Pharmacology - Antifungal Agents

Front 1

Aspergillosis
Immunosuppressed Txn

Back 1

- amphotericin B
- voriconazole

Front 2

Aspergillosis
Nonimmunosuppressed Txn

Back 2

- amphotericin B
- itraconazole
- voriconazole

Front 3

Blastomycosis
rapidly progressive or CNS Txn

Back 3

- amphotericin B

Front 4

Coccidioidomycosis
rapidly progressing txn

Back 4

- amphotericin B

Front 5

Coccidioidomycosis
meningeal

Back 5

- fluconazole
- intrathecal amphotericin B

Front 6

Crytococcosis
Non-AIDS txn

Back 6

- amphotericin B +/- flucytosine

Front 7

Crytococcosis
AIDS (maintenance) txn

Back 7

- fluconazole

Front 8

Histoplasmosis
chronic pulmonary txn

Back 8

- itraconazole

Front 9

histoplasmosis
disseminated (rapidly progressing) txn

Back 9

- amphotericin b

Front 10

histoplasmosis
disseminated (AIDS) txn

Back 10

- itraconazole

Front 11

Deep mycoses list

Back 11

- aspergillosis
- blastomycosis
- coccidioidomycosis
- crytococcosis
- histoplasmosis

Front 12

Candidiasis
vulvovaginal txn

Back 12

topical
- butoconazole, clotrimazole
- miconazole, nystatin
- terconazole, tioconazole
oral
- fluconazole

Front 13

Candidiasis
oropharyngeal txn

Back 13

topical
- amphotericin b, clotrimazole
- nystatin
oral
- fluconazole, itraconazole
- ketoconazole

Front 14

Candidiasis
cutaneous txn

Back 14

topical
- amphotericin b, clotrimazole
- econazole, ketoconazole
- miconazole, nystatin

Front 15

Superficial mycoses list

Back 15

- candidiasis
- ringworm

Front 16

Ringworm txn

Back 16

topical
- clotrimazole, econazole
- ketoconazole, miconazole
- naftifine, ciclopirox, terbinafine
oral
- griseofulvin
- itraconazole
- terbinafine

Front 17

Prokaryotes characteristics

Back 17

- lack nuclear membrane
- bacterias

Front 18

Eukaryotes characteristics

Back 18

- membrane enclosed nucleus
- includes fungi
- membranes in cell made up of lipids, proteins, cholesterol, and glycoproteins leading to side effects

Front 19

Fungi cell wall consists of:

Back 19

- glucan
- chitin
- mannan
- etc

Front 20

ergosterol

Back 20

sterol of fungi cell membrane that is not found in humans; major target

Front 21

Polyene antifungal agents

Back 21

- amphotericin b
- nystatin

Front 22

Amphotericin B
mechanism of action

Back 22

- fungicide produced by Streptmyces nodosus
- similar to membrane sterols
- binds to sterol component of fungal membrane and disrupts membrane permeability (creating pores), leading to cell death
- greater affinity toward ergosterol
- kidney cells and erythrocytes are mostly affected

Front 23

Amphotericin B
Pharmacokinetics

Back 23

- insoluble in aqueous solution
- no GI absorption
- poor penetration into CNS
- highly protein bound at 90%
- excreted unchanged in urine

Front 24

Amphotericin B
Antifungal activity

Back 24

broad spectrum
- cryptococcosis
- histoplasmosis
- coccidiodomycosis
- aspergillosis

Front 25

Amphotericin B
adverse reactions

Back 25

- dose dependent (can be severe)
- shaking chills, fever
- myalgias
- arthralgias
- fever and chills thought to be due to induction of tumor necrosis factor or production of prostaglandin E by macrophages
- thrombophlebitis at site of infusion (prophylaxis with heparin)

Front 26

Amphotericin B
chronic adverse effects

Back 26

- anemia (suppression of erythropoietin)
- renal dysfunction (reversible)
- increase in serum creatinine
- potassium and magnesium wasting

Front 27

Amphotericin B
monitoring parameters

Back 27

- complete blood counts
- serum creatinine
- potassium
- magnesium

Front 28

Ampho.B

Back 28

new and improved amphotericin B; goal was to improve delivery and decrease toxicity

