Term
A patient presents with Fever blisters, genital herpes and mild encephalopathy. You determine it is a viral infection.
What is your diagnosis and how might you treat? |
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Definition
Herpes Simplex Virus
(val)Acycovir (Nucleoside analog that acts on polymerase or Foscarnet (Polymerase inhibitor) if resistant. |
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Term
A patient presents with Chickenpox (or shingles in adulthood). You determine it is a viral infection.
What is your diagnosis and how might you treat? |
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Definition
VZV
1) (val)acyclovir (nucleoside analog that binds polymerase) |
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Term
A patient presents with Kaposi sarcoma. You determine it is a human herpes viral infection.
What is your diagnosis? |
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Definition
|
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Term
| What are the 5 human herpes viruses? |
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Definition
1) HSV
2) CMV
3) EBV
4) VZV
5) HHV-8 |
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Term
You diagnose a patient with an RSV infection.
How would you treat? |
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Definition
| 1) Ribavirin (nucleoside analogue that binds polymerase) |
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Term
You diagnose a patient with an HBV infection.
How would you treat? |
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Definition
All nucleoside analouges!
go TELA your doctor you got HBV
1) Tenofovir (Nucleoside analouge that binds polymerase)
2) Emtricitabine (Nucleoside analogue that binds polymerase)
3) Lamivudine (Nucleoside analogue that binds polymerase)
4) Adevofir (Nucleoside analogue that binds polymerase) |
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Term
You diagnose a patient with an HCV infection.
How would you treat? |
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Definition
1) Interferon-alpha (immunomodulator)
2) Ribavirin (nucleoside analogue that binds polymerase)
3) Telaprivir (protease inhibitor)
4) Boceprevir (protease inhibitor) |
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Term
| You diagnose a case of Influenza A. How do you treat? |
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Definition
1) Amantadine (ion channel blocker (HA)-uncoating)
2) Rimantadine (ion channel blocker (HA)- uncoating)
3) Oseltamivir (Sialic acid analogue/ inhibit drug release)
4) Zanamivir (Sialic acid analogue/ inhibit drug release) |
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Term
| You diagnose a case of Influenza B. How do you treat? |
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Definition
1) Oseltamivir (Sialic acid analogue/ inhibit drug release)
2) Zanamivir (Sialic acid analogue/ inhibit drug release) |
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Term
You diagnose a case of Lassavirus (from Arenavirus).
How do you treat? |
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Definition
| 1) Ribavirin (nucleoside analogue that binds polymerase) |
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Term
You diagnose a case of Enterovirus (Picornavirus).
How do you treat? |
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Definition
|
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Term
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Definition
| Imiquimod (cytokine inducer that works on host factors) |
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Term
| What 3 viruses cause immediately lethal viral infections, with vascular inflammation, hemorrhaging and pulmonary edema? |
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Definition
1) Ebola
2) Yellow Fever
3) Hantavirus (Bunyavirus) |
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Term
Which available vaccines are Live-attenuated, and which are Inactivated?
How common are they in practice? |
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Definition
Live
1) MMR
2) Small pox
3) Varicella
Inactive
These are short-lived and expensive options.
1) Hepatitis A/B
2) Polio
3) Rabies
4) HPV |
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Term
| What passive (Ig prep) immunizations are available? |
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Definition
1) VZ-IG (chicken pox)
2) R-IG (rabies)
3) CMV-IG
4) RSV-IG (respiratory syncytial virus) |
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Term
| What is the difference between how Hepatitis A and RSV are battled by the host immune system? |
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Definition
Both are Self limited infections
1) Hep A is protected from re-infection life-long
2) RSV immunity is only short duration, but may dull subsequent infections. |
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Term
| Which viruses are "contained viral infections"? |
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Definition
1) Hep C is chronic with persistent infection (liver cirrhosis)
2) VZV (dermatomal reactivation causing shingles),
remains latent until a stress or immunocompromised state in adulthood.
Other ex) HSV, CMV EBV and HHV-6 and 7 |
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Term
| What is the difference between Virucides, Antivirals and Immunomodulators? |
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Definition
1) Virucides directly inactive intact viral particles (detergents, solvents, UV light, ect)
- May be used for transmission prevention, but of little use in mucocutaneous HSV
2) Antivirals inhibit viral replication at the cellular level.
