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Pharmacology -- Test #2 > Anti-Fungals > Flashcards

Anti-Fungals Flashcards

(70 cards)

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1
Q

Two ways that fungi can grow

A 
Single Cell (Yeasts)
Filamentous Multicellular Aggregates (Molds)
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2
Q

Yeasts typically reproduce by…

A

budding

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3
Q

Molds are made of…

A

hyphae

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4
Q

What are dimorphic fungi?

A

Ones that can grow as either yeasts or molds

Yeast in host

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5
Q

Six important dimorphic fungi

A 
Sporotrichosis
Coccidiomycosis
Paracoccidiomycosis
Chromoblastomycosis
Blastomycosis
Histoplasmosis
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6
Q

How do fungi reproduce?

A

Forming spores through mitosis or forming sexual spores

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7
Q

Fungi growing sexual spores are said to be in…

A

the perfect state

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8
Q

Describe the cell wall of a pathogenic fungus

A

Nonmotile, Rigid

Contain Chitin and Polysaccharides

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9
Q

What mycoses are transmissible from person to person?

A

Scalp ringworm

Thrush in the newborn (from mom with Candida)

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10
Q

Important details for dermatomycoses.

A

Filamentous fungi on keratinized tissue (skin, hair, nails)
Symptoms - Itching, burning, crackling of skin
Examples - Athlete’s Foot, Ringworm, Jock Itch)

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11
Q

Important details for onychomycoses?

A

Localized fungal infection of the nail or nail bed
Caused by dermatophyte
Thickening of nail (white, yellow, or brown)

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12
Q

Two examples of yeast-like fungi involving internal organs

A

Histoplasmosis

Candidiasis

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13
Q

Anti-fungals for Dermatomycoses?

A

Tolnaftate (Tinactin)
Clotrimazole (Lotrimin)
Griseofulvin

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14
Q

Tolnaftate mechanism of action?

A

Inhibition of Fungal squalene epoxidase
Results in loss ergosterol synthesis in fungi
Loss of membrane stability

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15
Q

Why is tolnaftalate selective for the fungus and not the host?

A

Humans use cholesterol, not ergosterol

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16
Q

Three non-tolnaftate squalene epoxidase inhibitors?

A

Terbenafine
Naftifine
Butenafine

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17
Q

Clotrimazole is administered how?

A

Vaginal Tablet

Topical

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18
Q

Clotrimazole is a member of the _____ class of antifungal agents

A

Azole

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19
Q

What do azoles do against fungi?

A

Inhibit Cytochrome p450 (which catalyzes 14alpha demethylation of lanosterol in ergosterol production) by inhibiting the binding/activation of molecular oxygen

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20
Q

Selectivity of Azoles?

A

Greater affinity for fungal cytochrome p450 than human

Selectivity is not absolute

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21
Q

Non-Clotrimazole azoles listed?

A

Miconazole

Ketoconazole

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22
Q

Griseofulvin is used for…

A

Systemic treatment of dermatomycoses

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23
Q

How does Griseofulvin work?

A
  • It disrupts mitotic spindle binding to polymerized microtubules (inhibiting mitosis).
  • Binds in newly formed keratin to prevent fungal growth
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24
Q

Griseofulvin is used to treat..

A

Onychomycosis (fungal infections of the nails)

