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Pharm 28 Flashcards

1
Q

ketoconazole use

A

Used more as a topical agent than oral due to ADE of systemic (effects CYP enzymes and stops -sterol synthesis)

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2
Q

Clotrimazole & Miconazole MOA

A

inhibits ergosterol synthesis (ergosterols are essential for fungal cell membrane stability)

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3
Q

Clotrimazole & Miconazole

Indications

A

§ Cutaneous tinea infections of tinea unguium, pedis, corporis, capitis
§ Candida spp.
§ Oropharyngeal
§ Vulvovaginal candidiasis

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4
Q

oral and parenteral -azole
MOA

(like fluconazole, itraconazole, voriconazole, posaconazole, isavuconazonium)

A

▪ Inhibit fungal cytochrome enzymes
§ Causes a decreased ergosterol synthesis within the fungal cell (ergosterols are essential for fungal cell membrane stability)

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5
Q

oral and parenteral -azole

Indications

(like fluconazole, itraconazole, voriconazole, posaconazole, isavuconazonium)

A

▪ Yeasts and molds
▪ Efficacy of each individual drug varies greatly
▪ All of these azoles have some protection against Candida spp.

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6
Q

oral and parenteral -azole

Drug interactions

(like fluconazole, itraconazole, voriconazole, posaconazole, isavuconazonium)

A

§ Inducers of P450 substrates cause significant decreases in levels of -azoles in the body
□ May lead to therapeutic failure
□ Primarily occurs with ketoconazole, itraconazole, voriconazole
§ Increase serum levels of other medications

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7
Q

oral and parenteral -azole

ADE

(like fluconazole, itraconazole, voriconazole, posaconazole, isavuconazonium)

A

▪ Increased transaminases (ALT, AST) = HEPATOCYTE damage
▪ Soluble drug carrier of IV formulations
§ Accumulates in renal insufficiency (CrCl <50mL/min)
□ Warning against administering -azoles in those that have terrible renal function
▪ QT prolongation with certain drug-azole interactions

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8
Q

oral and parenteral -azole

Resistance

(like fluconazole, itraconazole, voriconazole, posaconazole, isavuconazonium)

A

§ Increased drug efflux
§ Altered or increased demethylase
§ Isolates resistant to fluconazole

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9
Q

Fluconazole - indications

A

§ Localized and systemic fungal infections
□ Antifungal prophylaxis
§ Candida spp.
§ UTI
§ Also effects:
□ Histoplasma capsulatum
□ Cryptococcal meningitis
□ Crytococcus neoformans - first line
□ Coccidioides immitis (valley fever) - first line
§ NOT active against molds like Aspergillus spp.

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10
Q

Crytococcus neoformans - first line

A

fluconazole

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11
Q

Coccidioides immitis - first line

A

fluconazole

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12
Q

Fluconazole metabolism

A

primarily renally excreted

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13
Q

Fluconazole ADE

A

Must be renally adjusted: 1/2 the dose in renally impaired

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14
Q

Aspergillus spp. - first line

A

Voriconazole

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15
Q

Scedosporium apiospermum - first line

A

Voriconazole

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16
Q

Voriconazole indications

A 
§ Localized/systemic infections
§ Antifungal prophylaxis
§ Candida spp.
§ Blastomyces dermatitidis
§ Cryptococcous neoformans
§ Cocidioides immitis
§ Aspergillus spp. - first line
§ Scedosporium apiospermum
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17
Q

Voriconazole ADE

A

§ Visual changes that resolve once the drug is stopped

§ Reduced dose in hepatic dysfunction

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18
Q

Posaconazole indications

A

§ Active against yeast and molds

§ Mucormycosis/zygomycosis fungi

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19
Q

Posaconazole ADE

A

thromboplebitis

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20
Q

Itraconazole spectrum

A

§ Treatment of blastomycosis and histoplasmosis (first line)
§ Dermatophytosis
§ Candida spp. - variably active against fluconazole-resistant strains
§ Cryptococcous neoformans
§ Coccidioides immitis
§ Aspergillus spp.

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21
Q

§ Histoplasma capsulatum - first line

A

Itraconazole

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22
Q

§ Blastomyces dermatitidis - first line

A

Itraconazole

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23
Q

Itraconazole drug interactions

A

§ Substrate and potent inhibitor of 3A4

§ When combined with PPI’s, H2 blockers, or antacids: absorption is reduced

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24
Q

Isavuconazonium drug metabolism

A

§ Prodrug: converted to isavuconazole
□ Isavuconazole:
® Swallow capsules whole and 45% renally excreted
® Substrate of 3A4

