PHARM Flashcards
Which genes are responsible for the structure of DNA topoisomerase II? Why is this important evolutionarily for the bug?
GyrA and GyrB, they code for proteins with the same name. Point mutations can confer resistance to fluoroquinolones
Which two fluoroquinolones are used in serious situations such as nosocomial pneumonia and inhalation anthrax? Why?
Ciprofloxacin and Levofloxacin; these are used because these serious situations require high doses and these two drugs have the best safety profiles. Gemifloxacin and Moxifloxacin do not have well established safety profiles
Which gene increases efflux of macrolides?
mef = macrolide efflux gene
By what two mechansims do macrolide antibiotics increase digoxin levels?
They inhbibit the P-glycoprotein mediated renal SECRETION of digoxin and they kill the normal flora of the gut that metabolize digoxin
T/F: Linezolid is a bacteriostatic drug
True but at high doses it may become bactericidal
A patient being treated for leukemia should probably not receive what inhibitor of the 50 S? Why?
Linezolid, it causes thrombocytopenia, anemia, and neutropenia, in patients with underlying bone marrow suppression (i.e. the chemotherapeutics this guy would get)
Which gene modifies domain V of the 23 S portion of the 50 S ribosome leading to macrolide resistance?
erm gene = erythromycin ribosome meythylase
Which 3 fluoroquinolones can be used for bacterial sinusitis?
All but Gemifloxacin? So moxifloxacin, ciprofloxacin, and levofloxacin
Why does erythromycin require enteric coating with stearates? Which ones have greater oral bioavailability and why?
Because it is a base that is destroyed by stomach acid; clarithromycyin, azithromycin and telithromycin are more acid stable
What is the most serious side effect of linezolid? What effect does it have on CYP3A4? It shares a neuro side effect with what other class of antibiotics?
Thrombocytopenia, neutropenia and anemia in pts with underlying bone marrow suppression? It has no effect on 3A4; it causes peripheral neuropathy like fluoroquinolones albeit much less often
What are the functions of the A, P, and E sites on the ribosome?
A site = entry of aminoacyl tRNA; P site is where the peptidly tRNA is formed and E is where the uncharged tRNA exits
Which drug is a lincosamide?
Clindamycin
Which genes are responsible for the structure of DNA topoisomerase IV? Why is this important evolutionarily for the bug?
ParC and ParE, make up subunits of topo IV, point mutations confer resistance against fluoroquinolones
Which gene for resistance against fluoroquinolones can be transmitted via a sex pilus?
The plasmid: quinolone resistance gene, this is exchanged between two bacteria via conjugation (use of a sex pilus)
Regarding the macrolides what are the adverse effects on the following 1) Cardiovascular 2) Musculoskeletal and 3) Hepatic
1) CV = QT prolongation 2) MSK = precipitate myasthenia gravis and 3) Hepatic = can cause cholecystitis and drug-induced hepatitis BUT telithromycin can cause FULMINANT LIVER FAILURE
This fluoroquinolone has good activity against anaerobes but overall activity on gram negatives not yet established:
Moxifloxacin (most anaerobes are gram negative, but whatever)
Which fluoroquinolones are used for community acquired pneumonia?
All but Cipro (recall: cipro is not very good against S. pneumo which is the major cause of CAP)
Which gene codes for a protein that hydrolyzes the lactone ring of macrolides?
ere which is the erythromycin esterase gene
Which macrolides are indicated for MAC pneumonia? What about syphilis?
MAC= clarithromycin and azithromycin; syphilis is erythromycin which is weird b/c most STI’s are Tx’d with azithromycin
A man who suffers from intermittent heart burn is taking fluroquinolones for an infection and isn’t getting better, why might that be?
He may be taking antacids. Antacids decrease the oral bioavailability of fluoroquinolones (as do ALL divalent and trivalent cations such as Ca and Zn)
What is indicated for Legionairre’s disease and Pertussis?
Erythromycin
Which 4 drugs can interact with the macrolides metabolized by CYP 3A4?
Theophylline, CCB’s, Warfarin, and Cyclosporine
A person with Haemophilus ducreyi is best treated with what macrolide? What should a person with H. pylori receive (macrolide-wise)?
Chancroid = Azithromycin b/c it is STI and azithromycin has good tissue penetrance and long half-life; Clarithromycin for H. pylori
What are the 3 general types of mechanisms of resistance to fluoroquinolones?
1) Mutation in the drug target via (GyrA/GyrB or ParE/ParC) 2) Mutations that affect drug accumulation (efflux pumps and porins) and 3) Plasmid mediated resistance (either/both quinolone resistance gene or variant aminoglycoside acetyltransferase)
Overall, what 5 drugs may be increased in the serum with concomittant use of macrolides (no azithromycin)?
CYP 3A4 drugs: theophylline, cyclosporine, CCB’s, and Warfarin? Also, Digoxin but not bc of 3A4 (azithromycin would only increase digoxin not the others)
Which macrolides are best for URT infections (pharyngitis, otitis media, and sinusitis)
Clarithromycin and Azithromycin
T/F: Fluoroquinolones are bacteriostatic
False. They are bactericidal
What kind of bugs is moxifloxacin best against? How is it metabolized?
Anaerobes, metabolized by the liver
If a bacterium is resistant to fluoroquinolones because it is able to modify the drug enzymatically then 1) How is it doing this? 2) How did it receive the capability to do this?
It is acetylating it with a variant of aminoglycoside acetyltransferase and it was received by conjugation (plasmid-mediated)
Where do tetracyclines and Aminoglycosides act?
30 S ribosome
Compare and Contrast the side effects of fluoroquinolones and macrolides on the cardiovascular and musculoskeletal systems:
1) CV = both cause QT prolongation leading to Torsades and maybe vent tachy 2) Quinolones cause MSK Sx of tendonitis and rupture w/ arthropathy whereas Macrolides can precipitate myasthenia gravis
Which fluoroquinolone is the only one to be metabolized by the liver?
Moxifloxacin
Ciprofloxacin is best against what kinds of microbes?
Gram negative