Term
| What is the prototype macrolide? |
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Definition
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Term
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Definition
derived in 1952 from Saccharopolyspora erythrea (Philippines)
disadvantages: poor bioavailability, drug interactions, four times a day dosing |
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Term
| What are the "newer" macrolides? |
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Definition
| clarithromycin and azithromycin |
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Term
| How are clarithromycin and azithromycin improvements on erythromycin? |
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Definition
better bioavailability
dose less frequently
more gram - activity
greater gram + activity
fewer drug interactions (mostly azithromycin) |
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Term
| How do you dose azithromycin? |
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Definition
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Term
| How do you dose clarithromycin? |
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Definition
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Term
| What is the macrolide's mechanism of action? |
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Definition
inhibition of protein synthesis
binds to Domain V of the 23s rRNA (part of the 50S ribosomal subunit) |
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Term
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Definition
reversible
stops growth
immune system does the killing |
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Term
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Definition
irreversible
damages cell leading to death
typically want to use these agents in patients that have a weakened immune system |
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Term
| Macrolide gram + spectrum of activity |
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Definition
Staph. aureus (resistance is common, MRSA very likely to be resistant)
Strep. pneumoniae (CAP, upper respiratory infections)
other strep.: variable activity against S. pyogenes, modest activity against Viridans strep.
poor enterococcus activity |
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Term
| macrolide gram - spectrum of activity |
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Definition
H. pylori
moraxella catarrhalis
H. influenzae
Campylobacter jejuni
N. gonorrhoeae
N. meningiditis
Bordetella pertussis
poor coverage of enterobacteriaceae |
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Term
| other macrolide spectrum of activity (besides gram - and gram +) |
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Definition
poor anaerobic coverage
excel in covering atypicals
mycoplasma
chlamydia
legionella
mycobacterium avium complex |
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Term
| What are the two mechanisms of resistance against macrolides? |
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Definition
efflux
target site modification |
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Term
| How do efflux pumps resist macrolides? |
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Definition
efflux pump mediated by mefA/E gene
affects macrolides only (some pumps may affect other drugs as well) |
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Term
| How does target site modification by bacteria resist macrolides? |
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Definition
target site modification mediated by erm gene
affects macrolides, clindamycin, and streptogramins |
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Term
| What is the percentage of resistance in S. pneumoniae to macrolides? |
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Definition
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Term
| Which conveys a higher level of resistance, efflux or methylation? |
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Definition
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Term
| How are the macrolides metabolized? |
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Definition
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Term
| Which macrolide has the longest half-life? |
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Definition
azithromycin (29-96 hours)
clarithromycin only has half-life of 4-7 hours and erythromycin has half-life of only 1-2 hours |
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Term
| What is the percentage bioavailability of erythromycin? |
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Definition
| 18-45% (because many different forms of drug) |
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Term
| What is the percentage bioavailability of clarithromycin? |
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Definition
| 50-55% (tends to be the best absorbed) |
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Term
| What is the percentage bioavailability of azithromycin? |
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Definition
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Term
| Which macrolide do you have to take into consideration a patient's renal function? |
|
Definition
clarithromycin (primarily eliminated via the kidneys)
erythromycin and azithromycin are eliminated via the liver/bile |
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Term
| What forms does erythromycin come in? |
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Definition
base (tablets)*
stearate salt (tabs)
ethylsuccinate (tabs, chew-tabs, liquid)
estolate (tabs, capsules, liquid)
gluceptate (IV)
lactobionate (IV) |
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Term
| What forms does clarithromycin come in? |
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Definition
| tabs, ER tabs, suspension |
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Term
| What forms does azithromycin come in? |
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Definition
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Term
| Which drug is less absorbed with food? (i.e. which drug should be taken without food?) |
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Definition
| erythromycin (except estolate and ethylsuccinate form) |
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Term
| How do macrolides penetrate tissues so well? |
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Definition
| they can get into the white blood cells to get carried to the site of infection |
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Term
| Do macrolides penetrate the CSF? |
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Definition
| no, poor CSF penetration (very hydrophilic drugs) |
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Term
| Which macrolides can cause drug interactions because they inhibit CYP enzymes? |
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Definition
| ertthromycin and clarithromycin |
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Term
| What are the drug interactions with macrolides? |
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Definition
theophylline (increased levels)
type I antiarrhythmic drugs (enhanced effect)
antacids (decrease absorption of azithromycin)
warfarin (increase bleeding risk)
carbamazepine (increase levels of this drug)
digoxin (increase drug levels)
cyclosporine (increase drug levels) |
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Term
| What are the macrolides therapeutic uses? |
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Definition
respiratory tract infections
sexually transmitted diseases
peptic ulcer disease
cat scratch fever
whooping cough
lyme disease
mycobacterium avium complex |
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Term
| How are macrolides used in the treatment of community acquired pneumoniae (CAP)? |
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Definition
potential empiric use
excellent agents when atypicals are suspected
typically not used as monotherapy (usually combined with beta-lactam) |
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Term
| What types of respiratory infections are macrolides used to treat? |
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Definition
CAP
streptococcal pharyngitis
acute exacerbations of chronic bronchitis |
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Term
| What are the macrolide's adverse effects? |
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Definition
gastrointestinal (abdominal pain, D, N)
mild elevatioin of liver enzymes
central nervous system (headache/dizziness, dose related hearing loss, tinnitus)
hypersensitivity reactions
cardiovascular |
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Term
| What are the precautions when giving macrolides? |
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Definition
pregnancy
azithromycin and erythromycin (category B)
clarithromycin (category C) |
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Term
| What are the unique properties of macrolides? |
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Definition
| anti-inflammatory and immunomodulatory |
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Term
| How do macrolides exhibit anti-inflammatory and immunomodulatory properties? |
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Definition
limit production of pro-inflammatory cytokines
reduce neutrophil chemotaxis
decrease sputum and mucus production |
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Term
| What are the macrolides role in cystic fibrosis? |
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Definition
maintenence therapy
reduced exacerbations
increased time to exacerbation
decreased toxins
inhibition of biofilms and quorum sensing |
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