Antiviral Treatmen Flashcards
(68 cards)
1
Q
How do antivirals work?
A
2
Q
What are the two approaches of antiviral therapy?
A
- Approach 1 – Directly Acting Antivirals / Small Molecule Inhibitors
- Approach 2 – Immunomodulators:
3
Q
How do the directly acting antivirals/small molecule inhibitors work? What do they target?
A
- Viruses encode proteins for… cell entry, genomic replication/transcription, assembly and release of progeny
- E.G. nucleic acid polymerases, proteases, integrase CCR5, terminase
- These proteins are a target for AV-drugs (e.g. protease inhibitors, polymerase inhibitors, integrase inhibitors)
- SMIs / DAAs block production/action of the above inhibit viral replication or action
4
Q
How do immunomodulators work?
A
- Viral replication is detected by PRRs (i.e. TLRs, RIG-like receptors) trigger innate immune responses
- This antiviral immune response can be boosted by giving immunomodulators
- E.G. interferon (tx HBV, HCV), IVIG (viral pneumonitis), imiquimod (HPV), steroids (HSE)
5
Q
What are the limiting factors of antiviral therapy?
A
- Limiting factors of antiviral therapy:
- The natural host immune response is critical; difficulties in treating:
- Transplant patients
- HIV patients
- Adherence to treatment
- Antiviral drug resistance
- Drug toxicity and interactions
- The natural host immune response is critical; difficulties in treating:
6
Q
How do we classify herpesvirus?
A
7
Q
What are the stages of herpes infection?
A
- Primary infection (e.g. chickenpox)
- Latency - e.g. in dorsal root ganglia
- Reactivation e.g. zoster-shingles
8
Q
What causes chickenpox? What are the complications?
A
- Caused by primary infection with varicella-zoster virus (VZV)
- Uncomplicated in children
- Susceptible to complications in adults (e.g. pneumonitis)
- Severe disease in immunocompromised
9
Q
What is zoster? What does it cause I the immuncompetent and immunocompromised?
A
- •Reactivation of latent infection (dorsal root ganglia)
-
Immunocompetent
- Dermatomal distribution
- Complication: Post-herpetic neuralgia
-
Immunocompromised
- Can experience multidermatomal or disseminated infection with severe complications
10
Q
What is a prodrug?
A
A prodrug is an inactive precursor of a drug, that is metabolized into the active form within the body.
11
Q
What antivirals used for the treatment of HSV and VZV?
A
12
Q
What is the MOA of acyclovir?
A
AKA ‘chain terminators’
13
Q
What does acyclovir require in order to be activated? How does It have selective activity?
A
14
Q
How do we treat HSV encephalitis?
A
- Immediate empirical treatment IV Aciclovir 10mg/kg TDS (without waiting for test results)
- I.E. 700mg TDS (for 70kg person)
- If confirmed, treat for 14-21 days
- I.E. 700mg TDS (for 70kg person)
- Should do a repeat LP before stopping abx
15
Q
What are the indications for tx of VZV?
A
- Chickenpox in adults (risk of pneumonitis)
- Zoster in adults >50 years (risk of post-herpetic neuralgia)
- Primary infection or reactivation in an immunocompromised patient
- Neonatal chickenpox
- If increased risk of complications (e.g. underlying lung disease, eye involvement)
16
Q
What are the stages of CMV virus?
A
- Primary infection → latent in blood monocytes and dendritic cells → reactivated e.g. following immunosuppression
17
Q
Where would CMV be in asymptomatic patients?
A
Shed in asymptomatic patients via saliva, urine, semen and cervical
18
Q
What are the consequences of CM infection in the immunocompromised
A
- Bone marrow suppression
- Retinitis
- Pneumonitis
- Hepatitis
- Colitis
- Encephalitis
19
Q
A
CMV pneumonitis
20
Q
A
Widespread retinal exudate and haemorrhage - CMV
21
Q
A
Owl’s eye inclusions - CMV
22
Q
What are the MCV antiviral drugs? What route are they given by?
A
- 1st line Gangciclovir (GCV) - IV
- Prodrug: Valganciclovir (VGC) - PO
- 2nd line Foscarnet (FOS) - IV/intravitreal
- 3rd lie Cidofovir (CDV) - IV
Letermovir - recently approved
23
Q
How does gangciclovir get activated?
A
24
Q
How do (val/)gangciclovir work? What does it have activity against? How is it excreted? What are the indication? What are the side effects and contraindications?
A
25
How does foscarnet work? What is it effective against? How is it given? What are the indications? What are the SEs?
26
How does cidofivir work? What is it active against? How is ti administered= What is the indications and side effects?
