DIT reveiw - Micro 8 Flashcards

1
Q

What are the subtypes of Filovirus

A
  • Ebola virus and Marburg Virus
    • = Marburg and eGOOOOALA
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2
Q

Presentation of Filovirus

A
  • Infected w/ filovirus and demonstrating hemorrhagic fever, petechial rash
    • à Goalie with jersey red spots (rash) and sweaty (fever)
  • Hemorrhagic fever
    • à Guy on ground surrounded by pool of blood
  • End organ failure
    • à Kidneys and liver shaped blood spots
  • Fatal – severe blood loss leading to hypovolemic shock (can occur within days)
    • à player is dead
    • à lightning bolt on shirt (hemorrhagic/hypovolemic shock)
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3
Q

Presentation of Hantavirus

A

Subtype of Bunyavirus

  • Hemorrhagic fever
  • Pneumonia
  • May end in respiratory failure
  • Spread by aerosolized mouse urine
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4
Q

Describe general characteristics of Arenavirus

A
  • (-)ssRNA
  • 2 segments
  • Rodent reservoir
  • Causes lymhocytic choriomeningitis virus (LCV)
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5
Q

What are the subtypes of Reovirus

A

Rotavirus

Colorado tick fever

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6
Q

Descrieb presentation and toxin associated with rotavirus

A
  • Fecal-oral transmission
  • Fatal diarrhea in children worldwide
  • Outbreaks occur in winter months, especially in day care centers
  • NSP4 toxin increases chloride permeability leading to secretory diarrhea
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7
Q

Describe presentation of Colorado tick virus

A
  • Colorado tick fever
  • Spread by woodtick
  • Acute, self-limited flu-like illness (fever, vomiting, myalgias)
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8
Q

MOA of interferons

A
  • Are host cytokines that exert antiviral, immunomodulatory, and antiproliferative effects
  • Interleukins upregulate interferon synthesis in infected cells
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9
Q

Uses of interferon alpha

A
  • Hepatitis B and C infections
  • Hairy cell leukemia
  • Malignant melanoma
  • Kaposi sarcoma caused by HHV8
  • Condyloma accuminata caused by HPV
  • Renal cell carcicoma
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10
Q

Uses of Interferon beta

A
  • Multiple sclerosis
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11
Q

Uses of interferon gamma

A
  • Chronic granulomatous disease (CGD)
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12
Q

Adverse effects of interferons

A
  • Flu-like symptoms, depression, myelosuppression, myopathy
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13
Q

What are the drugs used to treat hepatitis C

A

Interferon alpha

Ribavirin

Sofosbuvir

Simeprevir

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14
Q

MOA, uses, and adverse effects of Ribavirin

A
  • MOA:
    • Guanosine analog
      • Must be tri-phosphorylated intracellularly before becoming active
    • Inhibits synthesis of guanine via competitive inhibition of IMP dehydrogenase
  • Uses:
    • Chronic hepatitis C (daily dosage)
    • RSV
  • Adverse effects:
    • Hemolytic anemia
    • Severe teratogen
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15
Q

MOA, uses, and adverse effects of Sofosbuvir

A
  • MOA:
    • Nucleoside analog
    • Inhibits RNA-dependent RNA polymerase
  • Uses:
    • Chronic hepatitis C
      • Used in combo with Ribavirin +/- interferon alpha
      • Do not use as monotherapy
  • Adverse effects:
    • Fatigue, HA, nausea
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16
Q

MOA, uses, and adverse effects of Simeprevir

A
  • MOA:
    • HCV (NS3/4A) protease inhibitor
    • Prevents viral replication
  • Uses:
    • Chronic hepatitis C
      • Used in combo with Ledipasvir (NS5A inhibitor)
      • Do not use as monotherapy
  • Adverse effects:
    • Photosensitivity
    • Rash
    • CYP450 inhibitor
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17
Q

What are the 3 structural genes of HIV and what proteins does each encode for

A
  • pol:
    • Reverse transcriptase
    • Integrase
    • Protease
  • gag:
    • p24
    • p17
  • env:
    • gp120
    • gp41
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18
Q

