Antifungals Flashcards
1
Q
- MOA: fungicidal, causes loss of cell membrane integrity by forming pores in the membrane, allowing leakage
- Very toxic to the kidneys
- Amphipathic molecule, but poorly soluble
- Must be administered by IV
- Given with other lipid drugs to improve solubility and decrease renal toxicity
- MOR: Sterol modification
A
Amphotericin B
2
Q
- MOA: Inhibitor of Beta-1-2 glucan, an important structural component of the cell wall
- Must be given parentally
- Well tolerated
- Used against APERGILLUS and CANDIDA SP
- MOR: Altered synthetase
A
Caspofungin (Echinocandins)
3
Q
- MOA: Block synthesis of ergosterol, a major fungal sterol component of the cell membrane
- Prevent conversion of lanosterol to ergosterol
- Works through Cytochrome P450 Inhibition
- Eliminated in the urine
- Cannot give during pregnancy
- Can reach CSF
- Overall best profile w/ widest therapeutic index
- MOR: Efflux, Demthylase alteration, Bypass, Overproduction
A
Fluconazole
4
Q
- MOA: Block synthesis of ergosterol, a major fungal sterol component of the cell membrane
- Prevent conversion of lanosterol to ergosterol
- Works through Cytochrome P450 Inhibition
- Very poor ability to penetrate into CSF
- One of the highest incident of side-effects
- Poor oral bio-availability
- MOR: Efflux, Demthylase alteration, Bypass, Overproduction
A
Itraconazole
5
Q
- MOA: Block synthesis of ergosterol, a major fungal sterol component of the cell membrane
- Blocks conversion of squalene to squalene epoxide, leading to a toxic buildup of squalene
- No effects upon CYP activity
- Well tolerated, except with transient lymphopenia and neutropenia
- Avoid giving to immunosuppressed patients
- MOR: Efflux
A
Terbinafine
6
Q
- MOA: Block synthesis of ergosterol, a major fungal sterol component of the cell membrane
- Prevent conversion of lanosterol to ergosterol
- Works through Cytochrome P450 Inhibition
- Cannot give during pregnancy
- Can reach CSF
- Highest problem with cytochrome-mediated drug-drug interactions
- Associated with photosensitive dermatitis and hallucinations
A
Voriconazole
7
Q
- MOA: nucleic acid synthesis inhibitor that prevents cell replication
- Pyrimidine analog with narrow therapeutic window
- Enters fungal cell via enzyme cytosine permease
- Converted to 5-FU and mediated in intestinal microflora
- Associated with hematologic toxicities like anemia, leukopenia, and thrombocytopenia
- MOR: Permease or modifying enzymes mutation
A
Flucytosine
8
Q
- MOA: Block synthesis of ergosterol, a major fungal sterol component of the cell membrane
- Prevent conversion of lanosterol to ergosterol
- Works through Cytochrome P450 Inhibition
- Very poor ability to penetrate into CSF
- Can cause irreversible hepatic damage and adrenal insufficiency
- At high [conc], can inhibit aldosterone, cortisol, and testosterone, useful in treating prostate cancer
- MOR: Efflux, Demthylase alteration, Bypass, Overproduction
A
Ketoconazole
9
Q
- MOA: Inhibitor of Beta-1-2 glucan, an important structural component of the cell wall
- Must be given parentally
- Well tolerated
- Used against APERGILLUS and CANDIDA SP
- MOR: Altered synthetase
A
Micafungin
10
Q
- MOA: Block synthesis of ergosterol, a major fungal sterol component of the cell membrane
- Prevent conversion of lanosterol to ergosterol
- Works through Cytochrome P450 Inhibition
- One of the highest incident of side-effects
- Only azole with activity against MUCORMYCOSIS
- Oral administration w/ CYP-mediated drug-drug interactions
A
Posaconazole
11
Q
- MOA: Mitotic Spindle Inhibitor in cell nucleus, which also makes it a cell-cycle inhibitor
- Systemic treatment of dermatophytosis
- CYP3A4 inducer
- Drug interactions: warfairin, oral contraceptives, cyclosporine, and aprepitant
A
Griseofulvin
12
Q
- MOA: Topical form of Amphotericin B
- Topical drug used to treat CANDIDIASIS
- MOR: Sterol modification
A
Nystatin
13
Q
What drug(s) do you use for ASPERGILLOSIS?
A
Voriconazole IV
14
Q
What drug(s) do you use for BLASTOMYCOSIS (mild)
A
Itraconazole PO
15
Q
What drug(s) do you use for BLASTOMYCOSIS (severe)
A
Amphotericin B IV then Itraconazole PO
16
Q
What drug(s) do you use for CANDIDIASIS
A
Fluconazole PO
17
Q
What drug(s) do you use for CRYPTOCOCCUS
A
Amphotericin B IV + Flucytosine PO, then Fluconazole PO
18
Q
What drug(s) do you use for HISTOPLASMOSIS
A
Amphotericin B IV + Itraconazole PO
19
Q
What drug(s) do you use for MUCORMYCOSIS
A
Amphotericin B
20
Q
What drug(s) do you use for Sporotrichosis
A
Amphotericin B IV and/or Itraconazole PO
21
Q
What is a drug comparable to Amphotericin B?
A
Nystatin
22
Q
Topical drugs used to treat CANDIDIASIS infection
A
Clotrimazole and Miconazole
