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Antivirals and Antifungals Flashcards

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1
Q

What is an example of an M2 ion channel inhibitor? What is it used for?

A

Amantidine for prevention (70%) and treatment (20-30% reduction) of the influenza A virus

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2
Q

How does an M2 ion channel inhibitor work?

A

Blocks the M2 transmembrane ion channel, which prevents uncoating of the virus (essential in replication)
Virusatic

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3
Q

What are some adverse effects of M2 ion channel inhibitors?

A

Dose related, amphetamine like, mild GI upset
Rapid resistance
2:1 therapeutic index (toxic)

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4
Q

What is an example of a neuraminidase inhibitor? What is it used for?

A

Zanamivir and Oseltamivir (inhaled powder) are used for prevention (70%) and treatment (20-30% reduction) of influenza A and B infection.

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5
Q

How do neuraminase inhibitors work?

A

Inhibits viral neuraminidase, impairing the release and spread of influenza virions from infected cells due to aggregation of virions.

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6
Q

What are some adverse effects of neuraminase inhibitors?

A

Zanamivir may rarely cause bronchospasm.

Ostelamivir causes mild nausea and vomiting

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7
Q

What is an example of a DNA polymerase inhibitor? What is it used for?

A

Acyclovir, valacyclovir, famcicolvir
Treatment, prevention and supression of HSV and VZV infection of skin, mucous membranes and viscera.
Ganciclovir only for GMV

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8
Q

How do DNA polymerase inhibitors work?

A

Competitively inhibit DNA polymerase by acyclovir phophorylation and causes DNA chain termination

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9
Q

How does resistance to DNA polymerase inhibitors occur?

A

Only develops in immunocompromised patients during prolonged therapy due to mutation of an enzyme, thus reduced affinity.

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10
Q

What are some adverse effects of DNA polymerase inhibitors?

A

Rapid IV administration (acyclovir) can cause crystallization, leukopenia (GCV) and allergy (topicals)

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11
Q

Which DNA polymerase inhibitor is used in pregnant patients?

A

Acyclovir and vacyclovir

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12
Q

Which DNA polymerase inhibitors are used for HSV keratitis in the eye?

A

Idoxuridine, trifluridine, vidarabine

Can cause local irritation or corneal dystrophy if prolonged exposure

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13
Q

What is an example of a biological immune response modifier? What are they used for?

A

Imiquimod (topical) and interferon-alpha 2b (injection) to treat genital HPV infection (warts)
Podophyllin is ablative

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14
Q

How do biological immune response modifiers work?

A

Activates immune cells (monocytes, macrophages, NK cells) to produce antiviral cytokines (IFN-alpha and TNF)

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15
Q

What is the efficacy of biological immune response modifiers?

A

Imiquimod clears warts in 37-52%

Interferon-alpha 2b clears warts in 42-62%

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16
Q

What are some adverse effects of biological immune response modifiers?

A

Local irritation, erythema, ulceration, scabbing (must wash off residual drug after overnight application) for topical therapy
Pain, local irritation at injection site

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17
Q

What are some examples of provider administered biological response modifiers?

A

Cryotherapy, podophylline resin, trichloroacetic acid, excision, intralesion IFN

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18
Q

What are the 6 classes of drugs for HIV infection?

A

Fusion inhibitor, CCR-5 Coreceptor antagonist, nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI, integrase inhibitor, protease inhibitor

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19
Q

What is an example of a fusion inhibitor?

A

Enfuvirtide (subcutaneous injection) to treat HIV-1

Eliminated by proteolysis

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20
Q

What is maraviroc?

A

A CCR-5 Coreceptor antagonist used to treat HIV-1 orally. Should be last utilized for therapy
Eliminated by liver

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21
Q

What are some examples of NRTIs?

A

Zidovudine, lamivudine, stavudine, dideoxycytidine used to treat HIV-1 and 2
Eliminated by liver and renal

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22
Q

What are some examples of NNRTIs?

A

Efavirenz, delavirdine, nevurapidine used to treat HIV-1 orally
Eliminated by liver

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23
Q

What is an example of integrase inhibitors?

