Antibiotics TBL 3 Flashcards
How do aminoglycosides work?
Block the initiation of translation and cause the misreading of mRNA
How do tetracyclines work?
Block the attachment of tRNA to the ribosome
How do streptogramins work?
Interfere w/ different steps of protein synthesis
How do macrolides work?
Prevent the continuation of protein synthesis
How does chloramphenicol work?
Prevents peptide bonds from being formed
How do lincosamides work?
Prevent the continuation of protein synthesis
How do oxazolidinones work?
Interfere with the initiation of protein synthesis
What are macrolides?
Relatively broad-spectrum antibiotics that inhibit formation of the 50s ribosome, blocking transpeptidation or translocation
How do bacteria resist macrolides?
Decrease permeability of envelope; era gene encodes a methylater that alters the 23S ribosomal RNA; efflux proteins that remove macrolides may be found in a wide range of bacterial species
What is erythromycin and how is it used?
Macrolide w/ gram+ (s pneumonia do, viridians strep, group A/B strep, s. Aureus), gram - (pertussis, Neisseria, campylobacter, legionella), mycoplasma, chlamydia, treponema
What is azithromycin and how is it used?
Macrolides similar to erythromycin (gram + and -) with more enhanced gram-negative activity
What is clarithromycin?
Macrolide w/ similar activity to erythromycin but w/ more enhanced gram positive activity
What is distinctive about macrolide pharmacology?
Can be administered orally or parenterally - short half-lfie (erythromycin ~1.4 h, clarithromycin ~3-7h, azithromycin ~2-4 days); limited CNS penetration (NOT useful for treatment of meningitis); no major urinary excretion
When should you use a macrolide?
Community-acquired pneumonia, otitis media, pertussis, campylobacter gastroenteritis, MAC; as alternative treatments for strep, rheumatic fever prophylaxis, trachomatic urethritis
What are side effects of macrolides?
Generally well tolerated, but can cause GI symptoms (cramps, diarrhea b/c of motility stimulating effects - can be used in gastroparesis), prolonged QT interval, rare hepatitis, can inhibit P450 enzymes which means that you have to give more warfarin, cyclosporine, etc; can cause pyloric stenosis if given to infants
What are lincosamides? (Aka Clindamycin)
Similar to macrolides - bacterioSTATIC activity against gram-positives and anaerobes (typically used for anaerobes); used for penicillin-resistant anaerobic infections, S. Aureus strains of MSSA/MRSA; high bone concentrations, so great for osteomyelitis
What are the side effects of clindamycin?
Diarrhea (classic predisposing drug for C diff), allergy
What are aminoglycosides?
Complex sugars w/ glycosidic linkages that are bacteriCIDAL antibiotics primarily directed against gram-negs w/ some activity against strep and staph; narrow therapeutic window and significant toxicity; rarely used alone due to concerns about development of resistance
How do aminoglycosides work?
Diffuse through porin channels of gram-neg bacteria, disrupts cell wall, interferes w/ mRNA translational accuracy @ 30S ribosome (misreading and premature chain termination)
How do bacteria resist aminoglycosides?
Enzymatic modification of the aminoglycoside by adenylation, phosphorylation, or acetylation; anaerobes are intrinsically resistant b/c they lack an O2 dependent transport system; chromosomal mutations can also cause alterations in binding and uptake
What is the pharmacology of aminoglycosides?
Give IV (doesn’t absorb orally), limited tissue distribution, excreted unchanged by the kidney, rapid absorption after IM admin
What are the side effects of amingolycosides?
Nephrotoxicity, ototoxicity (cochlear and vestibular), rare neuromuscular blockade
What are tetracyclines?
Broad-spectrum bacterioSTATIC agents
How do bacteria become resistant to tetracyclines?
Plasmid-mediated in gram + and -: decreased uptake and increased excretion of the drug (efflux pumps); linked to extensive tetracycline use in animal feed
What are tetracyclines used for?
Gram +, Gram -, miscellaneous (spirochetes in particular, chlamydia, mycoplasma, legionella)
What is tigecycline?
