Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Antifungals fall into 3 categories:

A
  1. systemic drugs for systemic infections
  2. oral drugs for mucocutaneous infections
  3. topical drugs for mucocutaneous infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Amphotericin A and B are produced by _____

A

streptomyces nodosus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

General structure of amphotericin B

A

amphoteric polyene macrolide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is amphotericin B prepared for intravenous administration?

A

since it is nearly insoluble–> colloidal suspension with sodium desoxycholate, lipid-associated delivery system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

When is oral administration of amphotericin B effective?

A

only on fungi within lumen of the GI tract. It is poorly absorbed so, orally, it cannot be used for treatment of systemic diseases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Half-life of amphotericin B

A

LONG. 15 days… excreted slowly in urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is the dose of amphotericin B adjusted for hepatic or renal impairment and dialysis?

A

Its not.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Distribution of amphotericin B

A

total body fluid, but very little in CSF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What limits amphotericin B therapy?

A

toxicity– drug-induced renal impairment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the pros to using lipid delivery vehicle to administer amphotericin B?

A

serves as an amphotericin resevoir, reducing non specific binding to human cell membranes. This reduces toxicity and allows larger doses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Amphotericin B MOA

A

Fungicidal: binds ergosterol and alters permeability of cell forming pores (amphipathic)leakage, death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Resistance to Amphotericin B

A

impaired ergosterol binding by decreasing ergosterol concentration or modifying it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the spectrum of Amphotericin B?

A

It is the broadest spectrum antifunal: Yeast (candida, cryptococcus), mycoses (histoplasma, blastomyces, coccidioides) pathogenic molds (aspergillus and mucormycosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What fungal organisms display an intrincic resistance to amphotericin B?

A

candida lusitaniae and pseudallescheria bodyii

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

When is amphotericin B useful?

A

nearly all life-threatening mycotic infections. Can be used initally to reduce fungal burden. local or topical administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the 2 categories of amphotericin B toxicity?

A

Infusion related and cumulative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Infusion related toxicity

A

fever, chills, spasms, vomiting, hypotension, headache. Ameliorated by slowing rate or decreasing dose. Premedication and test dose to avoid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the most significnt toxic reaction to amphotericin?

A

renal damage: renal tubular acidosis and severe potassium and magnesium wasting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Cumulative toxicity

A

Reversible: decreased renal perfusion, prerenal failure
Irreversible: renal tubular injury. occurs with prolonged administration
Abnormal liver function test, anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Avoiding cumulative toxicity

A

prerenal component may be due to sodium loading–> normal saline infusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

General chemistry of flucytosine

A

water soluble pyrimidine related to 5-FU

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Is amphotericin highly or poorly serum protein bound?

A

Highly- 90%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Is flucytosine highly or poorly serum protein bound?

A

poorly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Flucytosine absorption

A

over 90%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Distribution of flucytosine

A

total body fluid including CSF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Elimination of flucytosin

A

via glomerular filtration or dialysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Does renal impairment affect flucytosine?

A

yes, levels rise rapidly and can cause toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Flucytosine MOA

A

taken up by cytosine permease–> converted to 5-FU–> 5-flurodeoxyuridine monophosphate (Fdump inhibits DNA synthesis) and flurouridine triphosphate (inhibits RNA synthesis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Flucytosine resistance

A

altered metabolism of flucytosine which develops rapidly in course of flucytosine monotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Flucytosine spectrum

A

C neoformans and some Candida and demateaceous molds that cause chromoblastomycosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Fluctyosine clinical use

A

confined to combination therapy because of its demonstrated synergy and avoiding resistance. With amphotericin B or cryptococcal meningitis or with itraconazole for chromoblastomycosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Adverse effects of flucytosine

A

metabolism by flora to toxic 5-FU–> bone marrow toxicity with anemia, leukopenia, thrombocytopenia, derangement of liver enzymes. Enterocolitis……GI, bone marrow suppression, hepatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Flucytosine therapeutic window

A

small–> increased risk of toxicity at higher levels and development of resistance at lower levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Method of administration of flucytosine

A

oral only

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How is flucytosine selective for funal cells?

A

human cells are not able to convert parent drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How is flucytosine synergistic with amphotericin B?

A

can enter through pores

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Flucytosine is used in combination therapy with _____

A

amphotericin B or azoles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

General chemistry/structure of azoles

A

synthetic compounds that can be classified as either imidazoles or triazoles according to the number or nitrogen atoms in the 5 membered azole ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

The imidazoles consist of :

A

ketoconazole, miconazole, clotrimazole

40
Q

The triazoles consist of:

A

itraconazole, posaconazole, fluconazole, voriconazole,

41
Q

The antifungal activity of azoles result from ____.

A

reduction of ergosterol synthesis by inhibition of fungal cytochrome p450 enzyme

42
Q

The selective toxicity of azole drugs result from :

A

greater affinity for fungal p450s than human.

43
Q

Which has a higher incidence of drug interactions and adverse effects imidazoles or triazoles?

A

Imidazole, due to lesser degree of selectivity

44
Q

Resistance to azoles

A

increasing use of these agents for prophylaxis and therapy may be selecting for clinical drug resistance

45
Q

Azole spectrum of action

A

broad. Includes Candida, C. neoformans, endemic mycosis (blastomycosis, coccidiodomycosis, histoplasmosis), dermatophytes, Aspergillus(itraconazole and voriconazole). P boydii (resistant to amphotericin)

46
Q

Azole adverse effects

A

GI upset, liver enzyme abnormalities, clinical hepatitis. Prone to drug interactions due to P450

47
Q

____ was the first oral azole introduced into clinical use

A

ketoconazole

48
Q

Why has ketoconazole fallen out of clinical use?

