Micro 2: Protein Synthesis Inhibitors
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1 Gentamicin gen tah MY sin Streptomycin strep toe MYE sin Clindamycin klin da MYE sin Quinupristin + Dalfopristin KWIN-ue-PRIStin/DAL-foe-PRIS-tin Garamycin NA Clindamax, Cleocin Synercid 1) Class: Aminoglycoside 2) Indication: mostly for serious Gram infections. a) Bactericidal b) Boxed warnings: ototoxicity, kidney failure and neuromuscular blockade. Fetotoxic. c) No PO. Available IM or IV (Usually TID 7-10 d), topical (cream, ointment, ophthalmic solution) e) Loop diuretics increase ototoxicity risk 1) Class: Aminoglycoside 2) Indication: IM for serious infections, including, potentially, TB. a) BW: ototoxicity, kidney failure, NMJ blockade. Fetotoxic. b) Give no more than 120 grams over entire course of therapy. c) Bactericidal 1) Class: Lincosamide = Restricted Range 2) Indication: SEVERE RTI, skin and soft tissue infections not treatable with other antibiotics. a) PO, IM, IV, Topicals b) Adults usually QID, Kids TID/QID i) PO: Take with a full glass of water to avoid irritation ii) IV: contains benzyl alcohol which may cause Gasping Syndrome in neonates c) BW: CDAD d) Curare- like effect e) Will exacerbate colitis and other GIT conditions f) May contain tartrazine g) Bacteriostatic 1) Resistance is common 1) Class: Streptogramin 2) Indication: Specific, serious, life- threatening infections a) P450 Inhibitors 4) Bacteriostatic alone; Bactericidal together Page 1 of 5
2 Azithromycin ay-zith-roe-myesin Erythromycin eh-rith-row-mysin Zithromax E- mycin, EryPed, Erythrocin, Eryzole, Pediazole 1) Class: Macrolide 2) Indication: mild to moderate RTI & UTI (including acute otitis media, pharyngitis, tonsillitis, GIT infections, etc.) a) PO/IV infusion SID 2-5 days (not acid stable, so pills are do not crush). NO IM. i) Give loading dose ii) Extended- release is NOT bioequivalent to or interchangeable with conventional formulas b) Ophthalmic (AzoSite) must be refrigerated c) Extremely long t ½ (~70 hours) i) Allergic reactions can occur weeks after treatment ii) Enterohepatically cycled (mainly excreted unchanged in bile) d) Long term use may cause hearing loss e) Bacteriostatic 4) Resistance is common 1) Class: Macrolide 2) Indication: Usually used in people allergic to penicillin for mild/moderate RTI, UTI and acne. Prokinetic alternative to metoclopramide for gastroparesis. a) PO, IV infusion (not acid stable, so pills are do not crush ) i) Normally give PO 2 hours before meal. Formulations available that can be given without regard to meals (chewable tablets and film- coated tablets). ii) Must adjust dose in kidney patients b) POTENT P450 INHIBITOR (Lots of drug interactions related to CYP3A4 inhibition) c) Half life hours d) Bacteriostatic 4) Resistance is common Page 2 of 5
3 Chloramphenicol KLOR-am-FEN-ihkahl Chloromycetin 1. Broad spectrum antibiotic 2. Indications: life- threatening infections for which other drugs cannot be used. 3. Notes: a) Available PO, IV and in ophthalmic and otic solutions. i) Avoid repeated courses ii) Causes a bitter taste seconds after injection that lasts for about 3-5 minutes. iii) Narrow therapeutic margin!! (1) Monitor plasma levels (2) Monitor body temperature every 4 hours until temp is normal for 48 hours, then discontinue chloramphenicol (3) Lots of individual/age differences (a) Succinate is a Prodrug, metabolized by liver, lung, kidney leading to variable IV bioavailability! (b) Half life in normal adult = hours (c) Half life in neonates/infants >= 24 hours (d) Impaired liver function increases half life b) Bacteriostatic c) Resistance is common d) Less likely to cause CDAD than other antibiotics e) Suppresses bone marrow (BW: serious and potentially fatal blood dyscrasias aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia). i) May be irreversible. ii) Monitor hematologic function before and then every other day during therapy. (1) CBC, platelets, serum iron, reticulocytes f) Long- term therapy leads to optic and peripheral neuropathies g) Gray (baby) Syndrome i) Neonates develop hypotension, cyanosis because they can t metabolize chloramphenicol. Potentially fatal. h) P450 INHIBITOR i) LOTs of drug interactions i) Increases the activity of sulfonylureas (increased risk of hypoglycemia) Page 3 of 5
