Antifungal Drugs Flashcards
What is the method by which most anti-fungal drugs work?
- what are the two outliers and what do they do?
- They produce alterations in the fungal membrane
Griseofulvin
- Mitotic Spindle Inhibitor
Flucytosine
- Antimetabolite (acts identical to 5 fluorouracile)
Why are antifungal drugs becoming increasingly important (3 reasons) ?
- There are more and more immunocompromised people
- Prescription of broad spectrum antibiotics also allows them to take over
- Use of things like catheters that can move fungus from skin into the patients blood
What are the 3 general categories of Antifungals based on what they treat?
- how are they given
- Systemic Drugs for Systemic Infections (orally or Parenteral)
- Oral Drugs for mucocutaneous infections
- Topical drugs for mucocutaneous infections
What drugs are prescribed for the majority of fugal infections?
- when is they only time you would use Flucytosine?
Majority:
- Amphotericin B
- Azoles
Flucytosine is only indicated in Cryptococcal Infections
Why does Amphotericin B cause renal toxicity?
- It acts on Ergosterols, which are similar to human sterols
- Because it binds some human sterols it can create pores in human cells too
- Exhibits most toxicity in the Kidney
What is the only administration method for Amphotericin B?
- what form is this drug put into to decrease toxicity
IV, putting it into micelles reduces toxicity
- Other forms (spheres, disks, and ribbons) have been formed but are way more expensive and only allowed for limited improvement
What are patients treated with amphotericin B given prior to treatment to reduce adverse drug effects?
- Antipyretics
- Antihistamines
- Meperidine
- Corticosteroids
Why is anemia a long term side effect of amphotericin use?
Anemia is secondary to renal damage. Kidneys produce ERYTHROPOIETIN that is needed to stimulate blood cell formation.
Azole use may result in a pro-arrthmogenic effect. Which have been indicated to produce this effect?
Fluconzazole, Posaconazole, and Voriconazole
T or F: no azole should be given during pregnancy if at all possible
True, Voriconazole and Fuconazole should especially be avoided
What unique affect sets ketoconazoles apart from the other azoles?
- Potential to cause Adrenal Insufficiency by causing adrenals to decrease corticosteriod production
What are some important Drug-Drug interactions of Voriconazole?
Cyclosporine and Tacrolimus
**This is due to its inhibitory effect on CYP3A4
If a patient has fungal meningitis which drugs would you most need to use?
Fluconazole
Voriconazole
**Both can access the CSF
What is the best azole drug that has been made thus far, and what are the 3 reasons for this?
- Penetrates into CSF
- Good oral Bioavailability
- Large Therapeutic Window
A patient has mucomycosis, what drug to you use to treat it?
Posaconazole - its the only drug with activity against this fungus
What are 3 important topical azoles?
- Clotrimazole
- Miconazole
- Nystatin
T or F: like Flucazole, Flucytosine has a broad therapeutic window.
False, Flucytosine has a very narrow therapeutic window
Which antifungals are associated with infusion reactions?
Amphotericin B
Echinocandins
Antifungals associated with Bone Marrow Supression?
5-Flurocytosine Amphotericin B (decreased erythropoetin production)
Antifungals associated with Cutaneous photosensitivity and malignancy?
Voriconazole
Antifungals associated with Photopsia?
Voriconazole
Antifungals associated with CNS issues?
Voriconazole
Antifungals associated with Renal Toxicity?
Amphotericin B
Antifungals associated with hepatic dysfunction?
All Azoles
Amphotericin B
5-flurocytosine
Echinocandins
Antifungals associated with Cardiac problems?
Azoles, especially in the presence of other drugs
Antifungals associated with GI issues?
Itraconazole
Posaconazole
5-flurocytosine
What are some side effects that characterize infusion reactions?
Chills, Fever, Flushing, Headache
Why do azoles cause drug-drug interactions?
They are metabolized by CYP3A4 which is a p450 that deals with a lot of different drugs
Why does 5-flurocytosine have such unique side effects?
- what is the cause of this?
5-flurocytosine is metabolized to 5-flurouricil in Fungi after it is pumped in.
- Humans don’t have the enzyme that converts 5-flurocytosine to 5-flurouricil, but our bacteria do
- In GI bacteria convert it so 5-flurouricil (a chemo drug)
- Because of this we see chemotherapeutic effects of the drug, such as bone marrow suppression, and GI perturbation
By what mechanism does resistance to Nystatin and Amphotericin arise?
Sterol Modification
By what mechanism does resistance to Caspofugin and micafungin arise?
Altered Glucan Synthase
By what mechanism does Flucytosine resistance arise?
Modifying Permease or Thymidine Synthase
What mechanism leads to resistance to Ketoconazole, Flutoconazole, and Itraconazole?
- Efflux
- Demthylase Alteration
- Bypass
- overproduction
What drug has replaced Griseofulvin in treatment of Dermatophytosis?
Terbinafine
Why does Amphotericin cause cardiac dysfunction?
K+ doesn’t get reabsorbed in the kidney and the heart relies a lot on K+ to contract properly
Why are antihistamines and/or hydrocortisone often given before administration of antifungals?
- which antifungals is this usually necessary for?
To Reduce the effects of Infusion reactions associated with Amphotericin B and Eichocandins
What antimicrobial is notorius for giving people Red Man Syndrome?
Vancomycin
