Infectious Disease 3: Antifungals & Antivirals Flashcards

1
Q

What are the 3 Fungal classifications?

Systemic Fungal Infections

A
  1. Yeasts
  2. Molds
  3. Dimorphic species ~ mold in cold, yeast in heat

RxPrep p 389

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2
Q

Mucormycosis is an invasive fungal disease

What species causes Mucormycosis?

Systemic Fungal Infections

A

Zygomycetes ~ mold fungi made up of Mucor & Rhizopus species

RxPrep p 389

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3
Q

What species are classified as Yeast?

Fungal Classifications

A
  1. Candida species
  2. Cryptococcus neoformans

C. albicans, tropicalis, parapsilosis, glabrata, krusei

RxPrep p 389

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4
Q

What species are classified as Molds?

Fungal Classifications

A
  1. Aspergillus species
  2. Zygomycetes (Mucor & Rhizopus)

AZMR

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5
Q

What fungi are classified as Dimorphic?

Fungal Classifications

A
  1. Histoplasma capsulatum
  2. Blastomyces dermatitidis
  3. Coccidioides immitis

HBC ~ mold in the cold, yeast in the heat

RxPrep p 389

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6
Q

What is Amphotericin B active against?

Ergosterol Binder

A
  1. Broad Spectrum; used for initial treatment
  2. Active against almost all fungi
  3. Cryptococcus neoformans & Aspergillus

Yeast & Mold

RxPrep p 390

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7
Q

Which Amphotericin B formulation has fewer toxicities?

Ampho B deoxycholate vs. Ampho B lipid formulations

A
  1. Lipid formulations - less infusion rxns & less nephrotoxicity

Ampho B deoxycholate is conventional formulation & more toxic

RxPrep p 390

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8
Q

What is the Brand Name?

Liposomal Amphotericin B

Injection

A

AmBisome

Injection

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9
Q

What are Boxed Warnings for Ampho B Deoxycholate & AmBisome?

Injections

A
  1. Cardiopulmonary Arrest
  2. Deoxycholate ~ NO > 1.5 mg/kg/day

Deoxycholate = Conventional Formulation

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10
Q

What are Side Effects of Amphotericin B?

All Injection Formulations

A
  1. Infusion Reactions - fever, chills, headache, malaise, rigors
  2. low K, low Mg, nephrotoxicity

RxPrep p 390

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11
Q

What are key Prep & Admin notes for Amphotericin B?

Injections

A
  1. D5W compatibility only!
  2. lipids must be filtered during prep!
  3. Deoxycholate requires pre-meds for infusion risk!

Pre-meds: APAP or NSAID + Benadryl +/- Hydrocortisone

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12
Q

What is Flucytosine converted to, and when is it usually indicated for?

Flucytosine, 5-FC (Ancoban)

A
  1. Converted to Fluorouracil
  2. Due to resistance, NOT used alone!
  3. Combo w/ Ampho B for invasive cryptococcal meningitis

SE: myelosuppression! (anemia, neutropenia, thrombocytopenia)

RxPrep p 390

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13
Q

3 Key Issues with Azole Antifungals

Class Effects

A
  1. Increase LFTs
  2. QT prolongation (except isavuconazonium)
  3. Drug Interactions (CYP3A4 inhibitors)

IV Administration: IV:PO ratio is 1:1 for ALL AZOLES!

RxPrep p 391

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14
Q

Azole Antifungals decrease ergosterol synthesis

Fluconazole (Diflucan)

Activity, Dosing, & Drug-Specific Concerns

A
  1. C. krusei is fluconazole-resistant
  2. Nail-bed infxns (onychomycosis); oral & vaginal yeast infxns; oral thrush (candidiasis) w/ white, sore patches; fungal meningitis
  3. Vaginal candidiasis: 150 mg PO x 1 dose
  4. only azole that requires renal dose adjustment
  5. Inhibits CYP2C9: increased WARFARIN effects

PENETRATES CNS TO TREAT FUNGAL MENINGITIS

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15
Q

Azole Antifungals decrease ergosterol synthesis

Itraconazole (Sporanox capsules)

