The -lides Flashcards
How do macrolides work?
Binds the 50s subunit to interfere with the initiation coplex (50s and 30s don’t come together)
Interferes with transfer of t-RNA complex from A to P site to prevent elongation
Name the macrolides
Erythromycin
Clarithromycin
Azithromycin
What do macrolides work against?
Gram + cocci, bacilli Chlamydia Legionella H influenzae H pylori Respiratory infections
What is the difference between the macrolides
Erythromycin was discovered from streptomyces erythreus
Clarithromycin has an OCH3 group
Azithromycin has an N-CH3 group
How are macrolides admnistered?
Enteric coated tablets bc they are inactivated by acid
True or False: Macrolides cross the BBB
False
True or False: Macrolides are safe in pregnancy
False - they cross the placenta
How are macrolides excreted?
Biliary excretion
What toxicities do you worry about with macrolides?
Cholestatic hepatitis
Sensitivity reactions
GI disturbances
Tinnitus, hearing loss (reversible!)
True or False: Hearing loss from macrolides is reversible
True
What is Erithromycin used for?
Can also be used to stimulate GI tract after surgery (can be used to treat gastroparesis)
Also used for pertussis
Which macrolides can cause QT prolongation? When?
Erithromycin
When given with antihistamines, ketoconazole?
Which macrolides can inhibit CYP3A4? What drug levels does this affect?
Erithromycin and azithromycin
Affects theophylline, warfarin, digoxin levels
What is clarithromycin used for?
H pylori
Community pneumonia
Mycobacterium avium - intracellular
What is azithromycin used for?
H influenzae
Community pneumonia
Mycobacterium avium-intracellular
What causes resistance with macrolides?
Active transport out of the bacteria
Decreased binding to ribosomes
Increased metabolism by esterases
50s ribosomal mutations
How do ketolides work?
Binds 50s subunit; interferes with initiation complex
Interferes with transfer of peptide t-RNA complex from A to P site
Prevents elongation
Name the ketolides
Telithromycin
What is telithromycin?
A ketolide; semi-synthetic derivative of erythromycin
How do ketolides differ from macrolides?
Less metabolic and efflux mediated resistance than macrolides
What is telithromycin used for?
Community acquired pneumonia in adults over 18 ONLY
What was the FDA debacle with telithromycin?
In 2001 FDA panel tried to approve it for community acquired pneumonia, bronchitis, and sinusitis
FDA approved in 2004
February 2007 withdrew approval due to hepatotoxicity! BAD
Which agent has a black box warning for myasthenia gravis?
Telithromycin
What are the toxicities associated with telithromycin?
Hepatotoxicity (leading to death or liver transplants)
Visual disturbances due to slow accomidation, anticholinergic effects
GI distress
QT prolongation, arrhythmias
Black box warning in myasthenia gravis
Drug interactions with telithromycin?
CYP3A4 inhibitor so don’t use with statins (can cause rhabdomyolsis)
What is clindamycin?
A lincosamide; drug of choice for lung abscess and anaerobic lung and pleural space infections
How do lincosamides work?
Binds 50S subunit; interferes with transfer of peptide t-RNA complex from site A to P site
Prevents elongation
What is clindamycin used for?
Gram+, anaerobic, penicillin resistant staph and strep
Drug of choice for lung abscess and anaerobic lung and pleural space infections
Also used in necrotizing fasciitis because it inhibits toxin production (caused by streptococcus pyogenes)
Which drug is used for necrotizing fasciitis?
Clindamycin; it inhibits toxin production, doesn’t actually kill the bacteria
What toxicities are associated with clindamycin?
Diarrhea (20%) - c diff
Skin rash (stevens johnson syndrome)
Can inhibit neuromuscular transmission, potentiates NM blockers
What resistance occurs with clindamycn?
Altered metabolism to increase methylation
