Antifungal Therapy

Question 1

What targets Lanesterol synthesis?

Answer 1

Terbinafine

Question 2

Ergosterol Synthesis Inhibitors?

Answer 2

Azoles
Fluconazole
Ketaconazole
etc

Question 3

Cell wall synthesis inhibitors?

Answer 3

Eichinocandins (EiSKINocandins)

The Fungins

Caspofungin
Micafungin
Anidulafungin

Question 4

Forms membrane pores in Ergosterol?

Answer 4

Polyenes

Amphotericin B
Nystatin

Question 5

Nucleic acid synthesis inhibitors?

Answer 5

5-Flycytosine

Question 6

What is Amphotericin B
MOA
Use
SE

Answer 6

Binds ergosterol and punches a hole into it and e-lytes leak out (AmphoTEARicin TEARS holes in the membrane)

Use: Serious systemic mycoses (has to be serious bc its toxic)

• Ampho B with/without fluctosine for Cryptococcus)
• Blastomyces
• Coccidiodes
• Histoplasma
• Candida
• Mucor

Intrathecal for fungal meningitis

Supplement with K and Mg bc of altered rental tubule permeability

SE: Fevers/chills (shake and bake)
HypOtn
Nephrotox (hydrate to reduce this)
Arrythmia
Anemia
IV Phlebitis

Question 7

Nystatin
MOA
Use

Answer 7

Same as Ampho B…Punches holes into ergosterol membrane

Too toxic so only used topically

For thrush, swish and swallow

For diaper rash or yeast infection

Question 8

Azoles?
MOA
Use
SE

Answer 8

Fluconazole, Ketoconazole, Clotrimazole, Miconazole, etc

Block ergosterol synthesis by BLOCKING FUNGI P450 which converts Lanosterol to Ergosterol

Use: Local and less serious systemic mycoses
Fluconazole - suppress Crypto in AIDS pts, all candidal infectiosn
Itraconazole - Blastomyces, Coccioides, Histoplasma
Clotrimazole and Miconazole - Topical infections

SE: Testosterone synthesis inhibition (gynecomastia, esp with Keto)
Liver dysfunction bc inhibits P450 (Inhibitor)

Question 9

Flucytosine
Use
MOA
SE

Answer 9

Block DNA & RNA synthesis by getting converted to 5 Flurouracil by Cytosine Deaminase

Use:
Systemic fungal infections (esp meningitis from Cryptococcus with Ampho B)

SE: Bone Marrow Suppression

Question 10

Echinocandins (eSKINocandins)
MOA
Use
SE

Answer 10

Caspofungin, Micafungin, Anidulafungin

Inhibits cell wall synthesis by blocking synthesis of B glucan

Use: Invasive Aspergillosis, Candida

SE: GI upset, Flushing (Histamine release)

Question 11

Terbinafine
MOA
Use
SE

Answer 11

Inhibits fungal enzyme SQUALENE EPOXIDASE

Use: Dermatophytoses esp Onychomycosis - fungal infection of finger or toe nails

SEs: GI upset, HA, Hepatotox, taste disturbance

Question 12

Griseofulvin
MOA
Uses
SE

Answer 12

MICROTUBULE FUNCTION, disrupts mitosis. Deposits in keratin-containing tissues (nails)

Use: Oral treatment or superficial infections, inhibits growth of dermatophytes (tinea, ringworm)

SE: Teratogenic, Carcinogenic, confusion, HA,
INCREASE P-450 AND WARFARIN METABOLISM

Question 13

Antiprotozoan Therapy

Answer 13

Pyrimethamine - Toxoplasma
Suramin and Melarsoprol - (Trypanosomes)
Nifurtimox - T. Cruzi
Sodium Stibogluconate - Leishmaniasis

Question 14

Chloroquine
MOA
Use
SE

Answer 14

Blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia

Treatment of plasmodia other than P. Falciparum bc its too resistant to stuff.

Resistance due to membrane pump efflux of drug

SE: Retinopathy, pruritis esp in dark skinned ppl

Question 15

Since P. Falciparum has such a high frequency of resistance, how is it treated?

Answer 15

Treat Falciparum with Artemether / Lumefantrine or Atorvaquone / Proguanil.

Question 16

How is life threatening malaria treated?

Answer 16

With quinidine or Artesunate (in US)

Quinine in other places

Question 17

What are the drugs for Helminths?

Answer 17

Mebendazole
Pyrantel Pamoate
Ivermectin
Diethylcarbamazine
Praziquantel

Immobilize Helminths

Use Praziquantel against flukes (trematodes) such as Schistosome