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Pharm SJSM > Block 3 material simplified (Antifungals) > Flashcards

Block 3 material simplified (Antifungals) Flashcards

1
Q

Amphotericin B

MOA:

Clinical use:

Adverse effects:

Resistance:

A

MOA: Systemic Antifungal

Binds ergosterol in fungi to form pores that leak electrolytes
“Tears holes through the fungi”

Clinical use:
Aspergillus
Blastomycosis
Cryptococcal meningitis
Coccidioides meningitis
Candida esophagitis
Histoplasmosis
Leishmaniasis
Mucormycosis

Adverse effects:
1) Shake & bake
2) Hypotension
3) Nephrotoxicity (K+ & Mg2+ loss)
4) Arrythmias
5) Anemia
6) IV phlebitis
(Give hydration!!!)

Resistance:
Reductions in ergosterol biosynthesis (Aspergillus terreus)

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2
Q

MOA: Systemic Antifungal

Binds ergosterol in fungi to form pores that leak electrolytes
“Tears holes through the fungi”

Clinical use:
Aspergillus
Blastomycosis
Cryptococcal meningitis
Coccidioides meningitis
Candida esophagitis
Histoplasmosis
Leishmaniasis
Mucormycosis

Adverse effects:
1) Shake & bake
2) Hypotension
3) Nephrotoxicity (K+ & Mg2+ loss)
4) Arrythmias
5) Anemia
6) IV phlebitis
(Give hydration!!!)

Resistance:
Reductions in ergosterol biosynthesis (Aspergillus terreus)

A

Amphotericin B

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3
Q

Nyastatin

MOA:

Clinical use:

A

MOA: Polyenes (Topical/oral antifungal)

Bind ergosterol in fungi to tear holes in the fungal cell membrane

Clinical use:
Swish & swallow for oral candidiasis
Topical for diaper rash

Adverse effects:
1) Skin irritation or hypersensitivity

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4
Q

MOA: Polyenes (Topical/oral antifungal)

Bind ergosterol in fungi to tear holes

Clinical use:
Swish & swallow for oral candidiasis
Topical for diaper rash

Adverse effects:
1) Skin irritation or hypersensitivity

A

Nyastatin

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5
Q

Flucytosine

MOA:

Clinical use:

Adverse effects:

Resistance:

A

MOA: Systemic Antifungal

Inhibits DNA/RNA synthesis by converting 5-fluorouracil via cytosine deaminase.

5FU is then converted to 5FUMP & incorporated into RNA or its turned into 5FdUMP to inhibit thymidylate synthase

Clinical use: Narrow spectrum fungistatic
1) Cryptococcus meningitis
(given with amphotericin B)

Adverse effects:
1) Myelosuppression (anemia, thrombocytopenia, & leukopenia)
2) Nephrotoxicity
3) Hepatotoxicity
4) N/V

Resistance:
Secondary resistance – used alone
Decreased UPRTase or cytosine deaminase

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6
Q

MOA: Systemic Antifungal

Inhibits DNA/RNA synthesis by converting 5-fluorouracil via cytosine deaminase.

5FU is then converted to 5FUMP & incorporated into RNA or its turned into 5FdUMP to inhibit thymidylate synthase

Clinical use: Narrow spectrum fungistatic
1) Cryptococcus meningitis
(given with amphotericin B)

Adverse effects:
1) Myelosuppression (anemia, thrombocytopenia, & leukopenia)
2) Nephrotoxicity
3) Hepatotoxicity
4) N/V

Resistance:
Secondary resistance – used alone
Decreased UPRTase or cytosine deaminase

A

Flucytosine

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7
Q

Azoles

MOA:

Clinical use:

Adverse effects:

A

Clotrimazole, Fluconazole, Isavuconazole, Ketoconazole, Miconazole, Voriconazole, & Itraconazole

MOA: Systemic & topical superficial antifungal

Inhibits ergosterol (sterol) synthesis by inhibiting CYP450 (14a-demethylase)

Clinical use:
1. All (Cryptococcal meningitis in HIV patients or candida infections)

  1. Itraconazole (Blastomyces, Coccidioides, Histoplasma, Sporothrix schenckii)
  2. Clotrimazole & Miconazole (Topical fungal infection)
  3. Voriconazole (Aspergillus & Candida)
  4. Isavuconazole (Aspergillus & Mucor)
  5. Ketoconazole (Non-CNS blastomycosis, coccidiomycosis, Oropharyngeal candidiasis)
  6. Fluconazole (Candidiasis)

Adverse effects:
1) Gynecomastia (Ketoconazole)
2) Liver dysfunction

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8
Q

Clotrimazole, Fluconazole, Isavuconazole, Ketoconazole, Miconazole, Voriconazole, & Itraconazole

MOA: Systemic & topical superficial antifungal

Inhibits ergosterol (sterol) synthesis by inhibiting CYP450 (14a-demethylase)

Clinical use:
1. All (Cryptococcal meningitis in HIV patients or candida infections)

