(From Lippincott’s and lecture, by Brian Buschman)
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Tetracyclines bind reversibly to the 30S subunit and block the A-site so the new amino acyl-tRNA cannon come in.
They are board spectra working on both gram + and – but there is a lot of resistance. They are the DOC for Mycoplasma pneumonia, Rickettsia and H. pylori. They can also be used for T. palladium (syphilis). In H. pylori they are the “T” of the cocktail BMT.
Resistance is due to decreased intracellular concentrations of the drug. They develop Mg2+ dependent mechanisms to pump the drug out. They also protect the 30S subunit.
Absorption is poor in the presence of milk and antacids. You need to educate patients not to take antacids for H. pylori near taking tetracyclines. It is distributed systemically but is of little use in meningitis. It crosses everything and concentrates in bones, skin and high perfusion organs. It is metabolized in the liver and excreted in the bile (except doxycycline), then reabsorbed and excreted by the kidney.
Adverse effects include:
1) Gastric discomfort
2) Deposition in bone, yellow teeth and student growth
3) Phototoxicity
4) Superinfections with Candida
5) Vestibular dysfunction
Tetracyclines, other than doxycycline, cannot be used on renally impaired patients.
Aminoglycosides used to be the DOC for serious gram – aerobes till safer 3rd generations cephalosporins. They work by binding to and blocking the resting 30S ribosomal subunit. It stops assembly of the translation apparatus. It only works in aerobes because it’s mechanism of transport into the bacterial is based on O2 transfer mechanisms.
Aminoglycosides are used to treat TB, plaque, Francisella (tularemia) and Viridans (in combination with penicillin). Resistance is from uptake deceleration and active site changes. They are not cross resistant.
Poor oral absorption so all are given IV/IM but neomycin (Neosporin) because of it’s nephrotoxicity which is given topically. It must be given intrathecally for CNS infection. IT accumulates in the endolymph and renal cortex causing ototoxicity and nephrotoxicity. Finally aminoglycosides are rapidly excreted, unchanged.
Other side effects include dermatitis (specifically to neomycis) and neuromuscular paralysis.
Macrolides like erythromycin and dirithromycin inhibit translocation by reversible binding to the 50S subunit and are substitutes for penicillin. It’s binding site is close to that of chloramphenicol.
It is effective against the same organisms as penicillin G and is used as a PCH alternative when allergic. It is a DOC for M. pneumoniae like tetracycline.
Azrithromycin is like erythromycin but it hits Chlamydia and H. influenza.
Clarthromycin is erythromycin plus is used as part of an AIDS coctail.
Resistance is like tetracyclines. Many staphylococci produce erythromycin esterase.
Erythromycin can be destroyed by stomach acid if not coated or etherified. It should be takes on an empty stomach or else decreased absorption. It is widely absorbed but has poor CNS penetration.
Erythromycin is metabolized and inhibits P-450 systems. Azithromycin does not undergo metabolism. The metabolized erythromycin and azithromycin are excreted in bile while clarithromycin is eliminated by the kidney and liver.
Adverse effects include cholestatic hepatitis/jaundice, GI discomfort. It decreases P-450 making it dangerous with theophylline.
Chloramphenical binds reversible to 50S RNA blocking protein synthesis. IT has cross reactivity with mammalian ribosomes.
Chloramphhenicol is used only as an alternate for severe infections against anaerobes like B. fragilis, salmonella, rickettsiae, N. meningitidis. It can be either static or cidal per organism.
Resistance is based on production of acetyl Co-A transferase. It is excreted after conversion to glucronide. It goes everywhere including the CSF because it’s lipophillic.
Adverse effects include:
1) Candida overgrowth.
2) Hemolytic anemias
3) Gray baby syndrome because of limits on the young drug metabolizing systems.
Like macrolides clindomycin reversible inhibits 50S blocking translocation. IT works as an alternative against anaerobes like B. fragilis. It’s also good on PCC in aids patients. The biggest side effect is C. difficile overgrowth which needs treatment with either vancomycin or metronidazole.
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