4 Linezolid lin-aze-oh-lid Doxycycline DOX i SYE kleen Tetracycline tet rah SYE kleen Zyvox Vibramycin, Adoxa, Oracea Sumycin 1) Class: Oxazolidinone 2) Indication: serious Gram + infections a) PO/IV usually TID b) Bacteriostatic c) MAO- I activity i) Avoid adrenergic and serotonergic drugs (1) E.g., OTC decongestants, SSRIs, SNRIs, TCAs, MAOIs ii) Avoid use in Hypertensive and/or hyperthyroid patients iii) Avoid tyramine rich foods (serotonin syndrome risk) d) Monitor CBCs weekly during therapy due to myelosuppression i) Thrombocytopenia e) Optic and peripheral neuropathies possible i) May cause vision loss monitor visual function in patients on linezolid for more than 28 days or if patient reports visual changes f) Lactic acidosis possible g) Decreases seizure threshold h) Contains aspartame (which is metabolized to phenylalanine) i) Protect tablets from light 4) Resistance is rare and mostly in Enterococci 1) Class: Broad spectrum Tetracycline 2) Indications: G+, G-, Protozoa, Rickettsia, Spirochetes a) NOT FOR STAPH infections b) PO, IV infusion usually SID or BID and may be given chronically (e.g., for weeks or months) c) Bacteriostatic e) Antibiotic of choice if patient is in renal failure f) Strong photosensitizer g) Don t take with divalent cations (NO DAIRY!!! No vitamin supplements, no antacids.) h) Permanently stains developing teeth brown i) Drug interactions: i) Divalent cations inactivate tetracyclines ii) Methoxyflurane may cause fatal renal toxicity with tetracyclines iii) Prothrombin time is increased (plasma prothrombin is suppressed) will increase Warfarin effects. Oral birth control pills may have reduced efficacy 1) SAME AS DOXYCYCLINE 2) SAME AS DOXYCYCLINE SAME AS DOXYCYLINE, except available PO, IV, IM and in Topicals. Tetracycline has a much shorter t ½ so is administered more often. Page 4 of 5
5 ADDITIONAL NOTES: Micro 2: Protein Synthesis Inhibitors 1. All of these antibiotics are protein synthesis inhibitors. 2. All antibiotics have the ability to cause Superinfections which are usually Clostridium difficile (anaerobic bacteria, part of the normal GIT flora) and/or Candida albicans (a fungus, a yeast, normally found on our bodies and on mucous membranes of the mouth, nose, and parts of the genitourinary tract). Oral antibiotics are more likely to disrupt the GIT microflora leading to a C. diff. infection, but any antibiotic can cause a Superinfection. a. Candida may be treated with an antifungal. For mild infections, Clotrimazole or a similar antifungal may be used. For more serious infections, Fluconazole or a similar antifungal may be used. For life threatening infections, Amphotericin B may be used. See Micro 5 for the antifungals. b. C. difficile may be treated with Metronidazole (Flagyl, see Micro 4). 3. You need to focus on the Generic and names, the class, know the mechanism (protein synthesis inhibitors) and the NOTES. If it s bold and in the NOTES, know it. 4. All the indications listed in this table and in lecture are generalized from the labels. All antibiotics have specific bacteria (usually by species) for which they have documented activity. These lists can be very, very long and I ve chosen to simplify the material. a. Resistance is COMMON. b. All antibiotics are indicated for SUSCEPTIBLE strains of the bacteria listed on their labels. Just because an antibiotic is indicated for Pseudomonas aeruginosa, for instance, doesn t mean it will work or should be used. Cultures must be grown to determine susceptibility. In practice, this is often not done, leading to resistant strains. 5. Except for the aminoglycosides, the protein synthesis inhibitors are considered to be bacteriostatic. In practice, many, like the Macrolides, are bactericidal. It depends upon the individual circumstances. 6. Oral antibiotics, of any kind, may interfere with the enterohepatic cycling of drugs that are conjugated in the liver and reabsorbed from the intestines after GIT bacteria cleave off the conjugate. This includes oral birth control pills (expect reduced efficacy of the birth control pills), so patients taking oral contraceptives should be cautioned to use a secondary method of birth control. Page 5 of 5
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