New broad-spectrum glycylcycline w/ activity against resistant gram-positives and negatives; NOW NOT USED B/C IT KILLED PEOPLE
What are tetracyclines used for?
Treatment of the common tick-borne illnesses, chlamydia, mycoplasma, acne, skin and soft tissue infections due to MRSA; rarely the initial drug of choice (except for tick-borne)
What is the pharmacology of tetracyclines?
Mostly oral - IV in sever disease; cations (like in dairy products) interfere w/ absorption; t 1/2 varies; excellent tissue distribution; concentrated in the bile
What are the side effects of tetracyclines?
GI symptoms (common), photosensitivity, discoloration of teeth due to binding of calcium (IRREVERSIBLE), hypersensitivity reactions (rare)
What is chloramphenicol?
Binds to peptidyl transferase (Component of 50s ribosomal subunit) - very cheap, primarily used in developing world; broad spectrum, mostly bacteriostatic; well distributed throughout the body (including CSF); not currently the drug of choice for any infection, but can be used for typhoid fever, meningitis in certain situations, and some rickettsial infections
What are the toxicity concernsw for chloramphenicol?
Irreversible bone marrow aplasia (need bone marrow transplant), gray baby syndrome
What is linezolid?
Binds 50s ribosomal subunit and inhibits formation of the initiation complex; bacterioSTATIC w/ activity against gram-positive cocci (even those resistant to other agents like VRE and MRSA); can be given parenterally or orally
What side effects does linezolid have?
Myelosuppression, peripheral and optic neuropathy
What are streptogramins?
Not frequently used - interfere w/ 50s ribosomal subunit; bactericidal combo; used for gram positive cocci; given parenterally; used to treat vancomycin or methicillin-resistant gram-positive infections
What are side effects of streptogramins?
Phlebitis, myalgias, arthralgias
What do you use to treat Staph aureus?
Usually penicillin-resistant (otherwise, use penicillin); can use penicillinase-resistant penicillins (oxacillin, nafcillin, dicloxacillin)
How do you treat MRSA?
Vancomycin
How do you treat MRSA/VRSA (vancomycin-intolerant)?
Daptomycin, linezolid
How do you treat Group A Strep (strep pyogenes)?
Penicillin, amoxicillin; if allergic, choose macrolide or 1st gen cephalosporin
How do you treat Group B Strep?
Penicillin or ampicillin
How do you treat strep pneumo?
Penicillin if sensitive, otherwise 3rd gen cephalosporin; if high-level resistant, you may need to use vancomycin or levofloxacin
How do you treat enterococcus?
Penicillin or ampicillin; uniformly resistant to cephalosporins; use vancomycin if resistant to penicillins; add an aminoglycoside (like gentamicin) for synergy if it’s endocarditis
How do you treat resistant gram positive cocci (like resistant enterococcus or staph)?
Linezolid, daptomycin, streptogramins
How do you treat anaerobes?
Metronidazole, 2nd gen cephalosporins like cefoxitin, clindamycin, carbapenems, extended-spectrum penecillins w/ a beta-lactamase inhibitors
How do you treat C diff?
Metronidazole or oral vancomycin
How do you treat enterobacteriaceae (like E. Coli, klebsiella, enterobacter)?
3rd gen cephalosporin, quinolones (cipro or levofloxacin), aminoglycosides, carbapenems, extended-spectrum penicillin, aztreonam
How do you treat pseudomonas?
Extended-spectrum penicillins, quinolones, aminoglycosides, carbapenems, 3rd gen cephalosporins (ONLY ceftazidime)
How do you treat Ricketssia/ehrlichia/Borrelia burgdorferi?
Tetracycline (doxycylcine); can also use amoxicillin and ceftriazxone for borrelia
How do you treat gonorrhea?
3rd gen cephalosporin (ceftriaxone); double coverage is now recommended, so add azithromycin
How do you treat syphilis?
Penicillin, maybe a doxycycline if patient is penicillin-allergic, but consider desensitization; NOTE: a pregnant woman should ALWAYS be desensitized if allergic
How do you treat chlamydia?
azithromycin, doxycycline
How do you treat atypical pneumonias?
Macrolides/azalides (azithromycin), quinolones, +/- tetracycline
How do you treat community-acquired pneumonia empirically?
