Nucleic Acid Inhibitors - SING - EXAM 4

Names and generations of Fluoroquinolones:

• Ciprofloxacin (Cipro)- gen 2

• Levofloxacin (Levaquin)- gen 3

• Moxifloxacin- gen 3

• Delafloxacin (Baxdela)- gen 4

RENAL ADJUSTMENTS:

• Which fluoroquinolone does NOT require renal dose adjustment?

• Does Bactrim require renal dose adjustment?

• Does Flagyl require renal dose adjustment?

• Do the rifamycins require renal dose adjustment?

• FQ w/ no adjustments—> Moxifloxacin

• Bactrim—> yes

• Flagyl—> no

• Rifamycins—>no

List the sulfonamide:

sulfamethoxazole/trimethoprim (Bactrim)

List the Rifamycins:

• Rifampin

• Rifabutin

• Rifapentine

• Rifaximin

• Rifamycin

List the nitroimidazole:

metronidazole

Describe the MOA of each of the following:

• Fluoroquinolones

• Sulfonamides

• Metronidazole

• Rifamycins

• Fluoroquinolones—> inhibit Top II and Top IV, prevents supercoiling, breaks DNA

• Sulfonamides—> inhibit folic acid pathway by inhibiting Dihydropteroate Synthase and Dihydrofolate Reductase= no DNA

• Metronidazole—> diffuses across cell membranes where it is activated and causes breakages in DNA strands

• Rifamycins—> inhibits bacterial RNA synthesis by inhibiting RNA polymerase

List each as bacteriostatic or cidal:

• Fluoroquinolones

• Sulfonamides

• Metronidazole

• Rifamycins

ALL bactericidal

• sulfonamides/bactrim—> bacteriostatic alone, bactericidal TOGETHER

Time, conc, or AUC:MIC dependent?

• Fluoroquinolones

• Sulfonamides

• Fluoroquinolones—> conc-dependent

• Sulfonamides—> time-dependent

Spectrum of FLUOROQUINOLONES:

• which covers “respiratory pathogens” (S. pneumoniae, atypicals)

• which covers pseudomonas?

• which covers MRSA?

• which covers anaerobes?

• which covers mainly G-, w/ little G+?

• respiratory pathogens—> M,L

• pseudomonas—> all but M (DLC)

• MRSA? D

• anaerobes? M

• mainly G-, little G+—> C

(I use the 1st letter of each fluoroquinolone, easier to remember… ex: C= ciprofloxacin)

Spectrum of SULFONAMIDES (BACTRIM):

• What G+?

• What G-?

  • DOC?

• What non-bacterial pathogens?

• G+ : MRSA

• G- : enteric G-

  • DOC: S. maltphilia

• non-bacterial:

  • toxoplasma gondii (parasite)

  • pneumocystis jjovecii (fungus)

Spectrum of METRONIDAZOLE:

• ONLY COVERS WHAT KIND OF BACTERIA?

• What non-bacterial pathogens?

• ONLY COVERS ANAEROBES

• covers protozoa

Spectrum of RIFAMYCINS:

• What 1 atypical?

• What 1 G+?

• What 1 G-?

• Which covers e.coli?

• atypical: mycobacteria

• G+ : S. aureus

• G- : N. meninigitis

• e.coli—> rifaximin

Should rifampin be used as monotherapy? why?

no—> bc of resistance

Uses of FLUOROQUINOLONES:

• Which for CAP?

• Which NOT for UTI?

• Which for IAIs as monotherapy?

• for CAP—> M, D, L

• NOT for UTI—> M, D

• for IAIs—> M

Uses of SULFONAMIDES (BACTRIM):

• Bactrim is used for what type of UTI and SSTI?

• What opportunistic infections?

• used for uncomplicated UTI, outpatient SSTI

• opportunistic infections—> T. gondii encephalitis and pneumocystis pneumonia

  • they cover the fungus/parasite talked about in spectrum

Uses of METRONIDAZOLE:

• used to combo to treat what?

