Antifungal Agents

Question 1

Interactions between this drug and cell membrane compnents can result in the formation of pores lined by hydrophilic group present in the drug molecule

Answer 1

Nystatin

• Polyene antifungal drugs amphotericin B and nystatin are ampiphatic moleciles

Question 2

A 14 year old patient has experience severe headache and double vision for a month. His temperature is 38.6. His CSF culture was positive for cryptococcal antigen. Which of the following drugs wiuld be apropriate (not intrathecally)

Answer 2

Fluconazole

• Amphotericin B- intrathecal

Question 3

If amphoteric B is administerd, the patient shpuld bne premedicated with ________

Answer 3

Diphenhydramine, Ibuprofen, Predsinone

Question 4

Prophylaxis for candida infection in the bloodstream

Answer 4

None

Question 5

Prophylactic against other fungi may be effective in some instances, including suppression of cyptococcal meningitis in AIDS patients with __________

Answer 5

Fluconazole

Question 6

Initial treatmentfor C. immitis pulmonary symptoms

Answer 6

none

Question 7

If persistent pulmonary c. immitis or disseminated disease.

Answer 7

Itraconazole

Question 8

Serious cardiac effects have occured when this drug was taken by patients using antihistamines astemizole or terfenadine

Answer 8

Ketoconazole

Question 9

Common azoles for esophageal candidiasis

Answer 9

“swish and swallow” formualtion of clotrimozaole and nystatin

Question 10

Liposomal formulations of amphoteric B

Answer 10

• They decrease the nephrotoxicity of amphotericin B
• do not have wider antifungal spectrum

Question 11

___________can cause renal tubular acidosis with magnesium and potassium wasting

Answer 11

Amphotericin B

Question 12

Selective toxicity of Flucytosine

Answer 12

Mammalian cells have low levels of permease and deaminase

Question 13

________ is responsible for the elimination of ketoconazole, itraconazole, posaconazole, voriconazole

Answer 13

Liver metabolism

Question 14

Broadest spectum triazole

Answer 14

Posaconazole

• only azole with activity against Rhizopus

Question 15

Elimination of griseofulvin

Answer 15

Biliary excretion

Question 16

Amphotericin B

Answer 16

Binds to ergosterol in fungal cell membranes, forming leaky pores

Used in Candidemia and infections caused by aspergillus, blastomyces, cryptococcus, histoplasma, mucor

Multiple forms, IV for systemic infections (liposomal forms less nephrotoxic) Topical or ocular/bladder inferctions

SE: nephrotoxicity is dose limiting, additive with other nephrotoxic drugs. Infusio reactions (chills, fever, muscle, spasms, hypotension)

Question 17

Azoles

Answer 17

Inhibit fungal P450 dependent enzymes blcoking ergosterol synthersis. Resitance can occur with long term use

Aspergillosis (voriconazole). Blastomycosis (Itraconazole,fluconazole). Mucormycosis (posaconzaole). Alternantive drugs in candidemia and infections caused by aspergillus, blastomyces, crytpococcus and histoplasma

Various topical and oral forms for dermatophytoses Oral, and parenterl for,s for mycoses (fluconazole, itraconazole, posaconazole, voriconazole). Most azoles undergo hepatic metabolism. FLuconazole is eliminated unchanged in urine. FLuconaole has excellent CNS pentration

SE; Ketoconazole is rarely used in systemic fungal infections owing to its inhibition of hepatic and adrenal P450s. Other Azoles are less toxic, but may cause GI upsets and rash. Voriconazole causes visual disturbances and class D risk in pregnancy

Question 18

Echinocandins

(Caspofungin, micafungin, anidulafungin)

Answer 18

Inhibit B-glucan synthase decrease fungal cell wall synthesis

treatment of candidemia. Caspofungin is also used as salvage therapy in aspergillosis

IV forms. Micafungin increases levels of nifedipine and cyclosporin. Anidulafungin: no drug-drug interactions

SE: gastrointestinal distress, flushing from histamine release

Question 19

Flucytosine

Answer 19

Inhibits DNA and RNA polymerases

Synergistic with amphotericin B in candidemia and cryptococcal infections

Oral; enters cerebrosponal fluid. Renal elimination

SE: bone marrow suppresion

Question 20

Terbinafine, Naftifine

Answer 20

Inhibits epoxidation of squalene. Squalene accumulation is toxic to fungi

Used in mucocutaneous fungal infections. Accumualtes in keratin

Oral. long duration of action (weeks)

SE: GI upsets, headache