Activity, Dosing, & Drug-Specific Concerns

A
  1. Main use: Nail-bed infxns
  2. BBWs: HEART FAILURE; QT prolong & ventricular tachyarrhythmias (d/t increasing other drug plasma concentrations)
  3. Absorption requires an acidic gut (higher pH, lower absorption)

Capsules: take with food; Solution: take on empty stomach

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16
Q

Azole Antifungals decrease ergosterol synthesis

Ketoconazole Topical (Nizoral A-D OTC)

Activity, Dosing, & Drug-Specific Concerns

A
  1. BBW: Hepatotoxicity leading to liver transplants; QT prolongation; use PO only when other antifungal therapy is unavailable or not tolerated
  2. PO absorption requires acidic gut (higher pH, lower absorption) - if PPIs/H2RAs used, take with acidic bev (non-diet cola) to provide acidic environment

Tablet, cream, foam, gel, shampoo

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17
Q

Azole Antifungals decrease ergosterol synthesis

Voriconazole (Vfend)

Activity, Dosing, & Drug-Specific Concerns

A
  1. TOC for Aspergillus
  2. CrCl < 50 ~ IV vehicle SBECD accumulates, so PO preferred (monitor SCr with IV formulation)
  3. Hepatoxicity, visual disturbances (optic neuritis), phototoxicity, CNS toxicity (hallucinations), QT prolongation
  4. Take PO on empty stomach; caution driving at night; avoid direct sunlight

Tablet, suspension, injection - store reconstituted PO susp at room temp

RxPrep p 392

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18
Q

Azole Antifungals decrease ergosterol synthesis

Posaconazole (Noxafil)

Acitivity, Dosing, & Drug-Specific Concerns

A
  1. CrCl < 50, IV vehicle SBECD accumulates, so PO preferred
  2. QT prolongation warning
  3. Tablet not equal to suspension dose; take both with food

DR tablet, suspension, injection

RxPrep p 392

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19
Q

Azole Antifungals decrease ergosterol synthesis

Isavuconazonium Sulfate

Activity, Dosing, & Drug-Specific Concerns

A
  1. Prodrug to isavuconazole
  2. QT shortening! (not prolonging)
  3. Requires filter during admin d/t possible particulates

capsule, injection

RxPrep p 392

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20
Q

Echinocandins

MOA, Activity, Dosing, & Class Concerns

A
  1. Inhibit synthesis of beta (1,3)-D-glucan within the fungal cell wall
  2. Effective against most Candida species
  3. Injections only! all given once daily with no renal dose adjustments required
  4. Histamine-mediated symptoms warning

Caspofungin, Micafungin, Anidulafungin

RxPrep p 393

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21
Q

Caspofungin

Brand Name

A
  1. Cancidas
  2. SJS/TEN severe skin rxns

Echinocandin

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22
Q

Micafungin

Brand Name & Indication

A
  1. Mycamine
  2. Candidemia 100mg IV
  3. Esophageal candidiasis 150mg IV
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23
Q

Antifungal Agent

Nystatin

Indications, Formulations, Counseling

A
  1. Oral Thrush & Intestinal Infections
  2. Tablet & Suspension
  3. Suspension ~ swish in mouth and retain for as long as possible (several min) before swallowing; shake well before using!

RxPrep p 394

24
Q

Antifungal Agent

Griseofulvin

Indications, Contraindication, Side Effects, DDIs, & Counseling

A
  1. Skin, Hair, & Nails infxns
  2. Contraindication: Pregnancy
  3. ADEs: Photosensitivity & Increased LFTs
  4. Take with fatty meal or at least food/milk

Increased metabolism of hormonal contraceptives - contraception failure!

