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Pharm Macrolides

Macrolides Erythromycin, Clarithromycin, Azithromycin
Macrolide MOA binds to the 50S portion of bacterial ribosome. Inhibits protein synthesis of bacterial cell. BACTERIOSTATIC. may be bacteriocidal at higher concentration to some bacteria.
Erythromycin MOA inhibits protein synthesis, bacteriostatic (cidal at higher concentrations), binds 50S ribosomal subunit.
Erythromycin spectrum efffective against gram + organisms similar to pen V. INEFFECTIVE AGAINST ORAL ANAEROBES
Erythromycin resistance problem in clinic setting, many staph and strep now resistanct to Erythromycin
Erythromycin mechanism of resistance Drug efflux, reduce drug up-take, methylase protection reduce drug binding to ribosomal subunit, esterases destroy drug, mutation of r-protein
Erythromycin available drugs Acid insoluble salts, Acid insoluble esters, enteric coated tablets, Polymer coated erythromuycin base, polymer coated (PCE dispertab) ALL WELL ABSORBED EVEN IN PRESENCE OF FOOD.
Erythromycin elimintation detoxified in liver, may use in presence of renal dysfunction, metabolized by P450, inhibits CYP3A4 (MANY DRUG INTERACTIONS)
Erythromycin toxicity GI irritation(#1 problem), rarely causes sensitization, cholestatic jaundice(liver toxicity), Ototxicity(transient deafness)
Erythromycin Pharmacokinetics: Oral route: Erratic absorption. best to give on an empty stomach. Well distributed in all body fluids except CSF. Inflammation allows greater tissue penetration.
Erythromycin ethyl succinate (acid insoluble ester) for penicillin allergic pts. (no cross reactivity). well absorbed event in presence of food. available in suspension form for pediatric pts.
Erythromycin use low allergenic potential. no cross sensitivty w/penicillin use in pts allergic to pen and atopic individuals, can use for S. aureus or penicillinase producing organisms rapid development of resistance
Clarithromycin MOA Acid stabel derivative of erythromycin, inhibits protein synthesis by binding to the 50S bacterial ribosomal protein
Clarithromycin spectrum includes gram+ aerobes, some gram- aerobes(H. inf., and N gon), Mycobacterium avium complex (AIDS pts.) and MOST ORAL ANAEROBES.(distinct advantage over Erythromycin) 2 to 4 times MORE ACTIVE against strept. and staph than erythromycin.
Clarithromycin side effects less GI than erythoromycin, afnormal taste rearely allergic reactions and possible anaphylactic shock.
Clarithromycin Uses acute OM, pharyngitis/tonsilitis acute maxillary sinusitis, Lower RTI, unconmplicated skin and skin structure infct. prevention and treatment of mycobacterial infections in HIV pts.
Clarithromycin drug interactions sama as erythro b/c it inhibits P450 drug metabolizing enzymes, results in elevation of plasma levels and increased toxicity of those drugs listed for erythro
Azithromycin MOA inhibits protein synthesis by binding to 50 S subunit of ribosomes
Azithromycin structure acid stable dericitive of erythromycing
Azithromycin spectrum similar to clarithromycin, 2-4X LESS EFFECIVE against strpt. and staph. than erythro, anaerobic activity poor, Effective against propionbacterium acnes, mycoplasma
Azithromycin Uses COPD, OM, pneumonia, Pharyngitis/tonsilitis, uncomplicated skin and skin structure infections
Azithromycin side effects less GI than erythro. similar to erythro and clarithro,
Azithromycin drug interactions Less than for erythro and clarithro
Clindamycin class OTHER
Clindamycin MOA Binds to 50S ribosoe at same site as erythro. Thus these two antibiotcs are antagonists.
Clindamycin spectrum similar to Pen V, ineffective against anaeroves. narrow spectrum, effective aainst mainly gram + bacteria(EXCEPT STREP. FACALIS)
Clindamycin effectiveness against bacteroides and other anaerobes(B. fragilis). BEST ANTIBIOTIC FOR ANAEROBES.
Clindamycin Uses osteomyelitic infections, Purulent osteitis, serious infectins casued by strep, staph, and pnuemococci in pts allergic to pen. bone infections caused by gram+ cocci and anaerobes, anaerobic inf. such as those caused by bacteroides.
Clindamycin Administration oral-cell absorbed w/ or w/o food Deep IM- relatively painless, an advantage over penicillin
Clindamycin pharmoco dynamics food delays absorption but 95% still absorbed, enters enterohepatic circulationa dn secreted into bile (major path of elimination), distribution is good in soft tissue. High antibacterial concentrations are achieved in bone (MAJOR ADVANTAGE)
Clindamycin and bone bone conc. of active antibiotic exceed plasma conc. bactericidal blood levels are easily attained w/ low doses.
Clindamycin resistance staph resis. develops slowly. some pneumococci and group A strep. are resistant. Cross resisstance with erythro occcurs sometimes. staph resistant to methi and erythro also resist to clinda
Clindamycin is similar to erythro although chemically unrelated to other antibiotics
Clindamycin adverse reactions GI disturbances, hypersensitivity reactions( also delayed hyper.) Hematopoetic problems(neutopenia, leukopenis, agranulocytosis)
Clindamycin drug interactions erythro- antogonism at site of action on 50S neuromuscular blocking agents
Clindamycin precautions Safety has not been evaluted in pregnancy, infants, liver, renal, endocrine or metabolic disturbances
Vancomycin class/structure Glycopeptide
Vancomycin MOA inhibits synthesis of bacterial cell wall, may affect protoplast membrane, BACTERICIDAL
Vancomycin pharmacocynamics NOT absorbed from oral or GI mucosa. IM INJECTION CAUSES PAIN AND TISSUE NECROSIS. must be given by IV, diluted in at least 200ml of saline or D5W, Slow IV drip over 60mins to minimize thrombophlebitis
Vancomycin uses reserved for strep and staph infc. in soft tissue and bone that cannot be treated with less toxic antibiotic(such as pen) S. aureus resistant to other antibiotics. Van + aminoglycoside for endocarditis caused by Strep faecalis
Vancomycin adverse reactions Ototoxicity(may be reversible if drug is withdrawn) Nephrotoxicity Thrombophlebitis at injection site Hypersensitivity Seizures and hypotension is infused too rapidly muscle loss at site of injection
Vancomycin is a glycopeptide antibiotic that is seldom used
Vancomycin spectrum narrow spectrum, gram pos bacteria ONLY usually effective against resistant staph and strep effective against Clostridia, Actinomyces, many other anaerobes, Cornebacterium and streptococcus faecalis and most other ORAL ANAEROBES
Vancomycin resistance Usually minor and no cross resistance with other antibiotics.
Vancomycin NOTES vanco has severe side effects and was seldomly used, with the emergence of staph. resistant to most antibiotics its use has increased
Vancomycin treatment of choice for MRSA, (for vanco resistant use linezoid) Also used orally for ACC (antibiotic-associated colitis) prophylactially for pts allergic to pen and cephalosporins
Vancomycin elimination widely distributed in body. 90% cleareed from kidney(need to adjust for renal impaired pts.)
Created by: Garzilla