Polyenes – Antifungals

by Pravin Shukle, MD

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    00:00 Let's take a look at some other classes of drugs that are used to treat fungal infections.

    00:06 The polyenes, nystatin being the prototypical drug is used for superficial infections.

    00:11 You can see where it acts on the cell wall down here.

    00:14 It's used topically to suppress candida infections.

    00:18 And it's used as "swish and swallow" for oral candidiasis.

    00:22 The mechanism of action, remember that these polyene antifungal agents bind to ergosterol and caused artificial pores in the cell membrane.

    00:34 This causes leakage of hydrogen ion, potassium ion, chloride ion and even sodium ion through that pore.

    00:41 It also increases free radical formations within the cell itself which causes toxic intermediates inside the cell.

    00:50 And causes fungal cell death.

    00:54 The next polyene I want to talk about is amphotericin B.

    00:57 And you'll notice that the slide is almost is exactly the same as nystatin.

    01:02 Now these polyenes binds to ergosterol and caused artificial pores.

    01:07 And once again as with the nystatin, it leaks hydrogen, potassium, chloride and sodium ions through this pore.

    01:14 And you also have free radical formation within the cell that causes toxicity inside the fungal cell and cell death.

    01:22 Now amphotericin B is a polyene and it is related to nystatin.

    01:27 But it's usually intravenously administered.

    01:30 Nystatin is usually what we call topical.

    01:33 And so it's gargling kind of an agent that we use in oral candidiasis.

    01:39 Amphotericin B is an intravenous drug and it's used for much more serious infections.

    01:44 It's eliminated through the slow hepatic metabolism of it.

    01:48 And it's half life is therefore quite long, 2 weeks.

    01:52 It has minimal renal excretion.

    01:54 But we do make small adjustments to this medication in class 4 or stage 4 renal failure.

    01:59 Clinically we use it for systemic mycoses.

    02:03 And usually ones that are fairly serious.

    02:05 It's the widest antifungal spectra of any antifungal agent on the market.

    02:11 It works against aspergillosis.

    02:12 It works against blastomycosis.

    02:15 It works against candida, cryptococcosis, histoplasmosis and mucor.

    02:22 It also used intravenous or rarely intrathecally.

    02:27 I have seen it used intrathecally once in my career.

    02:30 Now mycotic corneal ulcers and keratitis are one of the potential treatments of that we can use amphotericin B for.

    02:39 Now in terms of the toxicity of this medication, the most interesting thing that I've seen with this agent is, infusion related chills.

    02:49 So patients suddenly start feeling very cold and -- I don't really have an explanation as to why that's occurring.

    02:56 Patients will also have nausea, muscle spasms and vomiting.

    02:59 And sometimes patients will have this shock like fall in blood pressure.

    03:05 So a lot of time we will premedicate these patients with antihistamines or even glucocorticoids.

    03:11 You have to be very aware that ampho B can cause renal tubular acidosis.

    03:16 And can cause magnesium wasting and potassium wasting.

    03:19 Now the magnesium and potassium wasting are kind of coming hand in hand.

    03:23 Most of the time when you have magnesium wasting, you're also going to have potassium wasting.

    03:28 The other toxic effects include anemia.

    03:32 That's usually due to decreased erythropoietin production from the kidney.

    03:37 You can have those nephrotoxic effects.

    03:40 These are usually dose limited however.

    03:42 Now we have a liposomal version of amphotericin B.

    03:47 These amphotericin B liposomes package the amphotericin B on the inner surface or on the inside of these liposomes or I should say endozomes.

    03:59 And the reduce renal toxicity, we call that lysosomal amphotericin B or liposomal amphotericin B.

    04:08 The correct term is actually liposomal.

    04:10 We do give intrathecally this medication but it is associated with seizures in neurologic damage.

    04:18 So that is a treatment that we try to avoid unless we're really in trouble.

    About the Lecture

    The lecture Polyenes – Antifungals by Pravin Shukle, MD is from the course Antimicrobial Pharmacology.

    Included Quiz Questions

    1. They are both administered intravenously.
    2. They both bind ergosterol.
    3. They are both polyenes.
    4. They both increase free radicals in the cell.
    5. They both cause artificial pores in the fungal cell wall.
    1. Swish and swallow for oral candidiasis
    2. Intrathecal administration for mycotic meningitis
    3. Combined with a steroid for topical tina cruris infections
    4. Topical application for dermal fungal infections
    5. Intravenous administration for systemic mycoses
    1. Anemia
    2. Keratitis
    3. Lymphedema
    4. Salt wasting
    5. Cartilage damage

    Author of lecture Polyenes – Antifungals

     Pravin Shukle, MD

    Pravin Shukle, MD

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