tetracyclines/macrolides 68 Flashcards
tetracyclines (group)
oral absorption
4-ringed structure oral absorption: 30% chlortetracycline absorbed 60-70%: tetra 95-100% for doxy, mino!
do not take 1-2 hrs before bed or laying down, take with water, due to risk of esophageal ulceration, don’t take w. dairy
tetracycline
Short acting (T 1⁄2 = 6 - 12 hours approximately)
Doxycycline (generic, Vibramycin, Monodox)
Long-Acting (T 1⁄2 = 16 – 18 hours approximately)
preferred for serious infections, can be used IV
-avoids GI upset
excreted NON-renally, good for renal failure pts
NOT pumped out by Tet(K) efflux pump in Staph!
Minocycline (generic, Minocin, Arrestin, Dynacin, Myrac)
Long-Acting (T 1⁄2 = 16 – 18 hours approximately)
NOT pumped out by Tet(K) efflux pump in Staph!
-more lipid soluble, used as alt. (to Rifampin) to eliminate meningococcal carrier state
tetracyclines bind to ??
Ca2+ and multivalent cations in antacids, dec. oral abs. of the drugs
don’t admin tetras w. dairy or antacids
abx tx failure bc these abx often cause GI upset
tissue dist./excretion
widely, cross placenta
exc. via kidney, also bile and elimated in feces
- some drug my be reabsorbed via enterohepatic circulation
tetra pharmko
- enter bac by passive diffusion and active transport
- inhibit protein synthesis by binding 30S ribosomal unit
- block binding of aa containing aminoacyl-tRNA to acceptor site of ribosome, prevents adding new aa
mechs of tetra resistance
efflux pumps that “spit” drug out of bacteria
- Tet(AE) pump in G- bac
- doxy and mino NOT pumped out by Tet(K) efflux pump in Staph!
- Tet(M) ribosomal protection protein in G+ (prevents drug from binding)
tetra resistant usually marker of MDR
other resistance mechs: enzymatic inactivation, use in animal feed
tetra spectrum
broad spec but lots of resistance:
- G+: resistance to Staph, strep, some pneumococci, *not the drug of choice for many G+ aerobic infections
- G-: pseudomonals, gonorrheae, enterobacter are resistant, active against Brucella, Vibrio spp., CA-E.coli
- anaerobes are resistant (B. fragilis-use metronidazole)
- used for Spirochetes, Rickettsiae, Mycoplasma, Chlamydia
tetra use
Rickettsial-doxy
Mycoplasma-doxy (erythromycin for preggos, kiddos)
Chlamydia-doxy (can also use macrolides)
Spirochetes-doxy (drug of choice for Lyme)
Periodontitis-doxy tablests, or mino microspheres (inhibit enzyme collagenase)
Acne-(tetra, doxy, mino)
Cholera
others: UTIs, non-TB mycobac inf.
-alternative for: H. pylori (tetra)
used to be used for bac gastroent, pneumonias, bac UTIs, but resistance now a big problem
tetra SEs
- GI upset: reduce by giving food (NOT dairy/Ca2+)
- Superinfections: C. diff, candida
- CONTRAINDICATED during pregnancy and kiddos younger than 8:
- can bind Ca2+, can be deposited in teeth and bone: teeth discoloration, fluorescence, enamel deformities, inhibit bone growth, and cause bone deformities (when used in pregnancy)
tetra tox
- renal damage: outdated tetras can become nephrotoxic and cause renal tubular acidosis and renal damage (throw old pills away!)
- demeclocycline can inhibit actions of ADH in kidney and cause diabetes insipid us like state (peeing too much)
- photosensitivity, sun-burn prone
- impaired liver function in preggos, liver damage pts
Tigecycline (Tygacil)
IV admin, newer, eliminated by non-renal mechs
same MOA as tetras BUT
-not effectively pumped out of bacteria by the Tet(AE) or Tet(K) efflux pumps, which makes it useful in some tetra-resistant bac
-G+ Tet(M) ribosomal protection protein does not effectively block Tigecycline from binding to the 30S ribosomal subunit
Macrolide absorption/metab/excr
- erythromycin base: poor oral absorption, broken down by acid
- clarithromycin and azithromycin have ESTERS in their base: demonstrate improved oral absorption
- erythromycin can be used IV
- IM avoided (painful)
- distr. to most tissues, but DO NOT ENTER CNS: not used for meningitis
- crosses placenta
-conc. in liver and exc. in bile
*metab by hep p450 enzymes (p4503A, DYP3A)
5% excredted in urine
worry about hepatic dysfunction
macros pharmko
- bacteriostatic, any high conc. may be tidal
- bind to 50S subunit, prevent movement of pp chain from acceptor site to donor site–>prevents protein synthesis
- close to binding site for chloramphenicol-competition!*
macrolide resistance mechs
most important mech:
-modifications of 50S subunit by
mutation or by a macrolide-inducible/constitutive enzyme (Methylase, erm genes) which alters the binding site and prevents the drug from binding.
also:
-dec. influx or active efflux
-breakdown by esterases (i.e. Enterobacteriaceae)