A

Raltegravir
Used to treat HIV-1 orally
Elminated by glucuronidation

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24
Q

What are some examples of protease inhibitors?

A

Saquinavir, ritonavir, infinavir
Used to orally treat HIV-1 and 2
Eliminated by liver

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25
How do fusion inhibitors work?
Inhibits gp41-mediated fusion of virus with CD4 lymphocyte cell membrane (stops HIV entry into CD4 cells)
26
What are some adverse effects of fusion inhibitors?
Local inflammatory reactions at injection site, diarrhea, nausea
27
How do CCR-5 coreceptor antagonists work?
Binds to CCR-5 on the macrophage and CD4 cell to stop viral entry
28
What are some adverse effects of CCR-5 coreceptor antagonists?
Drug interactions, hepatotoxic (rash, eosinophilia or elevated IGE),
29
How do NRTIs work?
Inhibits RNA-dependent DNA polymerase (reverse transcriptase) by binding to the enzyme. DNA chain terminator
30
What are some adverse effects of NRTIs?
Inhibition of the mitochondrial DNA polymerase causing lactic acidosis, hyperlactemia, myleosuppresion, pancreatitis, peripheral neuropathy Hypersensitivity reaction predicted by HLA B 5701 POS Dideoxyinosine is least toxic followed by stavudine and zidovudine
31
How do non-NRTIs work?
Inhibit HIV reverse transcriptase non-competitively at an allosteric site (resistance arises in weeks)
32
What are some adverse effects of non-NRTIs?
Drug interactions | Nightmares, headache, dizziness, rash, depression
33
How do integrase inhibitors work?
Incompletely prevents insertion of HIV DNA into the human DNA genome, interfering with DNA replication
34
What are the adverse effects of integrase inhibitors?
Generally well tolerated, headache and nausea, diarrhea
35
How do protease inhibitors work?
Blocks viral replication by interfering with the protease enzyme that clips long HIV polypeptides into component structural and enzymatic proteins
36
What are some adverse effects of protease inhibitors?
Saquinavir has minimal Indinavir can give renal stones Ritonavir (most drug interactions) and darunavir can give nausea, diarhhea, paraesthesia Nelfinavit can give diarrhea Amprenavir and fosamprenavir can give nausea, vomiting and rash Lopinavir and atazanavir cause diarrhea and perirpheral neuropathy Darunavir can increase cholesterol
37
What are some drugs that NNRTIs and protease inhibitors interact with?
Anticonvulsants, coumadin, cisapride, antihistamines, antiarrythmics, Ca channel blockers
38
When is HIV infection therapy initiated? What is the duration of treatment?
Only initiated when CD4
39
What are the preferred NNRTI based treatments for previously untreated adults?
Efavirenz or tenofovir or emtricitabine
40
What are the preferred protease inhibitor based treatments for previously untreated adults?
Atazanavir or ritonavir and tenofovir or emtricitabine
41
What are the preferred integrase inhibitor based treatments for previously untreated adults?
Raltegravir and tenofovir or emtricitabine
42
What is the basis of HIV treatment for a previously untreated adult?
Dual nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) plus a NNRTI or a protease inhibitor or an integrase inhibitor
43
What is the treatment to prevent vertical transmission of HIV in pregnancy?
Start during pregnancy and post partum | Zidovudine or lamivudine and nivirapine
44
What is the regimen for post-exposure prophylaxis after need stick exposure to HIV?
Start within a few hours and treat for 4 weeks Zidovudine and lamivudine with or without lopinavir or ritonavir Or you can use tenofovir and emitricitabine
45
What is the most common route of acquiring HIV?
Blood transfusion, needle-sharing, receptive anal intercourse, percutaneous needle stick
46
How do you monitor hepatitis B and C treatment?
Monitor the treatment's antiviral effect by measuring HBV or HCV RNA in circulation.
47
How is chronic hepatitis B treated?
Nucleoside and nucleotide analogues
48
How do nucleoside and nucleotide analogues work?
Interfere with the replication of RNA intermediates of DNA genome catalyzed by reverse transcriptase Limited by resistance
49