Describe the functions of reverse transcriptase, integrase, and protease encoded by pol

A
  • Reverse transcriptase = synthesizes dsDNA from RNA
  • Integrase = integrates viral DNA into host genome
  • Protease = cleaves polypeptide products of HIV mRNA into their functional parts
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19
Q

Describe the functions of p24 and p17 encoded by gag

A
  • p24 = capsid directly surrounding viral DNA
  • p17 = matrix surrounding the capsid
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20
Q

Describe the functions of gp120 and gp41 encoded by env

A
  • gp120 = glycoprotein on membrane surface that binds to CD4+ of host
    • Binding leads to a conformational change so that virus can also bind a coreceptor on the host
      • CCR5 on macrophages (early infection)
      • CXCR4 on T-cells (late infection)
  • gp41 = transmembrane glycoprotein that allows fusion and entry into host
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21
Q

Describe the tests used to diagnose HIV

A
  • ELISA (use first)
    • High sensitivity (rule out test)
    • Captures all positive tests, but includes a lot of false positives
  • Western blot (use on those who got + ELISA)
    • High specificity (rule in test)
    • Low false positive (but on its own, would have had high false negative)
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22
Q

When are ELISA and Western blot not good to be used for HIV diagnosis

What test should be used instead during this time

A
  • Recall that both tests look for antibodies to viral proteins
    • May be falsely (-) in first 1-2 months or falsely (+) in newborn of infected mother
  • Use viral load for diagnosis instead
23
Q

Diagnostic criteria of AIDs

A
  • CD4 cell count < 200
  • % of CD4 cells < 14%
  • HIV + AIDs-defining illness (e.g. Pneumocystis pneumonia)
24
Q

WHat causes oral hairy leukoplakia

A

EBV

25
Q

How do you differentiate between Kaposi sarcome and Bacilliary angiomatosis (Bartonella henselae)

A

Kaposi = virus = lymphocytic inflammation

Bartonella = bacteria = neutrophilic inflammation

26
Q

What diseases and what medications must be treated prophylactically in HIV patients with:

  • CD4 < 200
  • CD4 < 100
  • CD4 < 50
A
  • CD4 < 200:
    • Pneumocystis prophylaxis:
      • TMP/SMX, Dapsone
  • CD4 < 100:
    • Toxoplasmosis (if positive IgG)
      • TMP/SMX, Dapsone
  • CD4 < 50:
    • Mycobacterium avium
      • Azithromycin
27
Q

What cell types does HIV affect?

A

Macrophages and CD4 cells

28
Q

What is the HAART regimen

A
  • Combo of at least 3 different HIV medications to prevent resistance
    • 2 NRTI (backbone) + 1 other drug class
29
Q

MOA of NRTI

A
  • Nucleoside analogs (guanosine or cytosine analogs)
    • Except for Tenofovir which is a Nucleotide analog
  • Competitive inhibitor
    • Inhibits HIV reverse transcriptase by attaching to nucleotide-binding site
    • Lack a 3’OH group, so cause chain termination
  • Must be phosphorylated or activated by thymidine kinase
    • Except for Tenofovir
30
Q

MOA of NNRTI

A
  • Noncompetitive inhibitors
    • Bind to HIV reverse transcriptase at a site different from NRTIs
  • Do not require phosphorylation to be active
31
Q

MOA of protease inhibitors

A
  • Prevent development of new viruses by Inhibiting protease, this inhibition HIV polypeptide cleavage into functional parts
32
Q

MOA of integrase inhibitors

A
  • Inhibits integrase so that HIV genome cannot be integrated into host chromosome
    • Not referring to fusion!
33
Q

MOA of Maraviroc

A
  • Binds CCR5 on surface of macrophages, inhibiting interaction with gp120 on HIV, thus preventing binding to host cell
  • Must make sure that patient is infected with all R5 viruses (determined by tropism test)
    • Not effective in patients with any X4 viruses
34
Q

MOA of Enfuviritide

A
  • MOA:
    • Binds gp41, inhibiting viral fusion and entry
    • Only given via injection
    • Very expensive
  • THINK: enFUvirtide = FUsion
35
Q

