Pharm Antifungal Agents

Front 1

What is the MOA of amphotericin B? What is it used for?

Back 1

Binds to ergosterol and causes formation of artificial pores.

Widest antifungal spectrum of any agent, and DOC, or codrug of choice for: Aspergillus, Blastomyces, Candida albicans, Crptococcus, histoplasma, and Mucor. Intrathecally for fungal meningitis; does NOT cross the BBB>

Front 2

What are the SE of amphotericin B?

Back 2

Dose-limiting nephrotoxicity; infusion reactions (chills, fever, muscle spasms, hypotension), IV phlebitis ("amphoterrible").

Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity.

Note: in the hospital, BUN and creatinine levels are drawn every day to assess kidney function.

Front 3

What is the MOA of flucyosine?

Back 3

Inhibits DNA synthesis by conversion to 5-fluorouracil.

Within fungal cell, it is converted into nucleotide analogues (5-FdUMP and 5-UTP), which acts to inhibit thymidylate synthetase that inhibits fungal DNA and RNA synthesis.

Front 4

What is flucytosine used for? How is it used?

Back 4

Used for Cryptococcus neoformans and candidal infections. Very narrow scope.

Rarely used alone. It is used with amphotericin B--amphotericin B punches holes into the fungus while flucytosine inhibits DNA/RNA synthesis.

Front 5

What are the SE of flucytosine?

Back 5

Bone marrow suppression (leukopenia, thrombocytopenia).

Note: Antimetabolite drugs cause bone marrow suppression (leukopenia and thrombocytopenia), such as methotrexate, sulfa drugs, 5-fluorouracil. They can cause cause nausea, vomiting, and diarrhea.

Front 6

What are some azoles? MOA?

Back 6

Ketoconazole, fluconazole, itraconazole, clotrimazole, miconazole, and voriconazole.

Inhibit fungal P450 enzyme that blocks ergosterol synthesis; therefore, inhibiting formation of fungal cell mm.

Front 7

What is ketoconazole used for and its SE?

Back 7

Rarely used due to its toxic effects. But used for chronic muocutaneous candidiasis. Also, Blastomyces, Coccidioides, Histoplasma.

Since it inhibits CYP450: inhibition of adrenal and gonadal steroid synthesis (decreased libido, gynecomastia, menstrual irregularities, infertility)

Front 8

What is fluconazole used for? What is special about it?

Back 8

This drug is used often. It is the DOC for Candida albicans and Cryptococcus neoformans (because fluconazole can cross the blood-brain barrier).

Front 9

Compaction of eukaryotic DNA is achieved through its binding to ____ which are basic proteins
The five major types of these are:

Back 9

-histones

-H1
-H2A
-H2B
-H3
-H4

Front 10

What is voriconazole used for? SE?

Back 10

Wide spectrum, but mainly against Aspergillosis.

Can cause transient visual disturbances and is class D drug for pregnancy risk.

Front 11

What drug belongs to echinocandins? Its MOA?

Back 11

Caspofungin and micofungin.

It inhibits synthesis of beta(1,2)glycan, a component of fungal cell wall.

Front 12

What is caspofungin used for? SE?

Back 12

For Candida infections who fail to respond to amphotericin B, and "salvage" therapy in apergillosis.

SE: flushing from histamine release.

Front 13

What drugs are used for treatment of dermatophytoses?

Back 13

Griseofulvin, terbinafine, and several azole.

Front 14

What is the MOA of Griseofulvin? SE?

Back 14

Interferes with microtubule function in dermatophytes, in keratin-rich tissues (eg, skin, nails, hair) to inhibit mitosis and replication. This is a slow acting, static drug. Largely replaced by terbinafine.

Mental confusion, carcinogenic, confusion, headaches, increase CYP450 and warfarin metabolism.

Front 15

What is the MOA of terbinafine?

Back 15

Inhibits a fungal enzyme, squalene epoxidase.

This causes accumulation of toxic levels of squalene, which interferes with ergosterol synthesis. This is fungicidal.

Front 16

What is Terbinafine used for?

Back 16

Dermatophytoses (sepcially onychomycosis).

Front 17

What is nystatin used for and its MOA?

Back 17

It disrupts fungal membranes by binding to ergosterol. It is used topically to suppress oral and cutaneous (diaper rash or vaginal) Candida infections.

Note: too toxic for systemic use.

