Flashcards in Anti-Fungal Drugs (Habal) Deck (61):
What fungi cause superficial infections?
What fungi cause subcutaneous infections?
What fungi cause primary systemic infections?
What fungi cause primary opportunistic infections?
What are possible targets of anti-fungal drugs?
What is the fungal cell wall made up of?
Chitin, glucan, mannan
What is the fungal cell membrane made up of?
Phospholipids & sterols (ergosterol)
What are the 3 classes of antifungal drugs?
Cell wall (glucan) synthesis
Cell membrane (ergosterol) synthesis
DNA/RNA synthesis (pyrimidine analogues)
An optimal antifungal will have?
Wide spectrum of availability
Adeqhate in vivo efficacy
High therapeutic index
Anti-fungal antibiotics include what drugs?
Polyenes - Amphotericine B, Nystatin
Anti-fungal antimetabolites include?
Anti-fungal azoles include?
Imidazoles - Ketoconazole, Miconazole
Triazoles - Itraconazole, Fluconazole
Anti-fungal allylamines include?
What do allylamines such as Terbinafine interfere with?
What do azoles such as Ketoconazole, Fluconazole, Itraconazole, and Miconazole interfere with?
Cytochrome P450 14-alpha demethylase
What do polyenes such as Amphotericine B and Nystatin do?
Interact with ergosterol and form holes in cell membrane, affecting the integrity of its structure.
What resistance might you see against polyenes?
Low amount of ergosterol. If there's nothing to interact with, then there can't be an anti-fungal activity.
Are polyenes stable or unstable when taken orally?
At what concentration are polyenes fungasidal?
What produces Amphotericin B?
What broad spectrum anti-fungal drug is indicated for treatment of severe to life-threatening fungal infections?
How is Amphotericin B administered? Why?
IV only; very toxic, especially to the kidneys. Slow-rate IV infusion in a hospital setting is the best way to overcome/sidestep this toxicity.
What causes tubular nephrotoxicity due to administration of Amphotericin B?
Leakage of Na+, K+, Ca+
Which anti-fungal drug is the big gun?
What produces Nystatin?
How is Nystatin administered?
Used topically for local infection. Too toxic to be administered systemically.
What is Nystatin routinely used to treat?
Oral thrush (swish and spit).
Why is Nystatin so toxic?
Poor bioavailability and absorption; have to take a large amount for it to be effective systemically.
What is a bad side effect of Azoles?
They impact liver enzymes, leading to potentiation of certain drugs that are metabolized in the liver.
What happens to some patients with hepatic issues who can't break down testosterone?
How can azoles be administered?
Topically, orally, IM, IV
What types of infections can Azoles treat, in general terms?
Most infections, from superficial to systemic
What is the mechanism of action for Azoles?
Inhibit ergosterol synthesis by inhibition of CYP450 - lanosterol 14-alpha demethylase
What are some drugs that Azoles can potentiate?
Diazepam, Cyclosporin, Phynetoin, Warfarin, Isoniazide
What are the 2 types of Azoles?
What are the Imidazoles?
Which Imidazole is broad spectrum, PO administration, and has been mostly replaced by Fluconazole, which does not have the gynecomastia and hepatic side effects generally seen with this drug?
Which Imidazole is used to treat dermatophytes and is administered topically or via vaginal suppositories?
What are the triazololes?
Clotrimazole, Fluconazole, Itraconazole, Voriconazole
Which Triazolole is administered topically or via vaginal suppositories?
Which Triazolole is used to treat oral/esophageal/vaginal candidiasis and Cryptococcal meningitis, and is administered orally or via IV?
Which Triazolole is a broad spectrum drug that is indicated for systemic fungal infections, as well as oral and esophageal candidiasis?
Which Triazolole is administered orally or via IV, has high bioavailability, and is indicated for invasive Aspergillosis?
What should you avoid taking while on Azoles?
Why is fluconazole used for Cryptococcal meningitis?
Highest CSF penetration rate & highest bioavailability
What is the mechanism of allylamines?
Inhibit squalene epoxidase, thus decreasing ergosterol synthesis
How are allylamines administered?
Orally or as a topical cream
What are allylamines mainly used to treat?
Superficial fungal infections
Are there any side effects of allylamines?
Very few, but they include upset stomach, nausea, vomiting, loss of taste. Usually given as a cream because of bad taste that leads to poor compliance.
What 2 drugs are used in conjunction against Cryptococcal meningitis?
Flucytosine & Amp-B
How does Flucytosine work?
It's deaminates to 5-FU, which then interferes with RNA & DNA synthesis
What is Flucytosine dose dependent for?
Bone marrow suppression (decreased white blood cells, platelets)
What is the mechanism of action for Echinocandins (Caspofungin)?
Cell wall synthesis inhibitor that inhibits 1,3-beta-glucan synthase
What drug is used for invasive Amp-B resistant Aspergillosis, esophageal candidiasis, and Pneumocystis pneumonia?
How is Echinocandins administered?
IV (low oral bioavailability)
What is the mechanism for Grieofulvin?
It binds fungal tubulin, interfering with microtubule function.
What anti-fungal is used orally to treat Taenia infections?
Which anti-fungal is highly effective against athlete's foot?
What are the side effects of Grieofulvin?
Teratogenic, increased CYP450 metabolism
What considerations must you take into account for anti-fungal medications?
Site of infection
Current and past medical history
Liver and kidney tests