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25
Why does Griseofulvin take so long?
Keratin in old tissues may still support fungal growth
26
Dissolution rate of Griseofulvin?
Very slow (because it is water insoluble)
27
How to improve the dissolution rate of Griseofulvin?
Microsize and ultramicrosize particles | Taken in a high fat diet
28
Adverse effects of Griseofulvin?
Photosensitivity, Hypersensitivity, Headache
29
Antifungals used to treat systemic infections?
``` Amphotericin B 5-Fluorocytosince Ketoconazole Fluconazole Itraconazole Echinocandins ```
30
Amphotericin B is amphoteric...what does that mean
Acidic and a Basic Group
31
Specific phillicities of Amphotericin B?
Lipophillic polyene region (bottom) | Hydrophilic polyalcohol region
32
Absorption info for Amphotericin B?
Poor water solubility Not absorbed well in GI Must be administered by slow IV infusion
33
What is the Amphotericin B deoxycholate complex or cholesterol complex?
A bile salt complex which is reconstituted with sterile water (you can also get it as a liposomal suspension for injection, but I don't feel like making another card for it)
34
Major acute rxns to Amphotericin B?
Fever and Chills | Sometimes HA, Nausea, Vomiting, nephrotoxicity, HTN
35
Major limiting toxicities of Amphotericin B?
Nephrotoxicity | Hypokalemia
36
Name six fungal infections that Amphotericin B is the drug of choice for?
``` Aspergillosis Blastomycosis Coccidiomycosis Cryptococcosis Histoplasmosis Mucormycosis ```
37
Mechanism of action for Amphotericin B?
Binding to ergosterol in the membranes Pores open in the membrane Leakage of ions and Small organic molecules
38
Selectivity of Amphotericin B?
Binds 10 times more strongly to vesicles containing ergosterol than those with cholesterol BUT some cholesterol binding still occurs, resulting in toxicity
39
Mechanism of 5-Fluorocytosine action?
Susceptible fungi convert 5-Fluorocytosine to 5-Fluorouracil, which is conversed to 5-fluorodeoxyuridine monophosphate
40
5-fluorodeoxyuridine monophosphate inhibits...
Thymidylate synthase | An enzyme required for DNA synthesis
41
Steps of Biosynthetic conversion of deoxyuridine monophosphate
1. Michael addition to Uracil to make an enolate 2. Added to iminium ion in methelene-THF 3. Intermediate eliminates THF, forming uracil derivative 4. In Michael addition, enolate is generated 5. Enzyme is eliminated to generate final product
42
How does the presence of 5-fluorouracil influence the deoxyuridine monophosphate mechanism?
Elimination of F+ is impossible Nothing around to be more electronegative Leaves a big-ole unbreakable chain
43
Aside from problems with the generation of thymidylate synthase, what else does 5-fluorouracil do to prevent fungi?
It incorporates into RNA in place of uracil Inhibited protein synthesis 5-fluorouracil = antimetabolite
44
What is an anti-metabolite?
The analog o an essential substrate that is accepted by the metabolic pathway, but cannot itself support life in the cell
45
5-Fluorocytosine selectivity?
Human cells have little or no cytosine deaminase activity
46
Therapeutic use of 5-Fluorocytosine?
Used w/ Amp. B on systemic Candida+Cryptococcus meningitis. | Sometimes torpulopsis glabrata, cladosporidium, and aspergillis
47
Resistance to 5-Fluorocytosine?
With with Amp. B to kill resistant strains
48
How does 5-Fluorocytosine function change with Amph. B added?
Amph. B fucks up the fungal cell permeability | Makes it easier for 5-Fluorocytosine to get up in there
49
Toxicity associated with 5-Fluorocytosine?
Depressed Bone Marrow Fxn - Leukopenia, thrombocytopenia Nausea, Vomiting, Diarrhea Rash, Entercolitis
50
5-Fluorocytosine should be administered with extreme caution to which patients?
Bone marrow depression | Diminished renal function
51
How might 5-Fluorocytosine nausea be diminished?
Capsules administered a few at a time over a 15 minute period
52
Important details on Ketoconazole?
Oral treatment of systemic infection | Better tolerated than AmpB, but less effective
53
What is Ketoconazole used to treat?
Bastomycosis Histoplasmosis Coccidiomycosis Paracoccioiomycosis
54
Describe the structure of Fluconazole?
``` A triazole (3 Ns in a 5 membered ring) Not an Imidazole (2Ns) ```
55
Bioavailability of Fluconazole?
High bioavailability | Penetrates into the CSF
56
Selectivity of Fluconazole?
Selective for Fluconazole cytochrome p450
57
Therapeutic use of Fluconazole?
IV infusion -- Cryptococcal memingitis in AIDS patients whose infection has been controlled by AB Single dose -- Vaginal candidiasis
58
Toxicity assocaited with Fluconazole?
Rare cases of hepatotoxicity (including fatalities)
59
Itraconazole is a mix of...
Four Diastereomers
60
Itraconazole availability....
90% bound to serum proteins, extensively bound in tissues
61
Can Itraconazole be used to treat CSF infections?
Nope | No detectable drug in the CSF
62
Therapeutic use of Itraconazole?
Preferred over keto for non-meningeal histoplasmosis. | AIDS pateints w/ disseminated Histo (stabilized by AB)
63
Untoward effects of Itraconazole?
GI distress (at 400mg/day or more), Nausea, Vomiting Hypokalemia, Rash Heart Failure Hepatotoxicity
64
Itraconazole cannot be coadministered with...
drugs metabolized by Cytochrome p450 | ex. cisapride, pimozide, quinidine, dofetilide
65
Functional activity of Echinocandins?
Inhibit 1,3 beta glucan synthesis in the fungal cell walls by non-competitive inhibition of 1,3 beta-glucan synthase
66
Selectivity of Echinocandins?
Good because mammalisn cells lack 1,3 beta-glucan synthase
67
Cross resistance of Echinocandins?
None
68
Echinocandins are synergistic with...
Voriconazole and Amph. B
69
Mode of administration for Echinocandins?
IV
70
Adverse reactions to Echinocandins?
Hepatotoxicity | Sensitivity/Allergic Reactions

Pharmacology -- Test #2 (13 decks)

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