  1. Itraconazole (Blastomyces, Coccidioides, Histoplasma, Sporothrix schenckii)
  2. Clotrimazole & Miconazole (Topical fungal infection)
  3. Voriconazole (Aspergillus & Candida)
  4. Isavuconazole (Aspergillus & Mucor)
  5. Ketoconazole (Non-CNS blastomycosis, coccidiomycosis, Oropharyngeal candidiasis)
  6. Fluconazole (Candidiasis)

Adverse effects:
1) Gynecomastia (Ketoconazole)
2) Liver dysfunction

A

Azoles

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9
Q

Terbinafine

MOA:

Clinical use:

Adverse effects:

A

MOA: Allylamines Antifungal

Inhibits fungal squalene oxidase

Clinical use:
Dermatophytes (tinea)
Onychomycosis (nail infections)
Ring worm (tinea capitis)

Adverse effects:
1) Metallic taste
2) Hepatotoxicity
3) Headache/Gi upset

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10
Q

MOA: Allylamines Antifungal

Inhibits fungal squalene oxidase

Clinical use:
Dermatophytes (tinea)
Onychomycosis (nail infections)
Ring worm (tinea capitis)

Adverse effects:
1) Metallic taste
2) Hepatotoxicity
3) Headache/Gi upset

A

Terbinafine

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11
Q

Fluconazole

MOA:

Effect

A

MOA:
Inhibits CYP2C9, CYP2C19 and CYP3A4

Effects:
Candida infection

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12
Q

MOA:
Inhibits CYP2C9, CYP2C19 and CYP3A4

Effects:
Candida infection

A

Fluconazole

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13
Q

Voriconazole

MOA:

Effect

A

MOA:
Inhibits CYP 2C9, CYP 3A4 ,CYP 2C19

Effects are↑ levels of:
Sirolimus, tacrolimus, cyclosporine, warfarin – lead to toxicity

Clinical uses:
1) Invasive aspergillosis
2) Esophageal candidiasis
3) Candedemia

Adverse effects:
1) Visual disturbances
2) Hepatotoxicity
3) Phototoxicity (SJS)
4) Confusion/hallucinations
5) Nephrotoxicity

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14
Q

MOA:
Inhibits CYP 2C9, CYP 3A4 ,CYP 2C19

Effects are↑ levels of:
Sirolimus, tacrolimus, cyclosporine, warfarin – lead to toxicity

Clinical uses:
1) Invasive aspergillosis
2) Esophageal candidiasis
3) Candedemia

Adverse effects:
1) Visual disturbances
2) Hepatotoxicity
3) Phototoxicity (SJS)
4) Confusion/hallucinations
5) Nephrotoxicity

A

Voriconazole

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15
Q

Itraconazole

MOA:

Effect

Clinical uses:

Adverse effects:

A

MOA:
Inhibits CYP 3A4

Effects are↑ levels of:
1) Cisapride, Astemizole, Terfinadine - severe cardiac arrythmias
2) Cyclosporine, Midazolam

Clinical uses:
1) Meningeal infections (H. capsulatum, C. immitis, P.brasiliensis)
2) Invasive aspergillosis (lungs)
3) Sublingual onychomycosis
4) AIDs associated histoplasmosis
5) Oropharyngeal/esophagitis candidiasis

Adverse effects:
1) Hepatotoxicity
2) Rash
3) Hypokalemia
4) N/V
5) Adrenal insufficiency, edema, & HTN (high doses)

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16
Q

MOA:
Inhibits CYP 3A4

Effects are↑ levels of:
1) Cisapride, Astemizole, Terfinadine - severe cardiac arrythmias
2) Cyclosporine, Midazolam

Clinical uses:
1) Meningeal infections (H. capsulatum, C. immitis, P.brasiliensis)
2) Invasive aspergillosis (lungs)
3) Sublingual onychomycosis
4) AIDs associated histoplasmosis
5) Oropharyngeal/esophagitis candidiasis

Adverse effects:
1) Hepatotoxicity
2) Rash
3) Hypokalemia
4) N/V
5) Adrenal insufficiency, edema, & HTN (high doses)

A

Itraconazole

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17
Q

Posaconazole

MOA:

Effect

Clinical uses:

Adverse effects:

A

MOA:
Inhibits CYP 3A4

Effects are↑ levels of:
1) Tacrolimus, cyclosporine, sirolimus, midazolam – increased toxicity

AVOID with drugs that prolong Qtc interval (methadone, haloperidol, pimozide, quinidine, risperidone, halofantrine)

CLinical uses:
Refractory oropharyngeal candidiasis
Aspergillosis
Mucormycosis

Adverse effects:
1) Gi upset & headache
2) Hepatotoxicity

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18
Q

MOA:
Inhibits CYP 3A4

Effects are↑ levels of:
1) Tacrolimus, cyclosporine, sirolimus, midazolam – increased toxicity

AVOID with drugs that prolong Qtc interval (methadone, haloperidol, pimozide, quinidine, risperidone, halofantrine)

