Anti-Fungal Drugs

Question 1

What are three types of fungal infections?

Answer 1

Superficial skin

Superficial GI and GU (oral and vaginal)

Systemic (pneumonia, meningitis, UTI, septicemia)

Question 2

Why is resistance increasing re anti-fungals?

Answer 2

Immunocompromised patients are living longer with chronic fungal infections

Antifungals are given to some patients as prophylaxis

Question 3

What are two polyenes and what is their MoA?

Answer 3

Amphotericin B and Nystatin

MoA: Bind to ergosterol and form a pore causing leakage leading to fungicide

Question 4

What are the adverse effects of Amphotericin B and how does this affect its indications?

Answer 4

It also binds with HOST cholesterol causing:
Infusion reactions: chills, fever, HA, Vomit, Hypotension (decreased if slow infusion + NSAIDS & antihistamines)

Long Term treatment leads to reversible then irreversible kidney damage.

Therefore, used only for life-threatening systemic infections.

Patient starts with AmphoB but then switches to safer azole.

Question 5

Why is Amphotericin B given intrathecally for meningitis?

Answer 5

It is poorly absorbed and does not really cross the blood brain barrier.

Question 6

Why is Nystatin only given topically as a cream, mouth rinse or suppository?

Answer 6

It is too toxic for parenteral

Question 7

What is the MoA of the “azoles”?

Answer 7

Inhibit fungal cytochrome P450 (14 alpha sterol demethylase) leading to decreased ergosterol synthesis

Question 8

What is the biggest down side to Azoles?

Answer 8

Drug Drug interactions because they also inhibit human P450s.

Otherwise they have few side effects.

Question 9

What are the indications for Fluconazole?

Answer 9

Best penetration + highest therapeutic index (safest) of azoles

Drug of choice for:

cyrptococcal meningitis

prophylaxis for candida

Also Tx for candidemia and mucocutaneous candida

Question 10

What are the adverse effects fo fluconazole?

Answer 10

Teratogenic

Stevens Johnson (but rare)

Inhibits CYP2C9 re phenytoin and warfarin

Question 11

What are the indications for itraconazole?

Answer 11

Drug of choice for:

Dimorphic fungi: histoplasma, blastomyces, sporthrix

Question 12

What are the adverse effects of Itraconazole?

Answer 12

It can cause CHF so contraindicated if ventricular dysfunction

Potent inhibitor of CYP34A re statins, medazolam

Question 13

What are the indications for Voriconazole?

Answer 13

InVasive aspergillosis

Also: candida and dimorphic fungi

Question 14

What are the adverse effects of voriconazole?

Answer 14

reversible Visual disturbances

(blurring, color, brightness x 30 mins)

Question 15

What is the newest class of antifungals and how do they work?

Answer 15

Echinocandins such as Caspofungin

MoA: inhibit Beta 1-3 glucan synthase

to inhibit cell wall synthesis

Question 16

What are the indications for Caspofungin?

Answer 16

Aspergillus and Candida only

(Aspergillis resistant to Voriconazole)

Question 17

What are the adverse effects of Caspofungin?

Answer 17

Hepatotoxicity, especially with cyclosporine

GI discomfort, flushing

Embryotoxic

Drug drug re tacrolimus and rifampin

Question 18

What is the MoA of Griseofulvin?

Answer 18

Mitotic inhibitor by disrupting microtibules

Keratophillic re NEW nail growth

so can take 6 mo to 1 year to work

Question 19

What are the adverse effects of Griseofulvin?

Answer 19

Oral administration as microcrystalline form

S/E: CNS problems, serum sickness, hepatotoxic, GI problems

P450 inducer (like rifampin) so decreases efficacy of other meds

WHY would anyone take this drug just to fix their toenail fungus?

Question 20

What is the MoA of terbinafine (Lamisil)?

Answer 20

Inhibits squaline epixidase (inhibits squaline from becoming squaline epoxide).

Increase in toxic squaline

Keratophilic and fungicidal

Oral x 3 mos (also comes topical)

Question 21

What are the indications for terbinafine?

Answer 21

Dermatophytoses

Onychomycosis

Question 22

What are the adverse effects of terbinafine?

Answer 22

Very few!

Some GI disturbance, headache

NO P450 or drug drug interactions

Question 23

Your patient is 80 years old and on multiple medications.

He has a fungal infection of his toenails and also has ringworm. What would be a good medication for him?

Answer 23

Terbinafine because it treats dermatophytoses and onychomycosis and has not P450 interactions.

Question 24

What is the MOA of Flucytosine?

Answer 24

Antimetabolite: Inhibition of DNA and RNA synthesis by fungal cells by blocking precursors.

Taken up by cytosine permease and converted to 5FU by cytosine deaminase by fungal cells only.

Question 25

Is flucytosine broad or narrow spectrum?

How does this affect how it is used?

Answer 25

Narrow spectrum but has synergy with other meds:

Used with AmphoB for cryptococcus

Used with Itraconazole for chromoblastomycosis

Question 26

So flucytosine is not converted into 5FU by human cells

so that eliminates its side effects right?

Answer 26

Nope. It can be converted into 5FU by our gut bacteria

especially in patients with renal insufficiency or AIDS

leading to serious hepatotoxicity and bone marrow suppression

Question 27

What antifungal is okay for pregnant women?

Answer 27

Surprisingly: Amphotericin B

Question 28

What is the big problem with azoles?

Answer 28

Inhibition of human P450s leading to drug drug interactions

Question 29

Your patient has cryptococcal meningitis. What do you prescribe?

Answer 29

Fluconazole: best penetration of azoles

Question 30

Your patient has aspergillus but did not respond to voriconazole. What do you try next?

Answer 30

Caspofungin

Question 31

Your patient has histoplasmosis. What do you prescribe and what warning do you give your patient?

Answer 31

Itraconazole

Can cause CHF