Macrolides Flashcards
Macrolide Drugs
Erthryomycin
clarithromycin
azrithromycin
Macrolide MOA
inhibit protein synthesis via the 50S rb subunit
- binds 50s and inhibits translocation (transfer of peptide from the A-P- block the peptide bond formation
- Chlorophemenicol binding site is located near by and they can have deleterious effects is used at the same time
Erythromycin
Macrolide
Fecal excretion, portion excreted in the bile and resorbed from the intestine
short half life , extensive protein bound
TX:
- DOC legionella, M. pneumonia, chlamydia
- mixed infections of skin soft tissue, body cavities, caused by gram + organisms
- as an alternate to penicillin for pts with pen. allergy
- tx Group A strep pathologies (scarlet fever, cellulitis, erysipela)
- prophlyatic in bacterial endocarditis and recurrent attacks of rheumatic fever
- tx diptheria (preferred for the carrier state)
- alternative to penicllin in cases of syphilis and uncompliated gonorrhea in preggers
Bacterial spectrum
- Gram + cocci (s. aureus, s. pneumo, s. viridans, s. pyrogene, s. fecalis)
- some gram + bacilli (c. tetani, C. perferingens, C. diptheria, A. isralii, Norcardia, helibacter)
- NOT effective against gram - (majority are resistant)
- Active against the atypicals (mycoplasma, legionella, and chlamydia)
Drug interactions:
- P450 Inhibitor
- –> SEVERE QT prolongation when administered with cisapride, pimozide, and sparfloxacin
toxicities
- Diarrhea - activates motilin receptors
- QT prolongation and V Tach- torsades des pointes
- Mild allergic reactions
- LFT elevated and cholestatic jaundice
- ototoxicty (tinnitus, deafness- temporary)
- IV admin: painful and phlebitis
Gastric acids destroy erythromycin base- modified fromulations are required (stearates, or estolates) to make it acid resistant
- passes thru the plancenta, but not the CNS
Clarithromycin
Macrolide, Oral Metabolized in the liver- more urine excretion than erythromycin penetrates well into tissues and cells plasma protein bound - NO incidence of GI issues
TX
- MAC- Penetrates the lung tissue and macrophages to a greater degree than erythromycin
- Effective against B.burgdorferi
- H.pylori associated duodenal ulcer
- CAP
- increased activity activity against organisms compared to erythromycin
- as effective as pen v for CAP, sinusitis, and pharyngitis
Bacterial Spectrum
- Same as erthryomycin
Drug interactions
- inhibits p450
Azithromycin
Macrolide,
Once daily dose
Less GI intolerance
Reaches higher intracellular concentration than erythromycin
- eliminated in the feces
- not metabolized by liver - no drug interactions
TX:
- gonorrhea (in combo with ceftriaxone)
- pediatritc otitis media
- pharyngitis
- MAC prophylaxis for pts with advanced HIV
Bacterial Spectrum
- Same as erthryomycin - S. Viridians, camplyobacter
- decreased activity against Staph Aureus, Strep pyrogenes, and strep pneumo
Telithromycin
Ketolides
Oral, long half life (9-10hrs), metabolized in the liver (CYP34A)
MOA: protein synthesis inhibitor binds to 23S site on the 50S rb
Spectrum
- broad spectrum > than macrolides
- good against respiratory pathogens including those resistant to erythromycin or penicillin pneumo
- good activity against intracellular and atypicals
SE
- Serious hepatotoxicity
- diarrhea
Clindamycin
Protein synthesis inhibitor
- ORAL with HCL, IV with phosphate salt, parenteral admin
- renal excretion
- widely distributed in the tissues with the highest concentration in the bone, bile and urine
- no CNS penetration
- Crosses the placenta readily and in breast milk
- highly protein bound
MOA: binds 50s subunit
Spectrum
- aerobic: gram + cocci (strep and staph are extremely susceptible)
- anaerobic: gram- and gram +
- –except for enterococci,
tx:
- used in combination with pyrimethaminae in treating toxoplasmic encephalitis in pts with AIDs
- effective anti-anerobic antibiotic
- ance- reduce concentraion of free fatty acid in sebum-> reduce inflammation
SE:
Pseudomembranous colitis j
Dalfopristin, Quinupristin
Streptogrannins
Dalfopristin: binds to the 70S and 50 ribosomal particle and inhibit the early phase of protein synthesis
Quinupristin; bind to the 50s of the 70s and inhibit the last phase of the protein synthesis
* administered together act synergistically against the
bacteria
- IV admin
TX:
- VR enterococcus
- complicated skin and skin structure infections due to s.aureus
Drug interactions
- inhibt p450 3A4 (cyclosporine, midalozam, nifedipine)
SE:
N/V, unspecified pain, pruritis, and rash
CI:
Children, pregnancy, breast feeding, hepatic disease, streptogrannin insensitive
Linezolid
IV or oral admin, oral bioavailability is 100%, low plasma protein binding,
- metabolized via non-enzymatic oxidation - no hepatic involvement, no renal involvement
MOA: inhibits bacterial protein syntheiss by inhibiting the formation of a functional 70s inititation complex - binds to 23S rb RNA on the 50S subunit
tx:
- bacterial pneumo
- skin and skin structure infections
- VRE infections
- MRSA
Spectrum
- aerobic gram +
Drug interaction
***MOA inhibitor !!! so anything that inc. the sympathetics is CI (inc. local anesthetic)
CI
hypersensitivity and pheochromocytoma
