Flashcards in Macrolides and Fluoroquinones Deck (67):
Macrolides are what general antibiotic type and for what are they named?
Protein synthesis inhibitors
Named for large macrolide ring structure
What is a prototype macrolide?
What drug does Erythromycin act like in its antibacterial activity?
Penicillin, which is a cell wall inhibitor.
What are the 2 new macrolides that are semisynthetic with an extended spectrum and improved pharmacokinetics?
What are the 2 new macrolides, Azithromycin and Clarithromycin used for?
Alternatives to penicillins for prophylaxis of bacterial endocarditis
What structure in the Macrolide makes it easily hydrolyzed in the stomach and thereby inactivating a large part of the drug?
The lactone ring
What is the erythromycin spectrum of activity (bacteriostatic/cidal), what bacteria is it active against?
Gram Positive Cocci
What is the spectrum of activity for Azithromycin and Clarithromycin?
somewhat broader, to include activity against gram negatives like H. influenza
What is the macrolide mechanism of action?
bind to 50S bacterial ribosome subunit to inhibit ribosomal translocase activity
What does inhibiting translocase activity of the 50S subunit mean?
It stops transfer of nascent peptide from A site to P site which stop the next amino acid from being added
Can Erythromycin be bacteriocidal?
Yes, depending on concentration of developing bacterial resistance
What is good about narrow spectrum in antibiotics?
It reduces the risk of developing bacterial resistance
What is the drawback of erythromycin's method of delivery and how is it avoided?
Destroyed by stomach acid so give w/ enteric coating or as ester salt (estolate, state)
What is the major difference in Azithromycin and Clarithromycin from Erythromycin?
Azithromycin and Clarithromycin are not sensitive to stomach acid
If bacteria are resistant to Erythromycin, Azithromycin, Clarithromycin, what does that mean for other drugs that bind the 50S subunit?
Bacteria are most likely resistant to those as well
What are the other two 50S subunit binding protein synthesis inhibitor antibiotics?
Of Erythromycin, Azithromycin, and Clarithromycin: which has the longest half-life?
Azithromycin (60-70 hrs)
What cells do Azithromycin and Clarithromycin concentrate in?
Azithromycin and Clarithromycin, due to their concentration in Macrophages, are useful against what opportunistic infection commonly found in HIV and immunocompromised patients?
Mycobacterium avium intracellulaire
Where is erythromycin metabolized?
What is the positive with the longer half-lives of Azithromycin and Clarithromycin?
Require dosing only 1-2 times/day
Most common side effects of Macrolides (erythromycin, azithromycin, clarithromycin)?
What metabolism do macrolides mess with leading to their drug interactions?
Inhibit cytochrome P450 drug metabolism by liver
How is Azithromycin metabolized?
In urine and bile, so it is safe for a person with liver disease.
What is the most common mechanism for resistance to Macrolides in bacteria?
Plasmids encoding erythromycin efflux transporters or methylation enzymes
What is Macrolide dosing for endocarditis prophylaxis that Dr. Ritter gave?
500 mg, 30-60 mins before surgery
What is a rare risk factor associated with erythromycin?
Cholestatic jaundice from ester salts of erythromycin interrupting bile flow
What Penicillin Class is Erythromycin similar to?
When would a macrolide be indicated?
Patient with penicillin allergy
Bacteria is penicillin resistant
What are 2 infections macrolides are commonly used to treat?
Respiratory (pneumonia, mycoplasm, Legionella) Skin
What is a prototype Fluoroquinolone?
What are 3 major advantages of Fluoroquinolones?
Activity toward gram positive and gram negative
Is Ciprofloxacin (fluoroquinolone) bacteriocidal or bacteriostatic? What bacteria is it effective against?
Gram Positive and Gram Negative
What is the method of action of Fluoroquinolone?
Inhibit DNA replication by inhibiting bacterial enzyme DNA gyrase
Bacterial DNA gyrase is related to what in humans and what are their purposes?
Human DNA topoisomerases
Relieve buildup of torsional strain during DNA replication
What is an administration consideration with fluoroquinolones?
don’t take with dairy or antacids because they bind divalent and trivalent metal cations(like tetracyclines do as well)
Which fluoroquinolone is useful for the treatment of UTIs because it does not have as good tissue penetration as Ciprofloxacin and Ofloxacin?
What can block the excretion of fluoroquinolones?
Probenecid (used in war to prolong supplies of penicillin [internet])
What is huge contraindiction for using fluoroquinolones?
Do not use in pregnant/nursing women or children under 18 due to potential to damage growing cartilage (Achilles tendon rupture)
What is a notable drug interaction for fluoroquinolones?
They increase plasma levels of warfarin
Which quinolone (older group) is used only for UTIs?
Large Glycopeptide druge whose most important use is treatment of Methicillin Resistant Staphylococcus infections (MRSA)
Is vancomycin bactericidal or static?
What is vancomycin's method of action?
inhibit cell wall synthesis but by different mechanism than penicillin
What is vancomycin the DOC for?
Treating pseudomembranous colitis from clindamycin
What are 2 methods of administration for vancomycin and is it absorbed systemically?
Orally (125 mg 4/day)
No systemic absorption
How is vancomycin excreted?
What are 2 side effect risks from vancomycin?
What is the mechanism of action for bacitracin?
Inhibit transport of building blocks of cell wall to outside cell membrane
What is the clinical use of bacitracin?
Topical treatment of skin & eye bacterial infections
With what drugs is bacitracin used in combination?
Polymyxin B and Neomycin
Clindamycin is an alternative drug for what?
Alternative to amoxicillin for endocarditis prophylaxis
What is the dosing of Clindamycin before surgery for endocarditis prophylaxis?
600 mg 30-60 min before surgery
Given how good it is against anaerobes, when should Clindamycinbe be used?
Late phase dental infections (bacteroides, prevotella, porphyromonas, fusobacterium)
For what is Clindamycin the DOC?
Anaerobic infections (e.g. B. fragilis)
What are 3 protein synthesis inhibitor drugs that are alternatives to amoxicillin for prophylaxis of endocarditis?
What is the major risk with Clindamycin?
Enterocolitis due to C. diff overgrowth (superinfection)
What is the drug used to treat the superinfection caused by Clindamycin?
Vancomycin (vancomycin vanquishes the turds)
What are two drugs other than Nalidixic acid and Norfloxacin that are used for UTIs?
Which five drugs are used to treat M. tuberculosum?
Which are the three major agents used to treat M. tuberculosum?
What is THE major agent used for M. tuberculosum
Isoniazid has hepatotoxicity when paired with what other Tb drug?
What is the mechanism of action for methambutol?
inhibits synthesis of tubercle bacilli cell wall component
What is the mechanism of action for Rifampin?
inhibits DNA-dependent RNA polymerase
What is the tuberculosis drug that is an inducer of hepatic microsomal drug-metabolizing enzymes leading to many drug-drug interactions?