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Pharm Exam 4 > Antifungal Antiviral > Flashcards

Antifungal Antiviral Flashcards

1
Q

What are 3 reasons fungal infections are difficult to treat?

A
  1. They are similar to animal cells
  2. Slow growth rate
  3. Occur in poorly vascularized tissue
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2
Q

What are three fungal infection classes?

A
  1. Systemic
  2. Superficial/mucocutaneous
  3. Dermatomycoses
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3
Q

What is the term for fungal infections of systemic organs (aspergillus, blastomyces, Cryptococcus, histoplasma, coccidioises)?

A

Systemic mycoses

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4
Q

What is the term for fungal infections involving the outer layers of skin, nails, or mucous membranes

A

Superficial/mucocutaneous mycoces

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5
Q

What is one of the most common mucocutaneous mycoses?

A

Candidiasis of mouth (thrush), GI, vagina

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6
Q

What is the term for slightly deeper fungal infections of the skin, hair, or nails by dermatophytes?

A

Dermatomycoces

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7
Q

Name 3 classes of drugs for treating systemic fungal infections

A
  1. Membrane pore formers
  2. Ergosterol synthesis inhibitors
  3. DNA/RNA synthesis inhibitors
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8
Q

What is the prototype for Membrane Pore Formers for fungal infection treatment?

A

Amphotericin B

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9
Q

Amphotericin B is a member of what drug class?

A

Polyene macrolide (polyene = series of conjugated double bonds)

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10
Q

What is amphotericin B’s mechanism of action?

A

selective binding to ergosterol in fungal membrane

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11
Q

What is chemical quality of Amphotericin B that allows it to form membrane pores by binding to ergosterols?

A

Amphoteric = likes both lipid and water

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12
Q

What is the administration for amphotericin B?

A

Parenterally (other than alimentary route). Intrathecal admin (under arachnoid membrane of brain or spinal cord[internet]) for fungal meningitis

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13
Q

For what is amphotericin B is the DOC?

A

Systemic fungal infections (blastomycoces, cryptococcal, histoplasmosis)

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14
Q

What is the main side effect of amphotericin B

A

Nephrotoxicity, especially in pt with renal problems or taking other nephrotoxic drugs (aminoglycosides)

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15
Q

What is an azole drug?

A

An ergosterol synthesis inhibitor for systemic fungal infection

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16
Q

Can azole drugs affect cholesterol in animal cells?

A

Yes, but they are selective for fungal ergosterol

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17
Q

What was the first orally available broad spectrum antifungal drug?

A

Ketoconazole

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18
Q

Name 3 systemic azole drugs (ergosterol synthesis inhibitors).

A

Ketoconazole
Fluconazole
Itraconazole

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19
Q

What are 3 topical azole drugs (ergosterol synthesis inhibitors) one of which can also be used systemically?

A

Miconazole
Clotrimazole
Ketoconazole

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20
Q

What are 3 disadvantages of ketoconazole?

A

Inhibit CYP3A4 causing drug interactions
Hepatotoxicity
Gynecomastia

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21
Q

What is the DOC for fungal meningitis?

A

Fluconazole (cryptococcal meningitis)

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22
Q

What are other uses of fluconazole?

A

Candidemia (blood borne candidiasis) Vaginal candidiasis
Oropharyngeal and esophageal candidiasis
Prophylaxis of fungal disease in immunocompromised and transplant patients

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23
Q

Name a DNA/RNA synthesis inhibitor

A

Flucytosine

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24
Q

Of what is flucytosine an analogue?

A

Cytosine (a nucleotide)

