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Antivirals Flashcards

1
Q

what is a polymorphonuclear cell?

A

A type of immune cell that has granules (small particles) with enzymes that are released during infections, allergic reactions, and asthma. Neutrophils, eosinophils, and basophils are PMNs.

PMN - is polymorphonuclear neutrophil

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2
Q

what processes does cellular infection trigger?

A
  1. Release of early inflammatory mediators;
    TNF
    Type 1 interferon’s; a/B
    CCL5,CCL11
  2. These trigger immune cells i.ee PMN’s to release cytokines
  3. Trigger NK cells to kill infected cells
  4. Dendritic cells take antigens and make their way to Lymph nodes to present to and activate CD4 T cells. they also trigger cytokine release
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3
Q

List some cytokines

A

IFN-Y

Interleukin 2,4,5,9,12

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4
Q

what do the CD4 t cells do after antigen presentation from dendritic cells?

A

activate CD8 t cells

activate B cells - later produce antibodies

trigger cytokine release

activate eosinophils ?

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5
Q

Viral replication detected by which receptors ?

A

pattern-recognition receptors, Toll-like receptors, RIG-like receptor

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6
Q

list some of restriction factors

A

type 1 interferons (IFNs)
CCL5,CCL11
tnf

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7
Q

Antiviral immune response can be boosted by exogenous immunomodulators. list some for some common viral conditions

A

Interferon Rx for HBV and HCV,
IVIG for viral pneumonitis,
imiquimod for HPV,
steroids for HSE (?)

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8
Q

list some Limiting factors of antiviral therapy?

A

Host immune response

Adherence to treatment / antiviral drug resistance

Drug toxicity

Drug interactions

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9
Q

List some alpha herpes viruses?

A

VZV
HSV1
HSV2

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10
Q

List some beta herpes viruses?

A

CMV
HHV6
HHV7

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11
Q

List some gamma herpes viruses?

A

EBV

HHV8

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12
Q

Which virus causes mononucleosis type illness, oesophagitis, colitis and retinitis?

A

CMV

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13
Q

Which virus causes sixth disease AND encephalitis?

A

HHV6

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14
Q

Which virus causes burkitts lymphoma and infectious mononucleosis?

A

EBV

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15
Q

Which virus causes kaposi sarcoma?

A

HHV8

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16
Q

Which H herpesviruses family is oncogenic?

A

gamma

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17
Q

Which H herpesviruses family has rapid growth and latency in sensory ganglia (dorsal root)?

A

alpha

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18
Q

Which H herpesviruses family has slow growth?

A

beta

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19
Q

Adults infected with VZV are at risk of which complications?

A

pneumonitis

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20
Q

those who get shingles are at risk of which complications?

A

Post-herpetic neuralgia

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21
Q

how does shingles affect the immunocompromised?

A

multidermatomal or disseminated infection with severe complications

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22
Q

define prodrug?

A

A prodrug is an inactive precursor of a drug, that is metabolized into the active form within the body.

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23
Q

what drug type is Valaciclovir?

A

prodrug of aciclovir

high bioavailability

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24
Q

Rx for HSV and VZV - 1st and 2nd line?

A

Aciclovir (po or iv)
Valaciclovir (po )
Famciclovir

2nd line: Foscarnet or cidofovir for ACV-resistant virus

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25
Q

how does acyclovir work?

what type of drug is it?

A

□ Nucleoside (Guanine) analogue that gets incorporated into the growing chain of viral DNA

□ elongation of DNA becomes blocked

□ So, this class of drugs is also known as ‘chain terminators’

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26
Q

why does acyclovir work at chain termination?

A

acyclovir lacks the 3’ hydroxyl group necessary for the insertion of an additional nucleotide

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27
Q

for hsv and vxv, for which is acyclovir most sentive?

A

HSV-1 > HSV-2&raquo_space; VZV

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28
Q

what processes does acyclovir undergo before it can carry out its chain terminatoin abilities?

