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Pharmacology > 27) Anti-Fungals > Flashcards

27) Anti-Fungals Flashcards

1
Q

Drugs acting on fungi actions

A
  • Alter cell membrane permeability
  • Block beta-glucan synthesis
  • Block nucleic acid synthesis
  • Disrupt microtubule functions
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2
Q

Anti-fungals altering cell membrane permeability

A
  • Azoles
  • Polyenes
  • Terbinafine
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3
Q

Anti-fungals that block beta-glucan synthesis

A
  • Echinocandins
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4
Q

Anti-fungals that block nucleic acid synthesis

A
  • Flucytosine
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5
Q

Anti-fungals that disrupt microtubule functions

A
  • Griseofulvin
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6
Q

Ergosterol

A
  • Sterol found in cell membranes of fungi

- Role like cholesterol in humans to keep the membrane integrity and fluidity

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7
Q

Polyene antibiotics (amphipathic)

A
  • Amphotericin B

- Nystatin

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8
Q

Polyene

A
  • Molecule with multiple conjugated double bonds
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9
Q

Amphotericin B and nystatin MOA

A
  • Change the permeability and transport properties of the fungal membrane
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10
Q

Polyenes’ lipophilic (or hydrophobic) region

A
  • Binds to ergosterol via hydrophobic interactions

- Causes formation of artificial pores, leading to leakage and cell death

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11
Q

Reduction of amphotericin B hydrophobic chain

A
  • May result in polyene binding to cholesterol

- Makes it toxic to animals/humans

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12
Q

Amphotericin B pharmacokinetics

A
  • Distributes to all tissues except CNS
  • Unknown metabolism
  • Hepatic elimination
  • T1/2 = 2 weeks
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13
Q

Amphotericin B immediate toxicity

A
  • Fever, chills
  • Muscle pain
  • Headache
  • Vomiting
  • Hpotension
  • Infusion reaction
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14
Q

Amphotericin B late toxicity

A
  • Reversible renal damage
  • Renal tubular acidosis, hypokalemia, hypomagnesemia
  • Abnormal liver function test (LFT)
  • Anemia and loss of erythropoietin formation
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15
Q

Cerebral damage associated with amphotericin B toxicity

A
  • When given intrathecally there is a risk of neurologic effects as seizures
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16
Q

Amphotericin B deoxycholate

A
  • Conventional form

- Deoxycholate to improve solubility

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17
Q

Amphotericin B lipid complex (ABLC)

A
  • Abelcet (brand)

- Linked to 2 phospholipids

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18
Q

Liposomal Amphotericin B (L-amphB)

A
  • Ambisome (brand)

- Liposome

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19
Q

Amphotericin B colloidal dispersion

ABCD

A
  • In cholesterol; lipid disk

- Amphotec (brand)

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20
Q

Amphotericin B lipid formulations

A
  • Amphotericin B lipid complex (ABLC)
  • Liposomal Amphotericin B (L-amphB)
  • Amphotericin B colloidal dispersion
    (ABCD)
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21
Q

Amphotericin B lipid formulations characteristics

A
  • Better tolerated
  • Less renal toxicity
  • Less infusion-related SE
  • Release the drug at the site of action
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22
Q

Amphotericin B side effects

A
  • Hypotension
  • Headache, chills
  • Hypokalemia
  • Hypomagnesemia
  • Anorexia, diarrhea, nausea, vomiting
  • Anemia
  • Local: pain at injection site
  • Respiratory: tachypnea
  • Fever
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23
Q

Nystatin characteristics

A
  • Bio-statin (brand)

- Poorly absorbed

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24
Q

Nystatin contraindication

A
  • Hypersensitivity
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25
Q

Nystatin side effects

A
  • Mostly GI
  • Diarrhea
  • Nausea
  • Stomach pain
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26
Q

Azoles

A
  • Inhibition of ergosterol synthesis

- Inhibit the step 14 α-demethylation of lanosterol (which is catalyzed by a fungal cytochrome P450 isozyme)

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27
Q

Imidazole (non-selective azoles) names

A
  • Ketoconazole (tablets, topical)
  • Clotrimazole (lozenges, topical)
  • Miconazole (tablets, topical)
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28
Q

Ketoconazole CI/warnings

A
  • Hypersensitivity
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29
Q

Ketoconazole side effects

A
  • Adrenal suppression
  • Bone fragility
  • Prthostatic hypotension
  • Fatigue
  • Pruritis
  • Decrease in platelets count
  • Menstrual irregularities
  • Decreased libido, impotency, - Gynecomastia
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30
Q