27
What are the strategies for Treatment of CMV in **Transplant Patients?**
* **(A) TREAT** established disease (**GCV** and **reduce immunosuppression**) – high mortality in HSCT
* **(B) PROPHYLAXIS** with **GCV/vGCV**
* **Indication**: solid organ transplant (i.e. renal)
* **SEs**: bone marrow toxicity
* **(C) Best - PRE-EMPTIVE THERAPY** with **Foscarnet** **\>** **GCV/vGCV**
* **Indication**: HSCT
* Twice weekly monitoring for the appearance of CMV on PCR in the blood
28
How is maribavir given? What is it effective against? What is it effective against? What are the SEs?
29
How is Letermovir given? What is it effective against? What is it effective against? What are the SEs? What are the interactions?
30
How is EBV transmitted? What illness does it cause? What are the stages? What is it associated with?
31
What is post-transplant Lymphoproliferative disease? What is it associated with? How do we diagnose and manage it?
32
IV acyclovir
33
What are the main surface proteins of influenza?
* 2 main surface proteins = haemagglutinin (HA) and neuraminidase (NA)
* HA = binding and entry into the target cell
* NA = release of progeny virus particles from the host cell
34
What are the NA inhibitors? What viruses are they effective against? when is it indicated?
* Oseltamivir (Tamiflu) – ORAL
* Zanamivir (Relenza) – Dry Powder
* Effective against influenza A and B
* Indications:
* Those unwell enough to be admitted to hospital due to influenza virus-related respiratory disease
35
What are the indications for NA inhibitors in the community?
36
What is Peramavir? Hows it given? What is effective against? What is the resistance like to this drug?
37
What is baloxavir? How is it administered? What is the MOA? What are the SEs? What is the resistance like?
38
What drug combination can be used for flu?
39
What does RSV cause? What is it associated with? What are the risk groups?
40
What is used to manage RSV?
Ribavarin
41
What is Ribavarin? How is it administered? What does it do? What is it effective against? What re the adverse effects?
42
Describe the role of IVIG in the tx of RSV?
* Derived from pooled donors
* Often used as an *adjunct to treatment* of viral pneumonitis in the immunocompromised
43
What is Palivizumab=?What is the indication? How is it given?
44
What is Nirsevimab?
Palivizumab-like drug
* Extended half-wife mAB
* Require single IM injection to provide protection for the whole winter
45
What tx are used in SARS-CoV-2?
* Antiviral drugs
* Neutralising monoclonal antibodies (nabs)
* Immunomodulators
46
What are the antiviral drugs given for SARS-CoV-2?
47
What are neutralising monoclonal Abs-"nMabs"?
48
How do monoclonal antibodies interact with SARS-CoV-2?
49
What are the immunomodulators used for SARS-CoV-2?
50
A
51
What is BK Virus? When does infection tend to occur? Who does it cause a problem in?
BMT - bone marrow transplant
52
How can hemorrhagic cystitis be treated?
* *If significant morbidity* Cidofovir (IV)
* *If nephrotoxicity* Cidofovir (intravesical)
* Avoids nephrotoxicity if direct into bladder
53
How should BK nephropathy be treated?
* Reduce immunosuppression
* IVIG
* NOTE: cidofovir cannot be used because it is nephrotoxic
54
Who does adenovirus cause a problem in? What does it cause? How is it treated?
55
What is Brincidofovir? How is it given? What is the advantage of using it?
56
What is cellular immunotherapy? What are the indications?
* Adoptive immunotherapy, virus-specific cytotoxic T cells, donor lymphocyte infusion
* **Indications**: CMV, adenovirus, BK virus, EBV… in transplant recipients
57
What are the causes of treatment failure?
58
What are the mechanisms of drug resistance?
* **Selection** → selection of **pre-existing resistant strains** due to **inadequate drug levels**
* **Diversity** → quasispecies (a population of the virus are genetically heterogenous rather than clonal)
59
What are the implications of drug resistance?
* Treatment failure
* Need to use second-line drugs – *less effective and often more toxic*
* Cross-resistance with other antivirals
60
How do we prevents drug resistance?
* Potent combination drug regimens
* Increase adherence to treatment (i.e. lower pill burden)
61
When should we test for drug resistance?
62
When should we test for drug resistance?
63
What are the different types of drug resistance assays?
* **Genotypic assays** – sequencing genome identify known drug resistance mutations:
* For… HIV, HBV, HCV, **CMV**
* **Phenotypic assays** – culturing in cell monolayers in presence of increasing concentrations of antiviral drugs:
* AKA: Plaque Reduction Assay
* For… **HSV**
64
What causes HSV drug resistance to acyclovir? When does it occur? When should it be suspected? How should it be treated?
65
What causes CMV resistance to Gangcyclovir? Who does it occur in? When should it be suspected? What is the second line for CNV tx?
66
What is the most important mutation conferring resistance in influenza A (H1N1)?
Oseltamivir (NA inhibitor) resistance through **H275Y mutation**
67
What are the different Ig preparations?
68
