P'col Exam 4

Front 1

Fungal infections are generally associated with what parts of the body?

Back 1

Skin (athletes foot) and mucous membranes (thrush)

Front 2

What are the three categories of antifungal agents?

Back 2

Systemic antifungal agents for systemic infections
Systemic antigfungal drugs for mucocutaneous infections and antifungal drugs for topical infections

Front 3

Fungal infections are fatal when?

Back 3

When the immune system is compromised or when fungi gain access to systemic circulation

Front 4

Are fungal infecitons benign or malignant?

Back 4

benign

Front 5

Cell wall synthesis?

Back 5

Caspofungin

Front 6

Membrane function

Back 6

Aphotercin B

Front 7

Nucleic Acid synthesis

Back 7

5-fluorocytosine

Front 8

Lanosterol synthesis

Back 8

Terbinafine and Nattifine

Front 9

Ergosterol synthesis

Back 9

Fluconazole
itraconazole
voriconazole

Front 10

What are the individual systemic antifungal agents for systemic infections?

Back 10

Amphotercin B
Flucytosine
Azoles
Echinocandins

Front 11

What are the systemic antifungal drugs for mucocutaneous infections?

Back 11

Griseofulvin
Terbinafine

Front 12

Antifungal drugs for toical infection?

Back 12

Nystatin
topical azoles
topical allyamines (terbinafine)

Front 13

Name some characteristics of the Amphotercin Structure

Back 13

Lacton
conjugated double bonds

Front 14

amphotercin B's solubility?

Back 14

insoluble in water, conventionall prepared as a colloid suspension for IV injection

Front 15

Ampotercin category?

Back 15

polyene macrolide

Front 16

What is the neewr formation of amphotercin B?

Back 16

Lipid-packaged

Front 17

Desribe Amphotercin B's absorption

Back 17

Poorly absorbed from the GI ( orally administered only for infection localized to GI lumen)

Front 18

Amphotercin B's Distribution

Back 18

widely distributed to most tissues, NOT in CSF
(sometimes used intrathecally for fungal meningitis)

Front 19

Can Amphotercin B get into CSF?

Back 19

NO

Front 20

Is Amphotercin B broad specturm or narrow spectrum?

Back 20

Broad Spectrum

Front 21

Name some fungus tha Amphotercin B kills?

Back 21

Candida albicans
Cryptococcous neorformans, HIstoplasma capsulatum, blastomyces dermatidis, Aspergills fumigatus

Front 22

What is ampotercin B's MOA?

Back 22

Binds to a sterol moiety, primarily ergosterol that is present in teh membrane of sensitive fungi. Then, forms pores or channels that increase teh permeability of the membrane, allowing leakage of a variety of small molecules

Front 23

What is Amphotercin B's selectivitiy?

Back 23

predominant sterol in mammalian membrane: cholesterol

Front 24

Name the two cause of resistance to Amphotercin B?

Back 24

Decreased fungus membrane concentration of ergosterol and modification of polyene binding site on ergosterol

Front 25

What is the main cause of resistance to Amphotercin b?

Back 25

due to impaired ergosterol binding

Front 26

What are the two main drug formulation for Amphotercin B?

Back 26

conventional formulation and lipid formulation for IV infusion

Front 27

Why is Amphotercin B's partical size relevant to pharmacy?

Back 27

Paritcle size for suspension 0.4 micrometers in diameter. IV lines are normally 0.22 micometers in diameter; therefore, you need a bigger pore size filter when giving this drug.

Front 28

The conventional formulation of Amphotercin B forms a ______ in water.

Back 28

colloid

Front 29

What conventional formulatiom of Amphotercin B is named?

Back 29

Amphotercin B deoxycholate complex (C-AMB)

Front 30

How many lipid formulations are in teh US?

Back 30

three

Front 31

The lipid carrier in Amphotercin B lipid formulation serves as what?

Back 31

Amphotercin B reservoir, which reduces binding to human cell membrane

Front 32

Name in order which has a higher affinity for Amphotercin B? ergosterol, cholesterol,and lipid vehicle

Back 32

ergosterol>lipid vehicle> cholesterol

Front 33

Why is there a lipid formulation for Amphotercin B?

Back 33

allow for reduction in toxicity, clinical efficacy only moderately increased,

Front 34

What is the problem with lipid formulation of Amphotercin B?

Back 34

very expensive

Front 35

What are the infustion related toxicities of Amphotercin B?

Back 35

fever, chills, muscle spasms, vomiting, HA, hypotension

Front 36

Are infustion related toxicities immeidate onset or slow onset?

Back 36

immediate reaction

Front 37

What causes the infustion related toxicities to stop?

Back 37

decrese daily dose or infusion rate

Front 38

What are the cumulative toxicties of Amphotercin B?

Back 38

renal damage (reversible or irreversible), heptotoxicity, and sezuires, anemia

Front 39

Is flucytosine narrow spectrum or broad spectrum compared to Amphotercin B?

Back 39

narrow spectrum

Front 40

What fungus is flucytosine restricted to?

Back 40

Crptococcus neoformans and some canidida species

Front 41

How is flucytosine administered?

Back 41

orally

Front 42

Describe the absoprtion of Flucytosine.

Back 42

well absorbed from GI

Front 43

Distribution of Flucytosine?

Back 43

Well distributed in tissue fluids, INCLUDING CSF

Front 44

Elimination of Flucytosine?

Back 44

renally

Front 45

When should the dose of flucytosien be adjusted?

Back 45

renal impairment becaues the drug is eliminated renally

Front 46

What drug exhibits synergism with flucytosine?