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25
Isavuconazonium Indications
§ Invasive aspergillosis § Invasive mucormycosis § Active against yeast and molds § Similar to posaconazole
26
Isavuconazonium ADE
§ Infusion rate adverse effects | - If administered to quickly, can have a histamine like reaction that causes a hypersensitivity reaction
27
Non-albicans spp. Infections - first line
Echinocandins
28
Invasive aspergillosis - second line
Echinocandins
29
Poor/no activity against Cryptococcus neoformans and Scedosporum prolificans
Echinocandins
30
Fungicidal against all Candida spp.
Echinocandins
31
Echinocandins ADE
``` ▪ Fever ▪ Thrombophlebitis ▪ HA ▪ Increased LFTs ▪ Rash ▪ Flushing ```
32
Echinocandins Formulations
IV only
33
Caspofungin
moderate liver dysfunction requires a reduced dose
34
Micafungin
no CYP metabolism and thus does not require a reduced dose for hepatic dysfunction
35
Broadest spectrum of antifungals with the worse SDE
Polyene Macrolides: like amphotericin B
36
Indications of Polyene Macrolides: like amphotericin B
▪ Severe systemic and CNS infections of susceptible fungi | § Reserved for infections resistant to first line (less toxic) options
37
Infusion related ADE of Polyene Macrolides: like amphotericin B
§ Immediate reaction: fever, chills, rigors, hypotension § Looks an awful lot like onset of sepsis and are occasionally mistaken § Premedicate with APAP or NSAID, diphehydramine, hydrocortisone
38
Other ADE of Polyene Macrolides: like amphotericin B
▪ Nephrotoxicity - lipid formulations are less toxic □ Can lead up to complete and total renal failure that requires life long dialysis □ If/when nephrotoxicity occurs, consider a reduced dose § Renal arterial vasoconstriction § Renal tubular epithelial cell damage § Electrolyte monitoring required
39
Amphotericin B deoxycholate
§ Test dose for infusion related ADE □ 1mg IV over 20-30 minutes □ If reaction occurs, reduce infusion rate § Severe nephrotoxicity
40
Amphotericin B Lipid complex
§ Less infusion related ADE than deoxycholate and thus do not require a test dose
41
Nystatin spectrum
§ effective against candida sp. | § DOES NOT have an effect against dermatophytes (tinea sp.)
42
Nystatin indications
§ Cutaneous candidiasis (use the cream, ointment, or powder) | § Oropharyngeal (oral suspension)
43
Onychomycosis (oral) - FIRST LINE TREATMENT
Terbinafine
44
Terbinafine MOA
▪ Blocks biosynthesis of ergosterol (sterol needed for fungal cell wall) by inhibiting squalene epoxidase (enzyme used in the cascade to make the ergosterol)
45
Terbinafine Indications
▪ Dermatophytosis (topical) | ▪ Onychomycosis (oral)
46
Terbinafine Metabolism
primarily hepatic - strong inhibitor of CYP2D6
47
Terbinafine ADE
``` ▪ Occur infrequently: § GI intolerance § HA § Rare (<1%): severe hepatitis □ Not recommended in chronic or active liver disease ```
48
Ciclopirox use
○ Highly effective nail lacquer for tinea unguium treatment | ○ Used as a shampoo for seborrheic dermatitis on the scalp
49
Griseofulvin MOA
▪ Systemically absorbed antifungal that integrates into the human skin structure and protects the new skin/hair/nails to prevent the fungal infection § Binds to human keratin § Protects new structures from fungal infection
50
Griseofulvin Drug Interactions
Reduces progestin levels of OCP
51
Griseofulvin ADE
▪ Disulfiram-like reaction with EtOH resulting in a "bad hangover": § HA, N/V, etc
52
Griseofulvin Contraindications
▪ Pregnancy - teratogenic ▪ Hepatic failure ▪ Porphyria
53
Flucytosine MOA
▪ Pyrimidine analogue § Converted into 5-fluoruracil inside the fungal cell □ becomes a chemotoxic agent within fungus and interferes with fungal DNA/RNA synthesis
54
Flucytosine Indications
▪ CSF penetration ▪ Cryptococcal infections ▪ Combo therapy with amphotericin B or fluconazole
55
Flucytosine resistance
§ Occurs quickly and rapidly during monotherapy and is thus hardly used as monotherapy
56
Flucytosine ADE
▪ Dose related hepatoxicity and BM toxicity | ▪ Renal dysfunction: USE WITH EXTREME CAUTION
57
Acute vulvovaginal mycosis (vaginitis): Systemic agents
Fluconazole 150mg x 1 dose
58
Acute vulvovaginal mycosis (vaginitis): Topical agents
Vaginal creams/suppositories
59
Oral mucosal Non-invasive yeast infections | treatment
nystatin "swish and swallow"
60
Identify two antifungal drugs that require renal dosage adjustments
1. Fluconazole | 2. Flucytosine
61
Tinea unguium - onychomycosis: Topical antifungals used to treat as first line
1) Ciclopirox nail lacquer 2) Efinaconazole 3) Tavaborole
62
Tinea unguium - onychomycosis: Systemic antifungals used to treat refractory cases
1) First line: Terbinafine for three months 2) Second line: Itraconazole for three months 3) Third line: fluconazole for six months (off label)
63
How do you treat Candidemia
Use: High dose fluconazole a. Treat for 14 more days after the following occurs: i. First negative blood culture AND ii. Resolution of signs of infection (when you see signs of improvement): leukocytosis; fever; bandemia
64
How do you treat Candidemia with severe illness or recent azole exposure
Echinocandins
65
Alternatives to treat Candidemia
i. Liposomal ampho B ii. Ampho B deoxycholate iii. Voriconazole
66
How do you treat Candidemia in the immunocompromised
Drug of choice: echinocandins | Treat for at least 14 days AFTER first negative blood cx
67
Alternatives to treat Candidemia in the immunocompromised
i. Ampho B ii. Fluconazole: if sensitive and not recently Rx an -azole iii. Voriconazole 1) If want to cover for suspected aspergillus
68
How do you treat suspected candidiasis
Treatment is the same as candidemia: fluconazole
69
How do you treat suspected candidiasis: immunocompromised
1. Voriconazole 2. Fluconazole as an alternative - Itraconazole is another alternative
70
Urinary candidiasis treatment
Fluconazole Alternative: amphotericin B
71
Pyelonephritis candidiasis treatment
Fluconazole If resistant: use Ampho B and fluyctosine
72
Salvage therapy: invasive asperillosis
a. Capsofungin b. Micafungin or Andiulafungin c. Posaconazole

Infectious Disease (8 decks)

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