A

Monophosphorylated by viral thymidine kinase (TK)

and then further phosphorylation by cellular kinases

to ACV-PPP (active form) - V high affinity

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29
Q

rx for HSV Encephalitis?

A

Start empiric treatment immediately

with iv Acyclovir 10mg/kg tds

	without waiting for test results
30
Q

when do you treat vzv?

A

Chickenpox in adults

Zoster in adults >50

Primary infection or reactivation in the immunocompromised

Neonatal chickenpox

Increased risk of complications

31
Q

Where does CMV become latent?

A

in blood monocytes and dendritic cells

32
Q

pt comes in, yous ee WIDESPREAD RETINAL EXUDATE
AND HAEMORRHAGE on ophthalmoscopy

‘OWL’S EYE’ INCLUSIONS on histology

and INTERSTITIAL PNEUMONIA

what is the diagnosis?

A

CMV

33
Q

what is the 1st and second line treatment for CMV?

A

1ST
Ganciclovir GCV iv
Valganciclovir (VGC) po

2ND
Foscarnet FOS iv / intravitreal

34
Q

Ganciclovir Requires activation by what?

A

viral UL97 kinase enzyme

activation is by phosphorylation

35
Q

Ganciclovir is what type of drug?

A

Guanosine analogue - Inhibits viral DNA synthesis

36
Q

what kind of drug is valgancyclovir?

A

oral prodrug of ganciclovir

37
Q

In patients with CMV pneumonitis, ganciclovir is used in conjunction with ?

A

IVIG

38
Q

side effects of Ganciclovir?

A

Bone marrow toxicity (leukopenia, thrombocytopenia, anaemia, pancytopenia)

Renal and hepatic toxicity

39
Q

Ganciclovir
Valganciclovir
Foscarnet

have what MOA?

A

Inhibits viral DNA synthesis - guanisine analgoues

foscarnet - inhibits viral dna polymerase

40
Q

Side effects of foscarnet AND cidofovir ?

A

Nephrotoxic

41
Q

Cidofovir is what type of drug?

A

Nucleotide (cytidine) analogue

42
Q

which is there a higher CMV associated mortality; Bone marrow tranplant or SOT?

A

BMT

43
Q

How to manage CMV in the following patients:

  • Bone marrow transplant
  • Solid organ tx
  • Stem cell tx
A

Bone marrow transplant;
- Treat ; gancyclovir

Solid organ tx
- Prophylaxis ; valgancyclovir

Stem cell tx
- monitor and give gan/valgan if pcr +

44
Q

which antivral Directly inhibits viral kinase (UL97)?

used in what condition?

A

Maribavir

works in vitro against CMV and EBV

45
Q

which antivral is a CMV DNA terminase* inhibitor?

A

Letermovir

46
Q

how is EBV tranmitted?

which group is commonly affected?

A

Salivary transmission, infection common in childhood

47
Q

what is Post-Transplant Lymphoproliferative Disease?

A

Associated with EBV infection
Breakdown of immunosurveillance
Latently infected B cells – polyclonal expansion -> lymphoma

48
Q

how to Post-Transplant Lymphoproliferative Disease manage?

A

Reduce immunosuppression

Anti-CD20 monoclonal Ab therapy (B cell marker) – rituximab –

49
Q

patient comes in, EBV viral load in blood is > 10^5 c/ml, waht is likely diagnosis?

A

post-Transplant Lymphoproliferative Disease

50
Q

A 42-year-old lady is admitted with a 2 day history of fever and confusion and presents with new onset seizures. What antiviral medication should she receive as soon as possible? Choose the best answer.

Oral aciclovir
IV foscarnet
Oral valaciclovir
IV ganciclovir
IV aciclovir
A

E because they have HSV encaphelitis

51
Q

list 2 influenxa surface proteins and their role?

