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Anti-fungal Flashcards

1
Q

what’s the difference between fungi and mammalian cells?

A

ergosterol cholesterol

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2
Q

what’s the difference between fungi and bacterial cells?

A

fungi: cell wall made of chitin
bacteria: cell made of peptidoglycan

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3
Q

can we use Abx to treat fungal infection?

A

No, vice versa (anti-fungal agents cannot be used to treat bacterial infection)

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4
Q

What are polyenes?

A

Amphotericin B and Nystatin

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5
Q

What are azoles?

A

SC/systemic infection: Triazole

Topical/Cutaneous: Imidazoles

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6
Q

What are echinocandins?

A

Caspofungin, Micafungin, Anidulafungin

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7
Q

Mechanism of action of polyenes?

A

binds to ergosterol in the cell membrane to form pores. Pores allow electrolytes (K) and small molecules to leak from the cell -> causing cell death

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8
Q

Amphotericin B indication?

A

Candida Albicans (Candidiasis), Histoplasmosis, Cryptococcus neoformans (Cryptococcus meningitis), Aspergillus (Aspergillosis)

an be fungicidal or fungistatic depending on organism and conc of drug

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9
Q

Formulation of Amphotericin; Adv/Disadv of each formulation

A

(1) sodium deoxycholate (conventional)
(2) artificial lipids forming liposome

(2) much more expensive than (1)
but (2) has reduced renal toxicity

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10
Q

dosage form/administration of Amphotericin B?

A

Mostly IV, sometimes topical

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11
Q

bioavailability and penetration to CSF for amphotericin B?

A

Poor oral f, poor CSF penetration but increases with inflammation
Liposomal have better CSF penetration

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12
Q

excretion of amphotericin B?

A

urine and bile

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13
Q

Adverse effect of amphotericin B?

A
  • NO (nephro and ototoxicity)
  • nephro = renal vasoconstriction by sodium deoxycholate formulation; avoid adding other nephrotoxic agents (e.g. vancomycin & AG), Hydrate patients adequately
  • bone marrow suppression
  • thrombophlebitis
  • hypotension (accompanied by hypokalemia)
  • fever & chills: 1-3hours after IV but subsides with repeated administration
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14
Q

preg cat for amphotericin B

A

B, safe to use in preg

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15
Q

Imidazoles have a wide range of activity against which fungi?

A
  1. Epidermophyton
  2. Microsporum
  3. Trichophyton
  4. Candida
  5. Malassezia
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16
Q

Topical imidazoles indications? Used for which type of fungal infections?

A 
Tinea corporis
Tinea cruris
Tinea pedia
Oropharyngeal 
Vulvovaginal candidiasis
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17
Q

Adv effects of topical imidazoles?

A

Contact dermatitis
Vulvar irritation and
oedema

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18
Q

What are 3 common tinea infections? (there are 8)

A
  1. Tinea capitis affects the scalp
  2. Tinea corporis affects the arms, legs, trunk
  3. Tinea pedis: athlete’s foot
  4. Tinea manuum: hands and palm
  5. Tinea faciei: face
  6. Tinea barbae: facial hair
  7. Tinea cruris: jock itch
  8. Tinea unguium: fingernails and toe nails
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19
Q

Clotrimazole metabolism and excretion?

A

Metabolised in liver and excreted in bile

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20
Q

Therapeutic uses of Clotrimazole

A
  • dures dermatophyte infections

- vulvovaginal candidiasis

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21
Q

Clotrimazole administration

A

cream (common), lotion, powder, pessary, troche

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22
Q

PK of miconazole

A

penetrates into stratum corneum of skin and persists there for >4days after application

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23
Q

Therapeutic uses of Miconazole

A
  • tinea pedia
  • tinea versicolor
  • vulvovaginal candidiasis
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24
Q

