[MEDICINAL CHEMISTRY] Antifungal Drugs

a. Antifungal drugs

MOA: Inhibition of ergosterol synthesis or injury to cell membrane.

a. Antifungal drugs

b. Antibacterial drugs

• Griseofulvin

• Nystatin

• Topical Azoles

• Terbinafine

• Naftifine

• Whitfield’s Ointment

• Selenium sulfide

Antifungals for Superficial mycoses include [6]

• Ketoconazole

• Fluconazole

• Itraconazole

Antifungals for Less Serious Systemic Mycoses include [3]

• Amphotericin B

• Itraconazole

• Caspofungin

• Voriconazole

• Flucytosine

Antifungals for Serious Systemic Mycoses include [5]

a. Propionic acid

Present in perspiration at low concentration (0.1%)

a. Propionic acid

b. Undecylenic acid

c. Sodium caprylate

b. 0.1%

Propionic acid is present in perspiration at _______ % concentration?

a. 0.01%

b. 0.1%

c. 1%

d. 5%

b. Perspiration

Propionic acid is naturally found in:

a. Coconut oil
b. Perspiration
c. Castor beans
d. Palm oil

b. Undecylenic acid

From destructive distillation of castor beans (Ricinus communis)

a. Propionic acid

b. Undecylenic acid

c. Sodium caprylate

c. Castor beans (Ricinus communis)

Undecylenic acid is obtained from destructive distillation of ______

a. Coconut oil

b. Palm oil

c. Castor beans (Ricinus communis)

d. Corn oil

a. Ricinus communis

Undecylenic acid is derived from Castor bean with a scientific name known as________

a. Ricinus communis

b. Cocos nucifera

c. Elaeis guineensis

d. Zea mays

c. Sodium caprylate

From caprylic acid (in coconut and palm oil)

a. Propionic acid

b. Undecylenic acid

c. Sodium caprylate

c. Coconut and palm oil

Sodium caprylate is derived from caprylic acid found in:

a. Castor beans

b. Perspiration

c. Coconut and palm oil

d. Corn oil

b. Polyenes

MOA: Pore formation; binds to ergosterol → disrupts membrane function → cell death.

a. Azoles

b. Polyenes

c. Allylamines

d. Echinocandins

a. Polyenes

Antifungal class that binds to ergosterol to disrupt membrane function.

a. Polyenes

b. Griseofulvin

c. Flucytosine

d. Terbinafine

c. Polyenes

Pore formation is the mechanism of action of which antifungal class?

a. Azoles

b. Allylamines

c. Polyenes

d. Echinocandins

c. Amphotericin B

Gold standard antifungal for systemic mycoses.

a. Nystatin

b. Natamycin

c. Amphotericin B

d. Ketoconazole

b. Streptomyces nodosus

Amphotericin B is derived from which source?

a. Streptomyces noursei

b. Streptomyces nodosus

c. Streptomyces natalensis

d. Streptomyces griseus

c. Amphotericin B

Drug of choice (DOC) for systemic mycoses.

a. Nystatin

b. Fluconazole

c. Amphotericin B

d. Ketoconazole

c. Amphotericin B

Antifungal drug that causes reversible azotemia as a side effect , requiring monitoring of BUN and CrCl.

a. Nystatin
b. Griseofulvin
c. Amphotericin B
d. Natamycin

a. Reversible azotemia

Amphotericin B is an antifungal drug that causes _______ as a side effect, requiring monitoring of BUN and CrCl.

a. Reversible azotemia
b. Hepatotoxicity
c. Ototoxicity
d. Peripheral neuropathy

c. Streptomyces natalensis

Natamycin is derived from which source?

a. Streptomyces noursei

b. Streptomyces nodosus

c. Streptomyces natalensis

d. Streptomyces griseus

b. Azoles

MOA: Inhibition of ergosterol synthesis through interaction with lanosterol 14α-demethylase to block demethylation of lanosterol to ergosterol in membranes.

a. Polyenes

b. Azoles

c. Allylamines

d. Echinocandins

b. Azoles

_______ contain an imidazole or 1,2,4-triazole ring bonded by a N-C linkage

a. Polyenes

b. Azoles

c. Allylamines

d. Echinocandins

a. Imidazole or 1,2,4-triazole ring

Azoles contain an ______ or ______ bonded by an N-C linkage.