RxPrep p 394

25
Q

Antifungal Agent

Terbinafine (Lamisil AT)

Warning, Side Effects, Formulations, & Counseling

A
  1. Hepatotoxicity!
  2. ADEs: Headache & increased LFTs
  3. Counseling: may take months after treatment to see full benefit (takes time for healthy nails to grow)

Tablet Rx; Topical Rx & OTC

RxPrep p 394

26
Q

Antifungal Agent

Clotrimazole

Indication & Formulation

A
  1. Oropharyngeal Candidiasis
  2. 10 mg troche / lozenge & topical/vaginal forms

RxPrep p 394

27
Q

Antifungal Agent

Miconazole

Indication & Formulations

A
  1. Oropharyngeal Candidiasis
  2. Buccal, Topical, & Vaginal

RxPrep p 394

28
Q

Preferred Empiric Regimens

Candida Albicans ~ Oral Thrush

Oropharyngeal Infection

A

Mild: Topical antifungals (Clotrimazole, Miconazole)
Severe or HIV+: Fluconazole

RxPrep p 395

29
Q

What are other QT-prolonging drugs to be cautiously aware of?

Azole Antifungal DDIs

A

Antiarrhythmics, quinolones, macrolides, antidepressants, antipsychotics, 5HT-3 receptor antagonists

RxPrep p 393

30
Q

Preferred Empiric Regimens

Candida albicans

Esophageal Infections

A
  1. Fluconazole
  2. Echinocandins (Cancidas, Mycamine)

RxPrep p 395

31
Q

Preferred Empiric Regimens

C. krusei & C. glabrata

All Candida Species Bloodstream Infections

A
  1. Echinocandins (Caspofungin, Micafungin)
  2. Amphotericin B

Remember: these strains are Fluconazole-Resistant!

RxPrep p 395

32
Q

Preferred Empiric Regimens

Aspergillus

Invasive Mold

A
  1. Voriconazole
  2. Amphotericin B
  3. Isavuconazonium

RxPrep p 395

33
Q

Preferred Empiric Regimens

Cryptococcus neoformans

CNS Meningitis

A

Amphotericin B + Flucytosine (5-FC)

RxPrep p 395

34
Q

Preferred Empiric Regimen

Dermatophytes

Nail Bed Infection

A
  1. Terbinafine or Itraconazole
  2. Fluconazole

RxPrep p 395

35
Q

Antifungals & Antivirals

What are the 2 strains of Influenza? What common diagnostic tests are used?

A
  1. Influenza A & B
  2. Antigen detection test
  3. Rapid test ~ nasopharyngeal swab

Fever, chills, fatigue, myalgia

RxPrep p 396

36
Q

Antivirals for Influenza

Neuraminidase Inhibitors

Drugs, Indication, & MOA

A
  1. Oseltamivir (Tamiflu) & Zanamivir (Relenza Diskhaler)
  2. Inhibits enzymes that enable new viral particles to release from infected cells
  3. Decrease symptoms by ~1 day & reduce complications
  4. Start within 48 hours of illness onset!

RxPrep p 396

37
Q

Antivirals for Influenza

Endonuclease Inhibitors

Drug & Indication

A
  1. Baloxavir marboxil
  2. Influenza treatment & post-exposure prevention (12+ age)
  3. Single dose regimen & start within 48 hours of symptom onset!

RxPrep p 397

38
Q

Antivirals for Influenza

Oseltamivir (Tamiflu)

Neuraminidase Inhibitor ~ Formulations, Dosing, Warning, & Side Effects

A
  1. Treatment & Prophylaxis (12+ age) - Capsules & Suspension
  2. Treatment: 75 mg BID x 5 days
  3. Prophylaxis: 75 mg Daily x 10 days
  4. Warning: Neuropsychiatric Events! - “may cause delirium”

Side Effects: headache, N/V

RxPrep p 397

39
Q

Antivirals for Influenza

Zanamivir (Relenza Diskhaler)

Indications & Warnings

A
  1. Influenza treatment ~ 7+ age
  2. Influenza prophylaxis ~ 5+ age
  3. Warnings: bronchospasms, breathing problems - DON’T use in asthma/COPD

Inhalations

RxPrep p 397

40
Q

SARS-CoV-2 Testing & Treatment

Guideline Agencies & Diagnostic Testing

A
  1. CDC, NIH, & IDSA
  2. PCR test - nasopharyngeal swab
  3. Rapid antigen test

RxPrep p 398

41
Q

What disease is commonly associated with HSV-1?

Herpes Simplex VIrus 1

A

Oropharyngeal Disease

RXPrep p 398

42
Q

What disease is commonly associated with HSV-2?

