Antifungals

Question 1

Five main classes of antifungals

Answer 1

Polyenes, azoles, pneumocandins, pyridines, drugs used to treat dermatophytosis

Question 2

Name for fungal infections

Answer 2

Mycosis

Question 3

Why fungi are harder to attack

Answer 3

They’re enkarjotic

Question 4

Main targets of anti-fungals

Answer 4

Cell wall and plasma membrane, less so protein synthesis and nuclei acid synthesis

Question 5

Component of fungal plasma membrane

Answer 5

Ergosterol

Question 6

Main polyene

Answer 6

Amphotericin B

Question 7

Mechanism of polyenes

Answer 7

Binds ergosterol and enters the membrane → forms pore and causes cell lysis

Question 8

Disadvantage of amphotericin B

Answer 8

Binds cholesterol to some extent

Question 9

Pk of amphotericin B

Answer 9

Long half-life (weeks); have to infuse slowly

Question 10

Spectrum of amphotericin B

Answer 10

Broad spectrum but ineffective against dermatophytes

Question 11

Adverse effects of amphotericin B

Answer 11

Most toxic AMD; dose-dependent nephrotoxicity, thrombosis, bile salt may add to toxicity (lipid complex is safer)

Question 12

Lipid formulations of amphotericin B

Answer 12

Much less toxic and can be infused at higher doses in a shorter time (uses unilamellar liposome)

Question 13

Clinical applications of amphotericin B

Answer 13

Life- threatening systemic mycosis, especially in immunocompromised

Question 14

Mechanism of action of azoles

Answer 14

Inhibit fungal p450 enzymes for ergosterol formation (fungistatic)

Question 15

Spectrum of azoles

Answer 15

Fairly broad spectrum

Question 16

Two main classes of azoles

Answer 16

Imidazoles, triazoles

Question 17

Imidazoles

Answer 17

Systemic (ketoconazole), topical (clotrimazole, miconazole); toxic if given systemically

Question 18

Triazoles

Answer 18

Fluconazole, itraconazole, posaconazole, voriconazole (increasing spectrum); have longer half-lives

Question 19

Adverse effects of Imidazoles

Answer 19

Inhibit sterol synthesis systemically

Question 20

Adverse effects of triazoles

Answer 20

Limited; have uncommon systemic endocrine effects

Question 21

Adverse effects of all azoles

Answer 21

Teratogenic, inhibit P450 enzymes

Question 22

Itraconazole

Answer 22

Type of triazole with good oral absorption, long half-life, can be used for non-life-threatening systemic infections, broad spectrum, sometimes used in place of or following amphotericin B

Question 23

Pneumocandins and echinocandins

Answer 23

Caspofungin, micafungin, anidulafungin

Question 24

Mechanism of action of pheumocandins and echinocandins

Answer 24

Inhibit an enzyme necessary for synthesis of cell wall (fungicidals)

Question 25

Spectrum of pneumocandins and echinocandins

Answer 25

Narrow spectrum (polyenes are sometimes required)

Question 26

Disadvantages of pneumocandins and echinocandins

Answer 26

Expensive

Question 27

Advantages of pneumocandins and echinocandins

Answer 27

Resistance is uncommon, few adverse effects and drug interactions

Question 28

Ringworm

Answer 28

Tinea corporis, infects epidermis

Question 29

Terbinafine mechanism

Answer 29

Inhibits ergosterol synthesis more than itraconazole (fungicidal)

Question 30

Pk of terbinafine

Answer 30

Given orally for serious infections and distributes to skin, hair, nails, tat

Question 31

Length of time terbinafine takes

Answer 31

Several months because of the growth of layers of the skin

Question 32

Adverse effects of terbinafine

Answer 32

Generally safe but can cause gi upset, headache, rash