Front 29

Ampho.B incorporated into:

Back 29

:lipid preparations
- allows larger doses
- nephrotoxicity reduced
- acute infusion related adverse effects still present
- premedication still necessary
- expensive

Front 30

Ampho.B used for pts w/:

Back 30

:impaired renal function or who develop nephrotoxicity on conventional Ampho.B

Front 31

Ampho.B agents

Back 31

- abelcet
- amphocil
- ambisone

Front 32

Nystatin
mechanism of action

Back 32

- similar to amphotericin B

Front 33

Nystatin
phamacokinetics

Back 33

- not absorbed orally
- only topical and mucous membrane formulations

Front 34

Nystatin
Indications

Back 34

- Skin, oral, GI, and vaginal candidiasis

Front 35

Nystatin
Adverse reactions

Back 35

- not much
- allergic reactions

Front 36

Pyrimidine antifungal agents

Back 36

- flucytosine

Front 37

Flucytosine
mechanism of action

Back 37

- developed as antitumor agent
- thymidylate synthetase impairs fungal DNA synthesis
- humans do not possess enzyme, cytosine deaminase

Front 38

Flucytosine
pharmacokinetics

Back 38

- rapidly and well absorbed from GI tract
- excreted unchanged in urine

Front 39

Flucytosin
clinical activity

Back 39

- widely distributed thru body, even in cerebrospinal fluid
- resistance develop rapidly (loss of deaminase)

Front 40

Drugs used for cyptococcal meningitis txn

Back 40

- flucytosine +
- amphotericin B

Front 41

Flucytosin
adverse reactions

Back 41

- bone marrow suppression - leukopenia, thrombocytopenia
- enterocolitis
- increased liver enyzmes but reversible after therapy stopped

Front 42

Azole list

Back 42

- imidazoles
- triazoles

Front 43

Imidazoles list

Back 43

- clotrimazole
- miconazole
- ketoconazole
- econazole
- butoconazole
- oxiconazole

Front 44

Triazoles list

Back 44

- terconazole
- itraconazole
- fluconazole
- variconazole

Front 45

Azole has antifungal activity against:

Back 45

- C. albicans
- Candida tropicalis
- Candida glabrata
- C. neoformans
- B. dermatitidis
- H. capsulatum
- C. immitis
- Paracoccidioides brasiliensis
- ringworm fungi
- aspergilus spp
- S. schenckii

Front 46

Azole
mechanism of action

Back 46

- inhibits sterol 14-a-demethylase (part of microsomal cytochrome P450-dependent enzyme system)
- impairs biosynthesis of ergosterol

Front 47

Ketoconazole
pharmacokinetics

Back 47

- oral
- acidic envt required for ketoconazole dissolution
- metabolized in liver

Front 48

Flucytosine
pharmacokinetics

Back 48

- rapidly and well absorbed from GI tract
- excreted unchanged in urine

Front 49

Flucytosin
clinical activity

Back 49

- widely distributed thru body, even in cerebrospinal fluid
- resistance develop rapidly (loss of deaminase)

Front 50

Drugs used for cyptococcal meningitis txn

Back 50

- flucytosine +
- amphotericin B

Front 51

Flucytosin
adverse reactions

Back 51

- bone marrow suppression - leukopenia, thrombocytopenia
- enterocolitis
- increased liver enyzmes but reversible after therapy stopped

Front 52

Azole list

Back 52

- imidazoles
- triazoles

Front 53

Imidazoles list

Back 53

- clotrimazole
- miconazole
- ketoconazole
- econazole
- butoconazole
- oxiconazole

Front 54

Triazoles list

Back 54

- terconazole
- itraconazole
- fluconazole
- variconazole

Front 55

Azole has antifungal activity against:

Back 55

- C. albicans
- Candida tropicalis
- Candida glabrata
- C. neoformans
- B. dermatitidis
- H. capsulatum
- C. immitis
- Paracoccidioides brasiliensis
- ringworm fungi
- aspergilus spp
- S. schenckii

Front 56

Azole
mechanism of action

Back 56

- inhibits sterol 14-a-demethylase (part of microsomal cytochrome P450-dependent enzyme system)
- impairs biosynthesis of ergosterol

