06b: Antibac and Antifungal Agents II Flashcards
Antifolates, such as (X), are (bacteriostatic/bactericidal).
X = Sulfonamides/Trimethorpim
Bacteriostatic
Antifolates are used primarily in (hospital/community) settings due to (good/poor) oral absorption and (many/few) adverse effects.
Community; good; few (hypersensitivity, hematologic, and photosensitivity)
Sulfonamides are in (X) class of drugs and work by (stimulating/inhibiting) (Y).
X = antifolates;
Inhibit (PABA structural analog) dihydropteroate synthetase
Trimethoprim is in (X) class of drugs and work by (stimulating/inhibiting) (Y).
X = antifolates;
Inhibit DHF reductase (thus inhibiting DNA synthesis/cell replication)
Antifolates spectrum includes gram (pos/neg) (aerobes/anaerobes). Give some special examples of its coverage.
Pos and neg aerobes;
MRSA, Listeria, P. jiroveci (PCP), Shigella
T/F: Sulfonamide/Trimethoprim can’t be used for CNS infections due to poor distribution into CSF.
False - good CSF distribution
List three clinical diseases that antifolates are typically used for.
- UTI (concentrate in urine)
- PCP
- S. aureus skin/soft tissue infections
List two examples of first-line antimycobacterial agents.
- Rifampin
2. Isoniazid
Rifampin mechanism of action.
Blocks RNA Pol (transcription)
Rifampin has (narrow/broad) spectrum of activity and is usually given as (mono/combination) therapy.
Broad;
COMBINATION! All anti-mycobacterial agents given in combo
Rifampin is (bacteriostatic/bactericidal). It acts (slowly/quickly) on (replicating/non-replicating) cells.
Bactericidal;
Slowly;
Both
T/F: Rifampin and Isoniazid should only be given via IV.
False - good oral absorption
(X) anti-mycobacterial agent has many drug interactions since it’s an (inducer/inhibitor) of CYP450 enzymes.
X = Rifampin
Inducer
T/F: Rifampin and Isoniazid should only be given in combo therapy due to their broad spectrum of activity.
False - isoniazid SELECTIVE for mycobac;
Given in combo therapy to avoid development of resistance
Isoniazid mechanism of action is to (stimulate/inhibit) (X). It’s (bacteriostatic/bactericidal) and acts on (replicating/non-replicating) cells.
Inhibit;
X = mycolic acids of mycobac cell wall
Bactericidal;
Rapidly growing
(Rifampin/Isoniazid) is metabolized by liver.
Both
A malnourished individual may develop (X) adverse effect when taking (Y) antibiotic. This can be avoided with vitamin (Z) supplementation.
X = peripheral neuropathy Y = Isoniazid Z = B
List the four types of anti-fungals and a prototype of each.
- Polyene (Amphotericin B)
- Azoles (Fluconazole)
- Echinocandins (caspofungin)
- Flucytosine
“Gold standard” antifungal.
Amphotericin B
Amphotericin B mechanism of action.
Binds ergosterol, inserts itself into membrane and increases its permeability
Amphotericin B is (fungicidal/fungistatic) and (time/conc)-dependent.
Fungicidal;
Conc-dependent
T/F: Amphotericin B is only given via IV.
True - poor oral absorption
Amphotericin B is mainly (hydrophilic/lipophilic) and has (good/poor) distribution.
Lipophilic; good (wide)
Reluctancy to use amphotericin B largely due to which reason?
Adverse effects/toxicity (esp nephrotoxicity)
K an Mg wasting can be seen in (X) drug adverse effect. Why does this happen?
X = amphotericin B
Drug binds to our cells’ cholesterol (instead of ergosterol of fungi membrane)
Amphotericin B lipid products can be given to (increase/decrease) free drug concentrations and thus (increase/decrease) (X). What’s a limiting factor for these drugs?
Decrease (drug released slowly from lipid carrier);
Decrease
X = nephrotoxicity
Expensive!
T/F: Over the years, use of amphotericin B has decreased due to lower incidence of fungal infections.
False - due to availability of less toxic agents
Azoles, such as (X), mechanism of action is to (stimulate/inhibit) (X).
X = fluconazole
Inhibit
Y = fungal CYP450 (which converts lanosterol to ergosterol)
T/F: Azoles are all fungistatic and metabolized in liver.
True
Fluconazole mainly covers which species?
Candida and Cryptococcus
T/F: All azoles can be used for mucocutaneous candidiasis.
True
Voriconazole is first-line therapy for (X).
X = invasive aspergillosis
T/F: All azoles cover aspergillus species.
False - voriconazole and itraconazole do, but not fluconazole
T/F: All azoles cover candida species.
True
(X) antifungal is second-line therapy for cryptococcal meningitis.
X = fluconazole
(X) antifungal should not be used in patients with (Y) disease due to hypokalemia, edema, and negative inotropic adverse effects.
X = Itraconazole (an azole) Y = HF
T/F: All azoles are CYP450 inhibitors.
True
T/F: Fluconazole is the most toxic of the azole antifungals.
False - generally very well tolerated
When giving patient a loading dose of (X) antifungal, it’s important to warm him/her about potential hallucinations until maintenance doses are given.
X = voriconazole
T/F: Azoles don’t treat histoplasmiosis.
False - itraconazole does
Echinocandins, such as (X), are (fungistatic/fungicidal) and work by (stimulating/inhibiting) (Y).
X = caspofungin
Fungicidal;
Inhibiting;
Y = glucan synthase (thus cell wall synthesis)
(X) antifungal, the second-line treatment for (Y) is not FDA approved for this disease.
X = caspofungin Y = invasive aspergillosis
Caspofungin has broad coverage of (X) species.
X = Candida
T/F: Caspofungin is given OTC for Candida infections.
False - only IV
T/F: Caspofungin has wide distribution and is generally very well tolerated.
True
Flucytosine (stimulates/inhibits) (X) process after undergoing (amination/deamination/acetylation/deacetylation) in cell.
Inhibits;
X = fungal DNA/RNA synthesis;
De-amination (to 5-flurouracil)
Flucytosine covers which species of fungi?
Candida and Cryptococcus
(X) is the “Rifampin” of the fungal world. This is because…
X = flucytosine
It’s given in combo therapy with amphotericin B
T/F: Flucytosine usually given in combo therapy due to poor oral absorption and distribution.
False - rapid oral absorption and wide distribution (including CSF)
Why might flucytosine/amphotericin B combo be especially problematic in patients with (hepatic/renal) dysfunction?
Renal;
Amp is nephrotoxic and flucytosine 90% excretion in urine (unchanged)
SO must monitor/adjust carefully!
