Exam 3 - Smith - Antifungals

Question 1

T/F - Most antifungals target the fungal cell membrane or fungal cell wall.

Answer 1

TRUE

Question 2

Fungi have a rigid cell wall composed of ________.

Answer 2

Chitin

Question 3

What are fungal cell membranes composed of?

Answer 3

Ergosterol

Acts like cholesterol acts in human cell membranes

Question 4

Antibacterial drugs are _____________ against fungal infections.

Answer 4

INEFFECTIVE

Question 5

Superficial fungal infections deal with what?

Answer 5

Skin

Other soft tissues
-Oral and vaginal candidiasis

Question 6

Systemic fungal infections involve what?

Answer 6

Whole body

-Major cause of death for immunocompromised pts

Question 7

What are the high risk groups for systemic fungal infections?

Answer 7

Cancer, or its chemotherapy

Organ transplantation

HIV-1 infection

Question 8

What is pulmonary aspergillosis?

Answer 8

Leading cause of death in immunocompromised pts, pts with asthma, or pts with cystic fibrosis

Question 9

What are 4 targets of antifungals?

Answer 9

Fungal cell membrane
-Fx, permeability or ergosterol synthesis

Cell wall glucan synthesis

Nucleic acid synthesis

Microtubule fx

Question 10

What are the primary drugs used for treating systemic fungal infections? (3, AAE)

What do they target?

Answer 10

Amphotericin B

Azoles

• Fluconazole
• Itraconazole
• Ketoconazole
• Voriconazole

Echinocandins

THESE INTERACT WITH OR INHIBIT ERGOSTEROL SYNTHESIS

Question 11

Polyenes include what two drugs?

Answer 11

Amphotericin B

Nystatin

Question 12

What do polyenes do?

Answer 12

Bind ergosterol in cell membranes and disrupt membrane fx and permeability

Question 13

What 2 drugs are imidazoles and triazoles?

Answer 13

Itraconazole

Fluconazole

Question 14

What do the imidazoles and triazoles do?

Answer 14

PREVENT ERGOSTEROL SYNTHESIS

Question 15

What 2 drugs are the allylamines?

Answer 15

Naftifine

Terbinafine

Question 16

What do the allylamines do?

Answer 16

PREVENT ERGOSTEROL SYNTHESIS

Question 17

Which drugs inhibit fungal cell wall synthesis?

-Inhibit glucan synthesis

Answer 17

Echinocandins

Like, caspofungin

Question 18

What is the polyene mechanism?

Answer 18

Bind to plasma membrane ergosterol and damage the membrane by forming pores
-K leaks out

Question 19

T/F - Amphotericin B is taken for most serious systemic fungal infections.

Answer 19

TRUE

Question 20

What does parenteral mean?

Answer 20

Cannot be absorbed orally

Question 21

How is Amphotericin B most often administered?

Answer 21

Slow IV infusion in a hospital setting

Question 22

What is the 1st line therapy for invasive, life-threatening systemic and localized Candidemia?

Answer 22

Amphotericin B

*Also works for aspergillus infections

Question 23

What are common side effects of Amphotericin B?

Answer 23

Toxic chronic rxns

• Nephrotoxic
• Neurotoxic

Question 24

What are immediate rxns of Amphotericin B?

Answer 24

• Infusion-related toxicity*
• Fever, chills, muscle spasms, vomiting, headache
• Avoided by:
• Slowing the infusion
• Decreasing the daily dose

Question 25

What are slower rxns to Amphotericin?

Answer 25

Renal toxicity Neurotoxicity Hypokalemia and hypomagnesaemia

Question 26

Nystatin should be used in what way ONLY?

Answer 26

TOPICAL only

Question 27

What is nystatin used for?

Answer 27

Oral and esophageal Candidiasis albicans (thrush) as mouthwash Topical cream for vaginal candidiasis

Question 28

Adverse effects of Nystatin?

Answer 28

Never administered systemically, due to toxicity Disulfiram-Like rxns - Hangovers

Question 29

Two types of Azoles?

Answer 29

Imidazoles Triazoles

Question 30

What are the 5 drugs that are imidazoles?

Answer 30

Bifonazole Clotrimazole Econazole Ketoconazole Miconazole

Question 31

What are the 3 drugs that are triazoles?

Answer 31

Fluconazole Itraconazole Vorionazole

Question 32

What is the mechanism for azoles?

Answer 32

Inhibit ergosterol synthesis | -Blocks lanosine 14alpha-demethylase

Question 33

How are azoles administered?

Answer 33

- Topically | - Systemically

Question 34

What are 3 big contraindications to remember with azoles?

Answer 34

PREGNANCY LACTATION PTS WITH HEPATIC DYSFX * Also inhibits gonadal and steroid synthesis * Also loss of libido, gynecomastia in males, menstrual irregularity

Question 35

What is the MOST COMMONLY prescribed systemic antifungal?

Answer 35

Fluconazole -An azole *DRUG OF CHOICE FOR CANDIDIASIS ALBICANS ***HIGHLY TERATOGENIC, AVOID DURING PREGNANCY***

Question 36

What is the first line tx for aspergillis infections?

Answer 36

Vorconizole

Question 37

What was the first azole?

Answer 37

Ketoconazole | -Systemic or topical

Question 38

What azole is more toxic than Fluconazole?

Answer 38

Itraconazole

Question 39

What 2 azoles are available OTC and treat vaginal yeast infections, oral candidiasis, athlete’s foot, and jock rash?

Answer 39

Clotrimazole Miconazole *Both of these are TOPICAL only

Question 40

Based on their mechanisms of action, co-administering Ketoconazole to a pt currently taking Amphotericin B would __________ its ability to treat a fungal infection. A - Help B- Hinder C - Not effect Why?

Answer 40

B - HINDER Ketoconazole decreases ergosterol in the membrane and this reduces the fungicidal action of Amphotericin B. Never give together.

Question 41

What drug is synergistic with Amphotericin B and these two drugs are given in combination for cryptococcal meningitis?

Answer 41

FLUCYTOSINE

Question 42

What is flucytosine’s mechanism?

Answer 42

Inhibits both DNA and RNA synthesis in fungi -Systemic Adverse effects: bone marrow suppression

Question 43

The echinocandins are called the _________ of the antifungal drugs.

Answer 43

Penicillins

Question 44

What is the mechanism for echinocandins?

Answer 44

Block cell wall synthesis and maintenance by inhibiting 1,3-beta glucan synthase Fungicidal against candida -Used especially for azole-resistant candida Fungistatic against some molds 2nd line agent for refractory aspergillosis Avoided in pregnancy *IV administration

Question 45

What is one common example of an echinocandins?

Answer 45

Caspofungin | -Used for invasive (Cryptic) Aspergillis or Candida

Question 46

What drug disrupts microtubule fx, inhibits fungal mitosis, and inhibit growth of dermatophytes?

Answer 46

Griseofulvin -Rarely used anymore —Teratogenic, carcinogenic, severe headaches

Question 47

What drug inhibits squalene epoxidase to inhibit ergosterol synthesis and disrupts cell membrane permeability?

Answer 47

Terbinafine -This drug has largely replace Griseofulvin for tx of onychomycosis *Hepatotoxicity is an adverse effect

Question 48

When are topical antifungals used?

Answer 48

For localized candidiasis in pts w/ NORMAL immune fx

Question 49

When are systemic antifungals used?

Answer 49

Disseminated disease AND IMMUNOCOMPROMISED PTS