- They act only on actively replicating viruses, and they are often given too late or with resistance.
3) Stimulate host immune response by inducing cytokines (IFN and imiquimod) or decreasing immunosuppresion (EBV with PTLD in transplant patient or HIV and Kaposis sarcoma with ART therapy ) |
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Term
| How can immunomodulation prevent cases of post-transplant lymphoproliferative disease (PTLD)? |
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Definition
| PTLD occurs because of reactivation of latent EBV infections, so you should turn down immunosuppresion to make sure that it is not reactivated. |
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Term
| How do IFN-a and Imiquimod induce host immunity? |
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Definition
| They inhibit viral protein synthesis, degrade viral RNA AND enhance CTL and NK cell activity. |
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Term
| Which anti-viral drugs can be used to treat Herpes viruses? |
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Definition
1) Nucleoside analogues (Acyclovir, Valacyclovir, Penciclovir and Famciclovir) that incorporate faulty nucleotides into the growing nucleotide chain.
2) Pyrophosphate analogues that inhibit viral polymerase (Foscarnet) |
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Term
| Which anti-viral drugs can be used to treat CMV infection? |
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Definition
1) Nucleoside analogues (Ganciclovir, Cidofovir)
2) Pyrophosphate analogue (Foscarnet) |
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Term
| How does Acyclovir work to treat HSV-1, HSV-2 and VZV? It is equally as good at treating each? |
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Definition
1) Initial phosphorylation of Acyclovir in the cytoplasm by viral Thymidine Kinase (TK)
2) 2nd and 3rd phosphorylations utilize host machinery
3) ACV-TP competitively inhibits viral DNA polymerase and acts as a chain terminator
**HSV-1>HSV-2>VZV** |
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Term
| Explain the clinical use of Acyclovir for treating herpes viruses. |
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Definition
Orolabial, Genital, Neonatal and Encephalitis
1) 1st episode of orolabial herpes offers a great benefit, but reccurent (only 1/2 day relief)
2) First episode of genital herpes offers great benefit, but recurrent is only 1d of help.
3) Neonatal herpes
4) Herpes encephalitis (prompt is better). |
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Term
| Under what clinical scenario is a high dose of Acyclovir required? |
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Definition
1) Varicella in adults with rash <3 days
2) Varicella and zoster in older adults because of complication risks
3) Immunocompromised hosts for Varicella and Zoster (don't vaccinate!). |
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Term
| Why might you use Valacyclovir instead of Acyclovir? |
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Definition
Oral bioavailability can treat more serious cases genital herpes and VZV infection, because of more convenient dosing.
Valacyclovir is a pro drug acyclovir that is converted to ACV in intestine or liver. |
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Term
| Which Nucleoside analogue can be given topically to treat herpes labialis? |
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Definition
| Penciclovir (Famciclovir is pro-drug) |
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Term
A donor that is CMV (-) receives blood from someone who is CMV (+) and develops leukopenia and anemia.
How might you treat? |
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Definition
Ganciclovir/Valganciclovir (CMV treatment in immunocompromised patients or as prophylaxis)
1) Ganciclovir- nucleoside analogue requiring phosphorylaton by UL97 (CMV kinase), which inhibits viral polymerase synthesis.
