Exam 3 - Smith - Antifungals Flashcards
T/F - Most antifungals target the fungal cell membrane or fungal cell wall.
TRUE
Fungi have a rigid cell wall composed of ________.
Chitin
What are fungal cell membranes composed of?
Ergosterol
Acts like cholesterol acts in human cell membranes
Antibacterial drugs are _____________ against fungal infections.
INEFFECTIVE
Superficial fungal infections deal with what?
Skin
Other soft tissues
-Oral and vaginal candidiasis
Systemic fungal infections involve what?
Whole body
-Major cause of death for immunocompromised pts
What are the high risk groups for systemic fungal infections?
Cancer, or its chemotherapy
Organ transplantation
HIV-1 infection
What is pulmonary aspergillosis?
Leading cause of death in immunocompromised pts, pts with asthma, or pts with cystic fibrosis
What are 4 targets of antifungals?
Fungal cell membrane
-Fx, permeability or ergosterol synthesis
Cell wall glucan synthesis
Nucleic acid synthesis
Microtubule fx
What are the primary drugs used for treating systemic fungal infections? (3, AAE)
What do they target?
Amphotericin B
Azoles
- Fluconazole
- Itraconazole
- Ketoconazole
- Voriconazole
Echinocandins
THESE INTERACT WITH OR INHIBIT ERGOSTEROL SYNTHESIS
Polyenes include what two drugs?
Amphotericin B
Nystatin
What do polyenes do?
Bind ergosterol in cell membranes and disrupt membrane fx and permeability
What 2 drugs are imidazoles and triazoles?
Itraconazole
Fluconazole
What do the imidazoles and triazoles do?
PREVENT ERGOSTEROL SYNTHESIS
What 2 drugs are the allylamines?
Naftifine
Terbinafine
What do the allylamines do?
PREVENT ERGOSTEROL SYNTHESIS
Which drugs inhibit fungal cell wall synthesis?
-Inhibit glucan synthesis
Echinocandins
Like, caspofungin
What is the polyene mechanism?
Bind to plasma membrane ergosterol and damage the membrane by forming pores
-K leaks out
T/F - Amphotericin B is taken for most serious systemic fungal infections.
TRUE
What does parenteral mean?
Cannot be absorbed orally
How is Amphotericin B most often administered?
Slow IV infusion in a hospital setting
What is the 1st line therapy for invasive, life-threatening systemic and localized Candidemia?
Amphotericin B
*Also works for aspergillus infections
What are common side effects of Amphotericin B?
Toxic chronic rxns
- Nephrotoxic
- Neurotoxic
What are immediate rxns of Amphotericin B?
- Infusion-related toxicity*
- Fever, chills, muscle spasms, vomiting, headache
- Avoided by:
- Slowing the infusion
- Decreasing the daily dose
What are slower rxns to Amphotericin?
Renal toxicity
Neurotoxicity
Hypokalemia and hypomagnesaemia
Nystatin should be used in what way ONLY?
TOPICAL only
What is nystatin used for?
Oral and esophageal Candidiasis albicans (thrush) as mouthwash
Topical cream for vaginal candidiasis
Adverse effects of Nystatin?
Never administered systemically, due to toxicity
Disulfiram-Like rxns - Hangovers
Two types of Azoles?
Imidazoles
Triazoles
What are the 5 drugs that are imidazoles?
Bifonazole
Clotrimazole
Econazole
Ketoconazole
Miconazole
What are the 3 drugs that are triazoles?
Fluconazole
Itraconazole
Vorionazole
What is the mechanism for azoles?
Inhibit ergosterol synthesis
-Blocks lanosine 14alpha-demethylase
How are azoles administered?
- Topically
- Systemically
What are 3 big contraindications to remember with azoles?
PREGNANCY
LACTATION
PTS WITH HEPATIC DYSFX
- Also inhibits gonadal and steroid synthesis
- Also loss of libido, gynecomastia in males, menstrual irregularity
What is the MOST COMMONLY prescribed systemic antifungal?
Fluconazole
-An azole
*DRUG OF CHOICE FOR CANDIDIASIS ALBICANS
HIGHLY TERATOGENIC, AVOID DURING PREGNANCY
What is the first line tx for aspergillis infections?
Vorconizole
What was the first azole?
Ketoconazole
-Systemic or topical
What azole is more toxic than Fluconazole?
Itraconazole
What 2 azoles are available OTC and treat vaginal yeast infections, oral candidiasis, athlete’s foot, and jock rash?
Clotrimazole
Miconazole
*Both of these are TOPICAL only
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?
B - HINDER
Ketoconazole decreases ergosterol in the membrane and this reduces the fungicidal action of Amphotericin B. Never give together.
What drug is synergistic with Amphotericin B and these two drugs are given in combination for cryptococcal meningitis?
FLUCYTOSINE
What is flucytosine’s mechanism?
Inhibits both DNA and RNA synthesis in fungi
-Systemic
Adverse effects: bone marrow suppression
The echinocandins are called the _________ of the antifungal drugs.
Penicillins
What is the mechanism for echinocandins?
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
What is one common example of an echinocandins?
Caspofungin
-Used for invasive (Cryptic) Aspergillis or Candida
What drug disrupts microtubule fx, inhibits fungal mitosis, and inhibit growth of dermatophytes?
Griseofulvin
-Rarely used anymore
—Teratogenic, carcinogenic, severe headaches
What drug inhibits squalene epoxidase to inhibit ergosterol synthesis and disrupts cell membrane permeability?
Terbinafine
-This drug has largely replace Griseofulvin for tx of onychomycosis
*Hepatotoxicity is an adverse effect
When are topical antifungals used?
For localized candidiasis in pts w/ NORMAL immune fx
When are systemic antifungals used?
Disseminated disease
AND
IMMUNOCOMPROMISED PTS