Administration of Miconazole

A

Pessary (common), cream, lotion, powder, oral gel

25
mechanism of action of 5-FC
enters fungal cells through cytosine specific permeases, converted by cytosine deaminase to 5-fluorouracil (5-FU); inhibit protein synthesis (FUTP replacing uridylic acid) AND inhibitor of thymidylate synthase, inhibiting DNA synthesis
26
how does resistance to 5-FC occur?
- decreased levels of any enzymes in conversion of 5-FC to 5-FU
27
Therapeutics uses of Nystatin
Broad-spectrum | Thrush oropharyngeal candidiasis and vulvovaginal candidiasis
28
excretion of 5-FC
urine, thus need dose adjustment with compromised renal function
29
indication of echinocandins?
first line: invasive candidiasis | second line: invasive aspergillosis (cant tolerate Amp B or azole)
30
excretion of echinocandins?
urine and faeces; but they are non-renally cleared drugs, so doesnt require dosage adjustment in presence of renal impairment
31
Bioavailability of Terbinafine?
40-60%; want the drug to accumulate in the keratin
32
Adverse effects of imidazoles
``` contact dermatitis vulvar irritation oedema GI disturbances (oral) oral use of clotrimazole associated with elevated liver enzymes ```
33
Nystatin falls under which antifungal category?
Polyene, like Amp B
34
Therapeutics uses of Nystatin
Thrush oropharyngeal candidiasis and vulvovaginal candidiasis
35
Anti-fungal activity of Terbinafine
active against trichophyton; a fungi that causes tinea
36
What is the adm of terbinafine for tinea capitis?
Oral, not topical antifungal therapy
37
Topical terbinafine is used to treat what kind of tinea?
Tinea pedis, Tinea corporis (ring worm), tinea cruris (infection of groin)
38
Bioavailability of nystatin
Poor F, systemic toxicity when used parenterally
39
Metabolism of oral terbinafine?
CYP450 isoenzymes
40
Pregnancy category for vaginal terbinafine
A
41
Pregnancy category for oral terbinafine
B
42
DDI of terbinafine
Terbinafine is an inhibitor of CYP450 isoenzymes
43
Adv effects of Terbinafine
GI disturbances HA rash elevated liver enzymes
44
Excretion of oral terbinafine
mainly via urine; avoided in pts w moderate to severe renal impairment or hepatic dysfunction
45
Oral F of nystatin
Poor F, systemic toxicity
46
DDI of azoles
inhibit the hepatic cyp450 3a4 enzyme, cyp2c9, cyp2c19 -> enhance activity of warfarin, cyclosporine, oral hypolycaemic agent
47
clearance of triazole
renal; dose adjustment needed in renal and hepatic impairment (due to DDI)
48
preg cat for triazole
flucanzole, itraconazole = cat C voriconazole = cat D Azoles are considered teratogenic
49
Bioavailability of Imidazoles
Poor F
50
how does resistance of azole come about?
- mutation in C14a-demethylase | - efflux pumps
51
PK of nystatin
Not abs from GIT, skin or vagina
52
Adv effects of nystatin
oral: rare | topical & vaginal forms: skin irritation
53
usual use of triazole (indication); name each and its indication
fluconazole = cryptococcal meningitis, vulvovaginal candidiasis itraconazole = aspergillosis, onychomycosis, broader antifungal spectrum than fluconazole voriconazole = treatment of choice for invasive asperigillosis
54
names of the triazoles
fluconazole, itraconazole, voriconazole
55
which anti-fungal; capsule to be taken after meal but solution on an empty stomach
itraconazole
56
which 2 azoles can be used to treat invasive aspergillosis and cryptococcal meningitis respectively? and what is the reason
voriconazole, fluconazole, both have good CSF penetration
57
which group of people is terbinafine contraindicated?
nursing mothers; distribute into milk
58
adverse effect of echinocandins?
GI effects, thrombocytopenia, fever & chills, rash, skin flush

PT (19 decks)

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