What are some examples of nucleoside and nucleotide analogues for chronic hepatitis B?
Lamividine, adefovir, telbivudine, tenofovir disoproxil fumurate (TDF)-DOC, entecavir-DOC, ribavirin and pegylated interferon (Peg IFN)
50
What is the adverse effect of adefovir?
Renal insufficiency
51
What occurs when a virus is resistant to telbuvidine?
The resistant virus is generally cross-resistant to lamivudine
52
What does tenofovir disoproxil fumarate (TDF) inhibit?
It inhibits lamivudine, adefovir and entecavir resistant HBV
53
What does entecavir inhibit?
It inhibits lamivudine-resistant hepatitis B virus
54
How does ribavirin work?
Incompletely understood, includes inhibition of RNA polymerase and nucleic acid synthesis
55
How must ribavirin be used?
For hepatitis C virus in combination with pegylated interferon alpha
56
What is the adverse effect of ribavirin?
Hemolytic anemia
57
How does pegylated interferon alpha work?
Triggers synthesis of enzymes that mediate antiviral, antiproliferative activity and enhanced phagocyte activity of macrophages
58
How does the interferon being pegylated change things?
Makes it a slow release formulation after subcutaneous injection (once a week)
59
What are the adverse effects of peg-IFN?
Frequent, severe ADR | Flu-like illness, myelosuppression and immunosuppression
60
What is the treatment regime for chronic hepatitis B?
Peg-IFN alpha subcutaneously once weekly or | Entecavir or tenofovir once daily for 24-48 weeks
61
How is chronic hepatitis C treated?
Using a sofosbuvir/ledipasvir tablet once daily for 12 weeks
62
How does sofosbuvir work?
Causes chain termination of the HCV genome
63
How does ledipasvir work?
Inhibits the NS5A protein
64
What are some adverse effects of sofosbuvir?
Well tolerated, headache and fatigue. Resistance is rare
65
What are the adverse effects of ledipasvir?
Drug interactions with digoxin and rosuvastatin
66
What are the 4 classes of antifungal drugs?
Allylamines (topical, oral), azoles (topical, oral), polyenes (oral, IV) and echinocandin (IV)
67
What are some examples of allylamines?
Topical naftifine for skin infections and oral terbinafine for nail infections or severe skin infections
68
What are allylamines effective against?
Dermatophytes (epidermophyton, microsporon, trichophyton)
69
How do allylamines work?
Fungistatic or fungicidal depending on the species | Inhibits squalene epoxidase in the cell membrane leading to ergosterol synthesis inhibition
70
What are the adverse effects of the allylamines?
Well tolerated Rash from topical (steven-johnson syndrome) Hepatitis from oral
71
What are some examples of azoles?
Topical clotrimazole Oral itraconazole, ketoconazole IV posaconazole Oral and IV fluconazole and voriconazole
72
What are azoles effective against?
Candida albicans, aspergillus, blastomycosis, coccidioidomycosis, zygomycetes
73
How do azoles work?
Fungistatic. Blocks CYP450 leading to inhibited replication and cell membrane synthesis
74
What are the adverse effects of azoles?
GI symptoms, hepatic necrosis, impotence, diminished libido
75
What are some of the drug interactions with ketoconazole?
CYP3A4 | H2 blockers, coumadin, loratidine, astemizole, terfenadine
76
What are some examples of polyenes?
Oral nystatin and IV amphotericin B with lipids (reduces toxicity)
77
What are polyenes effective against?
Broad spectrum including candida, blastomyces, aspergillus
78
How do polyenes work?
Creates pore or channels through which cytoplasmic contents can leak out
79
What are some adverse effects with polyenes?
Nausea, chills, anemia and azotemia | Hydocortisone pretreatment can help avoid this
80
What are some drug interactions with polyenes?
Additive nephrotoxicity with gentamicin
81
What are some examples of echinocandins?
Caspofungin and micafungin, both IV
82
What are echinocandins effective against?
Aspergillus and candida
83
What are some adverse effects of echinocandins?
Chills and fever, histamine mediated (rash, face swelling, pruritis, bronchospasm, anaphylaxis)
84
What are some drug interactions with echinocandins?
Rifampin

Pharmacology (11 decks)

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