BOTH ceftriaxone and azithromycin (2 drugs) or levofloxacin
How do you treat Lyme?
Doxycycline
How do you treat pertussis?
Azithromycin
What are quinolones?
Bactericidal broad-spectrum antibiotics that are increasingly used b/c of their relative safety and availability both orally and parenterally; bacteriCIDAL - they inhibit bacterial DNA synthesis causing rapid cell death and they bind to DNA-DNA gyrase complex to block further DNA replication
What are the commonly used fluoroquinolones?
Ciprofloxacin, levofloxacin, and moxifloxacin
What are fluoroquinolones used for?
Gram -, gram +, respiratory pathogens (commonly seen in community-acquired pneumonia), myobacterium TB, bacillus antrhacis, legionella; limited anaerobic and enterococcal activity
How are bacteria resistant to quinolones?
Use of quinolones in antimal feed is contributing as is length and intensity of quinolone therapy; a single mutation is enough to cause resistance; mutations occur in DNA gyrase and topoisomerase genes; also have active efflux system
What are the pharmacokinetics of quinolones?
Well-absorbed orally (some are available parenterally), excellent tissue distribution, concentrations in bone/CSF
What are side effects of quinolones?
GI, CNS symptoms can occur, allergic reactions (rash, drug fever), photosensitivity, liver function abnormalities, joint symptoms (arthralgias, joint swelling, tendinitis), QT prolongation w/ increased risk of ventricular arrhythmias, peripheral neuropathy
When should quinolones be used?
Empiric therapy of community-acquired pneumonia, oral therapy of complicated UTIs or respiratory tract infections, oral therapy for osteomyelitis or soft tissue infections, treatment for STDs, empiric therapy of travelers’ diarrhea, can be used for multidrug-resistant TB
What causes resistance to sulfas?
Resistance is reduced b/c of sequential interference w/ steps involved in folic acid synthesis; sulfas have decreased permeability and increased production of PABA
What is the pharmacology of sulfa drugs?
Available orally or parenterally, achieves good levels in lungs, kidneys, CNS, biliary tree; serum half-life is 9-11h
When should trimethoprim-sulfamethoxazole be used?
Broad-spectrum activity against a diversity of organisms (gram +, gram - but NOT enterococci; pneumocystis), particularly in recurrent UTIs, prostatitis, salmonella, shigella, E. Coli
What are toxicity concerns for trimethoprim-sulfamethoxazole?
Hypersensitivity reactions (rash, fever), GI symptoms (nausea, vomiting, diarrhea), nephroxicity, hepatitis, megaloblastic anemia; Stevens Johnson syndrome is dramatically increased in subjects w/ AIDS
What is daptomycin?
Bactericidal antibiotic that binds and inserts into the cytoplasmic membrane in a calcium-dependent process; active against many antibiotic-resistant gram POSITIVES (VRE, MRSA, penicillin-resistant pneum)
What is the pharmacology of daptomycin?
Only available through IV; cleared by the kidneys; CAN’T BE USED FOR PNEUMONIA (does not achieve adequate concentrations in the lung)
What are the adverse reactions to daptomycin?
Myopathy
What is metronidazole?
Causes release of short-lived free radicals that damage bacterial DNA; has activity against all anaerobes; can be administered in any way; well distributed (including CNS)
When should metronidazole be used?
Anaerobic infections like those in CNS (brain abscess), pseudomembranous colitis, bacteroides infections
What are the side effects of metronidazole?
Very few, but disulfiram effect occurs with alcohol (copious vomiting) and not used in pregnancy; interferes w/ coumadin
What is polymixin?
Functions as detergent (binds to LPS and disrupts the membrane)
When should polymyxin be used?
Multidrug resistant Enterobacteriaceae, acinetobacter, p. Aeruginosa (NOTE: NO GRAM POSITIVE ACTIVITY)
What are toxicity concerns w/ polymyxin?
Nephrotoxicity, neurotoxicity
What are the classes of protein synthesis inhibitors?
Macrolides, aminoglycosides, tetracyclines, chloramphenicol, oxazolidinones, streptogramins