Back 46

Amphotercin B

Front 47

Explain the synergism of Amphotercin B and flucytosine.

Back 47

enhanced penetration of fucytosine through amphotercin B damaged membranes

Front 48

To become an antifungal what does flucytosine need to be converted to?

Back 48

5-flura uracil (5-FU)

Front 49

Flucytosine is converted to___, then to ____, and further ______

Back 49

5-fluorouracil, FdUMP, FUTP

Front 50

Fucytosine inhibits?

Back 50

DNA and RNA synthesis

Front 51

Flucytosine is unable to affect human cells because?

Back 51

human cells are unable to convert parent drug to 5-FU

Front 52

Resistance of Flucytosine?

Back 52

altered metabolism of flucytosine

Front 53

What caued ADE of flucytosine?

Back 53

due to metabolism to 5 FU

Front 54

What are the ADE of flucytosine?

Back 54

bone marrow toxicity and less frequently hepatotoxicity

Front 55

Name the synthetic compounds that are derivatives of imidazoles:

Back 55

ketoconazole
miconazole (topical)
clotrimazole (topical)

Front 56

Synthetic compounds that are derivated of Triazoles:

Back 56

itraconazole
fluconazole
voriconazole

Front 57

What is the MOA of Azoles?

Back 57

inhinit fungal p450 enzymes involved in ergosterol synthesis

Front 58

What is less selective for fungal p450s?

Back 58

imidazoles

Front 59

Azoles exhibit ___ affinity for fungal than human p450 enzymes

Back 59

greater

Front 60

Are azoles broad spectrum or narrow spectrum?

Back 60

broad spectrum

Front 61

What fungus do Azoles kill?

Back 61

Candida sp. Cryptococcus neoformans, endemic mycoses (blastomycosis, coccidiodmycosis, histoplasmosis) and Asperigillus

Front 62

What are azoles prone to drug interaction?

Back 62

effect on mammalian p450

Front 63

How well tolerated are Azoles?

Back 63

relatively well tolerated: minor GI distubrances and abnormallities in liver enzymes

Front 64

What drug has the greatest propensity to inhibit mammalian p450 enzymes

Back 64

ketoconazole

Front 65

Name the two ways Itraconaole is administered?

Back 65

Orally and IV

Front 66

Does itraconazole have high or low bioavailibity?

Back 66

low

Front 67

Which azole affect mammalizan cells more than itraconazole?

Back 67

ketoconazole

Front 68

Does itraconazole perentrate into CSF?

Back 68

penetrated poorly in CSF

Front 69

Which drug has high oral bioavaiblity? itraconazoel or fluconazole

Back 69

fluconzole

Front 70

Which azole is least effet on mammalian p450s?

Back 70

Fluconazole

Front 71

Does fluconzole penetrate into CSF?

Back 71

yes

Front 72

What fungus is fluconazole not active against?

Back 72

Asperigillus

Front 73

What drug has excellent oral bioavailability?

Back 73

Voriconazole

Front 74

Name in order which has the greatest effect on mammalian cells? azole

Back 74

Ketoconazole>itraconazole> voriconazole>fluconazole

Front 75

Is voriconazole active against Asperigillus?

Back 75

Yes

Front 76

Which azole causes rash, hepatotoxicity, vision problems

Back 76

Voriconazole

Front 77

What fungus are Echinocandins active against?

Back 77

candida and aspergillus, NOT against cryptococous

Front 78

Echinocandins are large cyclic peptides attatched to ____

Back 78

fatty acid chain

Front 79

Caspofungin, MIcafungin, anidulafungini are examples of what?

Back 79

are examples of Echinocandins

Front 80

Echinocandins are adminstered?

Back 80

IV only

Front 81

What is the MOA of Echinocandins?

Back 81

disrupt fungal cell wall (inhibit synthesis of B (1-3) glucan

Front 82

What are the ADEs of Echinocandins?

Back 82

very well tolerated; can cause minor GI disturbances and flushing

Front 83

Name two drugs that are systemic antifungal for mucocuntaneous infections?

Back 83

Griseofulvin and Terbinafine

Front 84

Name the three drugs used for topical antifunal therapy?

Back 84

Nystatin, clotrimazole, miconazole, and topical terbinafine and naftifine

Front 85

Oral absorption fo Griseofulvin is improved when given with______

Back 85

fatty foods

Front 86

Explain how Griseofulvin works?

Back 86

MOA unkown; however deposited in newly formed skin (binds to keratin and protects skin from new infection)

Front 87

What are the administration requirements for Griseofulvin?

Back 87

requireds prolonged administration

Front 88

How long should Griseofulvin be givin for hair and skin infections?

Back 88

2-6 weeks

Front 89

How long should Griseofulvin be given for nail infections?

Back 89

months

Front 90

What is the MOA for terbinafine?

Back 90

binds to keratin and interferes with erogosterol synthesis by inhibiting fungal enzyme squalene epoxidase (toxic squalene accumulates in fungi

Front 91

Does terinafine affect p450?

Back 91

no

Front 92

Name the ADEs of Terbinafine:

Back 92

well tolerated (mild GI upset)

Front 93

Why is Nystatin only used orally?

Back 93

to toxic for parental administration

Front 94

What is nystatin used for?

Back 94

candidial infections

Front 95

Nystastin is not absorbed from....

Back 95

GI, Skin, and mucous membranes

Front 96

What are clotrimazole and miconazole used for?

Back 96

Used for vuvlvovaginal candidiasis and dermatophytic infections