a. Imidazole or 1,2,4-triazole ring
b. Pyridine or pyrimidine ring
c. Pyrrole or furan ring
d. Benzene or naphthalene ring

b. N-C linkage

Azoles contain an imidazole or 1,2,4-triazole ring bonded by a _______

a. C-C linkage
b. N-C linkage
c. S-C linkage
d. O-C linkage

• Voriconazole

• Itraconazole

• Posaconazole

• Fluconazole

📌Mnemonic: “VIPF”

[Groups of Azoles Based on Structure]

Triazoles [4]

• Ketoconazole

• Miconazole

• Clotrimazole

• Isoconazole

• Tioconazole

📌Mnemonic: “KMCIT”

[Groups of Azoles Based on Structure]

Imidazoles [5]

a. Triazole

[Groups of Azoles Based on Structure]

Voriconazole

a. Triazole

b. Imidazole

a. Triazole

[Groups of Azoles Based on Structure]

Itraconazole

a. Triazole

b. Imidazole

a. Triazole

[Groups of Azoles Based on Structure]

Posaconazole

a. Triazole

b. Imidazole

a. Triazole

[Groups of Azoles Based on Structure]

Fluconazole

a. Triazole

b. Imidazole

b. Imidazole

[Groups of Azoles Based on Structure]

Ketoconazole

a. Triazole

b. Imidazole

b. Imidazole

[Groups of Azoles Based on Structure]

Miconazole

a. Triazole

b. Imidazole

b. Imidazole

[Groups of Azoles Based on Structure]

Clotrimazole

a. Triazole

b. Imidazole

b. Imidazole

[Groups of Azoles Based on Structure]

Isoconazole

a. Triazole

b. Imidazole

b. Imidazole

[Groups of Azoles Based on Structure]

Tioconazole
a. Triazole

b. Imidazole

c. Ketoconazole

Nizoral®.

a. Fluconazole

b. Itraconazole

c. Ketoconazole

d. Miconazole

b. Ketoconazole

Topical azole that inhibits androgen and adrenal steroid synthesis

a. Clotrimazole

b. Ketoconazole

c. Terbinafine

d. Griseofulvin

a. Gynecomastia

Ketoconazole side effect is ______

a. Gynecomastia
b. Hepatotoxicity
c. Nephrotoxicity
d. Ototoxicity

c. Acidic pH

Ketoconazole needs ______ pH to be absorbed?

a. Alkaline pH

b. Neutral pH

c. Acidic pH

d. Any pH

b. Androgen and adrenal steroid synthesis

Side effect of Ketoconazole is gynecomastia due to inhibition of ______

a. Ergosterol synthesis

b. Androgen and adrenal steroid synthesis

c. Cell wall synthesis

d. Protein synthesis

c. Itraconazole

Sporanox®.

a. Fluconazole

b. Ketoconazole

c. Itraconazole

d. Voriconazole

b. Itraconazole

Alternative to Ketoconazole that is not hepatotoxic and causes no adrenal suppression.

a. Miconazole

b. Itraconazole

c. Clotrimazole

d. Terbinafine

c. Acidic pH

Itraconazole needs _______ pH condition to increase absorption?

a. Alkaline pH

b. Neutral pH

c. Acidic pH

d. Any pH

c. Fluconazole

Diflucan®

a. Itraconazole

b. Ketoconazole

c. Fluconazole

d. Voriconazole

a. PO and IV

Fluconazole is available in ______ and ______ formulations.

a. PO and IV
b. Topical and IM
c. IV and topical
d. IM and PO

a. Lipophilic

Fluconazole is _____

a. Lipophilic
b. Hydrophilic
c. Amphiphilic
d. Lipophobic

b. Fluconazole

Lipophilic azole that crosses the blood-brain barrier (BBB).

a. Ketoconazole

b. Fluconazole

c. Miconazole

d. Clotrimazole

d. Fluconazole

Drug of choice (DOC) and prophylaxis for Cryptococcal meningitis.

a. Itraconazole

b. Amphotericin B

c. Ketoconazole

d. Fluconazole

c. Posaconazole

Broad-acting synthetic antifungal structurally similar to Itraconazole

a. Voriconazole
b. Fluconazole
c. Posaconazole
d. Ketoconazole

• GI disturbances

• Nausea and vomiting

• Diarrhea

• Headache

Posaconazole side effects include:

a. Visual and auditory hallucinations, hepatotoxicity

b. Gynecomastia, adrenal suppression

c. GI disturbances, nausea and vomiting, diarrhea, and headache

d. Nephrotoxicity, ototoxicity

a. Voriconazole

Broad-acting synthetic antifungal structurally similar to Fluconazole

a. Voriconazole

b. Fluconazole

c. Posaconazole

d. Ketoconazole

b. Posaconazole

Drug of choice (DOC) for invasive aspergillosis.