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25
What must happen to Flucytosine for it to be active
Must be metabolized in fungal cell to active form
26
What is the active form of flucytosine?
5-fluorouracil
27
What is the mechanism of flucytosine?
Active form 5-fluorouracil inhibits thymidylate synthesis, required for synthesis of DNA and RNA
28
Is flucytosine narrow spectrum or broad spectrum?
Narrow because fungus must be able to metabolize flucytosine to activate it to 5-fluorouracil
29
What infection can flucytosine be used for (second line)?
Cryptococcal meningitis
30
When is flucytosine most useful and why?
When used in combo therapy because fungi develop quick resistance
31
What is a side effect of flucytosine?
Bone marrow depression
32
Nystatin is used for what fungal infections?
Topical infections
33
What drug class does nystatin belong to?
Polyene class (pore formers[amphoteric] same as Amphotericin B)
34
Can Nystatin be used orally?
Yes, but not for systemic due to toxicity. Used orally to treat oral candidiasis
35
What are 2 oral formulations of Nystatin for treatment of oral candidiasis?
1. ) Aqueous suspension: 5mL 4 times/day 2 min/swish. Has sucrose so diabetic consideration 2. ) Nystatin pastilles:dissolve in mouth 15 min/4 times day. Better b/c in there longer
36
For how long are topical antifungals used?
10-14 days or for at least 48 hrs after infection symptoms subside
37
What are 2 reasons viral infections are hard to treat?
Viruses are small, therefore have fewer drug targets Viruses utilize host functions so hard to selectively kill
38
What type of drugs are used to treat Herpes virus infections?
Nucleoside analogues
39
What is required for a nucleoside analogue drug to be used by a virus?
Must first be phosphorylated to the nucleotide form
40
Why do nucleoside analogues target viruses better than human DNA?
Viral DNA polymerases are less discriminating so they use the nucleoside analogue quicker
41
Once the nucleoside analogue has been incorporated into viral DNA, what do they lack and what does this cause?
Lack 3’ hydroxyl group required for next nucleotide to be added to chain causing chain termination
42
Viral nucleoside analogues are also called what?
Chain terminators
43
Which Herpes virus produces cold sores and eye infections?
HSV I (herpes labialis, herpes Keratitis)
44
HSV II causes what diseases?
Genital herpes (latent periods w/ sporadic outbreaks) Shingles (Herpes Zoster) Cytomeglovirus (CMV retinitis)
45
What takes genital herpes (HSVII) out of latency into active infection?
Stress or UV light
46
Which HSVII infections are problems in immunocompromised?
``` Herpes Zoster (shingles) CMV retinitis ```
47
What is an orally available nucleoside analogue for the relief of symptoms from active herpes infection or prophylaxis of herpes in immunocompromised?
Acyclovir
48
What is the mechanism of action for acyclovir?
It is taken up by herpes virus infected cell, converted to acyclovir monophosphate by viral thymadine kinase
49
Why does acyclovir only work in herpes virus infected cells?
Only infected cells have the thymadine kinase, unifected don’t have it so can’t convert the acyclovir to active
50
What is the active form of acyclovir and what is required to convert it to that?
Acyclovir monophosphate | Viral thymadine kinase
51
Can herpes virus become resistant to acyclovir, and if so, how?
Yes, by decreased thymadine kinase activity
52
What are common side effects for acyclovir?
Headache and insomnia
53
What is the prodrug form of acyclovir designed to give higher bioavailability?
Valacyclovir (Valtrex)
54
Is acyclovir curative or only symptom relief?
Symptom relief only
55
Gancyclovir (cytovene) is structurally similar to acyclovir but requires what type of administration?
Parenteral (other than alimentary canal)
56
What is the main use for Gancyclovir?
Treatment of serious infections (retinitis or pneumonia) caused by Cytomeglovirus (CMV)
57
What is a major negative side effect for Gancylclovir?
Bone marrow depression
58
What is an alternative drug for treating CMV and especially thymadine kinase deficient herpes (resistant herpes)?
Foscarnet (Foscavir)
59
What is Foscarnet(Foscavir) a derivative of and how must it be administered?
Phosphonic acid derivative, administrated intravenously
60
What are antivirals from pooled IgG immunoglobulins (antibodies) extracted from plasma of over one thousand blood donors
Immunoglobulins
61
How are immunoglobulins administered and what is their duration of action?
Administered intravenously or parenteral injection | Effective for 2 weeks to 3 months
62
)Immunoglobulins used for treatment of what?
Immunodeficient patient low antibiody levels
63
Natural proteins produced in the body for antiviral and immunomodulation are what?
Interferon
64
What are 3 natural classes of interferon?
1. Interferon Alpha 2. Interferon Beta 3. Interferon Gamma
65
What is the most common use for Interferons?
treat Hepatitis B, Hepatitis C Leukemia Multiple Sclerosis (autoimmune affecting brain and spinal cord [internet])
66
What is the common side effects from interferon treatment?
flu-like (myalgia, fatigue, headache, chills, nausea, vomiting, diarrhea)
67
What are 2 new anti-Influenza drugs?
Amantadine (Symmetrel) | Rimantadine (Flumadine)
68
Amantadine and Rimantadine are only effective against what influenza?
Influenza A
69
What is the administration of amantadine and rimantadine and when is it taken?
Oral administration after initial symptoms of flu
70
Can Amantadine and Rimantadine be used prophylactically to prevent flu virus infection?
Yes
71
What are the goals of Amantadine and Rimantadine treatment or prophylaxis?
Reduce severity of influenza A virus Decrease risk of serious influenza virus Minimize flu spread in institutions
72
How are Amantadine and Rimantadine believed to act on Influenza A?
Via M2 channel binding, it blocks the uncoating of the flu virus after it has penetrated the host cell
73
What is another disease, not viral, that Amantadine and Rimantadine are used to treat?
Parkinson's
74
Name 2 Neuraminidase inhibitors
Zanamivir (Relenza) Oseltmavir (Tamiflue)
75
What is neuraminidase
Enzyme spike on influenza A and influenza B viral coat
76
What does neuraminidase do to the host cell surface?
Cleaves sialic acid residue on cell surface necessary for final release of viral progeny from infected cell
77
How do Zanamivir (Relenza) and Oseltmavir (Tamiflu) work?
They are sialic acid analogues that bind and inhibit neuraminidase
78
What are 2 uses of Zanamivir (Relenza) and Oseltmavir(Tamiflu)?
reduce flu symptoms if taken within 30 hours of symptoms | prophylaxis

Pharm Exam 4 (8 decks)

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