(7) Antimicrobials: Antifungals (5.1-5.3)

Question 1

MOA: Amphotericin B

Answer 1

Binds ergosterol

⇒ Pores in membrane

⇒ Osmotic lysis

(Same MOA for Nystatin)

Question 2

What serves the role of cholesterol in a fungus’ cell membrane?

Answer 2

Ergosterol

Question 3

ROA: Amphotericin B

Answer 3

(1) IV
(2) Intrathecal
* (Intrathecal only for severe fungal CNS infections)*

Question 4

Name 2 methods used to reduce the toxicity of Amphotericin B

Answer 4

(1) Liposomal formulation
(2) Volume expansion with saline prior to administration
* (Liposomal formulation ⇒ Reduced affinity for human cholesterol)*

Question 5

Why is Amphotericin B so toxic to humans?

Answer 5

AmphoB is poorly selective for ergosterol over cholesterol

(∴ It significantly damages human cell membranes)

Question 6

Adverse Effects - Unrelated to kidneys (4) : Amphotericin B

Answer 6

(1) Infusion reaction ⇒ Hypotension
(2) “Shake and bake” chills
(3) Seizures
(4) Thrombophlebitis
* (Note: Seizures usually due to intrathecal administration)*

Question 7

Under what scenario does Amphotericin B most commonly cause seizures and CNS side effects?

Answer 7

Intrathecal administration

Question 8

Adverse Effects - Related to kidney (4) : Amphotericin B

Answer 8

(1) Type I renal tubular acidosis
(2) ⇒ Hypokalemia
(3) & ⇒ Mg2+ wasting
(4) ↓ EPO ⇒ Anemia
* (Type I RTA ⇒ More (-) luminal voltage ⇒ ↓ Driving force for Mg2+ reabsorption || ↑ Driving force for K+ secretion)*

Question 9

MOA: Flucytosine

Answer 9

Incorporates into DNA/RNA ⇒ Halts DNA and protein synthesis

(Not completely specific for fungal DNA ∴ ⇒ bone marrow suppression as a side effect)

Question 10

What is the active form of Flucytosine?

Answer 10

5-Fluorouracil

(Activated by cytosine deaminase)

Question 11

What combo regimen is used to treat Cryptococcus?

Answer 11

(1) Flucytosine
(2) Amphotericin

Question 12

What drug has the exact same MOA as Amphotericin B?

Answer 12

Nystatin

Question 13

Name 3 topical agents used for vaginal/mucocutaneous candidiasis?

Answer 13

(1) Nystatin
(2) Clotrimazole
(3) Miconazole

Question 14

What is the topical treatment for oropharyngeal candidiasis?

Answer 14

MOUTH RINSE of Nystatin

Question 15

MOA: Azoles

Answer 15

Inhibits conversion of Lanosterol → Ergosterol

(Via inhibition of 14α-demethylase)

Question 16

What effect do azoles have on the CYP450 system?

Answer 16

Inhibit the CYP450 system

Question 17

Which azole is the strongest inhibitor of the CYP450 system?

Answer 17

Voriconazole

(Strong enough to throw house onto car)

Question 18

Adverse Effects (2) : Voriconazole

Answer 18

(1) Blurry vision with flashes of light
(2) Changes in color vision

Question 19

Name 2 antibiotics which may cause changes in color vision

Answer 19

(1) Voriconazole
(2) Ethambutol
* (Not an antibiotic, but Digoxin also causes this side effect)*

Question 20

Name 2 first-line treatments for invasive aspergillosis

Answer 20

(1) Echinocandins
(2) Voriconazole
* (Amphotericin B is used for angioinvasive aspergillosis)*

Question 21

Name 4 systemic antifungals which can be used to treat esophageal candidiasis

Answer 21

(1) Voraconazole
(2) Fluconazole
(3) Amphotericin B
(4) Capsofungin

Question 22

Which systemic antifungal is used to treat mucocutaneous candidiasis?

Answer 22

Fluconazole

(Whereas Nystatin is the TOPICAL antifungal which is used)

Question 23

What is the azole of choice for the treatment of Cryptococcal meningitis?

Answer 23

Fluconazole

(Combined with Flucytosine)

Question 24

Which azole has a particularly high level of CNS penetration?

Answer 24

Fluconazole

Question 25

Which azole is used to treat infections by dimorphic fungi?

Answer 25

Itraconazole

(“ITTTraconazole for fungi with two ITTTerations”)

Question 26

Which azole is used to treat onychomycosis and dermatophytosis?

Answer 26

Itraconazole

Question 27

Name 2 azoles used to treat tinea infections

Answer 27

(1) Clotrimazole
(2) Miconazole

Question 28

Other than Itraconazole, which azole can be used to treat dermatophytosis?

Answer 28

Ketoconazole

(However, it’s not used due to extensive side effects)

Question 29

What anabolic mammalian enzyme does Ketoconazole strongly inhibit?

Answer 29

Desmolase

(Thus inhibiting the conversion of Cholesterol → Pregnenolone and ∴ synthesis of androgens, aldosterone, and cortisol)

Question 30

Name a (1) diuretic and (2) antimicrobial which can cause gynecomastia

Answer 30

(1) Diuretic: Spironolactone
(2) Antimicrobial: Ketoconazole

Question 31

MOA: Griseofulvin

Answer 31

Binds microtubules ⇒ Halts mitosis

Question 32

Name an antifungal which activates the CYP450 system

Answer 32

Griseofulvin

(Note: Griseofulvin is also associated with a disulfiram-like reaction similar to Metronidazole)

Question 33

Treatment (2) : Tinea capitis

Answer 33

(1) Griseofulvin
(2) Terbinafine
* (Note: Griseofulvin is fungistatic whereas Terbinafine is fungicidal**)*

Question 34

Treatment (2) : Onychomycosis

Answer 34

(1) Griseofulvin
(2) Terbinafine
* (∵ it accumulates in keratin)*

Question 35

MOA: Terbinafine

Answer 35

Inhibits squalene epoxidase

Question 36

What type of infections is Griseofulvin used to treat?

Answer 36

Dermatophytic

Question 37

Other than tinea capitis in children, what is Terbinafine used to treat?

Answer 37

Dermatophytosis

Question 38

Adverse Effects (2) : Terbinafine

Answer 38

(1) GI distress
(2) Hepatotoxicity

Question 39

MOA: Echinocandins

Answer 39

Inhibit synthesis of β-1,3-glucan

(At the fungal cell wall, NOT cell membrane)

Question 40

Where in the fungal cell are echinocandins active?

Answer 40

Cell wall

Question 41

ROA: Echinocandins

Answer 41

IV