C.12 Flashcards
Tetracyclins and glycyclines
Doxycycline,
Tigecycline
Tetracyclines
MOA: Binding to 30S subunit → blockade of the binding of aminoacyl tRNA → bacteriostatic;
Spectrum: Originally broad, but with dissemination of resistance due to efflux pump or ribosomal protection (→ alteration of binding site/formation of ribosomal protection protiens that interfere with drug binding → inability to bind);
Pharmacokinetics:
-Older drugs- 70% absorption (higher risk of dysbacteriosis) → liver → urine (kidney excretion).
-Newer drugs- Almost complete absorption, elimination is less dependent on kidney function (bile), longer T1/2. Divalent cations influence the absorption → binds them (Ca2+, Mg2+, Fe2+) → Decreases their absorption → never give with milk, antacids or ferro-sulphate!, wide distribution (incl. placenta), but NOT CNS!;
IND: Sever types of zoonosis (→ brucellosis, tularemia, plague, leptosirosis (→ in combination with aminoglycosides)), Alternatives in case of infections with intracellular bacteria (mycoplasma, chlamydia, rickettsia), Helicobacter eradication, campylobacter enteritis, cholera, atypical tuberculosis, acnes;
SEs: Disturbed bone and teeth formation in children, Dysbacteriosis, candidiasis, photosensitivity, hepatotoxicity, teratogenic;
Contra-IND: Children (teeth) < 8 years old!
Doxycycline
IND:
- Tick born diseases → rickettisa (IC), Borrelia (spirochete), Francisella (G-).
- Gonorrhea
- Chlamydia (cervicitis & urethritis: 1st line agent! + pelvic inflammatory disease, bronchitis, CAP)
- Zoonotic diseases (Brucellosis, coxiella Q-fever, Yersinia (Plaque))
- Alternative treatment to macrolides in community acquired pneumonia
- Acne treatment (Propionibacterium acnes (skin anaerobe)
Pharmacokinetics: IC accumulation, excreted in feces, safe to use in renal dysfunction
Mechanism of resistance: as in general tetracyclines
SEs: Same as general tetracyclines
Tigecyclin
Glycyclines
Tigecyclin - a tetracycline-like drug
NOT the substrate of the efflux pump (only in case of pseudomonas and proteus!)
Spectrum: Broad
IND: Organisms resistant to standard tetracyclines → Reserve antibiotic for- Gram(+) cocci (MRSA, VRSA), Gram (+) rods, IC, Gram (-) Anaerobe infections, NOT UTIs!
Resistant: Proteus and pseudomonas are resistant:
Pharmacokinetics: 2xDay I.V- elimination with bile - not effective enough in UTI!! T1/2: 40h
SE: Same as general tetracyclines
