Antifungals Flashcards
Which Antifungals alter cell membrane permeability?
3
Azoles
Polyenes
Terbinafine
Which antifungals block nucleic scid synthesis?
Flucytosine
Which antifungals disrupt microtuble function?
Griseofulvin
Name the drugs that make up the azole class of antifungals? 7
Miconazole Clotrimazole Ketoconazole Fluconazole Itraconazole Voriconazole Posaconazole
Name the drugs that make up the polyene class of antifungals? 2
Nystatin
Amphoteracin B
What are the topical Drugs for Cutaneous Fungal Infections
4
Azoles:
Miconazole;
Clotrimazole;
Ketoconazole
Polyene: Nystatin
What are the Systemic Drugs for Superficial Fungal Infections?
3
Griseofulvin
Terbinafine
Itraconazole
What are the Systemic Drugs for Systemic Fungal Infections?
7
Amphoteracin B
Azoles: Ketoconazole; Fluconazole; Itraconazole; Vorconazole; Posaconazole
Flucytosine (5-FC)
Are topical antifungals fungicidal or fungostatic?
Fungicidal
MOA of topical azole antifungals?
Impairs the formation of fungal cell membranes therefore increasing permeability
-Intracellular contents leak out leading to cell death
What kind of infections are topical azole antifungals used for?
4
Tinea corporis,
tinea cruris,
tinea pedis,
cutaneous candidiasis
Contraindications for topical azole antifungals?
3
- Pregnancy, lactation
- Use with caution in liver failure
- Ketoconazole not for use with history of sulfa allergy
Dosage forms of topical azole antifungals?
Lotion or powder
Apply twice daily for 2-4 weeks
Continue therapy for 1 week after lesions clear
What do topical azole antifungals inhibit?
CYP450
Mechanism of action
–Inhibit synthesis of ergosterol (cell membrane)
SE of topical azole antifungals?
4
Pruritis, irritation, burning or stinging
Topical Azole Antifungals: Clotrimazole indications?
3
- Cutaneous candidiasis (topical)
- Vulvovaginal candidiasis (topical)
- Oropharyngeal candidiasis (thrush) oral formulation
Topical Azole Antifungals: Clotrimazole contraindaicaitons?
Hypersensitivity to clotrimazole or any component of the formulation
Dosage for Topical Azoles: Clotrimazole?
3
Lotion
Intravaginal sepository
Troche
Clotrimazole: MOA
Absoprtion? 2
Binds to phospholipids in the fungal cell membrane altering permeability and loss of intracellular elements
Very little systemic absorption from topical formula
Troche- 3hours inhibitory concetraion
Clotrimazole adverse effects
Topical?
Oral?3
HOw would we monitor Clotrimazole?
vulvovaginal burning
Abnormal liver function tests
Pruritus
Nausea, vomiting
Periodic liver function tests
Topical Azoles: Ketoconazole
formulations?4
Cream, foam, gel or shampoo
Indications for Ketoconazole?
6
What can’t we use it with?
Tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis (Same as clotrimazole)
+ Seborrheic dermatitis and Tinea Versicolor
Sulfas
Topical Azoles: Miconazole formulations?
4
Aerosol,
Powder Aerosol,
intravaginal suppository,
cream, ointment, lotion
Indications for Miconazole?
6
Tinea corporis,
tinea cruris,
tinea pedis,
cutaneous candidiasis
+ Tinea Versicolor + Vulvovaginal candidiasis
What dosage forms of miconazole would interfere with warfarin?
Intravaginal suppositories may interfere
Topical Polyene: Nystatin (Mycostatin) indications?
Contraindications?
Cutaneous and mucocutaneous infections caused by Candidia
Oral and intestinal Candidia infections
Hypersensitivity reaction
Mycostatin mechanism of action?
Binds to sterols in fungal cell membrane and changes the cell wall permeability leading to leakage of intracellular contents
Mycostatin pharmacokinetics/dynamics
Onset of action?
Systemic absorption?
Drug interactions?
Onset of action: Relief of symptoms within 24-72 hours Systemic absorption None Drug interactions None
Mycostatin adverse effects
3
Contact dermatitis
Stevens-Johnson syndrome
Oral
Nausea, vomiting, diarrhea
Griseofulvin indications?
2
- Used to treat tinea infections of the skin, hair and nails
- Most commonly used for the treatment of tinea capitis
Mechanism of action for Griseofulvin?
2
- Inhibits fungal cell division
2. Binds to human keratin making it resistant to fungal invasion
Duration of therapy for Griseofulvin?
Tinea capitis:
Tinea unguium:
Tinea capitis 4-6 weeks
Tinea unguium 4-6 months or longer
Things to remember about administration?
2
Administration
- -Fatty meal (peanut butter or icecream) can increase GI absorption
- -With food or milk to decrease GI upset
Contraindications and precautions with the administration of Griseofulvin?3
Pregnancy category?
Lactation?
Liver failure
Porphyria
Use with caution if history of penicillin allergy as potential for cross reactivity
Pregnancy (category X)
Breast feeding not recommended
Periodic monitoring required if long term use necessary for
Griseofulvin. What should we monitor?
3
Renal function
Liver function
CBC to watch for granulocytopenia
Describe Griseofulvin drug interactions?
What specific ones?
5
Many drug interactions due to it’s effects on CYP1A2, CYP2C9 and CYP3A4.
Warfarin,
oral contraceptives,
alcohol (disulfiram-like reaction), barbiturates,
cyclosporine and others
Griseofulvin adverse reactions?
Photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme Jaundice, elevated liver function tests Granulocytopenia Dizziness, fatigue, headache Diarrhea, nausea, vomiting Drug induced lupus like syndrome
Describe how the dosing changes with Griseofulvin and the particle size of the two formulas?
The smaller the particle size the greater the bioavailablity requiring dose adjustments between the two formulations
Microsize and Ultramicrosize
Terbinafine(Lamisil) indications?
2
Contraindications?
Oncychomycosis of the toenails, fingernails
Tinea capitis
Hypersensitivity
Terbinafine mechanism of action
Creates ergosterol deficiency within the cell wall leading to cell death
Terbinafine pharmacodynamics/kinetics: Half life? Distribution? Protein bound? Metabolism?
Effective half life 36 h
Distribution to the sebum and skin
99% plasma bound (drug interactions)
Hepatic metabolism
What are two very important Terbinafine drug interactions
we should remember?
Due to inhibition of CYP450 enzymes there are some significant drug interactions including metoprolol and tramadol (for oral formulation)
Terbinafine side effects
3 big ones
5 others that happen occassionally
Headache
Diarrhea
Liver function tests
Burning Contact dermatitis Dryness Pruritus Rash
Itraconazole (Sporanox) indications for topical fungus?
Onychomycosis
lamisil first line though
Itraconazole (Sporanox) contraindications
5
- Hypersensitivity to intraconazole or other azoles
- Concurrent administration with other drugs that act at the CYP450 system
- Ventricular dysfunction (negative inotrope)
- CHF
- Pregnancy or intend to become pregnant
Itraconazole (Sporanox) Pharmacodynamics/kinetics
What does it require for optimal absorption?
Protein bound?
Half life?
Metabolism?
- Requires gastric acidity for optimal absorption
Better absorbed with food (capsule) - 99.8% protein bound
- Half life is about 21 hours
- Metabolized by the liver
Itraconazole (Sporanox) Drug interactions?
A LOT
Need to do a drug interaction checker before you prescribe
Itraconazole (Sporanox) Adverse effects
Nausea, diarrhea Edema Headache Rash Abnormal LFTs Heart failure Arrhythmia Hearing loss Many others….
Itraconazole (Sporanox) Monitoring. 3
- Baseline liver function tests
- Monthly LFTs (if long term therapy)
- Serum concentrations to assure therapeutic levels
Amphoteracin B is used when?
Dosage form?
Indications?
Side effects?
4
Systemic antifungal for use in severe fungal infections.
IV only
severe systemic fungal and fungal CNS infections that are progressive and potentially life threatening
Anaphylaxis,
infusion reaction, leukoencephalopathy (damage to brain white matter),
nephrotoxicity
Amphotericin B Mechanism of Action?
Monitoring?
4
Some drug interactions?
4
Binds to ergosterol and alters cell membrane permeability and may also stimulate the macophages.
renal and liver function, electrolytes,
PT/PTT,
CBC
aminoglycosides,
other antifungal agents, corticosteroids,
cyclosporine
Itraconazole (Sporanox) systemic indications?
5
- Aspergillosis
- Blastomycosis
- Esophageal and oropharyngeal candidiasis (oral soln)
- Coccidioidomycosis
- Histoplasmosis
Itraconazole (Sporanox) systemic contraindications?
- Hypersensitivity to intraconazole or other azoles
- Concurrent administration with other drugs that act at the CYP450 system
- Ventricular dysfunction (negative inotrope)
- CHF
- Pregnancy or intend to become pregnant
Fluconazole (Diflucan) indications
4
Blastomycosis -CNS disease Candidiasis -Candidemia, endocarditis, oropharyngeal, prophylaxis, vaginal, and more… Coccidioidomycosis -Meningitis, pneumonia, prophylaxis Crypococcosis -Meningitis, pneumonia
Blastomycosis
Candidiasis
Coccidioidomycosis
Crypococcosis
Can use as a one time dose for a vaginal yeast infection. it is a oral medication?
Fluconazole (Diflucan)
Fluconazole (Duflucan) contraindications?
2
- Hypersensitivity to fluconazole or other azoles
2. Coadministration of CYP3A4 substrates which may lead to QT prolongation (cisapride, primozide or quinidine)
Fluconazole (Diflucan) dosage forms?
IV and oral formulations
Fluconazole (Diflucan) pharmacokinetics/dynamics
Distribution?
Protein bound?
Half life?
Widely throughout the body
Good penetration into CSF, eye, peritoneal fluid, sputum, skin and urine
Protein binding
11-12% in the plasma
Not highly protein bound
But increases reavitity of other drugs
Half life - 30 hours
Fluconazole (Diflucan) Adverse effects?
5
- Pregnancy category C/D
- Headache, dizziness
- Nausea, vomiting, diarrhea
- Elevated liver function tests
- QT prolongation
Fluconazole (Diflucan) Monitoring?
3
- Baseline liver function tests
2. Periodic liver function, renal function and potassium
Systemic Ketoconazole Warnings
Indications?
Only give it if they will die without it
Use restricted only for the treatment of SYSTEMIC life threatening fungal infections when other safer agents cannot be used
–Blastomycosis, coccidiomycosis, histoplasmosis, chromomycosis, paracoccidioiodmycosis
Should NOT be used for candida or dermatophyte infections
Ketoconazole: Close monitoring is warranted. Of what?
Baseline and weekly monitoring of liver function
