ANTIFUNGAL DRUGS FOR SUBCUTANEOUS

Question 1

What is the drug of choice for the treatment of several life-threatening mycoses?

Answer 1

Amphotericin B

MOA:
Binds to ergosterol in the plasma membranes of fungal cells which creates pores that leak electrolytes resulting in cell death

Question 2

Targets of Amphotericin B

Answer 2

• Candida albicans
• Histoplasma capsulatum
• Cryptococcus neoformans
• Coccidioides immitis
• Blastomyces dermatidis
• Aspergillus
• Leishamniasis

Question 3

Pharmacokinetics of Amphotericin B

Answer 3

• Administered by slow IV
• Bound to plasma protein
• Can be found in CSF or synovial fluid

Question 4

What are the adverse effects of Amphotericin

Answer 4

a. Fever (occurs 1 to 3 hr after administration
b. Renal impairment
c. Hypotension
d. Thromboplebitis

Question 5

what is the antimetabolite antifungals?

Answer 5

Flucytosine (5-FC) - synthetic pyrimidine antimetabolites

MOA:
Enters the fungal cells and inhibit conversion of dUMP to dTMP, resulting in disruption of nucleic acid and protein synthesis

Question 6

what is the enzyme that is only found in fungus, which also serves important function in 5-FC

Answer 6

cytosine-specific permase

Question 7

Antifungal spectrum of Flucytosine

Answer 7

• Fungistatic
• 5-FC + itraconazole = treating chromoblastomycosis
• with amphotericin B = meningitis caused by C. neoformans and C. albicans

Question 8

Pharmacokinetics of Flucytosine

Answer 8

• Oral administration
• penetrates CSF well

Question 9

Adverse effect of Flucytosine

Answer 9

• neutropenia and bone marrow related depression
• hepatic dysfunction = elevation of serum transaminase
• Nausea, vomitting and dirarrhea
• Severe enterocolitis

Question 10

What are the two types of Azole antifungals?

Answer 10

imidazole - applied topicallty for cutaneous inf

Triazoles - prophylaxis of cutaneous and systemic mycoses

Question 11

MOA of Azole antifungal

Answer 11

inhibit 14-alpha demethylase (cytochrome P450), thus blocking demethylation of lanosterol to ergosterol, inhibiting fungal cell growth

Question 12

what are azoles drugs that are metabolized by CYP450-3A4 and isoenzyme?

Answer 12

itraconazole and variconazole

Question 13

what are the inducer and inhibitors drug of CYP450

Answer 13

inhibitors - ritonavir
inducers - rifampin and phenytoin

Question 14

what is the contraindication of azole antifungal

Answer 14

• teratogenic, thus should be avoided in pregnant unless potential benefit outweights the risk of fetus

Question 15

what is the first triazole antifungal agent?

Answer 15

Fluconazole

Question 16

Spectrum of Fluconazole

Answer 16

• aspergillosis or zygomycosis
• highly active against = C. neoformans, C. albicans and C. parapsopsilosis
• effective against most of the forms of mucocutaneous candidiasis

Question 17

Fluconazole is a drug of choice for?

Answer 17

Cryptococcus neoformans

Question 18

Pharmacokinetics of fluconazole

Answer 18

• single dose oral treatment for V. candidiasis
• ORal and IV dosage

Question 19

Adverse effect of fluconazole

Answer 19

• nausea
• vomting
• headache
• skin rashes

Question 20

Synthetic triazole that has abroad antifungal spectrum compared to fluconazole

Answer 20

Itraconazole

Question 21

Spectrum of itrazonazole

Answer 21

• Blastomycosis
• Sporotrichosis
• Paracoccidioidomycosis
• Histoplasmosis

Question 22

Pharmacokinetics of Itraconazole

Answer 22

available as
- Capsule
- tablet
- oral solution

Question 23

Adverse effects of itraconazole

Answer 23

• nausea
  -vomiting
• rashh
• hypokalemia
• hypertension
  -edema
• headache
• liver toxicity

Question 24

itraconadazole contraindication

Answer 24

• pt with heart failure or ventricular dysfunction

Question 25

synthetic triazole similar to itraconadazole

Answer 25

Posaconazole

Question 26

Spectrum of pocasonazole

Answer 26

• prophylaxis of invasive Candida and Aspergillus infection in immunocompromised pt.
• Scedosporium and Zygomycetes

Question 27

Pharmacokinetics of Posaconazole

Answer 27

-oral tablet
- IV formulation

Question 28

synthetic triazole related to fluconazole

Answer 28

Voriconazole

Question 29

spectrum of voriconazole

Answer 29

• replaced amphotericin B for aspergillosis
• scedosporium and
• Fusarium species

Question 30

adverse effect of variconazole

Answer 30

• visual
• auditory
• hepatotoxicity

Question 31

new extended-spectrum triazole

Answer 31

Isavuconazole

Question 32

spectrum of isavuconazole

Answer 32

• aspergillosis
• mucormycosis
• Isavuconazonium

Question 33

adverse effect of isavuconazole

Answer 33

-nausea
- vomiting
- diarrhea
- hypokalemia

Question 34

group of semisynthetic, cyclic lipopeptides with an N-linked acyl lipid side chain.

Answer 34

Echinocandins

Question 35

spectrum of Echinocandins

Answer 35

• Aspergillus
• Candida species

Question 36

MOA of EChinocandins

Answer 36

• inhibitys the synthesis of Beta(1,3)-D-glucan, leading to lysis and cell death

Question 37

is the only Echinocnadins that does not require a loading dose

Answer 37

Micafungin

Question 38

Adverse effect of Echinocandins

Answer 38

• FEver
• Rash
  -Nausea
• and phlebitis at the infusion site

Question 39

1st line option for patient with candidemia

Answer 39

Caspofungin

Question 40

drug for prophylaxis of invasive candidiasis. Also hematopoietic stem cell transplation

Answer 40

Micafungin and Anidulafungin