Anti-fungal drugs

Question 1

What are treatments for oral candidiasis?

Answer 1

Topical treatments include nystatin (swish), clotrimazole (lozenge), and miconazole (buccal). For more severe infections, fluconazole (systemic) is used.

Question 2

What is the mechanism of action of azole antifungals?

Answer 2

Azoles inhibit ergosterol synthesis by inhibiting CYP51A1 (lanosterol 14-α-demethylase), which demethylates lanosterol.

Question 2

What is the role of CYP51A1 in fungi?

Answer 2

CYP51A1 (lanosterol 14-α-demethylase) demethylates lanosterol, a crucial step in the production of ergosterol.

Question 2

What class does ketoconazole belong to?

Answer 2

Ketoconazole is the first in class of azole antifungals.

Question 2

Why is ketoconazole less frequently used now?

Answer 2

It shows greater affinity for mammalian CYP enzymes, leading to greater adverse effects compared to later azole drugs.

Question 2

How is ketoconazole absorbed?

Answer 2

Ketoconazole requires high stomach acidity for absorption and is taken orally for systemic and superficial mucocutaneous infections.

Question 3

Where does ketoconazole distribute in the body?

Answer 3

Ketoconazole attains high concentrations in the CNS.

Question 4

How is ketoconazole eliminated from the body?

Answer 4

Ketoconazole is metabolized hepatically to an inactive metabolite

Question 5

What is ketoconazole’s effect on cytochrome P450s?

Answer 5

Ketoconazole is a broad-spectrum inhibitor of cytochrome P450 enzymes.

Question 6

What causes the adverse effects of ketoconazole?

Answer 6

The ability of ketoconazole to inhibit endogenous cytochrome P450s, which are required for steroid synthesis.

Question 7

What effect does ketoconazole have on male hormones?

Answer 7

Ketoconazole inhibits testosterone and glucocorticoid synthesis in males, leading to gynecomastia (enlarged breasts).

Question 8

What is a major drug interaction concern with ketoconazole?

Answer 8

Ketoconazole is a strong inhibitor of CYP3A4, affecting the metabolism of many drugs, including phenytoin, warfarin, and oral hypoglycemic agents.

Question 9

What class does fluconazole belong to?

Answer 9

Fluconazole is a newer azole antifungal.

Question 10

What is a key advantage of fluconazole over ketoconazole?

Answer 10

Fluconazole has more consistent absorption, unaffected by stomach acid.

Question 11

How is fluconazole excreted from the body?

Answer 11

Fluconazole is primarily excreted unchanged through the kidneys.

Question 12

What are the drug interaction concerns with fluconazole?

Answer 12

Fluconazole is a strong CYP2C9 inhibitor, which can interact with warfarin. It is a weaker CYP3A4 inhibitor.

Question 13

What are the uses of fluconazole?

Answer 13

Fluconazole is used as a systemic (oral) agent for both systemic and superficial fungal infections, and as a second-line drug for nystatin-refractory oropharyngeal candidiasis (OPC).

Question 14

What type of antifungal is miconazole?

Answer 14

Miconazole is a topical azole antifungal.

Question 15

What are the drug interaction concerns with miconazole?

Answer 15

Miconazole is a CYP3A4 and CYP2C9 inhibitor.

Question 16

What forms of miconazole are available?

Answer 16

Miconazole is available in a buccal tablet (Oravig®), as well as cream or solution forms for other fungal infections.

Question 17

What are the uses of miconazole?

Answer 17

Miconazole is used for oropharyngeal candidiasis and superficial fungal infections.

Question 18

What is a possible side effect of oral miconazole?

Answer 18

Nausea is possible with the oral form of miconazole.

Question 19

What type of antifungal is clotrimazole?

Answer 19

Clotrimazole is a topical azole antifungal.

Question 20

Why is clotrimazole used topically?

Answer 20

Clotrimazole is too toxic for systemic use and is used topically only.

Question 21

What forms is clotrimazole available in?

Answer 21

Clotrimazole is available as a troche/lozenge for oral use (by prescription), and in cream or solution forms for other fungal infections.

Question 22

What side effects can clotrimazole cause?

Answer 22

Clotrimazole can cause gastrointestinal upset, nausea, and vomiting after using the oral lozenge.

Question 23

What are the uses of clotrimazole?

Answer 23

Clotrimazole is used for oropharyngeal candidiasis and superficial fungal infections.

Question 24

What class of antifungal is terbinafine?

Answer 24

Terbinafine is an allylamine antifungal.

Question 25

How does terbinafine work?

Answer 25

Terbinafine inhibits ergosterol synthesis by targeting squalene monooxygenase (squalene epoxidase), with greater affinity for the fungal enzyme than the human enzyme.

Question 26

Where does terbinafine accumulate in the body?

Answer 26

Terbinafine accumulates in hair, skin, nails, and fatty tissue.

Question 27

What are the topical uses of terbinafine?

