Topic 15-Macrolides. Ketolides. Flashcards
What is the mechanism action for macrolides
Inhibition of protein synthesis by irreversibly binding to a site on the 50 S ribosome
Spectrum for macrolides?
similar to penicillin spectrum 1.)Gram positive and gram negative cocci neisseria, bordetella pertusis, campylobacter gastroenteritis, trepenoma pallidum, H. influenze (50% resistant), Staph, cornybacterium, mycobacterium avium and kansisii, listeria+H pylori+oral anaerobes (weak effect) and 2.)community acquired pneumonia -streptococci -pneumococci (40% resistant) -legionella -mycoplasma 3.)Intracellular pathogens Mycoplasma pneumoniae, Leionella, Ureplasma urealyticum, chlamydia ureithritis, lymes disease Chlamydia -ocular -pneumonia -genital 4.)Antiprotazoal Toxoplasmosis in pregnancy
What does the Macrolide spectrum not cover
Enteric gram negative rods
enterococci, strep dificile, bacteriods fragilis
UTI
Marcolides Pharmacokinetics Bactericidal or bacteriostatic Administration (special capsule?) Metabolism Distribution Length of treatment
Bacteriostatic unless bacteria is highly susceptible, then bacteriocidal
Administration is oral and needs enteric coated tables since it is gastric acid sensitive
Metabolized in liver
Good distribution, 100x more concentrated intracellularly via active transport
3 day treatment since it takes 2 days to take effect
Which Macrolide makes an active metabolite? Which bacteria does it treat?
Clarithromycin forms an active metabolite to treat H. influenzae and H. pylori
Which Macrolide accumulates in the macrophages and granulocytes
Azithromycin
Therapeutic indications of macrolides?
- )atypical and upper respiratory infections
- )Penicillin allergy
- )Stomach ulcer, skin infection, periodontal infection
- )toxoplasmosis in pregnancy (spiramycin)
- )Toxic shock syndrome for strept with penicillin
- )STDs, Diptheria, pertussis, listeriosis
Resistance to Macrolides is called? Methods of resistance?
MLS resistance (3 abx that all bind to the same site on 50s ribosome)
Macrolides, LIncosamides (Clindamycin) and Streptogramin B (Quinupristine)
1.)hysteresis, enzyme degrades macrolides
2.)efflux pump and decreased permeability
Adverse effects in Macrolides?
- ) GI symptoms- motilin like metabolite, stimulates gut to increase motility (nausea and diarrhea)
- ) Enzyme inhibitor, inhibition of P450 system
- ) Hepatotoxic, prolongued QT intervals
- ) Similar in structure to penicillin, might have allergy if they have penicillin allergy
Natural Macrolide compounds?
Erythromycin
Josamycin
Spiramycin
Semisynthetic Macrolide compounds?
Clarithromycin
Roxithromycin
Azithromycin
What is Erythromycin used for?
Equal Gram positive and negative activity
Gram positive upper respiratory tract infection, skin infection, intracellular pathogens, penicillin allergy.
Strong GI adverse effects
What is Roxithromycin used for?
Same as Erythromycin, less GI effects
What is Clarithromycin used for?
More potent against Gram positive bacteria
Effective against gram positive cocci, gram negative bacteria
Metabolite treats H. influenzae, H. pylori, and Mycobacterium avium
Used in respiratory tract infection, gastric ulcer and gastritis
How is Clarithromycin administered
IV or per os
What are the adverse effects of Clarithromycin?
GI effects and acute cholestatic hepatitis
What are the interactions of Macrolides
inhibits CYP450 causing anti-histamines to not get degraded leading to building up and arrhythmia
Which Macrolide doesn’t inhibit the CYP450
Azithromycin
What is Azithromycin effective against
Most potent against gram negative bacteria
Effective against gram-positive cocci (respiratory tract infection), gram-negative cocci (H. influenzae), borrelia burgdorferi (lymes)
Accumulates highly intracellular and less GI effects and no interactions
What is Spiramycin effective against?
First choice drug, active against toxoplasma, especially during pregnancy
Second choice drug is tetracycline then fluoroquinolones
What is the Ketolide drug name?
Telithromycin
Where does Telithromycin originate
Part of the macrolide group but probably structurally different
What is the pharmacokinetics of Telithromycin Bactericidal or bacteriostatic Absorption Time or concentration dependent Elimination
Bactericidal
Good GI absorption, given once daily
Concentration dependent effect
Metabolized in liver and removed in bile (70%) and kidney (30%)
Spectrum of effect for Telithromycin
Similar spectrum to macrolides plus gram neg. cocci, rods (in repsiratory infection, only used in noscomial acquired pneumonia), and effective in macrolide resistant strains
Adverse effects of Telithromycin
Nausea, vomiting, diarrhea
Hepatitis
Inhibits CYP3A4