Label each of the following drugs as NRTI, NNRTI, Protease inhibitor, or integrase inhibitor:

  • Raltegravir
  • Efavirenz
  • Ritonavir
  • Abacavir
  • Nevirapine
  • Lamivudine
  • Tenofovir
  • Indinavir
  • Dolutegravir
  • Didonasine
  • Emtricitabine
  • Delavirdine
  • Zidovudine
  • Atazanavir
  • Stavudine
A
  • Raltegravir = integrase inhibitor (tegr)
  • Efavirenz = NNRTI (vir)
  • Ritonavir = protease inhibitor (navir)
  • Abacavir = NRTI (abracadabra)
  • Nevirapine = NNRTI (vir)
  • Lamivudine = NRTI (Sir Lancelot)
  • Tenofovir = NRTI (Sir Tristan)
  • Indinavir = protease inhibitor (navir)
  • Dolutegravir = integrase inhibitor (tegr)
  • Didonasine = NRTI (Sir Dan)
  • Emtricitabine = NRTI (Excalabir)
  • Delavirdine = NNRTI (vir)
  • Zidovudine = NRTI (Princess Isolde)
  • Atazanavir = protease inhibitor (navir)
  • Stavudine = NRTI (Sir Steve)
36
Q

Specific uses of Zidovudine

A
  • Decrease risk of fetal transmission during pregnancy
  • HIV (+) women at time of deliver
  • Newborns born to HIV + mothers
37
Q

Which NRTIs treat Hepatitis B

A
  • Lamivudine or Tenofovir
38
Q

General adverse effects of NRTIs

A

Lactic acidosis

39
Q

Which NRTIs are associated with lipodystrophy (redistribution of fat in a Cushing-like syndrome)

A

Zidovudine, Stavudine

40
Q

Which NRTIs are associated with peripheral neuropathy

A

The diners

Lamivudine, Stavudine, Didanosine

41
Q

Which NRTI is associated with bone marrow suppresion

A

Zidovudine

42
Q

Which NRTI is associated with pancreatitis

A

Didanosine

43
Q

Which NRTI is associated with hyperpigmentation of palms and soles

A

Emtricitabine

44
Q

Which NRTI is associated with hypersensitivity reaction, and how do you prevent this?

A
  • Abacavir
  • Hypersensitivity reaction – delayed type IV ​
    • Abacavir contraindicated if patient has HLA-B*5701 mutation
45
Q

Adverse effects of NNRTIs

A
  • Rash (Stevens-Johnson syndrome)
  • Hepatotoxicity (jaundice and liver failure)
  • Neuropsychiatric symptoms (nightmares, vivid dream, dizziness, worsening depression)
    • Efavirenz
  • False-positive drug test to cannabinoids
    • Efavirenz
  • Teratogenic
    • Efavirenz and Delavirdine
46
Q

Adverse effects of protease inhibitor

A
  • GI intolerance (nausea, diarrhea)
  • Hyperglycemia
  • Hyperlipidemia/hypertriglyceridemia
  • Lipodystrophy (redistribution of fat in a Cushing-like syndrome)
47
Q

WHich protease inhibitor is associated with nephrolithiasis and hematuris

A

Indinavir

48
Q

Which protease inhibitor is associated with inhibition of CYP450

A

Ritonavir

  • Inhibits CYP-450 – can boost other drug concentrations (especially Ritonavir)
49
Q

What drug should not be given when taking protease inhbitors

A
  • Rifampin use is contraindicated with protease inhibitors because it is a CYP450 inducer and will decreased concentration of protease inhibitors
50
Q

Adverse effects of integrase inhibitors

A
  • Nausea, rash, myopathy
  • Increased creatinine kinase (rhabdomyolysis)
51
Q
A
52
Q

Mutation in the pol gene will cause resistance to which classes of HIV drugs?

A

NRTI, NNRTI, protease inhibitors, integrase inhibitors

Pol encodes for reverse transcriptase, protease, and integrase

53
Q

Mutation in what gene will cause resistance to Maraviroc

A

Env gene (encodes for gp120)

54
Q

Mutation in what gene will cause resistance to Enfuvirtide

A

Env gene (encodes gp41)