A

it is less selective for fungal P450 (over human) than newer azoles

49
Q

Itraconazole administration

A

oral and intravenous

50
Q

Itraconazole absorption

A

increased by food and low gastric pH

51
Q

Itraconazole drug interactions

A

reduced bioavailability when taken with rifamycins. Its effects on the metabolism of other hepatically cleared medications are much less than those of ketoconazoles

52
Q

what limits the effectiveness of Itraconazole

A

reduced bioavailability

53
Q

Distribution of Itraconazole

A

poorly into CSF

54
Q

Itraconazole spectrum

A

dimorphic fungi, histoplasma, blastomyces, sporothrix, dermatophytsoses, oncychomycosis, asperbillus (but not used)

55
Q

Fluconazole distribution

A

high degree of water solubility, good CSF penetration

56
Q

Fluconazole bioavailability

A

high

57
Q

Fluconazole drug interactions

A

less common, least effect of all the azoles on hepatic microsomal enzymes

58
Q

Fluconazole therapeutic index

A

widest of azoles, permitting more aggressive therapy

59
Q

Fluconazole is the azole of choice for treatment of ______

A

cryptococcal meningitis (and secondary prophylaxis)

60
Q

Fluconazole clinical use

A
  1. IV equivalent to amphotericin in rx of candidemia
  2. agent most commonly used for mucocutaneous candidiases
  3. dimoprhic fungi limited to coccidiodal
  4. no activity against aspergillus
61
Q

voriconazole administration and F

A

Admin: oral or intravenous. well absorbed orally with 90% F.

62
Q

voriconazole metabolism

A

hepatic. Inhibitor of CYP3A4 (drug interactions)

63
Q

voriconazole toxicities

A

rash, elevated hepatic enzymes, visual disturbances, photosensitivity

64
Q

The treatment of choice for invasive aspergillosis is ____.

A

voriconazole

65
Q

_____ is the newwest triazole.

A

posaconazole

66
Q

Absorption, administration of posaconazole

A

Admin: oral only.
Abs: improved with high fat meals

67
Q

_____ is the broadest spectum member of the azole family.

A

posaconazole

68
Q

Echinocandins chemistry and PK

A

large cyclic peptides linked to a long fatty acid. Active against Candida, aspergillus, but NOT C neoformans or agents of zygomycosis and mucormycosis. IV only.

69
Q

Echinocandins MOA

A

act at the level of the fungal cell wall by inhibiting synthesis of B (1-3) glucan that results in disruption of fungal cell wall and death

70
Q

What are the 3 echinocandins?

A

anidulafungin, caspofungin, micafungin

71
Q

Griseofulvin clinical use

A

systemic treatment of dermatophytosis

72
Q

Griseofulvin administration

A

microcrystallin form, improves with fatty foods

73
Q

Griseofulvin MOA

A

binds keratin to protect new skin/hair from infection. Fungostatic

74
Q

Griseofulvin adverse effects

A

allergic syndrome, hepatitis, drug interactions with warfarin and phenobarbital

75
Q

terbinafine use

A

dermatophytoses, esp onychomycosis

76
Q

terbinafine Moa

A

fungicidal: interferes with ergosterol biosynthesis by inhibiting squalene epoxidase which leads to accumulation of sterol squalene which is toxic to the cell.

77
Q

Nystatin

A

polyene macrolide, topical use only, little toxicity but bad taste, active against Candida, good for local infections

78
Q

Topical azoles

A

Clotrimazole and miconazole godo for dermatophytic infections including tinea corporis, tinea pedia, and tinea cruris

79
Q

Topical allylamines

A

terinafine and naftifine tinea cruris and tinea corporis

80
Q

which 2 antifungals are closest in their spectrum?

A

azoles and flucytosine

81
Q

Which antifungals function at the cell membrane?

A

azoles, polyenes (amb), allylamines (terbinafine)

82
Q

Which antifungals work at the cell wall?

A

echinocandins

83
Q

which antifunals work at the intracellular level?

A

flucytosine and griseofulvin

84
Q

What are the types of echinocandins?

A

anidulafungin, caspofungin, micafungin

85
Q

Antifungals that have hepatic toxicities

A

all azoles, Amb, 5-FC, echniocandins

86
Q

antifungals that have renal toxicity

A

AMB, voriconazole

87
Q

Antifungals with CNS toxicities

A

voriconazole

88
Q

Antifungals with photopsia toxicity (possible malignancy)

A

voriconazole

89
Q

Antifungals with cutaneous toxicities

A

all

90
Q

Antifungals with GI toxicity

A

itraconazole, posaconazole, 5-FC

91
Q

Antifungals with cardiac toxicity

A

itraconazole

92
Q

Antifungals with QT prolongation

A

all azoles

93
Q

Antifungals with infustion reactions

A

amb, echinocandins

94
Q

Antifungals with bone marrow suppression

A

AMB, 5-FC,

95
Q

How do azoles interact with CYPS?

A

they inhibit ergosterol synthesis by blocking 14-alpha demethylase, a CYP enzyme needed to convert lanosterol and ergosterol

96
Q

What is the significance of CYP2c19 polymorphisms?

A

significant interpatient variability for voriconazole serum levels

97
Q

ketoconazole inhibits what synthesis?

A

steroid (androsterone)

Pharmacology (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions