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Pharm > Antifungals > Flashcards

Antifungals Flashcards

1
Q

What three drugs are considered to be Echinocandins and act on the cell wall of fungi?

A
  1. caspofungin
  2. anidulafungin
  3. micafungin
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2
Q

What are the main indications for use of Caspofungin and are there any stipulations with it?

Is this more for oral use or IV use?

A
  • for candida (fungicidal)
  • for aspergillis (fungistatic)
  • use this drug when others (azols) fail
  • IV use, poor oral availability
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3
Q

What is the MOA of Echinocandins?

A
  • inhibits beta 1,3 glucan synthase enzyme (within the membrane) that contributes to the cell wall synthesis - thus blocking cell wall glucan chain synthesis
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4
Q

What are the drug interactions and contraindications for Echinocandins?

A
  • avoid use with cyclosporin and other immunosuppressants
  • use dose adjustments for hepatic impaired pts
  • C. albicans is known to gain resistance for it
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5
Q

What is an indication for micafungin and what is an AE of micafungin?

A
  • indication: prophylaxis for candida infection in neutropenic patients
  • AE: histamine release with cyclosporins and sirolimus
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6
Q

What is the class distinction and indication for Amphotericin B?

A
  • Polyenes (work on cell membrane)
  • indication: life threatening system fungal infection (broad spectrum)
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7
Q

What is the class designation and indication for Nystatin?

A
  • Polyene (works on cell membrane)
  • Indication: oroesophageal thrush, diaper rash, vaginal candidiasis
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8
Q

What is the MOA behind Amphotericin B and Nystatin?

A
  • drug binds to cell membrane ergosterol, aggregates and forms a pore causing leakage, lysis, and cell death of the fungus
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9
Q

Which polyenes should be used orally? IV? Do they reach the CNS?

A
  • AmpB - minimal oral absorption, IV slow infusion; will reach the CNS if inflammation has occurred, ie meningitis
  • Nystatin - topical only, no absorption through skin or mucous membranes; too toxic for IV use
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10
Q

What are some adverse reactions and contraindications for AmpB and Nystatin?

A
  • renal toxicity - do not use with other nephrotoxic drugs (cisplatin, cyclosporin, tacrolimus, aminoglycosides, NSAIDs); there are less toxic, lipid forms available
  • azotemia - high N2 compounds in blood
  • anemia due to decreased erythropoietin production from kidneys
  • infusion induced chills and aches (aspirin given in the hospital with drug)
  • GI disturbance
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11
Q

What are the drugs that belong to the azole group? Technically they can be split into what two groups?

A
  • Ketoconazole
  • Itraconazole
  • Fluconazole
  • Voriconazole
  • Posaconazole
  • Miconazole and Clotrimazole

They can be split into imidazoles and triazoles

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12
Q

What is the indication for Ketoconazole?

A
  • topical mycoses
  • not systemic
  • occasional use with prostate cancer because of anti-androgen activity
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13
Q

What is the indication for Itraconazole?

A
  • dimorphic fungi
  • dermatophytoses
  • second line for onychomycosis
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14
Q

What is the most commonly used azole and what is the indication for it?

A
  • Fluconazole
  • first line for fungal meningitis
  • secondary prophylaxis for cryptococcal meningitis
  • m. common for mucocutaneous candidiasis
  • not for Aspergillus
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15
Q

What is the indication for Voriconazole?

A
  • Candida sp. esp. fluconazole resistant (like C. krusei)
  • invasive aspergillus
  • active against both yeasts and molds
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16
Q

What is the indication for Posaconazole?

A
  • only azole against Mucorales
  • use as step down tx after improvement seen with AmpB
17
Q

What is the indication and AE for both Miconazole and Clotrimazole?

A
  • superficial mycoses
  • AE: hepatotoxicity
18
Q

What three drugs do all azoles interact with?

A
  • Warfarin
  • Rifampin
  • most anti-seizure drugs
19
Q

What is a contraindication for Voriconazole? With what drugs should you look at changing doses of Voriconazole? Why is that?

A
  • pregnancy
  • change doses of or with cyclosprine and tacrolimus because this drug inhibits CYP3A4
20
Q

Rifampin specifically decreases the bioavailibility of which azole?

What are the AE of this azole?

A
  • Itraconazole
  • AE: HTN, hypokalemia, cardiac suppression, liver injury
21
Q

What is the MOA of the azoles?

Is it fungistatic or fungicide?

A
  • inhibits ergosterol synthesis
  • targets complex of 1,2 -alpha- demethylase and cytochrome P450 which normally will bind with lanosterol to make ergosterol; binds to complex, stopping lanosterol from binding
  • ultimately inhibiting the cell membrane from synthesizing (fungicide)
22
Q

What are the AEs to ketoconazole?

A
  • CYP inhibitor causing hepatotoxicity - no longer used in the US for skin/nail infections
  • most toxic azole, though safer than AmpB
23
Q

Which azole can penetrate the CNS? Is it able to be taken orally? What is special about its elimination?

A
  • Fluconazole penetrates CNS
  • has high oral availability
  • it is 100% eliminated in urine, so not hepatotoxic
24
Q

What two drugs are allylamines and what do they work on?

A
  • Naftifine
  • Terbinafine
  • works on cell membrane
25
Q

What is the MOA of allylamines?

A
  • inhibits squalene epoxidase (the precursor molecule to lanosterol)
  • inhibiting ergosterol synthesis and disrupting the fungal cell membrane
26
Q

What is the indication for Naftifine and why is it considered to have “triple action”?

A
  • dermatophytes (topical cream)
  • athlete’s foot, ringworm on groin and body
  • anti-fungal, anti-bacterial, anti-inflammatory
27
Q

What is the indication for Terbinafine? Why?

A
  • first line against onychomycosis
    • less toxic than itraconzaole
28
Q

What anti-fungal drug works against nucleic acid synthesis? Is this a fungicide or fungistatic?

A
  • Flucytosine
  • fungistatic
29
Q

Resistance to Flucytosine is easy, so we do what when we administer it?

A
  • combine with AmpB causing a synergistic relationship
30
Q

What is the indication for Flucytosine? Does it have a broad spectrum of action or narrow?

A
  • cryptococcus and chromoblastomycosis
  • very narrow spectrum of action
31
Q

What is the MOA of Flucytosine?

A
  • prodrug - converts to 5-FU (fluorouracil)
  • 5 FU is a thymine analogue, inhibiting thymydylate synthase
  • selectively inhibiting DNA and RNA synthesis in fungi becuase of decreased thymine
32
Q

What are the AE of Flucytosine?

A
  • myelosuppression because 5-FU is an anti-cancer drug
  • systemically toxic to host because of DNA and RNA damage
33
Q

What antifungal drug acts on mitosis of fungi? Is this a fungistatic or fungicide?

A
  • Griseofulvin
  • fungicide
34
Q

What is the indication for Griseofulvin?

A
  • systemic dermatophytosis
  • skin and hair infections
35
Q

What is the MOA of Griseofulvin?

A
  • first: drug is deposited in newly formed keratinocytes, binds to keratin protein and protects from new infections
  • second: irreversibly binds to the microtubule of fungi and prevents spindle formation and mitosis
36
Q

What form is Griseofulvin administered?

A
  • as microcrystalline oral form

Pharm (3 decks)

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