Front 57

Ketoconazole
pharmacokinetics

Back 57

- oral
- acidic envt required for ketoconazole dissolution
- metabolized in liver

Front 58

Decrease ketoconazole bioavailability with:

Back 58

:H2-histamine blockers or proton pump inhibitors

Front 59

Ketoconazole
adverse reactions

Back 59

- dose-dependent GI symptoms
- allergy
- menstual irregularities
- gynecomastia
- decrease libido and potency
- increase asymptomatic elevation liver fxn tests

Front 60

Ketoconazole
drug interactions

Back 60

- cytochrome P450 enzyme inhibitor

Front 61

Ketoconazole
anti-fungal activity

Back 61

- candida but not good enough for aspergillus

Front 62

Itraconazole
pharmacokinetics

Back 62

- oral and IV
- capsules - better absorption at acidic envt
- oral solutions - absorption better on empty stomach
- highly protein bound for both parent drug and metabolit
- metabolized by liver, potent enzyme inhibitor

Front 63

Itraconazole
adverse reactions

Back 63

- GI, hypertriglyceridemia
- hypokalemia
- increased LFTs
- potential adverse effects resulting from interaction with other drugs

Front 64

Itraconazole
drug interactions

Back 64

- plenty due to potent enzyme inhibiting effects

Front 65

Itraconazole
antifungal activity

Back 65

- candidas
- aspergillus

Front 66

Fluconazole
pharmacokinetics

Back 66

- oral and IV
- well absorbed from GI tract
- bioavailability not affected by food
- <15% protein bound
- >90% eliminated by kidney
- less susceptible to drug interactions

Front 67

Fluconazole
antifungal activity

Back 67

- similar to ketoconazole
- very good CNS penetration

Front 68

Fluconazole
adverse reactions

Back 68

- reversible alopecia
- should not be used during pregnancy
- elevated LFTs, rare cases of hepatic failure

Front 69

Fluconazole
drug interactions

Back 69

- not much clinically significant drug interaction at low doses

Front 70

Voriconazole
pharmacokinetics

Back 70

- oral and IV
- well absorbed
- 60% protein bound
- hepatic metabolism
- half-life is variable - nonlinear kinetics; depends dose
- adjust dose for renal compromised pts

Front 71

Voriconazole
antifungal activity

Back 71

- candida
- aspergillus

Front 72

Voriconazole
adverse reactions

Back 72

- visual changes (photophobia, color changes, blurred visions)
- cardiovascular (HTN, tachycardia, hypotentions, peripheral edema)
- CNS (fever, headache, dizziness, hallucinations)
- rash, hepatoxicity

Front 73

Voriconazole
drug interactions

Back 73

- hepatic enzyme inhibitors
- plenty of drug interactions

Front 74

Posaconazole
pharmacokinetics

Back 74

- well absorbed with food
- >90% protein bound
- hepatic metabolism
- feces excretion (60% unchanged)

Front 75

Posaconazole
activity

Back 75

- aspergillus
- candida
- zygomycetes

Front 76

Posaconazole
adverse reactions

Back 76

- GI, HTN, increased LFTs
- hypokalemia
- HA, dizziness

Front 77

Posaconazole
drug interactions

Back 77

- moderate inhibitor of CYP3A4 enzymes

Front 78

Topical imidazoles and triazoles formulations list

Back 78

- clotrimazole
- miconazole
- terconazole
- butoconazole
- tioconazole
- oxiconazole

Front 79

Topical imidazoles and triazoles effective for:

Back 79

:many superficial infections
- dermatophytosis (ringworm)
- candidiasis
- tinea versicolor
- piedra
- tinea nigra
- fungal keratitis

Front 80

Imidazoles and triazoles topical formulations are not effective for:

Back 80

:mycoses of the nails and hair

Front 81

Echinocandins list

Back 81

- caspofungin
- micafungin
- anidulafungin

Front 82

Echinocandins - caspofungin, micafungin, anidulafungin
mechanism of action

Back 82

- inhibits cell wall synthesis of glucan which is essential component of cell wall (not in mammals)

Front 83

Echinocandins - caspofungin, micafungin, anidulafungin
pharmacokinetics

Back 83

- IV
- highly protein bound and hepatic metabolism
- minimal CNS penetration

Front 84

Echinocandins
adverse reactions

Back 84

- inc LFTs, serum alkaline phosphatase
- infusion site rxns histamine-mediated symptoms

