ANTIFUNGAL AGENTS

CLASSIFICATION OF ANTIFUNGAL DRUGS

CLASSIFICATION DRUGS
Amphotericin B
ANTIBIOTICS Griseofulvin
Nystatin
ANTIMETABOLITE Flucytosine
Imidazoles
-KMC & E
AZOLES Triazoles
-Itraconazole
-Fluconazole
Clotrimazole
Econazole
TOPICAL Nystatin
(SUPERFICIAL INFECTIONS) Miconazole
Tolnaftate
Amphotericin B
Ketoconazole
Miconazole
SYSTEMIC Itraconazole
Fluconazole
Flucytosine
ALLYLAMINE Terbinafine
Griseofulvin
ORAL Ketoconazole

DRUG PK MOA RESISTANCE USES ADVERSE EFFECTS

1. Electrolyte imbalance ass.
-poorly absorbed from GI 1. Histoplasma capsulatum w/fall in BP; pts manifest as
tract hypokalemia
-polyene antibiotic binds to sterol 2. Cryptococcus neoformans 2. IV admin may be ass.
-poor penetration into component of fungal cell w/fever, chills, pain, n/v (tx
AMPHOTERICIN B CNS membrane -due to decreased levels 3. Blastomyces dermatitides w/hydrocortisone)
(polyene disruption of permeability of of ergosterol and 3. Reversible nephrotoxicity
compound) -IV cell membrane by creating punch alteration in fungal cell 4. Aspergillus -azotemia
holes, allowing electrolytes to membrane -↑ plasma creatinine
-intrathecal infusions can leak out of cell  cell death 5. Candida albicans -renal tubular acidosis
be done for CNS 4. Neurological defects
infections 6. Topical Amph B for 5. Anemia due to suppression of
-Unchanged excretion mucocutaneous candidiasis erythrocyte production esp in
(lotion, cream, ointment) HIV pts taking AZT
6. Thrombophlebitis at IV site
-ABCD, ABLC, AmBisome

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 ANTIFUNGAL AGENTS
DRUG PK MOA RESISTANCE USES ADVERSE EFFECTS
1. Cryptococcus
-Susceptible organisms deaminate -Occurs due to loss of 2. Candida (esp UTI’s) 1. Bone marrow depression
-well absorbed from GI flucytosine to 5-fluorouracil and permeases which 3. Torulopsis glabrata that causing leukopenia and
is then incorporated into RNA transports drug into causes chromomycosis thromobytopenia
-reaches CSF causing functional disability and fungal cell
FLUCYTOSINE structural changes Predominantly used 2. N/V, diarrhea, severe
-p.o. antimycotic -can also occur due to w/amphotericin B enterocolitis
-(mammalian cells do not convert decreased activity of (Ampho B punches holes
flucytosine into 5-fluorouracil; uridine monophosphate allowing Flucytosine to (damage of DNA during rapid
they do not have permeases to deaminases which enter) division of cells such as bone
take up and have low levels of convert flucytosine into **This combo is DOC in marrow and GI epithelium
deaminase) 5-fluorouracil Meningitis caused by crypto could be a possible reason )
or Candida**
-p.o. 1. N/V, anorexia, dizziness,
-acidic environment 1. Non-meningeal rash
required for dissolution blastomycosis 2. Inhibits steroid synthesis by
of detoconazole inhibiting p450 decreasing
-simultaneous admin of 2. Coccidioides immitis androgen synthesis,
H2 blockers/antacids can gynecomastia, decreased libido
impair absorption 3. Paracoccidioidomycosis and azoospermia (high doses
KETOCONAZOLE -compete w/cyclosproine ass.w/transient fall in
for hepatic metabolism 4. Candida albicans testosterone and ACTH)
 increased levels  -Impairs biosynthesis of 3. Liver dysfunction ass. w/ an
nephrotoxicity ergosterol for cytoplasmic 5. pts who are not gravely ill increase in transaminases
-Warfarin effect membrane (inhibits sterol 14 α and immunologically 4. Teratogenic effect in
enhanced demethylase: microsomal cyto competent experimental animals;
-Rifampin enhances P450 dependent enzyme) syndactyly in rats
ketoconazole met 5. Cardiotoxicity if admin
w.terfenadine or astemizole
1. Esophageal candidiasis in 1. Rash, eosinophilia, SJS
pts w/AIDS 2. Thrombocytopenia in AIDS
-well absorbed from GI 2. Single dose in vaginal pts
candidiasis 3. Concurrent admin of
FLUCONAZOLE -enters CSF 3. Prevent relapses of fluconazole can increase plasma
cryptococcal meningitis in conc of phenytoin,
AIDS pts after initial tx solfonylureas, warfari and
w/Amphotericin cyclosporine
-available as cream 1. local erythema
ECONAZOLE 1. Candida and other 2. burning
dermatophytes 3. itching

