wound infections) - Actinomyces israelii (actinomycosis) - Streptobacillus - Bacillus anthracis (antrax) - L. pneumophila (Legionnaire's disease) - H. ducreyi (Chancroid) - C. tetani (tetanus) - C. perfringens (gas gangrene) So...doxycycline can treat just about anything. SUPER broad spectrum.

Tetracycline

- oral management of acne - oral management of *GI ulcers due to H. pylori* (Helidac, Pylera)

Doxycycline is a 1st line drug for which diseases?

1) C. pneumoniae (pneumonia) 2) C. trachomatis (trachoma) 3) V. cholerae (cholera) 4) Brucella (brucellosis)

What are the members of the tetracyclines?

1) Doxycyline 2) Minocycline 3) Tetracycline 4) Tigecycline 5) Demeclocycline....although he literally never says a thing about it in the packet...?

Doxycycline is the DOC for which infections?

1) Rickettsia (RMSF) and (Typhus) 2) C. trachomatis (Lymphogranuloma venereum) 3) C. psittaci (Psittacosis) 4) U. urealyticum (nonspecific urethritis) 5) Mycoplasma pneumoniae (atypical/walking pneumonia) 6) B. burgdorferi (Lyme disease) 7) Klebsiella granulomatis (Granuloma inguinale)

If an organism is resistant to minocycline will it be resistant to all tetracyclines?

All except tigecycline.

If a pregnant patient has walking pneumonia, what do you treat it with?

Azithromycin, NOT doxycycline (even though it is the DOC)

Are tetracyclines bacteriostatic or bactericidal?

Bacteriostatic

Why are tetracyclines associated with the development of superinfection?

Because they are very broad spectrum. Knocking out *Bacteroides* can cause C. diff overgrowth. Candida albicans overgrowth leads to yeast infections.

Why are tetracyclines contraindicated in children under 8?

Because they bind to teeth and bones (tissues undergoing calcification). This is the basis for contraindication in pregnant and nursing women.

What is the only backup for Rickettsial diseases, after doxycycline?

Chloramphenicol. Both are contraindicated in pregnancy, nursing and children under age 8.

The oral bioavailability of tetracyclines is decreased by what?

Concominant ingestion of *dairy, antacids containing Ca2+, Mg2+, aluminum or iron.*. The decrease in absorption results from *chelation* of the tetracyclines with *divalent and trivalent cations*.

You put a 13 year old beauty pageant contestant on tetracycline for a bad breakout of acne right before the Lil' Miss Kentucky Sugar Pie Pageant. What should you tell her NOT to do while taking this drug?

Do not get exposure to UV light (tanning beds, beach, etc.). The conjugated ring system in tetracylines causes photosensitivity.

Patients with heartburn or GERD must be advised not to do what an hour before or after taking tetracylines?

Do not take antacids. Also, no dairy products.

What is the most widely prescribed tetracycline?

Doxycycline

Which tetracycline is least likely to form non absorbable chelates?

Doxycycline

Which tetracyclines metabolites do not accumulate in patients with reduced renal function?

Doxycycline and Tigecycline

Which tetracyclines exhibit the greatest oral absorptions?

Doxycycline and minocycline

Which tetracyclines are safe to use in patients with renal disease?

Doxycycline or tigecycline.

What is the general structure of the tetracyclines?

Four 6-membered rings (*conjugated ring system causes photosensitivity*). The tetracyclines all have similar spectrums of activity but differ in their pharmacokinetic profiles. Where the *hydroxyl group is located* determines pharmacokinetics.

Minocycline

Minocin/Solodyn - Less commonly employed than doxycycline because of adverse side effects. - *Better than doxycycline for treating NOCARDIA (pulmonary lesions)* - Management of acne - Tetracyclines are ineffective at treating bacterial meningitis, bc they don't cross BBB, but minocycline is *useful for eradication of the carrier state of N. meningitidis*! - Accumulates in the endolymph

Which tetracycline is most indicated with vestibular problems such as vertigo?

Minocycline, because it *accumulates in the endolymph*

Which tetracycline is used to eliminate carrier status of N. meningitidis?

Minocycline, because it concentrates in saliva and tears.

Which tetracycline is most indicated with pseudo tumor cerebri (benign intracranial hypertension)?

Minocycline; this can cause blurred vision and headaches.

What is Fanconi's syndrome and how are tetracyclines associated with it?

Nausea, vomiting, polyuria, polydipsia, proteinuria and glycosuria. It can result from ingesting *outdated and degraded tetracyclines*.

What are the mechanisms by which microbes become resistant to tetracyclines?

Plasmid mediated resistance is caused by: 1) Decreased accumulation due to increased efflux 2) Alterations in the tetracycline target site 3) Enzymatic inactivation

What non-bacterial microbe can doxycycline treat?

Plasmodium falciparum (malaria)

Fatal hepatotoxicity due to tetracyclines was most observed in what group?

Pregnant females....again, CONTRAINDICATED!

Which tetracycline is shortest acting?

Tetracycline (6-8 hr half-life)

Which tetracyclines are contraindicated in patients with reduced renal fxn?

Tetracycline, demeclocycline, minocycline.

What are the broadest spectrum antibiotics?

Tetracyclines

How are tetracyclines metabolized and excreted?

Tetracyclines accumulate in the *liver*, are metabolized and *glucoronidated*. Parent compounds and metabolites are *secreted into the bile, reabsorbed by the intestine and excreted by glomerular filtration.* *Decreased hepatic function or biliary obstruction leads to accumulation*.

Which drug classes can accumulate in macrophages in order to eliminate intracellular microbes such as Ureaplasma, Mycoplasma, Mycobacteria, Chlamydia, Legionella)?

Tetracyclines, Macrolides, Fluoroquinolones Macrolides are the only group that are safe during pregnancy and nursing.

How do the tetracyclines exert their antibiotic effect?

Through binding to bacterial ribosomes and inhibiting bacterial protein synthesis. These agents bind to *30S* ribosomal RNA, blocking tRNA from binding to mRNA-ribosome complex. They are *reversible inhibitors of bacterial protein synthesis*.

Which tetracycline is longest acting?

Tigecycline (36 hr half-life)

Which tetracycline must be administered parenterally?

Tigecycline, IV only.

Can tetracyclines be taken with meals to reduce adverse GI side effects?

Yes, but no dairy. They should be taken with plenty of fluids to decrease risk of esophageal ulceration.

You have a female patient with walking pneumonia. You decide to prescribe doxycycline. You randomly remember that she follows attachment parenting and still nurses her 6 year old. What should you tell her?

You must NOT nurse while taking tetracyclines. Also, if your kid can do a cartwheel, it's time to let go...