Antifungals and Antiparasitcs Flashcards
Amphotericin B is a fungi_____ agent given for ____ fungal infections.
cidal
systemic
Which types of fungus does Amphotericin treat?
Aspergillus
Cryptococcus
Histoplasma
AE of Amphotericin include:
Infusion reaction (decr. rate, premed)
Nephrotoxicity
Electrolyte abnormalities- hypokalemia, hypomagnesemia
Liposomal formulation of Amphotericin and adequate hydration help to prevent what AE?
Nephrotoxicity
DI associated with amphotericin are relative to ______ toxicity with other ______ agents
cumulative
nephrotoxic
Fluconazole is mainly used for what organisms?
Yeast (Candida, Cryptococcus)
Itraconazole is mainly used for what organisms?
Endemic fungi (Histoplasma) and yeasts
Voriconazole and Posconazole arre mainly used for what organisms:
Expanded yeasts, molds (Asperigillus)
Serious systemic infections
Tx and prophylaxis in immunocompromised patients
How do Triazoles work?
Inhibition of CYP450-dependent enzyme that converts lanosterol to ergosterol (an important component in funal cellular membranes). This causes cell membrane permeability, lysis, and death
(some are fungistatic)
Triazoles AE:
Generally well tolerated
GI upset- N/V/D
Hepatotoxicity
PK of Fluconazole (PO, IV)
Well absorbed, no food or pH effect
CNS penetration
Long half-life (1x/day)
Renal excretion
What is different between the capsules and the oral solution of Itraconazole?
Not interchangeable
Capsules: Food and acidic pH requirement, lower bioavailability
Oral solution: Empty stomach increases absorption, no pH effect, more GI upset
Itraconazole is highly ______ with a high Vd, and extensive _______ metabolism.
lipophillic
hepatic
Therapeutic drug monitoring for itraconazole includes which to values?
Itraconazole level
OH-itraconazole level (active metabolite)
AE of Itraconazole:
HTN
Hypokalemia
Peripheral edema
(avoid in patients with congestive HF)
PK of Voriconazole (PO, IV):
Empty stomach increases absorption
High Vd, CSF penetration, extensive hepatic metabolism
Little none is renally excreted unchanged
What is true of the IV formulation of voriconazole and what should patients be monitored for?
Cyclodextrin vehicle used. This can accumulate with renal impairment.
Use only in patients that have CrCl >50ml/min
AE of Voriconazole include:
Transient vision changes (flashes, color changes)
Visual hallucinations
Photosensitivity, rash
PK of Posaconazole (oral suspension):
Optimal absorption with high-fat meal or liquid nutritional supplement
Long half life but multiple dose/day increase absorption
Hepatically metabolized
DI of Fluconazole:
CYP2C19 (Plavix) and 2C9 (warfarin) inhibitor
DI of Ketoconazole/itraconazole:
CYP450 3A4 substrate and inhibitor
(ex of how this can be used to the drugs advantage-if itraconazole used with PI to treat histoplasmosis it can be dose daily)
DI of Voriconazole:
CYP 450 2C19, 2C9, 3A4 inhibitor
CYP 2C19 and 3A4 substrate
DI of Posconazole:
CYP 3A4 inhibitor
Metabolized by glucuronidation = not usually affected by other drugs but can affect other drugs
Terbinafine (Lamisil) is fungi_____
cidal
Terbinafine (Lamisil) PO treatment for onchomycosis length of treatment:
6 wks for fingernails
12wks for toenails
AE and DI of Terbinafine (Lamisil):
Less toxic and DI than -azoles
AE: GI upset, HA, taste disturbances, hepatotoxicity esp in patients with pre-existing liver disease
DI: CYP450 2D6 inhibitor (ritonavir may be affected but not enough to dose adjust)
Efficonazole (Jublia) for onchomycosis: Adminstration, pros/cons
Topical
Cons: 48wks of treatment (and may not be better than typical tx: terbinafine or oral azoles)
Pros: may be safer than oral meds, less toxicity risk
Common AE of the fungistatic Griseofulvin (Grifulvin):
Common: HA, fatigue, confusion, syncope, lethargy
Rare: hepatotoxicity, neutropenia, angioedema, urticaria
MOA of Flucytosine:
Prodrug converted to 5-FU by fungal enzymes
Causes formation of faulty fungal proteins and enzymes
What drug is flucytosine use in combination with for the treatment of cryptococcal meningitis?
Amphotericin B
Echinocandins: Caspofungin, micafungin, anidulafungin are all given:
IV (low bioavailability)
MOA of echinocandins:
Inhibits fungal synthesis of Beta (1, 3) D-glucan
What is the spectrum of action of echinocandins?
- *Candida (fungicidal)
* *Aspergillus (fungistatic)
AE of echinocandins:
N/V, flushing, injection site reaction
Which echinocandin can be induced by rifampin?
Caspofungin
Do echinocandins have CYP reactions?
No
Metronidazole (Flagyl), Tinidazole (Tindamax, Fasigyn) are used for the treatment of what type of organisms?
Anaerobic bacteria, amebiasis, giardiasis, trichomoniasis
C.diff colitis
What should patients taking Metronidazole (Flagyl) avoid doing?
Drinking alcohol during and for 48hrs after stopping the drug- it can produce a disulfiram effect and causes the build up of alcohol in the system making people feel sick
The antiprotozoal agent Nitazoxanide (Alinia) is used to treat:
Giardiasis, Crytosporidosis
The antiprotozoal agent Pentamidine (Nebupent, Pentam) is used to treat:
PCP- inhaled or IV
The antiprotozoal agent Atovaquone is used to treat:
PCP, toxoplasmosis- oral liquid (give with food)
Malaria
What is the MOA of the antihelminthic, Ivermectin?
Binds selectively to glutamate-gated Cl channels
Paralyzes worms by causing hyperpolarization of nerve and muscle cells
Low affinity for human ligand-gated Cl channels
Poor CNS penetration
What is the MOA of the antihelminthics, Albendazole and Mebendazole?
Inhibits formation of worm microtubules
AE: bone marrow suppression, hepatotoxicity, acute renal failure
What is the usual length of a course of antihelminthics?
Very short, sometimes even just one dose
