Anti-Fungal Drugs - Fitzpatrick

Question 1

Amphotericin B falls under what class of drugs?

Answer 1

polyenes

Question 2

what is the MOA of Amphotericin B?

Answer 2

Penetrate cell membrane and bind to ergosterol to create pores thus disrupts membrane integritiy and increase osmotic fragility (allows nutrients and electrolytes to leak out and thus killing the cell. )

Question 3

What AE are associated iwith Amphotericin B

Answer 3

Onset at infusion: chills, fever, anemia, hypotension

Later onset: nephrotoxicity

Question 4

How does amphotericin B cause nephrotoxicity?

Answer 4

Direct damage to distal tubule membrane leading to Na, K, and Mg wasting and the drug induced hypokalmeia and hyponatremia leads to decreased GFR and arteriole constriction

Question 5

Commonly what other drugs are affected due to nephrotoxicity caused by amphotericin B?

Answer 5

Cyclosporine, sirolimus, tacrolimus as used in transplant pts

Foscarnet, pentamidine as used in HIV pts

Aminoglycosides, vancomycin as used in MRSA and other gram negatives

Question 6

what are the 1st generation Triazole drugs

Answer 6

Fluconazole and Itraconazole

Question 7

What are the 2nd generation Triazoles

Answer 7

Voriconazole and posaconazole

Question 8

Trizole and imidazole are azoles. what is the MOA of azoles?

Answer 8

Inhibits Lanosterol to ergosterol biosynthetic pathway. Thus creating a ergosterol deficit and disrupt sterol content of lipid bilayer. The specific enzyme blocked is 14-a-demethylase (cypP450)

Question 9

what are the indications for Fluconazole?

Answer 9

• Narrow spectrum drug used to treat 1. Candida albican (candidemia, local candidiasis); 2) Cryptococcus (meningitis, with AMP-B)

Question 10

what two triazoles have good CSF access?

Answer 10

Flu and voriconazole

Question 11

which Triazole has strong drug interactions due to CYP450 inhibition

Answer 11

Itraconazole

Question 12

which Triazole is mainly cleared by renal and thus effective against renal infections

Answer 12

Fluconazole

Question 13

Fluconazole is usually finrst line for candida, but if it does not work, whats the next drug of choice?

Answer 13

Voriconazole

Question 14

what drug is clearedly renal mostly and thus is used for candiduria

Answer 14

Fluconazole (renal excretiona nd high bioavailability)

Question 15

Which azole is used for aspergillus?

Answer 15

Voriconazole. If that doent work then try Itraconazole as 2nd line

Question 16

HIV pt presents with cyryptococus infection, what is the drug of choice?

Answer 16

Fluconazole

Question 17

Mechanism of resistance to azoles

Answer 17

• Mutation or overexpression of lanosterol 14-a-demethylase
• efflux
• changes in sterol and/or phospholipid composition

Question 18

what is the drug of choice for Histoplasmosis, cocidioides, blastomycoses?

Answer 18

Itraconazole

Question 19

Caspifungin is an Echinocandins. what is the MOA of Echinocandins?

Answer 19

• Inhibit fungal Cell wall synthesis by blocking b(1,3) glucan synthase thus depleting b(1,3 glucan) and creating osmotic fragility

Question 20

Is caspifungin given IV or PO?

Answer 20

IV. No PO meds available

Question 21

Pertinent PK of caspofungin

Answer 21

• well tolerated
• Hepatic metabolism
• Few drug interactions

Question 22

Indication for Caspofungin

Answer 22

• Opportunistic infections (serious): invasive candidiasis, candidemia, invasive aspergillosis
• Esp useful if refractory to other therapies. Active against most candida and aspergillus spp.

Question 23

An AIDS pts with oropharyngeal candidiasis failed on fluconazole, Amphotericin B, and itraconazole. What is the next choice of drug?

Answer 23

Caspofungin

Question 24

Will caspofungin work for Histoplasmosis, coccidiodomycosis or fusarium ssp?

Answer 24

NO

Question 25

Pt presents with histoplasmosis who was treated with anti-TNFa therapy (9-infliximab, 1-etanercept) and did not recover. what else can be given?

Answer 25

Itracanazole

Question 26

what is the drug of choice for invasive aspergillosis?

Answer 26

Voriconazole

Question 27

what is the 3rd line therapy of Triazole that is given PO and requires gastric acid.

Answer 27

Ketoconazole

Question 28

Which triazole is known to inhibit human adrenal and gonadal steroid synthesis causing gynecomastia and decreased libido

Answer 28

Ketoconazole.

Question 29

A GERD pt who routinely takes an PPI develops a fungal infection and is given an oral antifungal drug. but symptoms did not improve. what drug was he most likely given?

Answer 29

Ketoconazole, an oral triazole. It requires gastric acid (low pH) and becuase this pt was taking an PPI, the drug did not work. Similar to Itraconazole, it also requires gastric acidity to dissolve.

Question 30

What AE are associated with Triazoles?

Answer 30

• terotogenic thus avoid in pregnancy
• Liver damage
• Voricoanzole disturbs vision

Question 31

What is the drug of choice for mucormycosis?

Answer 31

Amphotericin B

Question 32

What is the drug of choice for cryptococcal meningitis?

Answer 32

Amphotericin B, given with 5-FC (5-fluorocytosine anti metabolite).

Question 33

What is the role of 5-FC in treating cryptococcal meningitis?

Answer 33

It uses cytosine deaminase to ultimately inhibit DNA synthesis by blockign thymidyate synthase and also inhibits protein synthesis.

Question 34

What is the mechanism of resistance to 5-FC

Answer 34

• mutated cytosine permease

- mutated cytosine deaminase