• What STIs?

• in penicillin allergy, can be used in combo for what?

• used in combo for IAIs

• STIs—> bacterial vaginosis, PID, Trichomoniasis

• in pen allergy used in combo for H. PYLORI

Uses of RIFAMYCINS:

• Which is used in prosthetic infections for Staph coverage?

• Are used in 2,3, or 4 drug combos for?

• Rifampin is used for prophylaxis against what?

• Which are used for traveler’s diarrhea and hepatic encephalopathy?

• prosthetic infections—> Rifampin

• used in 2,3, or 4 combos for tuberculosis

• Rifampin pro—> meningococcal

• Traveler’s diarrhea, hepatic encephalopathy—> Rifaximin, Rifamycin

Which class has a BBW for tendonitis and tendon rupture?

fluoroquinolones

Which agent has a BBW for possible carcinogenic properties?

metronidazole

Which class(es) cause QTc prolongation?

fluoroquinolones

Which agent may cause a disulfiram-like reaction when co-administered with alcohol?

How long should patients be counseled to avoid alcohol?

• METRONIDAZOLE

  • counsel: avoid alcohol DURING therapy and 3 days after d/c

What agent can cause red-orange discoloration of body fluids?

What should you counsel a patient on regarding this?

• rifampin

  • counsel: remove soft contact lenses to prevent staining permanently

Which class(es) cause photosensitivity?

fluoroquinolones

Which class(es) can be hepatotoxic?

• rifamycins

• fluoroquinolones

• METRONIDAZOLE

What agent can cause neuropathies (peripheral and optic) and a metallic taste?

METRONIDAZOLE

Which class(es) cause dysglycemia?

fluoroquinolones

Which class(es) can be teratogenic?

• Which can cause neural tube defects?

• Which can cause kernicterus?

  • Who should you avoid this in?

• teratogenic—> fluoroquinolones

• neural tube defects? SMX/TMP

• Kernicterus? SMX/TMP

  • avoid in neonates

Which class(es) can cause severe blood dyscrasias?

SMX/TMP

This class can commonly cause rash (allergy) and rarely severe derm reactions (SJS/TEN)

• Can you challenge a patient with an allergy?

• SMX/TMP

  • CANNOT challenge

Which class(es) cause hyperkalemia and crystalluria?

• What should you counsel a patient to do to reduce this risk?

• SMX/TMP

  • counsel: avoid other drugs that cause hyperkalemia, TAKE with >/= 8 oz of water

Which class has a BBW for exacerbation of myasthenia gravis?

Fluoroquinolones

Which class had a published safety alert for risk of aortic dissection or rupture?

• Who is at risk for this and therefore should avoid these agents?

• Fluoroquinolones

  • who is at risk? pts. with an existing aortic aneurysm or in pts. with an existing risk of that (peripheral vascular disease, HTN, blood genetic disorders)

Which class(es) can chelate with multivalent cations, thus decreasing absorption? What can you do to mitigate this?

fluoroquinolones—> avoid 2hrs before, 4-8 hrs after

Which agents can significantly increase warfarin effect/INR?

• SMX/TMP

• Metronidazole

Which agent can increase hypoglycemic effects of sulfonylureas?

SMX/TMP

What class are potent CYP450 inducers?

• Because of this they should not be co-administered with what class of drug?

  •   Which agent is preferred if no other option, d/t less potent induction?

• RIFAMYCINS

  • cannot co-administer with PROTEASE INHIBITORS

  • less potent interactions w/ Rifabutin

REVIEW:

Which nucleic acid inhibitors cover P. aeruginosa?

• Ciprofloxacin

• Levofloxacin

• Delafloxacin

REVIEW:

Which nucleic acid inhibitors cover MRSA?

• Delafloxacin

• SMX/TMP (BACTRIM)