Front 85

Echinocandins
drug interactions

Back 85

- neither an inducer nor an inhibitor

Front 86

Increases level of caspofungin

Back 86

cyclosporin; increased risk for transient elevations of LFTs

Front 87

Echinocandins
therapeutic uses

Back 87

- systemic fungal infections
(aspergillus and candida species)

Front 88

Griseofulvin
mechanism of action

Back 88

- inhibits fungal cell mitosis
- binds to human keratin and makes it resistant to fungal invasion

Front 89

Griseofulvin
pharmacokinetics

Back 89

- poor absorption, fatty meal can improve absorption
- eliminated renally

Front 90

Griseofulvin
adverse reactions

Back 90

- headache
- peripheral neuritis, lethargy, mental confusion
- fatigue, syncope, vertigo
- hepatotoxicity
- hematologic effects - leukopenia, neutropenia, basophilia
- photosensitivity
- albuminuria

Front 91

Griseofulvin
drug interactions

Back 91

- hepatic enzyme inducers (warfarin, OCP)

Front 92

Griseofulvin
therapeutic uses

Back 92

- mycotic disease of the skin, hair and nails

Front 93

Terbinafine
mechanism of action

Back 93

- inhibits squalene epoxidase and leads to deficiency in ergosterol w/in fungal cell wall resulting in death

Front 94

Terbinafine
pharmacokinetics

Back 94

- well absorbed
- 99% protein bound
- accumulates in skin, nails and fat
- releases slowly from skin and adipose tissues
- hepatic metabolism (no effect on CYP)
- renally excreted

Front 95

Terbinafine
adverse reactions

Back 95

- very well tolerated, minimal GI
- uncommon hepatoxicity, severe neutropenia, stevens-johnson syndrome

Front 96

Terbinafine
drug interaction

Back 96

- not many, cimetidine may increase its level

Front 97

Terbinafine
therapeutic uses

Back 97

- mycoses of nails
- ringworm
- pulse therapy

Front 98

Tolnaftate
class

Back 98

thiocarbamate

Front 99

Tolnaftate
MOA

Back 99

suppression of fungal squalene epoxidase to result in accumulation of squalene and decreased ergosterol production

Front 100

Naftifine
class

Back 100

allylamine

Front 101

Terbinifine
class

Back 101

allylamine

Front 102

Naftifine
MOA

Back 102

suppression of fungal squalene epoxidase to result in accumulation of squalene and decreased ergosterol production

Front 103

Terbinifine
MOA

Back 103

suppression of fungal squalene epoxidase to result in accumulation of squalene and decreased ergosterol production

Front 104

Griseofulvin
class

Back 104

benzofuran cyclohexene

Front 105

Griseofulvin
MOA

Back 105

binding to fungal RNA to cause malformation of spindle and cytoplasmin microtubules

Front 106

Amphotericin B
class

Back 106

polyene

Front 107

Nystatin
class

Back 107

polyene

Front 108

Amphotericin B
MOA

Back 108

binding to ergosterol in fungal cell membranes to result in membrane disorganization

Front 109

Nystatin
MOA

Back 109

binding to ergosterol in fungal cell membranes to result in membrane disorganization

Front 110

5-Fluorocystosine
class

Back 110

pyrimidine

Front 111

5-Fluorocystosine
MOA

Back 111

deamination by fungal cells to 5-fluorouracil which is incorporated into RNA in place of uracil

Front 112

Clotrimazole, miconazole, ketoconazole, fluconazole, itraconazole, terconazole, voriconazole, posaconazole
class

Back 112

azole

Front 113

Clotrimazole, miconazole, ketoconazole, fluconazole, itraconazole, terconazole, voriconazole, posaconazole
MOA

Back 113

Inhibition of cytochrome P-450 that catalyzes 14 α- demethylation of lanosterol to ergosterol, accumulation of 14-methylated sterols cause permeability disruption

Front 114

Caspofungin, micafungin, anidulafungin
class

Back 114

Echinocandins

Front 115

Caspofungin, micafungin, anidulafungin
MOA

Back 115

inhibition of cell wall glucan synthesis