Antifungals

Question 1

What are 3 echinocandins?

Answer 1

Capsofungin
Andulafungin
Micafungin

Question 2

What is the MOA of echinocandins? Is the target located in the cell membrane or the cell wall?

Answer 2

Cell wall inhibition by inhibition B-1-3 glucan synthase located in the cell membrane

Question 3

What two organisms are targeted by echinocandins? Is it fungicidal?

Answer 3

Candida (yeast)
Aspergillus (mold)
Yes

Question 4

What is the preferred route for capsofungin? Effective or ineffective? When is it given?

Answer 4

IV
Very effective
Given when not responding to Azol

Question 5

Where is capsofungin metabolized? What are 2 relatively mild AE? Contraindications and drug interactions?

Answer 5

Liver
Headache/chills
DI: Cyclosporine
Contraindications: Hepatic impaired patients

Question 6

What is a pharmokinetic advantage of andulafungin?

Answer 6

48 hour half like

Question 7

What is micafungin regularly prescribed for? What is its main AE?

Answer 7

Prophylactic for candida treatment in neutropenic patients (transplant pts)
Histamine release with cyclospoins and sirolimus

Question 8

What organism has been reported to have resistance to capsofungin?

Answer 8

Candida albicans

Question 9

What is the MOA of Polyenes?

Answer 9

Targets cell membrane, punches hole in egosterol

Question 10

What are two polyenes?

Answer 10

Amphotericin B

Nystatin

Question 11

How does the route differ for each of the two polyenes?

Answer 11

Amphotericin - oral/slow IV

Nystatin - topical use/oral

Question 12

Is amphotericin B narrow or broad spectrum? What types of fungal infections is it mainly used for?

Answer 12

Extremely broad

Life-threatening fungal infections

Question 13

What is a major AE of amphotericin B? What are two subsequent conditions this causes? What two problems does it cause in the kidney?

Answer 13

Nephrotoxicity - Azotermia (high N2) and Anemia - reduction of erythropoetin synthesis
Clogs renal artery
Necrosis of Distal tubual

Question 14

What other forms of Amphotericin are available?

Answer 14

Less toxic forms

Question 15

When is the only time when Amphotericin B can penetrate the CNS?

Answer 15

When CNS is inflammed

Question 16

What is Nystatin the drug of choice to treat? What two other conditions does it topically treat?

Answer 16

Oroesophageal thrush

Diaper rash and Vaginal Candidiasis

Question 17

Why can’t nystatin be given IV?

Answer 17

Too toxic for systemic

Question 18

What is the one mild AE of oral Nystatin?

Answer 18

GI disturbance

Question 19

What is the MOA of Azoles? What essential enzyme does it target?

Answer 19

Inhibits membrane by inhibiting formation of ergosteral from lanosterol
Targets Cytochrome P450 mediated 14-alpha demethylase

Question 20

What route is ketoconazole typically given? Due to being a CYP inhibitor, what AE can it cause? It is more harmful or safer than amphotericin B? Is it used in the US for nail and skin infections?

Answer 20

Topically (was first oral drug)
Hepatotoxic
Safer
Not used in US for nail and skin infections

Question 21

What subset of fungi does itraconazole target? Is it recommended for systemic infections?

Answer 21

Dimorphic

No

Question 22

What is the most commonly given azole? Is it good for systemic infections?

Answer 22

Fluconazole

Yes

Question 23

Which azole is good at penetrating the CSF and strictly eliminated int he urine, thus safe in hepatic dysfunction patients?

Answer 23

Fluconazole

Question 24

Which fungal infection is fluconazole most commonly used for? Prophylaxis for which? Used in most stable patients for?

Answer 24

Mucocutaneous Candidiasis
Crytococcal meningitis
Candida Albicans

Question 25

Which fungus does fluconazole have no activity against?

Answer 25

Aspergillus

Question 26

Which azole can be given when a fungus is resistant to fluconazole and which is also active against aspergillus?

Answer 26

Voriconazole

Question 27

What does voriconazole inhibit, therefore requiring a dose reduction if a person is on cyclosporine or tacrolimus?

Answer 27

CYP3A4

Question 28

Which three AE reactions are unique to the azole voriconazole?

Answer 28

Neurotoxicity Visual changes Photosensitivity

Question 29

Which azole is the only one active against mucorales? It is also a step-down therapy from amphotericin B.

Answer 29

Posaconazole

Question 30

What is the major AE of all azoles besides fluconazole?

Answer 30

Hepatotoxicity

Question 31

What are miconazole and clotrimazole used for?

Answer 31

Superficial mycoses

Question 32

What do allylamines target? What are two main allylamines?

Answer 32

Fungal cell membrane inhibition Naftifine Terbinafine

Question 33

What is the route of naftifine? What does it subsequently treat? It is trip action against what?

Answer 33

Topical Dermatophyte (athlete's foot, ring worm of groin/body) Anti-bacterial, fungal, and inflammatory

Question 34

What does terbinafine target to reduce ergosterol production?

Answer 34

Squalene epozide synthase

Question 35

What route is terbinafine typically given? What drug is it superior to?

Answer 35

Onychomycosis | Superior to itraconazole

Question 36

What mild AE does terbinafine cause?

Answer 36

Mild GI

Question 37

What is the only agent to act on nucleic acids/DNA synthesis? What is its unquie MOA? What does the active form inhibit

Answer 37

Flucytosine Pro-drug, active form 5-FU Inhibits thymydylate synthase (thymine production)

Question 38

Since it can develop resistance easily, what can flucytosine be used synergistically with?

Answer 38

Amphotericin B

Question 39

What is the fairly severe AE of flucytosine?

Answer 39

Myelosuppression

Question 40

What is the only drug to act on mitosis? What is this drug only used for?

Answer 40

Griseofulvin | Systemic dermatophytosis

Question 41

What are the two MOA of Griseofulvin, human and fungi respectively?

Answer 41

Human - binds to keratin in new formed keratinocytes, protecting skin from new infections Fungi - irreversibly binds to microtubule, preventing spindle formation