2) Because of low oral bioavailability, you could also try Valganciclovir (pro-drug) |
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Term
| How can resistance arise to Acyclovir and Ganciclovir? |
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Definition
Both nucleoside analogues (Herpes or CMV)
1) Acyclovir- TK mutations or viral polymerase mutations
2) Ganciclovir- UL97 mutations or viral polymerase mutations
Remember, Cidofovir and Foscarnet are not plagued by kinase-mediated resistance. |
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Term
| How might you treat Ganciclovir-resistant CMV infections? |
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Definition
1) Cidofovir of 2) Foscarnet
1) Monophosphate nucleoside analogue that only requires host-cell-mediated phosphorylation
- Watch out for NEPHROTOXICITY
2) Pyrophosphate analogue that inhibits DNA polymerase of herpes viruses by blocking PPi binding site
**Watch out for NEPHROTOXICITY and ELECTROLYTE IMBALANCE** |
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Term
| How might you treat Acyclovir-resistant HSV infections? |
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Definition
Foscarnet
- Pyrophosphate analogue that inhibits DNA polymerase of herpes viruses by blocking PPi binding site
**Watch out for NEPHROTOXICITY and ELECTROLYTE IMBALANCE** |
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Term
| You have a patient with acyclovir-resistant herpes. You treat with Foscarnet. What side effects should you look for? |
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Definition
| Nephrotoxicity and Electrolyte imbalances (perhaps penile ulcers as well) |
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Term
| You have a patient with ganciclovir-resistant CMV. You treat with Cidofovir. What side effects should you look for? |
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Definition
NEPHROTOXICITY
Maybe GI side-effects as well. |
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Term
| Which anti-virals can be used to treat Influenza A? |
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Definition
1) Ion channel blockers (M2 inhibition prevents pH lowering which is responsible for un-coating) such as Amantadine and Rimantadine. (Resistance is a problem)
2) Sialic acid analogues (Neuraminidase inhibitors) such as Oseltamivir and Zanamivir that block cleavage of HA leading to viral release. |
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Term
When might you decide to treat with Oseltamivir or Zanamavir?
What side effects should you look for? |
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Definition
1) Sialic acid analogues (Neuraminidase inhibitors) that are given from Influenza A/B/Avian to prevent viral egression (especially in A, if it is resistant to Adamantine)
2) Oseltamivir is a pill that can cause GI symptoms and nausea
3) Zanamavir is an inhalant that can cause Bronchospasm in people with Asthma or COPD. |
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Term
| A patient presents with Hep C infection. How might you treat? What side-effects should you look for? |
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Definition
No vaccine available and transmitted through blood/semen
Give PEG-IFN-a, Ribavirin and Protease inhibitors all at once (genotypes 1 and 4 are less responsive than 2 and 3)
1) PEG-IFN-a (flu-like and neuropsychiatric SE)
2) Ribavirin (HEMOLYTIC ANEMIA, headaches SE)
3) Protease inhibitors (Telaprevir/anemia and sygeusia SE and Bocepravir/anemia and rash SE) |
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Term
| Which Hepatitis C genotypes are most resistant to anti-viral treatments? |
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Definition
2 and 3 are 75%
1 and 4 are closer to 50% |
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Term
| How does IFN-a treat Hepatitis C and Hepatitis B infection/ what are some side effects? |
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Definition
1) Subcutaneous injections of cytokine have immunomodulator effects (PEGylated form sticks around longer)
2) Flu-like symtpoms and Neuropsychiatric symptoms (depression) |
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Term
A patient of yours is being treated for Hepatitis C and is exhibiting depression, flu-like symptoms and hemolytic anemia.
What treatments are they on? |
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Definition
1) PEG-INF-a (Flu-like and Neuropsychiatric)
2) Ribavirin (Hemolytic anemia) |
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Term
| How does Ribavirin work to treat, Lassa virus, RSV in infants and Pneumonias in immunocompromized patients |
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Definition
1) Requires intracellular phosphorylation by host cell
- inhibits inosine 5'-monophosphate dehydrogenase (IMP-DH), depleting GTP synthesis and blocking viral RNA synthesis.
Look out for hemolytic anemia! |
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Term
| How do Telaprevir and Boceprevir treat HCV genotype 1? What side effects should you be careful of? |
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Definition
Give in combination with PEGIFN/ribavirin
1) Bind reversibly to active site of HCV NS3 protease to inhibit HCV replication
2) Look for anima and dysgeusia (Boceprevir) and rash/nausea (Teaprevir) |
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Term
| When and how can you treat chronic HBV infection? |
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Definition
Treat if there is persistently positive Hep B surface antigen (HBsAg) AND chronic active hepatitis (liver inflammation)
1) IFN
2) Nucleoside analogues that supress HPV replication by acting as chain terminators
(Lamivudine, Adefovir, Entecavir, Telbivudine, Emtricitabine and Tenofovir) |
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Term
| Which drug used to treat chronic HBV infection is most prone to resistance? |
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Definition
| Lamivudine is 70% resistant (YMDD mutation) at 4 years. |
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Term
| Why treat with Palivizumab and how does it work? |
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Definition
mAB against RSV ($$$$$)
- use for RSV prophylaxis for infants at risk. |
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