Herpes Simplex Virus 2

A

Genital Disease

43
Q

Antivirals for HSV & VZV

Zovirax

Generic, Warnings, & Dosing Pearls

A
  1. Acyclovir
  2. Caution: renal impairment, nephrotoxic drugs, & elderly
  3. Based on IBW, even in obese patients!

capsule, tablet, buccal tablet, suspension, injection, topical

RxPrep p 399

44
Q

Antivirals for HSV & VZV

Valtrex

Generic, PK/PD Pearls, & Warnings

A
  1. Valacyclovir - Prodrug of Zovirax
  2. Caution in renal impairment, nephrotoxic drugs, & elderly

Tablet

RxPrep p 399

45
Q

Herpes Simplex Labialis (Cold Sores)

When is the optimal time to treat cold sores to reduce blister duration?

A
  1. Prodrome ~ symptoms before the lesions appear (“eruption”)
  2. TIngling, itching, soreness

RxPrep p 399

46
Q

Herpes Simplex Labialis (Cold Sores)

What are common topical treatments for Herpes Labialis?

Drugs & Treatment Duration

A
  1. Docosanol cream (Abreva) - OTC at first sign of outbreak, continue until healed
  2. Acyclovir cream (Zovirax) - Rx x 4 days
  3. Apply 5x daily!

RxPrep p 399

47
Q

Genital Herpes

When should treatment for Genital Herpes be initiated? What are the treatment options?

A
  1. Initiate within 1 day of lesion onset (papules, vesicles that rapidly spread)
  2. Acyclovir ~ least expensive; 5x daily dosing
  3. Valacyclovir ~ reaches higher concentrations (prodrug); less frequent dosing to enhance adherence

RxPrep p 400

48
Q

Invasive HSV Infections

What is the most commonly identified disease caused by HSV? How is it treated?

A
  1. Viral Encephalitis
  2. Acyclovir IV (Zovirax)

RxPrep p 400

49
Q

Varicella Zoster Virus (Chickenpox)

How does the recurrence of chickenpox present? What are the main viral symptoms?

A
  1. Herpes Zoster (Shingles)
  2. Unilateral manifestation, band/cluster of fluid-filled blisters (itchy, tingly, & painful)

RxPrep p 400

50
Q

Herpes Zoster (Shingles)

  1. When should shingles antiviral therapy be initiated?
  2. What is the duration for antiviral therapy?
  3. What is the term for chronic pain associated with shingles?
A
  1. 72 hours of zoster rash onset
  2. Zovirax or Valtrex x 7 days
  3. Postherpetic Neuralgia (PHN)

RxPrep p 400

51
Q

Shingrix Recommendations

Shingles Vaccine

A
  1. Adults 50+ years
  2. Immunosuppressed adults 19+ years

RxPrep p 400

52
Q

Cytomegalovirus (CMV)

What does CMV commonly cause? What are the treatment options for CMV?

A
  1. Retinitis, colitis, or esophagitis (occurs in severly immunocompromised states, like AIDS & transplant)
  2. Ganciclovir or Valganciclovir (Valcyte)

Refractory Cases: Foscarnet & Cidofovir

RxPrep p 401

53
Q

CMV

Ganciclovir & Valganciclovir

Boxed Warning & Admin/Prep Pearls

A
  1. BBW ~ myelosuppression
  2. Ganciclovir Injection ~ do NOT reconstitute in bacteriostatic water
  3. Valcyte solution ~ refrigerate!

Valcyte - Prodrug of Ganciclovir!

RxPrep p 401

54
Q

What is Epstein-Barr Virus (EBV)?

A
  1. “Mono” - mononucleosis
  2. Spread by kissing, saliva, bodily fluids

RxPrep p 402

55
Q

What are key counseling points for Zovirax & Valtrex?

A
  1. Does not cure herpes infections, so use safe sex practices
  2. Start within 24 hours of symptom onset
  3. Acyclovir ~ drink plenty of fluids; topical cream may burn/sting

Cold sores, chickenpox, shingles, genital herpes

RxPrep p 402