Answer 27

Terbinafine is used for Tinea cruris (jock itch), Tinea pedis (athlete’s foot), and Tinea corporis (ringworm).

Question 28

What are the oral uses of terbinafine?

Answer 28

Terbinafine is used orally for onychomycosis (infection of toe or fingernails).

Question 29

What drug interactions are important for terbinafine?

Answer 29

Terbinafine is a CYP2D6 inhibitor, which can affect SSRIs, beta-blockers, antiarrhythmics, and MAO-I type B medications.

Question 30

What is the chemical property of polyenes?

Answer 30

Polyenes are amphoteric, meaning they can react as either an acid or a base.

Question 31

What type of antifungal is amphotericin B?

Answer 31

Amphotericin B is a polyene antifungal.

Question 32

How does amphotericin B work?

Answer 32

Amphotericin B binds to ergosterol in fungal membranes and forms pores, increasing membrane leakiness.

Question 33

How is amphotericin B administered?

Answer 33

Amphotericin B is administered parenterally (i.v.) for systemic effects, with liposomal formulations to reduce immediate side effects. It can also be given intrathecally for fungal meningitis.

Question 34

How is amphotericin B excreted?

Answer 34

Amphotericin B is excreted unchanged by the kidneys.

Question 35

What is the half-life of amphotericin B?

Answer 35

Amphotericin B has a 15-day half-life.

Question 36

What are the immediate side effects of amphotericin B?

Answer 36

Immediate side effects include fever, chills, and vomiting (1-3 hours after administration).

Question 37

What are the cumulative side effects of amphotericin B?

Answer 37

Cumulative side effects include nephrotoxicity, which may be irreversible.

Question 38

What is the main use of amphotericin B?

Answer 38

Amphotericin B is used for parenteral therapy in life-threatening systemic mycoses.

Question 39

What is the mechanism of action of echinocandins?

Answer 39

Echinocandins inhibit the synthesis of beta-glucan in the fungal cell wall by inhibiting the enzyme 1,3-β glucan synthase.

Question 39

Why is nystatin safe for topical use?

Answer 39

Nystatin is not absorbed orally or through the skin after topical use, leading to little toxicity.

Question 40

What type of antifungal is nystatin?

Answer 40

Nystatin is a polyene antifungal with activity towards Candida.

Question 40

How does nystatin work?

Answer 40

Nystatin binds to ergosterol and acts as a membrane pore-forming agent.

Question 41

What is the primary use of nystatin?

Answer 41

Nystatin is used topically for oropharyngeal candidiasis (first-line drug) and other superficial mycoses.

Question 42

What formulations of nystatin are available?

Answer 42

Nystatin is available as an ointment, cream, and suspension.

Question 43

What are examples of echinocandins?

Answer 43

Caspofungin, micafungin, and anidulafungin.

Question 44

How are echinocandins administered?

Answer 44

Echinocandins are administered intravenously (IV) due to low oral bioavailability.

Question 44

What is the mechanism of action of flucytosine?

Answer 44

Flucytosine is converted inside the fungal cell to 5-fluoro-uracil (5-FU), which inhibits DNA and RNA synthesis.

Question 45

What is the role of echinocandins in treatment?

Answer 45

Echinocandins are now first-line treatments for Candida infections before species identification.

Question 45

How is flucytosine administered?

Answer 45

Flucytosine is orally effective and attains effective concentrations in the CNS.

Question 46

What are the common side effects of echinocandins?

Answer 46

Side effects include fever, vomiting, rashes, and infusion-related issues, but they are generally safe with minimal toxicity.

Question 47

What is the spectrum of activity of flucytosine?

Answer 47

Flucytosine has a narrow spectrum, primarily effective against Cryptococcus and Candida.

Question 48

What are the major limitations of flucytosine?

Answer 48

Major limitations include rapid development of resistance and toxic bone marrow depression. Caution is needed in patients with renal impairment.

Question 49

What are the typical uses of flucytosine?

Answer 49

Flucytosine is reserved for serious systemic mycoses and is often used in combination with other antifungal drugs like amphotericin B.

Question 50

What is the mechanism of action of griseofulvin?

Answer 50

Griseofulvin binds to the mitotic spindle (tubulin) and interferes with mitosis.

Question 51

How does griseofulvin distribute in the body?

Answer 51

Griseofulvin binds to keratin in new skin cells, which are present in skin, hair, and nails, so it requires replacement of old cells to be effective.

Question 51

What are the uses of griseofulvin?

Answer 51

Griseofulvin is used for oral therapy of dermatophytic infections of hair, nails, and the scalp. It does not work topically.

Question 52

Why has griseofulvin been largely replaced?

Answer 52

Griseofulvin has been largely replaced by terbinafine and itraconazole (azole antifungals).

Question 53

Is griseofulvin useful for treating oropharyngeal candidiasis (OPC)?

Answer 53

no