Ketoconazole pharmacokinetics

A
  • Well distributed in body except in BBB

- Metabolized hepatically

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31
Q

All non-selective imidazole (azoles) pharmacokinetics

A
  • Substrate and inhibitor of CYP3A4
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32
Q

All non-selective imidazole (azoles) US box warning

A
  • Hepatotoxicity

- QT prolongation

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33
Q

Imidazole (non-selective) MOA

A
  • Inhibits adrenal and gonadal sterioids
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34
Q

Clotrimazole CI/warnings

A
  • Hypersensitivity

- Hepatic impairment

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35
Q

Clotrimazole side effects

A
  • Increase LFT
  • Pruritis
  • Nausea, vomiting
36
Q

Miconazole CI/warnings

A
  • Hypersensitivity

- Hepatic impairment

37
Q

Miconazole brand name

A
  • Oravig
38
Q

Miconazole side effecs

A
  • Headache
  • Pruritis
  • Nausea
  • Diarrhea
39
Q

Triazoles (selective azols) names

A
  • Fluconazole (PO and IV)
  • Itraconazole (capsule, solution)
  • Voriconazole (tablets, IV)
  • Posaconazole (tablet, IV)
  • Terconazole (vaginal cream, suppositories)
  • Isavuconazonium
    sulfate (capsule, solution)
40
Q

Fluconazole brand name

A
  • Diflucan
41
Q

Itraconazole brand name

A
  • Onmel
  • Sporanox
  • Pulsepak
42
Q

Voriconazole brand name

A
  • Vifend
43
Q

Posacnonazole brand name

A
  • Noxafil
44
Q

Terconazole brand names

A
  • Terazol

- Zazole

45
Q

Isavuconazon brand name

A
  • Cresemba
46
Q

Fluconazole (Difulcan) side effects

A
  • Arrythmias
  • Dizziness
  • Seizures
  • Hepatotoxicity
  • Prolongs QT interval
47
Q

Fluconazole (Difulcan) pharmacokinetics

A
  • Inhibitor of CYP2C19
  • Crosses BBB
  • Excreted in the urine
48
Q

Itraconazole (Onmel, Sporanox, Pulsepak) CI/warnings

A
  • US Box warning: congestive heart failure (CHF)
49
Q

Itraconazole (Onmel, Sporanox, Pulsepak) side effects

A
  • CNS depression
  • Hearing loss
  • Heart failure
  • Hepatotoxicity
  • Neuropathy
  • Diarrhea
  • Nausea
  • Hypertension
  • Increase LFTs
50
Q

Itraconazole (Onmel, Sporanox, Pulsepak) pharmacokinetics

A
  • Substrate of CYP3A4

- Food increase its absorption

51
Q

Voriconazole (Vifend) CI/warnings

A
  • Arrythmia, QT prolongation
  • Blurred vision
  • Renal toxicity
52
Q

Voriconazole (Vifend) side effects

A
  • Tachycardia
  • Hypokalemia
  • Increase LFTs
  • Hepatotoxicity
  • Increased serum creatinine
  • Visual changes
  • Intensified hallucinations
53
Q

Voriconazole (Vifend) pharmacokinetics

A
  • Substrate for CYP2C19 and CYP2C9
  • Inhibits CYP2C19
  • Crosses BBB
54
Q

Posaconazole (Noxafil) CI/warnings

A
  • Arrythmia

- Renal impairment

55
Q

Posaconazole (Noxafil) side effects

A
  • Thrombophlebitis
  • Hyper/hypotension
  • Tachycardia
  • Hepatotoxicity
  • Hypokalemia, hypocalcemia hypomagnesemia
  • Hyperglycemia
56
Q

Posaconazole (Noxafil) pharmacokinetics

A
  • Substrate for UGT1A4

- Excretion in feces

57
Q

Terconazole (Terazol, Zazole) CI/warnings

A
  • Epidermal necrolysis: life-threatening dermatologic disorder characterized by spread erythema, necrosis
58
Q

Terconazole (Terazol, Zazole) side effects

A
  • Headaches
  • Abdominal pain
  • Dysmenorrhea
59
Q

Terconazole (Terazol, Zazole) pharmacokinetics

A
  • Not known
60
Q

Isavuconazon (Cresemba) side effects

A
  • Hepatotoxicity
  • Peripheral edema
  • Hypokalemia, hypotension
  • Hypomagnesemia, hypoalbuminemia, hypoglycemia, hyponatremia
  • Hematuria, agranulocytosis
  • Leukopenia
  • Back pain
61
Q

