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Infectious Disease > Pharm 28 > Flashcards

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
Q

Isavuconazonium Indications

A

§ Invasive aspergillosis
§ Invasive mucormycosis
§ Active against yeast and molds
§ Similar to posaconazole

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26
Q

Isavuconazonium ADE

A

§ Infusion rate adverse effects

- If administered to quickly, can have a histamine like reaction that causes a hypersensitivity reaction

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27
Q

Non-albicans spp. Infections - first line

A

Echinocandins

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28
Q

Invasive aspergillosis - second line

A

Echinocandins

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29
Q

Poor/no activity against Cryptococcus neoformans and Scedosporum prolificans

A

Echinocandins

30
Q

Fungicidal against all Candida spp.

A

Echinocandins

31
Q

Echinocandins ADE

A 
▪ Fever
▪ Thrombophlebitis
▪ HA
▪ Increased LFTs
▪ Rash
▪ Flushing
32
Q

Echinocandins Formulations

A

IV only

33
Q

Caspofungin

A

moderate liver dysfunction requires a reduced dose

34
Q

Micafungin

A

no CYP metabolism and thus does not require a reduced dose for hepatic dysfunction

35
Q

Broadest spectrum of antifungals with the worse SDE

A

Polyene Macrolides: like amphotericin B

36
Q

Indications of Polyene Macrolides: like amphotericin B

A

▪ Severe systemic and CNS infections of susceptible fungi

§ Reserved for infections resistant to first line (less toxic) options

37
Q

Infusion related ADE of Polyene Macrolides: like amphotericin B

A

§ 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
Q

Other ADE of Polyene Macrolides: like amphotericin B

A

▪ 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
Q

Amphotericin B deoxycholate

A

§ Test dose for infusion related ADE
□ 1mg IV over 20-30 minutes
□ If reaction occurs, reduce infusion rate
§ Severe nephrotoxicity

40
Q

Amphotericin B Lipid complex

A

§ Less infusion related ADE than deoxycholate and thus do not require a test dose

41
Q

Nystatin spectrum

A

§ effective against candida sp.

§ DOES NOT have an effect against dermatophytes (tinea sp.)

42
Q

Nystatin indications

A

§ Cutaneous candidiasis (use the cream, ointment, or powder)

§ Oropharyngeal (oral suspension)

43
Q

Onychomycosis (oral) - FIRST LINE TREATMENT

A

Terbinafine

44
Q

Terbinafine MOA

A

▪ Blocks biosynthesis of ergosterol (sterol needed for fungal cell wall) by inhibiting squalene epoxidase (enzyme used in the cascade to make the ergosterol)

45
Q

Terbinafine Indications

A

▪ Dermatophytosis (topical)

▪ Onychomycosis (oral)

46
Q

Terbinafine Metabolism

A

primarily hepatic - strong inhibitor of CYP2D6

47
Q

Terbinafine ADE

A 
▪ Occur infrequently:
§ GI intolerance
§ HA
§ Rare (<1%): severe hepatitis
□ Not recommended in chronic or active liver disease
48
Q

Ciclopirox use

A

○ Highly effective nail lacquer for tinea unguium treatment

○ Used as a shampoo for seborrheic dermatitis on the scalp

49
Q

Griseofulvin MOA

A

▪ 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
Q

Griseofulvin Drug Interactions

A

Reduces progestin levels of OCP

51
Q

Griseofulvin ADE

A

▪ Disulfiram-like reaction with EtOH resulting in a “bad hangover”:
§ HA, N/V, etc

52
Q

Griseofulvin Contraindications

A

▪ Pregnancy - teratogenic
▪ Hepatic failure
▪ Porphyria

53
Q

Flucytosine MOA

A

▪ Pyrimidine analogue
§ Converted into 5-fluoruracil inside the fungal cell
□ becomes a chemotoxic agent within fungus and interferes with fungal DNA/RNA synthesis

54
Q

Flucytosine Indications

A

▪ CSF penetration
▪ Cryptococcal infections
▪ Combo therapy with amphotericin B or fluconazole

55
Q

Flucytosine resistance

A

§ Occurs quickly and rapidly during monotherapy and is thus hardly used as monotherapy

56
Q

Flucytosine ADE

A

▪ Dose related hepatoxicity and BM toxicity

▪ Renal dysfunction: USE WITH EXTREME CAUTION

57
Q

Acute vulvovaginal mycosis (vaginitis): Systemic agents

A

Fluconazole 150mg x 1 dose

58
Q

Acute vulvovaginal mycosis (vaginitis): Topical agents

A

Vaginal creams/suppositories

59
Q

Oral mucosal Non-invasive yeast infections

treatment

A

nystatin “swish and swallow”

60
Q

Identify two antifungal drugs that require renal dosage adjustments

A
  1. Fluconazole

2. Flucytosine

61
Q

Tinea unguium - onychomycosis: Topical antifungals used to treat as first line

A

1) Ciclopirox nail lacquer
2) Efinaconazole
3) Tavaborole

62
Q

Tinea unguium - onychomycosis: Systemic antifungals used to treat refractory cases

A

1) First line: Terbinafine for three months
2) Second line: Itraconazole for three months
3) Third line: fluconazole for six months (off label)

63
Q

How do you treat Candidemia

A

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
Q

How do you treat Candidemia with severe illness or recent azole exposure

A

Echinocandins

65
Q

Alternatives to treat Candidemia

A

i. Liposomal ampho B
ii. Ampho B deoxycholate
iii. Voriconazole

66
Q

How do you treat Candidemia in the immunocompromised

A

Drug of choice: echinocandins

Treat for at least 14 days AFTER first negative blood cx

67
Q

Alternatives to treat Candidemia in the immunocompromised

A

i. Ampho B
ii. Fluconazole: if sensitive and not recently Rx an -azole
iii. Voriconazole
1) If want to cover for suspected aspergillus

68
Q

How do you treat suspected candidiasis

A

Treatment is the same as candidemia: fluconazole

69
Q

How do you treat suspected candidiasis: immunocompromised

A
  1. Voriconazole
  2. Fluconazole as an alternative
  • Itraconazole is another alternative
70
Q

Urinary candidiasis treatment

A

Fluconazole

Alternative: amphotericin B

71
Q

Pyelonephritis candidiasis treatment

A

Fluconazole

If resistant: use Ampho B and fluyctosine

72
Q

Salvage therapy: invasive asperillosis

A

a. Capsofungin
b. Micafungin or Andiulafungin
c. Posaconazole

Infectious Disease (8 decks)

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