A

Haemaglutinin: Haemaglutinin regulates binding to airway and entering cells

Neuraminidase: responsible for exit of new virus back out of cells and into the airways.

52
Q

list 2 neuramnidase inhibitors and which flu viruses they work against?

A

1st line - Oseltamivir PO
2nd line - zanamivir NG

Effective for both influenza A and B

53
Q

who are those making up the influenza riisk group?

A 
Aged ≥ 65 years
Immunosuppressed
Chronic respiratory disease
Chronic heart disease
Chronic liver disease
Chronic neurological disease
Diabetes mellitus
Pregnant women
Morbid obesity (BMI ≥ 40)
Children < 6 months
54
Q

Commonest cause of severe respiratory tract illness and hospitalisation of infants worldwide?

A

RSV - resp syncytial virus

causing bronchiolitis

55
Q

which antivirals are effective for Lassa fever and HEV?

A

ribavarin

56
Q

Charcaterise BK virus infection ?

A

in childhood minimal symptoms,

but subsequent lifelong carriage in kidneys and urinary tract - > reactrivation in immunosuppressed

57
Q

name the Treatment of BK haemorrhagic cystitis?

A

Bladder washouts
Reduce level of immunosuppression if possible
Cidofovir iv (+ probenicid) if significant morbidity

58
Q

Treatment of BK nephropathy

A

Normal human immunoglobulin (~ IVIG)

Reduce level of immunosuppression if possible

59
Q

who contracts Adenovirus?

rx?

A

Paeds transplant recipients
Severe multi-organ involvement

Rx: Ribavirin
Cidofovir iv
IVIG

60
Q

which interferons can be used in hep b treatment?

A

IFN-Y

Peg-IFN a-2a (pegasys)

61
Q

list hep b treatment and mmemonic?

A

Tenofovir and Entecavir - told on placement

T - tenofovir
I - interferon
L - lamivudine
E - entecavir

62
Q

list 3 types of hep c viral drugs and targets of action/effect?

give examples of their names

A

protese inhibitors - targets NS3 on hcv RNA (boceprevir)

NS5A inhibitors - elbasivir

polymerase inhibitors - NS5B , Dasabuvir

63
Q

list 2 mechanims via which viruses acquire resistance?

A

Diversity
- Quasispecies, mutation / recombination

Selection
- Replication (eg in the presence of suboptimal drug concentrations)

64
Q

list 2 ways to Prevent drug resistance?

A

Use potent drug regimens to achieve maximal suppression of viral replication (combination Rx / HAART)

Increase adherence to treatment
(low drug burden, once-daily regimens,
patient education…)

65
Q

list 2 Drug resistance assays?

give examples of use

A

Genotypic: Sequencing / resistance mutations
Example: HIV drug resistance

Phenotypic: Cell culture
Plaque reduction assay
example: used for HSV drug resistance testing

66
Q

list 2 mechanisms of HSV drug resistance (to acyclovir)?

A

Mutations usually in viral thymidine kinase (95%), and

rarely in the viral DNA polymerase (5%)

67
Q

how to Treat Acyclovir -resistant HSV ?

and also gancyclovir resistant cmv?

A

foscarnet

cidofovir

68
Q

HSV drug resistance (to acyclovir) mediates cross-resistance to what drug?

A

gancyclovir

69
Q

list 2 mechanisms of CMV drug resistance to ganciclovir

A

In protein kinase gene (UL97) - most common
In the DNA polymerase gene (UL54) – rare
UL56 terminase gene (letermovir)

70
Q

Name a type of mutation found in influenza A H1N1 that confers resistance to neuraminidase inhibitors?

A

H275Y - neuraminidase mutation

71
Q

Immunoglobulins are usually given when?

list some conditions ?

A

for prophylaxis or PreP in the following;

RSV - palivizumab
VZV
Hep B
Rabies

therapeutic in EBV and viral pneumonitis

path - microbiology (27 decks)

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