Ellen - Pharmacology 3: Anti-Fungals

Front 1

What part of the fungi's membrane is targeted in systemic antifungal therapy?

Back 1

The ergosterols they use.

Front 2

Name the 8 opportunistic pathogens involved in systemic fungal infections.

Back 2

Candida albicans
Cryptococcus neoformans
Pneumocystis jiroveci (carinii)
Aspergillus
Mucor
Blastomyces dermatitidis
Paracoccidiodes brasiliensis
Histoplasma capsulatum

Front 3

What is the most common fungal pathogen involved in systemic infections?

Back 3

Candida albicans

Front 4

How common are systemic fungi infections?

Back 4

They're very rare but if they do occur, they're often very serious

Front 5

Name the 4 main fungis involved in superficial infections.

Back 5

Dermatophytes: Epidermophyton
Trichophyton
Microsporum

Candida albicans

Front 6

Name the 5 drugs used in systemic fungal infections.

Back 6

Polyene Antibiotics
Imidazole and Triazole Drugs
Flucytosine
Pentamidine

Front 7

Name the 4 drugs used in superficial fungal infections.

Back 7

Polyenes, Azoles and
Griseofulvin
Naftifine

Front 8

Name the 3 polyene antibiotics.

Back 8

Amphotericin B
Candicidin
Nystatin

Front 9

What is the general chemical structure of polyene antibiotics?

Back 9

large lipophilic, water insoluble molecules

Front 10

What is the mechanism of action of polyene antibiotics?

Back 10

They bind to ergosterol in the fungi membrane and increase the permeability to ions and metabolites

Front 11

What is the selectivity of Polyene antibiotics?

Back 11

toxic to fungi, protozoa and some algae. Selectivity is poor because human cell membranes also contain sterols (cholesterol) = drugs can be quite toxic.

Front 12

What is the clinical use of Amphotericin B?

Back 12

systemic fungal infections

Front 13

What is the clinical use of Nystatin?

Back 13

topical treatment of skin, oral and intestinal Candida infections

Front 14

What is the clinical use of Candicidin?

Back 14

topical treatment of vaginal candidiasis

Front 15

What are the adverse reactions of systemic use of Polyene antibiotics?

Back 15

Fever*, gastrointestinal distress, cardiotoxicity, hemolytic anemia, leukopenia, hepatotoxicity, nephrotoxicity*
* = most common

Front 16

What's one concern with delivering Amphotericin B IV?

Back 16

Can cause an initial shock-like response due to histamine release - test pts first or give antihistamines/steroids to avoid this reaction.

Front 17

Name the 4 Azole antifungal drugs.

Back 17

Imidazole
Triazole
Itraconazole
Ketoconazole

Front 18

What's the elimination like for Polyene antibiotics?

Back 18

Renal but very slow due to plasma membrane binding.

Front 19

What is the mechanism of action of azoles?

Back 19

increase permeability of fungal cell membranes by inhibiting ergosterol synthesis via inhibition of a microsomal cytochrome P450 enzyme system, sterol 14alpha-demethylase

Front 20

Route and half-life of Ketoconazole?

Back 20

Orally effective, long half-life (12 hr)

Front 21

Clinical use of Ketoconazole?

Back 21

Second line agent due to toxicities (after Amphoteracin B)
Systemic and mucocutaneous infections.

Front 22

What are the adverse reactions of Ketoconazole?

Back 22

Mild: GI distress and pruritus
Serious: Hepatic toxicity - drug must be stopped if hepatitis occurs. Inhibition of steroid synthesis – Cytochrome P450

Front 23

What are the clinical uses of Miconazole?

Back 23

topical treatment of dermatophyte infections and treatment of vaginal candidiasis

Front 24

What are the clinical uses of Clotrimazole?

Back 24

topical treatment of cutaneous and vaginal infections

Front 25

What are the clinical uses of Itraconazole?

Back 25

wider spectrum of activity than ketoconazole and fewer adverse effects. Drug of choice for several systemic infections (mycoses)

Front 26

What are the clinical uses of Fluconazole?

Back 26

Cryptococcus (HIV+), Candida
Best therapeutic index of all azole compounds

Front 27

What other condition has been treated by ketoconazole? Why?

Back 27

Because it decreases cortisol levels ketoconazole has been used to treat Cushings disease

Front 28

Clincial use of Econazole?

Back 28

Topical

Front 29

What is the active form of flucytosine?

Back 29

Transported into sensitive cells and then converted to 5 flurouracil by fungal cytosine deaminase

Front 30

What is the mechanism of action of flucytosine?

Back 30

5 fluoruracil and its metabolites reduce RNA and DNA synthesis by blocking the thymidylate synthe¬tase reaction

Front 31

How does flucytosine affect fungal cells but not human cells?

Back 31

Mammalian cells lack cytosine deaminase, so the drug does not get activated to toxic metabolites in host cells.

Front 32

What is the spectrum of flucytosine?

Back 32

Spectrum of activity is narrow.
Resistance emerges when the drug is used alone.

Front 33

What are the clinical uses of flucytosine?

Back 33

(limited): Combined with amphotericin B - systemic Cryptococcus and Candida infections

Front 34

What are the adverse reactions of flucytosine?

Back 34

Bone marrow depression - leukopenia + thrombocytopenia
Gastrointestinal distress
Reversible hepatotoxicity

Front 35

What is the mechanism of action of Pentamidine?

Back 35

Binds to kinetoplast DNA and inhibits mitochondrial DNA synthesis. Blocks polyamine biosynthesis, blocks topoisomerase II.

Front 36

What are the clinical uses of Pentamidine?

Back 36

Pneumocystis jiroveci (carinii) - used prophylactically in AIDS
Also effective against African trypanosomes.

Front 37

What is the mechanism of action of Griseofulvin?

Back 37

binds to tubulin, preventing proper separation of the chromosomes during mitosis and interfering with microtubule transport

Front 38

How is Griseofulvin selectively toxic?

Back 38

There's lack of active transport of the drug into mammalian cells

Front 39

What are the clinical uses of Griseofulvin?

Back 39

Dermatophytes - Trichophyton, Epidermophyton and Microsporum

Front 40

What are the adverse reactions of Griseofulvin?

Back 40

Temporary h/a is common.
CNS: mental confusion, fatigue, visual impairment.
Gastrointestinal distress

Front 41

What is special about the distribution of Griseofulvin?

Back 41

Binds to keratin and reaches high concentrations in the keratinized cells of the skin and the hair.

Front 42

What can increase the absorption of Griseofulvin?

Back 42

Fatty meals with ingestion
The drug is only effective if given orally.

Front 43

What is the mechanism of action for Naftifine & Terbinafine?

Back 43

fungicidal: inhibits squalene epoxidase, causing buildup of intracell squalene and decreases ergosterol synthesis

Front 44

What are the clincal uses of Naftifine & Terbinafine?

Back 44

Dermatophytes (tinea cruris & tinea corporis), Candida.

Front 45

What is the adverse reaction of Naftifine & Terbinafine?

Back 45

Can cause local irritation.

Front 46

What is the mechanism of action and use of Undecylenic acid?

Back 46

Antifungal: Mechanism unknown. Used for Epidermophyton in tinea pedia.

Front 47

What is the mechanism of action and use of Tolnaftate?

Back 47

Antifungal: Mechanism unknown. Used for superficial dermatophyte infections.