Front 18

Questions: Interactions between this drug and cell membane components can result in the formation of pores lined by hydrophilic groups present in the drug molecule.

Back 18

Nystatin and amphotericin.

Front 19

Questions: What is true about fluconazole?

Back 19

It has the least effect of all azoles on hepatic drug metabolism.

Voriconazole and itraconazole has activity against Aspergillus.

Fluconazole is the best absorbed orally and readily penetrates into CSF. It also has the least effect of all azoles on hepatic microsomal drug-metabolizing enzymes.

Front 20

Clotrimazole and miconazole are used for what?

Back 20

Topical fungal infections.

Front 21

A woman with leukemia undergoes chemotherapy with IV of antineoplastic drug. She developes a systemic infection from an opporutnistic pathogen. There was a white vaginal discharge. Empiric antibiotic therapy was started with gentamicin, nafcillin, and ticarcillin TV. THe PTs condition did not improve. Her throat was sore, and white plaques had appeared in her pharynx. Cultures did not have bacterial growth, but her blood and urine grew Candida albicans.

Back 21

*****

Front 22

***Question: At this point, the best course of action is to?

Back 22

Stop current antibiotics and start griseofulvin.

This PT did not have bacterial infection, instead had a fungal infection.

Front 23

****Questions: If amphotericin B is administered, the PT should be premedicated with?

Back 23

Diphenhydramine, ibuprofen, prednisone: any or all that is mentioned.

Infusion of amphotericin B include chills and fevers, muscle spasms, nausea, headache, and hypotension. Antipyretics, antihistamines, and glucocorticoids all can help.

Front 24

***Questions: The does-limiting toxicity of amphotericin B is?

Back 24

Renal tubular acidosis.

Note: Azotemia can be severe enough to warrant dialysis. Decrease in GFR is reversible, but irreversible damage can occur with acidosis with hypokalemia and hypomagnesemia.

Front 25

***Questions: Candida is a major cause of nosocmial bloodstream infection. The opportunistic fungal infection in this PT could have been prevented by administration of?
The PT should be treated with?

What is the DOC if the PT is suffering from persistent lung lesion or disseminated disease caused by Coccidioides immitis?

What drug is least likely to be effective in the treatment of esophageal candidiasis if it is used by the oral route?

Back 25

He should not be treated with any medications. Pulmonary symptoms of coccidioidomycosis are self-limiting.

Itraconazole or fluconazole.

Griseofulvin has no activity against C. albicans. "Swish and swallow" formulations of clotrimazole and nystatin are commonly used though. Most of the azoles are effective in esophageal candidiasis.

Front 26

Question: A PT living on the East Coast was transferred to California for 6 months for work. On his return, he had influenza-like symptoms with fever and cough. He has red, tender nodules on his shins. The physician suspects the symptoms are due to coccidioidomycosis.

The PT should be treated with?

What is the DOC if the PT is suffering from persistent lung lesion or disseminated disease caused by Coccidioides immitis?

What drug is least likely to be effective in the treatment of esophageal candidiasis if it is used by the oral route?

Back 26

He should not be treated with any medications. Pulmonary symptoms of coccidioidomycosis are self-limiting.

Itraconazole or fluconazole.

Griseofulvin has no activity against C. albicans. "Swish and swallow" formulations of clotrimazole and nystatin are commonly used though. Most of the azoles are effective in esophageal candidiasis.

Front 27

Question: What is true about flucytosine?

Back 27

It is bioactivated by fungal cytosine deaminase to the antimetabolite fluorouracil, which causes inhibition of thymidylate synthase. It can enter the CSF and can be used with amphotericin B in cryptococcal meningitis.

Front 28

Question: Serious cardiac effects have occurred when this drug was taken by PTs using the antihistamines astemizole or terfenadine

Back 28

Ketoconazole due to inhibit metaoblism of hepatic CYP450.

Front 29

Which drug is most appropriate for oral use in the treatment of vaginal candidiasis?

Back 29

Fluconazole and itraconazole.

Clotrimazole and nystatin is used topically for vaginal candidiasis.

Front 30

Regarding the clinal use of liposomal formulation of amphotericin B, which statement is accurate?

Back 30

They decrease nephrotoxicity of amphotericin B.

Front 31

Which drug used IV for disseminated and mucocutaneous candida infection is an inhibitor of the synthesis of fungal cell wall components?

Back 31

Caspofungin, and echinocandins.