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Pharmacology > 27) Anti-Fungals > Flashcards

27) Anti-Fungals Flashcards

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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
Nystatin side effects
- Mostly GI - Diarrhea - Nausea - Stomach pain
26
Azoles
- Inhibition of ergosterol synthesis | - Inhibit the step 14 α-demethylation of lanosterol (which is catalyzed by a fungal cytochrome P450 isozyme)
27
Imidazole (non-selective azoles) names
- Ketoconazole (tablets, topical) - Clotrimazole (lozenges, topical) - Miconazole (tablets, topical)
28
Ketoconazole CI/warnings
- Hypersensitivity
29
Ketoconazole side effects
- Adrenal suppression - Bone fragility - Prthostatic hypotension - Fatigue - Pruritis - Decrease in platelets count - Menstrual irregularities - Decreased libido, impotency, - Gynecomastia
30
Ketoconazole pharmacokinetics
- Well distributed in body except in BBB | - Metabolized hepatically
31
All non-selective imidazole (azoles) pharmacokinetics
- Substrate and inhibitor of CYP3A4
32
All non-selective imidazole (azoles) US box warning
- Hepatotoxicity | - QT prolongation
33
Imidazole (non-selective) MOA
- Inhibits adrenal and gonadal sterioids
34
Clotrimazole CI/warnings
- Hypersensitivity | - Hepatic impairment
35
Clotrimazole side effects
- Increase LFT - Pruritis - Nausea, vomiting
36
Miconazole CI/warnings
- Hypersensitivity | - Hepatic impairment
37
Miconazole brand name
- Oravig
38
Miconazole side effecs
- Headache - Pruritis - Nausea - Diarrhea
39
Triazoles (selective azols) names
- Fluconazole (PO and IV) - Itraconazole (capsule, solution) - Voriconazole (tablets, IV) - Posaconazole (tablet, IV) - Terconazole (vaginal cream, suppositories) - Isavuconazonium sulfate (capsule, solution)
40
Fluconazole brand name
- Diflucan
41
Itraconazole brand name
- Onmel - Sporanox - Pulsepak
42
Voriconazole brand name
- Vifend
43
Posacnonazole brand name
- Noxafil
44
Terconazole brand names
- Terazol | - Zazole
45
Isavuconazon brand name
- Cresemba
46
Fluconazole (Difulcan) side effects
- Arrythmias - Dizziness - Seizures - Hepatotoxicity - Prolongs QT interval
47
Fluconazole (Difulcan) pharmacokinetics
- Inhibitor of CYP2C19 - Crosses BBB - Excreted in the urine
48
Itraconazole (Onmel, Sporanox, Pulsepak) CI/warnings
- US Box warning: congestive heart failure (CHF)
49
Itraconazole (Onmel, Sporanox, Pulsepak) side effects
- CNS depression - Hearing loss - Heart failure - Hepatotoxicity - Neuropathy - Diarrhea - Nausea - Hypertension - Increase LFTs
50
Itraconazole (Onmel, Sporanox, Pulsepak) pharmacokinetics
- Substrate of CYP3A4 | - Food increase its absorption
51
Voriconazole (Vifend) CI/warnings
- Arrythmia, QT prolongation - Blurred vision - Renal toxicity
52
Voriconazole (Vifend) side effects
- Tachycardia - Hypokalemia - Increase LFTs - Hepatotoxicity - Increased serum creatinine - Visual changes - Intensified hallucinations
53
Voriconazole (Vifend) pharmacokinetics
- Substrate for CYP2C19 and CYP2C9 - Inhibits CYP2C19 - Crosses BBB
54
Posaconazole (Noxafil) CI/warnings
- Arrythmia | - Renal impairment
55
Posaconazole (Noxafil) side effects
- Thrombophlebitis - Hyper/hypotension - Tachycardia - Hepatotoxicity - Hypokalemia, hypocalcemia hypomagnesemia - Hyperglycemia
56
Posaconazole (Noxafil) pharmacokinetics
- Substrate for UGT1A4 | - Excretion in feces
57
Terconazole (Terazol, Zazole) CI/warnings
- Epidermal necrolysis: life-threatening dermatologic disorder characterized by spread erythema, necrosis
58
Terconazole (Terazol, Zazole) side effects
- Headaches - Abdominal pain - Dysmenorrhea
59
Terconazole (Terazol, Zazole) pharmacokinetics
- Not known
60
Isavuconazon (Cresemba) side effects
- Hepatotoxicity - Peripheral edema - Hypokalemia, hypotension - Hypomagnesemia, hypoalbuminemia, hypoglycemia, hyponatremia - Hematuria, agranulocytosis - Leukopenia - Back pain
61
Isavuconazon (Cresemba) pharmacokinetics
- Substrate for CYP3A4
62
ALL triazole (selective) azoles share CI/warning with
- Hypersensitivity
63
ALL triazole (selective) azoles are inhibitors of
- CYP3A4
64
ALL triazole (selective) azoles lack
- Endocrine side effects
65
Allylamine derivative
- Terbinafine
66
Allylamine derivative (terbinafine) MOA
- 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
Allylamine derivative (terbinafine) contraindication
- Hypersensitivity
68
Allylamine derivative (terbinafine) adverse effects
- 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
Allylamine derivative (terbinafine) pharmacodynamics
- Renally excreted | - Inhibits CYP2D6
70
Echinocandins (cell wall inhibitors)
- Caspofungin - Anidulafungin - Micafungin
71
Echinocandins (caspofungin, anidulafungin, micafungin) MOA
- Inhibit the synthesis of β-(1-3) glucan (a critical component of fungal cell wall)
72
Echinocandins (caspofungin, anidulafungin, micafungin) contraindication
- Hypersensitivity
73
Caspofungin and micafungin (echinocandins) pharmacokinetics
- Hepatically metabolized | - Renally excreted
74
Anidulafungin (echinocandins) pharmacokinetics
- Renally excreted only
75
Caspofungin and anidulafungin (echinocandins) side effects
- Hypotension - Headaches - Skin rash - Anemia - Increase serum creatinine - Hyperglycemia - Hypomagnesemia, hypokalemia - NVD
76
Micafungin (echinocandins) side effects
- Neutropenia - Thrombocytopenia - Anemia - Hypernatremia - Hypomagnesemia, hypokalemia
77
ALL echinocandins...
- Increase FLTs | - Have infusion side effects
78
Nucleic acid inhibitor
- Flucytosine (5-FC)
79
Flucytosine (5-FC)
- Nucleic acid inhibitor | - Antimetabolite specifically uracil/pyramidine analogue
80
Flucytosine (5-FC) MOA
- 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
Humans lack
- Permease | - Cytosine deaminase
82
Flucytosine (5-FC) contraindication
- Hypersensitivity
83
Flucytosine (5-FC) side effects
- 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
Flucytosine (5-FC) pharmacokinetics
- Renally excreted unchanged - Widely distributed, penetrates well the CSF - Fungistatic
85
Anti-mitotic
- Griseofulvin
86
Griseofulvin (anti-mitotic) MOA
- Interferes with microtubule function in dermatophytes (ringworms) - Inhibit the synthesis of nucleic acids - Inhibit fungal cell mitosis at metaphase
87
Griseofulvin (anti-mitotic) pharacokinetics
- Fungistatic - Hepatically metabolized - Induction of hepatic CYT P450 by griseofulvin

Pharmacology (27 decks)

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