a. Fluconazole

b. Posaconazole

c. Amphotericin B

d. Voriconazole

• Visual and auditory hallucinations

• Hepatotoxicity

Voriconazole side effects include:

a. Visual and auditory hallucinations and hepatotoxicity
b. Gynecomastia and adrenal suppression
c. GI disturbances, nausea, vomiting, diarrhea, and headache
d. Nephrotoxicity and ototoxicity

c. Echinocandins

MOA: Inhibits synthesis of β(1,3)-D-glucan, thus inhibiting fungal cell wall synthesis.

a. Polyenes

b. Azoles

c. Echinocandins

d. Allylamines

c. Echinocandins

Potent against Aspergillus and most Candida species.

a. Griseofulvin
b. Nystatin
c. Echinocandins
d. Terbinafine

a. Aspergillus and Candida

Echinocandins are potent against ______ and most ______ species.

a. Aspergillus and Candida
b. Cryptococcus and Histoplasma
c. Blastomyces and Coccidioides
d. Trichophyton and Microsporum

b. Flushing (Rapid infusion)

Side effect of Echinocandins is ______

a. Hepatotoxicity
b. Flushing
c. Nephrotoxicity
d. Ototoxicity

b. Rapid infusion

Side effect of Echinocandins is flushing, especially with _______

a. Slow infusion

b. Rapid infusion

c. Oral administration

d. Topical application

• Anidulafungin

• Caspofungin

• Micafungin

Echinocandins include:

a. Anidulafungin, Caspofungin, and Micafungin
b. Fluconazole, Itraconazole, and Ketoconazole
c. Nystatin, Amphotericin B, and Natamycin
d. Griseofulvin, Terbinafine, and Naftifine

c. Flucytosine

MOA: Inhibits thymidylate synthase by replacing uracil in nucleic acid synthesis (both DNA and RNA).

a. Griseofulvin
b. Terbinafine
c. Flucytosine
d. Nystatin

c. Flucytosine

_______ is a nucleoside antifungal (pyrimidine antimetabolite).

a. Griseofulvin
b. Terbinafine
c. Flucytosine

d. Nystatin

c. Flucytosine

Prodrug of 5-Fluorouracil (5-FU)

a. Griseofulvin
b. Terbinafine
c. Flucytosine

d. Nystatin

a. 5-Fluorouracil (5-FU)

Flucytosine is a prodrug of:

a. 5-Fluorouracil (5-FU)
b. 5-Fluorocytosine
c. Fluorouracil
d. Fluorocytosine

c. Flucytosine

_______ is used in combination with Amphotericin B in Cryptococcal meningitis

a. Griseofulvin
b. Terbinafine
c. Flucytosine

d. Nystatin

c. Amphotericin B

Flucytosine is used in combination with ______ for Cryptococcal meningitis?

a. Fluconazole

b. Ketoconazole

c. Amphotericin B

d. Itraconazole

c. Penicillium griseofulvum

Griseofulvin is derived from which source?

a. Penicillium notatum

b. Penicillium chrysogenum

c. Penicillium griseofulvum

d. Penicillium marneffei

b. Griseofulvin

MOA: Interacts with microtubules within the fungus and inhibits mitosis (metaphase)

a. Flucytosine
b. Griseofulvin
c. Terbinafine
d. Nystatin

b. Griseofulvin

Mitotic spindle / microtubule poison

a. Flucytosine
b. Griseofulvin
c. Terbinafine
d. Nystatin.

c. Griseofulvin

Drug of choice (DOC) for refractory ringworm infections of the body, nails, hair, and feet.

a. Ketoconazole

b. Terbinafine

c. Griseofulvin

d. Itraconazole

c. Griseofulvin

Long duration of treatment (3-6 mos)
a. Ketoconazole

b. Terbinafine

c. Griseofulvin

d. Itraconazole

c. 3-6 months

Griseofulvin requires a long duration of treatment of:

a. 1-2 weeks

b. 2-4 weeks

c. 3-6 months

d. 6-12 months

a. Micronized and taken with fatty food

Griseofulvin has poor bioavailability. To increase absorption, it should be:

a. Micronized and taken with fatty food

b. Taken on an empty stomach

c. Taken with antacids

d. Dissolved in water before intake