CLinical uses:
Refractory oropharyngeal candidiasis
Aspergillosis
Mucormycosis

Adverse effects:
1) Gi upset & headache
2) Hepatotoxicity

A

Posaconazole

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19
Q

Echinocandins

MOA:

Clinical use:

Adverse effects:

A

Anidulafungin, Caspofungin, & Micafungin

MOA:
Inhibits B-glucan synthesis

Clinical use:
1) Invasive candidiasis (Caspo & Andidula)
2) Esophageal candidiasis
3) Invasive aspergillosis (Caspo)

Adverse effects:
Gi upset
Phlebitis
Flushing (histamine)
Hepatotoxicity

20
Q

Anidulafungin, Caspofungin, & Micafungin

MOA:
Inhibits B-glucan synthesis

Clinical use:
1) Invasive candidiasis (Caspo & Andidula)
2) Esophageal candidiasis
3) Invasive aspergillosis (Caspo)

Adverse effects:
Gi upset
Phlebitis
Flushing (histamine)
Hepatotoxicity

A

Echinocandins

21
Q

Griseofulvin

MOA:

Clinical use:

Adverse effects:

A

MOA:
Inhibits microtubule formation to disrupt mitosis (eat with a fatty meal)

Clinical use:
1) Dermatophytes (tinea & ring worm)
2) Onychomycoses (nail infection)

Adverse effects:
1) Peripheral neuritis, dizziness, headaches
2) Hepatotoxicity
3) Albuminuria
4) Disulfiram-like reaction
5) Induce CYP450 (reduce warfarin levels)
6) Photosensitivity rash

22
Q

MOA:
Inhibits microtubule formation to disrupt mitosis (eat with a fatty meal)

Clinical use:
1) Dermatophytes (tinea & ring worm)

Adverse effects:
1) Peripheral neuritis, dizziness, headaches
2) Hepatotoxicity
3) Albuminuria
4) Disulfiram-like reaction
5) Induce CYP450 (reduce warfarin levels)

A

Griseofulvin

23
Q

Topical antifungals:

Clomitrazole (clinical use)

A

Vaginal:

Dermatophyte infections
Cutaneous candidiasis

24
Q

Topical antifungals:

Miconazole (clinical use)

A

Tinea infections
Vulvovaginitis

25
Q

Topical antifungals:

Tioconazole

A

Candida vulvovaginitis

26
Q

Topical antifungals:

Oxiconazole, Sulconazole, & Sertaconazole (clinical use)

A

Dermatophyte infections

27
Q

Topical antifungals:

Terconazole & Buticonazole (Clinical use)

A

Vaginal candidiasis

28
Q

Topical antifungals:

Ciclopirox & Olamine (clinical use)

A

Broad spectrum for:
C. albicans
E. floccosum
M. canis
T. mentagrophytes
T. rubrum
Malassezia furfur

29
Q

Topical antifungals:

Haloprogin (clinical use)

A

Dermatophyte infections

30
Q

Topical antifungals:

Tolnaftate (clinical use)

A

Cutaneous mycoses

31
Q

Topical antifungals:

Naftifine & Terbinafine (clinical uses)

A

Broad spectrum:
Tinea infections

32
Q

Topical antifungals:

Nyastatin (clinical use)

A

Candidiasis only (cutaneous, oral, vaginal etc)

33
Q

What does Pyrimethamine treat?

A

Toxoplasmosis

34
Q

What do Suramin & Melarsoprol treat?

A

Trypanosoma brucei

35
Q

What does Nifurtimox treat?

A

T. cruzi (chagas)

36
Q

What does Sodium Stibogluconate treat?

A

Leishmaniosis

37
Q

Chloroquine

MOA:

Clinical use:

Adverse effects:

Resistance:

A

MOA:
Inhibits the detoxification of heme into hemozoin

Clinical use:
Antimalarial (plasmodium spp)

Adverse effects:
1) Retinopathy
2) Pruritis (dark skinned people)

Resistance:
Efflux pump

For P. falciparum use Atroquore & Proguanil

38
Q

MOA:
Inhibits the detoxification of heme into hemozoin

Clinical use:
Antimalarial (plasmodium spp)

Adverse effects:
1) Retinopathy
2) Pruritis (dark skinned people)

Resistance:
Efflux pump

For P. falciparum use Atroquore & Proguanil

A

Chloroquine

39
Q

What do Pyrantel pamoate, Mebendazole, & Ivermectin treat?

A

Microtubule inhibitors that treat helminth infections

40
Q

What does Praziquantol treat?

A

An antihelminth that causes increased Ca2+ & vacuolization in helminths

41
Q

Antifungals that inhibit cell wall synthesis?

A

Echinocandins (fungins)

42
Q

Antifungals that inhibit cell membrane integrity?

A

Polyenes (amphotericin B & Nystatin)

43
Q

Antifungals that inhibit nucleic acid synthesis?

A

Flucytosine

44
Q

Antifungals that inhibit Ergosterol synthesis?

45
Q

Antifungals that inhibit Lanosterol synthesis?

A

Terbinafine

Pharm SJSM (23 decks)

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