Isavuconazon (Cresemba) pharmacokinetics

A
  • Substrate for CYP3A4
62
Q

ALL triazole (selective) azoles share CI/warning with

A
  • Hypersensitivity
63
Q

ALL triazole (selective) azoles are inhibitors of

A
  • CYP3A4
64
Q

ALL triazole (selective) azoles lack

A
  • Endocrine side effects
65
Q

Allylamine derivative

A
  • Terbinafine
66
Q

Allylamine derivative (terbinafine) MOA

A
  • Inhibit the enzyme squalene epoxidase which decreases the concentration of ergosterol in the fungal cell membrane
  • Inhibition of squalene epoxidase leads to the accumulation of squalene which is toxic to the fungi
67
Q

Allylamine derivative (terbinafine) contraindication

A
  • Hypersensitivity
68
Q

Allylamine derivative (terbinafine) adverse effects

A
  • CNS: headache
  • NVD
  • Vision color change (especially in children)
  • Upper respiratory tract infection (especially in children)
  • Depression
  • Taste disturbance
  • Reversible neutropenia
  • Hepatic failure cases
  • Thrombotic microangiopathy
69
Q

Allylamine derivative (terbinafine) pharmacodynamics

A
  • Renally excreted

- Inhibits CYP2D6

70
Q

Echinocandins (cell wall inhibitors)

A
  • Caspofungin
  • Anidulafungin
  • Micafungin
71
Q

Echinocandins (caspofungin, anidulafungin, micafungin) MOA

A
  • Inhibit the synthesis of β-(1-3) glucan (a critical component of fungal cell wall)
72
Q

Echinocandins (caspofungin, anidulafungin, micafungin) contraindication

A
  • Hypersensitivity
73
Q

Caspofungin and micafungin (echinocandins) pharmacokinetics

A
  • Hepatically metabolized

- Renally excreted

74
Q

Anidulafungin (echinocandins) pharmacokinetics

A
  • Renally excreted only
75
Q

Caspofungin and anidulafungin (echinocandins) side effects

A
  • Hypotension
  • Headaches
  • Skin rash
  • Anemia
  • Increase serum creatinine
  • Hyperglycemia
  • Hypomagnesemia, hypokalemia
  • NVD
76
Q

Micafungin (echinocandins) side effects

A
  • Neutropenia
  • Thrombocytopenia
  • Anemia
  • Hypernatremia
  • Hypomagnesemia, hypokalemia
77
Q

ALL echinocandins…

A
  • Increase FLTs

- Have infusion side effects

78
Q

Nucleic acid inhibitor

A
  • Flucytosine (5-FC)
79
Q

Flucytosine (5-FC)

A
  • Nucleic acid inhibitor

- Antimetabolite specifically uracil/pyramidine analogue

80
Q

Flucytosine (5-FC) MOA

A
  • Enters fungal cell via permease enzyme and converted by cytosine deaminase to 5-FU
  • This false nucleotide inhibits thymidylate synthase
  • Deprives organism of thymidine (which is essential for DNA synthesis)
81
Q

Humans lack

A
  • Permease

- Cytosine deaminase

82
Q

Flucytosine (5-FC) contraindication

A
  • Hypersensitivity
83
Q

Flucytosine (5-FC) side effects

A
  • Bone marrow toxicity
  • Cardiotoxicity
  • Hypoglycemia, hypokalemia
  • Ulcerative colitis
  • Azotemia
  • Anemia
  • Agranulocytosis
  • Leukopenia
  • Eosinophilia
  • Thrombocytopenia
  • Hepatic injury
  • Hearing loss
  • Increased blood urea nitrogen
  • Dyspnea
  • Fever
84
Q

Flucytosine (5-FC) pharmacokinetics

A
  • Renally excreted unchanged
  • Widely distributed, penetrates well the CSF
  • Fungistatic
85
Q

Anti-mitotic

A
  • Griseofulvin
86
Q

Griseofulvin (anti-mitotic) MOA

A
  • Interferes with microtubule function in dermatophytes (ringworms)
  • Inhibit the synthesis of nucleic acids
  • Inhibit fungal cell mitosis at metaphase
87
Q

Griseofulvin (anti-mitotic) pharacokinetics

A
  • Fungistatic
  • Hepatically metabolized
  • Induction of hepatic CYT P450 by griseofulvin

Pharmacology (27 decks)

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