antifungal drugs Flashcards
list 3 situations where there is an increase risk of fungal infection
- chemotherapy
- leukemia, AIDS
- placement of indwelling catheters
why aren’t there many antibacterial agents against fungi
fungi infection is eukaryotic invading eukaryotic, small differences
what is a difference between fungi and mammals
cell wall of fungi have chitin and ergosterol
what is the mechanism of action for amphotericin B
- binds to ergosterol of fungal plasma membrane
- alters membrane permeability
- leakage of ions
- death
when does amphotericin B work as a fungistatic and fungicidal
depends on concentration
what is the distribution for amphotericin B
poor CSF penetration
what is the major and minor adverse effect of amphotericin B
Main: nephrotoxicity
minor: hematologic, electrolyte imbalance
what causes hematologic effects in amphotericin
- erythropoietin production decrease
- anemia
what causes electrolyte imbalance effects in amphotericin
- K, bicarbonate, Mg wasting
is the nephrotoxicity adverse effect in amphotericin B reversible
yes
what are some infusion related adverse effects of amphotericin B
shaking, chills, fever
how is infusion related adverse effects avoided
premedicate with NSAIDs, acetaminophen, antihistamines or meperidine
what is the spectrum of activity for amphotericin B
broad
when is amphotericin B used for topical use for what disease
Candida
when is amphotericin B given as a medication
for severe cases
amphotericin B is mixed with what other component for drug use
lipids
what makes the lipid formulations of amphotericin B better than amph B by it self
- less nephrotoxicity
- equivalent efficacy
where does Flucytosine (5-fluorocytosine) work
penetrates fungal cell wall
what does Flucytosine do in the cell wall of fungus
deaminated to 5-fluorouracil by cytosine deaminase
what does 5-fluorouracil do
- competes with uracil
- decreases production of DNA, RNA, and protein synthesis
how is Flucytosine distributed
CSF penetration
what are 2 adverse effects for Flucytosine
- bone marrow hypoplasia
- increase hepatic enzymes in serum
what is the domino effect of Flucytosine because of bone marrow hypoplasia
anemia
leukopenia
thrombocytopenia
who is more likely to get bone marrow hypoplasia from Flucytosine
- prolonged therapy
- combination with amphotericin B
dosing by itself what can flucytosine treat
candida
cryptococcus
combined with amphotericin B, flucytosine can treat
cryptococcus meningitis in AIDS patients
is it better to use flucytosine in combination or by itself and why
combination, resistance can develop if used alone
what is the mechanism of action for Azole Antifungal
interfere with fungal cytochrome P-450 dependent enzyme
what is P450 responsible for
demethylation of lanosterol and conversion to ergosterol
is Azole antifungal static or cidal
both
what are 4 main adverse effects of Azole antifungal
- nausea/vomiting
- decrease testosterone and ACTH
- hepatits (rare)
- increase aminotransferase (not rare)
Antacids, PPI, H2 antagonists have what interaction in the body
decrease absorption due to decreased acidic environment
what happens when azoles are taken with warfarin
increase anticoagulation effect
Ketoconazole is absorbed how well
rapidly from GI
Ketoconzaole largely replaced what drug
Itraconazole
how well is fluconazole absorbed
rapidly from GI
how well is fluconazole distributed
widely distributed even into CSF
how is Fluconazole eliminated
renal excreted unchanged in urine
Fluconazole treats what
cyrptococcal infections- meningitis
- coccidiomycosis
- candidiasis
how well is Itraconazole distributed
widely distributed, poorly into CSF
what does Itraconazole covers what diseases
wide spectrum
Itraconazole can be administered and how and what does it treat
orally for histoplasmosis/blastomycosis
amphotericin B should be used if severe life-threatening cases, once there is clinical improvement the patient can be switched to what drug
itraconazole
what effects the absorption of Voriconazole
high fat meals
Voriconazole interacts with what
cytochrome P450
Rifampin treats what
tuberculosis
what does Rifampin do to Voriconazole
increases metabolism of V, so don’t give V to patients on Rifampin
what happens with Voriconazole is given with Sirolimus
sirolimus concentration increases
what is sirolimus used for
prevent organ rejection
immuno-suppresent
Voriconazle has what adverse effects
visual disturbances
Voriconazole is used for what disease
- invasive aspergillosis
- candidiasis
what does posaconazole treatt
Candida and aspergillus infections in severely compromised patients
what is the mechanism of action for caspofungin
blocks fungal cell wall synthesis
- glycogen synthesis inhibitor
is caspofungin acetate the first line of drug
no
what are adverse effects of caspofungin acetate
phlebitis, headache, fever, increased LFT, SrCr needs to be monitered
phlebitis
inflammation of walls of vein
what is the mechanism of action for Griseofulvin
disrupts cell mitotic spindle structure
- arrested in metaphase
how is Griseofulvin administered
orally
how is Griseofulvin absorbed
microsize: variable- fat food increase
- ultramicrosize: completely absorbed
Griseofulvin targets what in the body
dermatophytosis: fungal infection of skin
how is Griseofulvin administered
orally, not topically
what is the major side effect of Griseofulvin
headache/dizziness
what is the mechanism of action for Terbinafine
inhibits squalene epoxidase
what is squalene epoxidase
key enzyme in sterol biosynthesis in fungi
what are 5 adverse effects of Terbinafine
- nausea/diarrhea
- hypersensitivity/rash
- liver enzyme abnormalities
- hematologic effects
- headache ( most common)
Terbinafine treats what disease
onychomycosis
Terbinafine is not recommended for what patients
liver or renal dysfunction
-pregnant women
Terbinafine is just as effective as what other drug
itraconazole
name treatments for Oral Candidiasis (thrush)
Nystatin
clotrimazole troches
how is Nystatin administered
swished in mouth then swallowed
- no absorbed from GI
severe Histoplasmosis
AmB
moderate Histoplasmosis
Itr > Flu
mild Histoplasmosis
Itr> Flu
severe blastomycosis
AmB
moderate blastomycosis
Itr > Flu
mild blastomycosis
Itr> flu
severe Candidiasis
AmB
moderate Candidiasis
AmB or Flu or Cas
mild Candidiasis
Flu or Cas
Severe coccidioidomycosis ( meningeal, disseminated, pulmonary)
AmB/Flu
AmB> Flu
AmB >Flu
moderate coccidioidomycosis ( meningeal, disseminated, pulmonary)
Flu
Azole
Azole
Mild coccidioidomycosis ( meningeal, disseminated, pulmonary)
Flu
Azole
Azole
Severe Aspergillosis
AmB
moderate Aspergillosis
AmB > Itr
mild Aspergillosis
Itr > AmB
severe cryptococcal meningitis
AmB/5-FC
moderate cryptococcal meningitis
Flu or AmB
Mild cryptococcal meningitis
Flu
following amphotericin B therapy for deep-seated candidisasis?
Fluconazole
flucytosine
following amphotericin B therapy for cryptococcal meningitis
fluconazole
following amphotericin B therapy for disseminated coccidioidomycosis
Fluc,
Itr
following amphotericin B therapy for paracoccidioidomycosis
sufonamide
following amphotericin B therapy for blastomycosis
Itr
following amphotericin B therapy for Histoplasmosis
Itr
