DIT reveiw - Micro 8 Flashcards
1
Q
What are the subtypes of Filovirus
A
-
Ebola virus and Marburg Virus
- = Marburg and eGOOOOALA
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)
3
Q
Presentation of Hantavirus
A
Subtype of Bunyavirus
- Hemorrhagic fever
- Pneumonia
- May end in respiratory failure
- Spread by aerosolized mouse urine
4
Q
Describe general characteristics of Arenavirus
A
- (-)ssRNA
- 2 segments
- Rodent reservoir
- Causes lymhocytic choriomeningitis virus (LCV)
5
Q
What are the subtypes of Reovirus
A
Rotavirus
Colorado tick fever
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
7
Q
Describe presentation of Colorado tick virus
A
- Colorado tick fever
- Spread by woodtick
- Acute, self-limited flu-like illness (fever, vomiting, myalgias)
8
Q
MOA of interferons
A
- Are host cytokines that exert antiviral, immunomodulatory, and antiproliferative effects
- Interleukins upregulate interferon synthesis in infected cells
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
10
Q
Uses of Interferon beta
A
- Multiple sclerosis
11
Q
Uses of interferon gamma
A
- Chronic granulomatous disease (CGD)
12
Q
Adverse effects of interferons
A
- Flu-like symptoms, depression, myelosuppression, myopathy
13
Q
What are the drugs used to treat hepatitis C
A
Interferon alpha
Ribavirin
Sofosbuvir
Simeprevir
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
- Guanosine analog
- Uses:
- Chronic hepatitis C (daily dosage)
- RSV
- Adverse effects:
- Hemolytic anemia
- Severe teratogen
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
- Chronic hepatitis C
- Adverse effects:
- Fatigue, HA, nausea
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
- Chronic hepatitis C
- Adverse effects:
- Photosensitivity
- Rash
- CYP450 inhibitor
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
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
19
Q
Describe the functions of p24 and p17 encoded by gag
A
- p24 = capsid directly surrounding viral DNA
- p17 = matrix surrounding the capsid
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)
- Binding leads to a conformational change so that virus can also bind a coreceptor on the host
- gp41 = transmembrane glycoprotein that allows fusion and entry into host
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)
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
How do you differentiate between Kaposi sarcome and Bacilliary angiomatosis (Bartonella henselae)
Kaposi = virus = lymphocytic inflammation
Bartonella = bacteria = neutrophilic inflammation
26
What diseases and what medications must be treated prophylactically in HIV patients with:
* CD4 \< 200
* CD4 \< 100
* CD4 \< 50
* CD4 \< 200:
* Pneumocystis prophylaxis:
* TMP/SMX, Dapsone
* CD4 \< 100:
* Toxoplasmosis (if positive IgG)
* TMP/SMX, Dapsone
* CD4 \< 50:
* Mycobacterium avium
* Azithromycin
27
What cell types does HIV affect?
Macrophages and CD4 cells
28
What is the HAART regimen
* Combo of at least 3 different HIV medications to prevent resistance
* 2 NRTI (backbone) + 1 other drug class
29
MOA of NRTI
* 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
MOA of NNRTI
* Noncompetitive inhibitors
* Bind to HIV reverse transcriptase at a site different from NRTIs
* Do not require phosphorylation to be active
31
MOA of protease inhibitors
* Prevent development of new viruses by Inhibiting protease, this inhibition HIV polypeptide cleavage into functional parts
32
MOA of integrase inhibitors
* Inhibits integrase so that HIV genome cannot be integrated into host chromosome
* Not referring to fusion!
33
MOA of Maraviroc
* 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
MOA of Enfuviritide
* MOA:
* Binds gp41, inhibiting viral fusion and entry
* Only given via injection
* Very expensive
* THINK: enFUvirtide = FUsion
35
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
* 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
Specific uses of Zidovudine
* Decrease risk of fetal transmission during pregnancy
* HIV (+) women at time of deliver
* Newborns born to HIV + mothers
37
Which NRTIs treat Hepatitis B
* Lamivudine or Tenofovir
38
General adverse effects of NRTIs
Lactic acidosis
39
Which NRTIs are associated with lipodystrophy (redistribution of fat in a Cushing-like syndrome)
Zidovudine, Stavudine
40
Which NRTIs are associated with peripheral neuropathy
The diners
Lamivudine, Stavudine, Didanosine
41
Which NRTI is associated with bone marrow suppresion
Zidovudine
42
Which NRTI is associated with pancreatitis
Didanosine
43
Which NRTI is associated with hyperpigmentation of palms and soles
Emtricitabine
44
Which NRTI is associated with hypersensitivity reaction, and how do you prevent this?
* Abacavir
* Hypersensitivity reaction – delayed type IV
* Abacavir contraindicated if patient has HLA-B\*5701 mutation
45
Adverse effects of NNRTIs
* 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
Adverse effects of protease inhibitor
* GI intolerance (nausea, diarrhea)
* Hyperglycemia
* Hyperlipidemia/hypertriglyceridemia
* Lipodystrophy (redistribution of fat in a Cushing-like syndrome)
47
WHich protease inhibitor is associated with nephrolithiasis and hematuris
Indinavir
48
Which protease inhibitor is associated with inhibition of CYP450
Ritonavir
* Inhibits CYP-450 – can boost other drug concentrations (especially Ritonavir)
49
What drug should not be given when taking protease inhbitors
* Rifampin use is contraindicated with protease inhibitors because it is a CYP450 inducer and will decreased concentration of protease inhibitors
50
Adverse effects of integrase inhibitors
* Nausea, rash, myopathy
* Increased creatinine kinase (rhabdomyolysis)
51
52
Mutation in the pol gene will cause resistance to which classes of HIV drugs?
NRTI, NNRTI, protease inhibitors, integrase inhibitors
Pol encodes for reverse transcriptase, protease, and integrase
53
Mutation in what gene will cause resistance to Maraviroc
Env gene (encodes for gp120)
54
Mutation in what gene will cause resistance to Enfuvirtide
Env gene (encodes gp41)