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 ANTIFUNGAL AGENTS
DRUG PK MOA RESISTANCE USES ADVERSE EFFECTS
-Topical application/local use
-Tinea, otomycosis
CLOTRIMAZOLE -versicolor infections
-Cutaneous and vulvovaginal
candida
-dermatological cream,
spray, powder, lotion,
vaginal cream
MICONAZOLE -Tinea pedis
-Cruris
-Versicolor
-Vulvovaginal candidiases,
---Trichophyton
-structurally similar to
-too toxic for IV use Amphotericin B;
-polyene antibiotic binds to sterol
-more toxic on systemic component of fungal cell 1. Candidiasis of skin, vagina
NYSTATIN admin membrane and GI not dermatophytes
disruption of permeability of
-not absorbed from GI, cell membrane by creating punch
skin, vagina holes, allowing electrolytes to
leak out of cell  cell death
1. h/a disappears when therapy
discontinues
2. peripheral neuritis
-absorption increased 3. lethargy
w/fatty meal 4. mental confusion
5. fatigue, syncope
-barbituates decrease 1. Fungistatic effect against 6. blurred vision, vertigo
absorption of drug from -microsporum, 7. augmentation of OH effects
GRISEOFULVIN GI tract Disrupting mitotic spindles by -epidermophyton, 8. GI:
interacting w/polymerized tubules -trichophyton -n/v, diarrhea, flatulence
-drug distributed to -heartburn,
keratin and stratum -dry mouth, angular stomatitis
corneum 9. induce hepatic microsomal
enzymes; increase rate of met
of warfarin and reduce efficacy
of BC pills
10. Teratogenic, carcinogenic
TOLNAFTATE 1. Candida albicans
HALOPROGIN 2. Dermatophytes
UNDECYLENIC ACID

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 ANTIFUNGAL AGENTS
FUNGUS CONDITION CAUSED 1 LINE TREATMENT
ST
OTHER TREATMENT OPTIONS
Cutaneous and Vaginal thrush Topical Nystatin Ketoconazole
Imidazole derivative Fluconazole
CANDIDA Oral thrush Clotrimazole Ketoconazole
Nystatin
Deep-seated infection Amphotericin B + Flucytosine
Disseminated non-meningeal infection Amphotericin B Ketoconazole
COCCIDIOIDES IMMITIS Itraconazole
Meningeal infections Intrathecal Amphotericin B Intrathecal Miconazole
Chronic pulmonary disease Ketoconazole Amphotericin B
HISTOPLASMA CAPSULATUM Itraconazole
Disseminated infection Amphotericin B Ketoconazole
Superficial Ketoconazole Amphotericin B
BLASTOMYCOSIS DERMITITDES Deep-seated infections includuing Itraconazole
cutaneous, mucous, resp and CNS
infection
PARACOCCIDIOIDES BRASILIENSIS Superficial and deep-seated infections Ketoconazole Amphotericin B followed by sulfonamide
Itraconazole
MUCORMYCOSIS Superficial and deep-seated infections Amphotericin B
SPRORTHRIX SCHENCKII Cutaneous manifestations Itraconazole
Extracutaneous manifestations Amphotericin B
ASPERGILLUS Invasive type in IC pts Amphotericin B Itraconazole
CRYPTOCOCCUS NEOFORMANS Pulmonary lesions Amphotericin B
Meningitis Amphotericin B + Flucytosine

Questions:

Matching I (MOA)
1. Griseofulvin
2. Flucytosine
3. Fluconazole
4. Amph B / Nystatin
a. MOA involves disruption of microtubular association……………………………………………………………….griseofulvin
b. Drug converted to 5FU and inhibits thymidylate synthase; uses permeases and deaminases………………………...flucytosine
c. Inhibits cyt P450 mediated demethylation of lanosterol, leading to inhibition of sterol synthesis……………………fluconazole
d. Polyene binds to fungal steroid component and causes damage to integrity of cell membrane………………………Amph B/ Nystatin

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 ANTIFUNGAL AGENTS
Mathing II (AE)
5. Ketoconazole
6. Flucytosine
7. Amph B
8. Griseofulvin
a. Produces antiandrogenic effect and gynecomastea……………………………………………………………ketoconazole
b. Neutropenia, thrombocytopenia, depression of bone marrow could occur……………………………………Flucytosine
c. Electrolyte imbalance, n/v. fever with chills, nephrotoxicity………………………………………………….Amph B
d. Increase in rate of metabolism of warfarin and oral contraceptives……………………………………….. …Griseofulvin

9. Which of the following is the DOC in systemic infection of Cryptococcus neoformans?

a. Griseofulvin
b. Nystatin
c. Clotrimazole
d. Miconazole
e. Amphotericin B
f. Econazole

Amphotericin B

10. All of the following are true about Fluconazole except:

a. It has good distribution and enters the CSF
b. It’s used in AIDS to prevent relapse of Cryptococcus meningitis
c. Associated with Steven Johnson Syndrome
d. Concurrent administration of phenytoin, sulfonylureas, warfarin, cyclosporine is associated w/and increase in plasma concentration
e. Associated with high incidence of gynecomastea and loss of libido

Answer: E; it is NOT ass. w/gynecomastea or loss of libido