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Antivirals Flashcards

1
Q

how viruses work?

A
  1. Attach
  2. enter
  3. uncoat
  4. synth proteins
  5. synth nucleic acids
  6. package and assembly
  7. viral release
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2
Q

Basic concepts

A
  • viruses are intracellular
  • depend on host machinery
    antivirals do 3 things: only on active replicators
    1. block entry into cell
    2. block exit from cell
    3. interfere with virus specific proteins once translated in cytosol

DO NOT HAVE ANY EFFECT ON VIRUSES IN LATENT STATE
agents specific to certain viruses or viral classes

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3
Q

Viruses currently tx

A
  1. Herpes
  2. Hepatitis B&C
  3. HPV
  4. influenza A&B
  5. RSV
  6. HIV
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4
Q

Herpes virus

A

DNA enveloped virus
six types:
1. herpes simplex virus 1
2. herpes simplex virus 2
3. varicella-zoster virus
4. cytomegalovirus
5. epstein barr virus
6. human herpes virus 8- HIV

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5
Q

Herpes antivirals:

A

anti hsv and vzv
* Valacyclovir
* penciclovir
* acyclovir
* famciclovir
* trifluridine

anti-cmv
* Ganciclovir
* Valganciclovir
* Foscarnet
* Cidofovir

interact with protein synth

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5
Q

Acyclovir

zovirax

A

synthetic quanosine analogue which leads to terminaiton of viral replication
Activity: HSV1, HSV2, VZV
low bioavailability
can take with food but give frequently bc of short half life=5x daily=low pt compliance
renal adjustment
monitor pts on zidocudine (hiv meds) and acyclovir-> increase somnolence and lethargy

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6
Q

Acyclovir activation and Clinical uses

A

activation: must have active infection-> viral thymidine kinase requried-> leads to chain termination by competing in dna polymerase

Uses:
* primary genital herpes
* secondary tx for genital herpes
* suppression therapy
* primary oral herpes
* shingles
white plaques w/ erythematous base, herpetic gingiiostomatatis

IV- serious
Topical-initial type 2 infection- not curative but may help with symptoms->prevention of recurrence during pregnancy @ 36 wks gestation

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7
Q

IV acyclovir clinical uses

almost only one thats IV

A
  1. herpes simplex encephalitis
  2. neonatal hsv infxn
  3. serious hsv or vzv in immunocomp host

Caution:
reversible renal toxicity
neurologic effects-> seizures
need adequate hydration

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8
Q

other anti hsv agents

A

Valacyclovir- more bioavail, SE: NVRash, suppressive therapy in pregnant woman
Famciclovir- good bioavail and expensive
Penciclovir cream- only topically
Trifluridine- used topically by opthalmologists

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9
Q

TX of varicella or cutaneous zoster

get picture

A

Tx decreases:
* total # of lesions
* duration of sxs
* viral shedding
* risk of post herpetic neuralgia
w/in 24 hours of rash (varicella-chkn pox) onset or 72 for cutaneous zoster

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10
Q

Cytomegalovirus

common virus infects all age groups

infants and HIV- vulnerable

A

over half of adults by age 40 have been infected- w/out sxs
Congenital cmv- 1 out of 200 born with it
* 15% develop progressive hearing loss
Transmission: person to person-> kissing, intimate contact, vertical transmission-mother child, blood transfusions, stem cell transplantation

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11
Q

Anti CMV AGENTS

A
  1. Ganciclovir- older used IV for CMV- also for CMV volitis, esophagitis, pneumonitis
    * SE: myelosuppresion and peripheral nueropahty
  2. Valganciclovir- great oral bioavail- prophyl for transplant or AIDS pt
  3. Foscarnet- poor bioavail- used for cmv and acyclovir resistant HSV
    * electrolyte abnormalities, renal impairment
  4. Cidofovir- IV for CMV retinitis
    * renal impairment, uveitis
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12
Q

Anogenital warts

Condyloma acuminatam

A

caused by HPV types 6 or 11, 16 or 18 are occasional
Goal: remove wart and ameliorate sxs

patient applied tx:
1.Imiquimod cream-> stim interferon
2.Sinecatechins-> upreg apop genes

Provider administration:
1. Cryotherapy with liquid nitrogen
2. Surgical removal

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13
Q

Hepatitis A

A

Vaccine preventable liver infxn
* stool and blood of infected
* very contagious by fecal/oral or person to person
* SXS: fatigue, nausea, vomiting, anorexia, stomach pain, then jaundice
* Not usually long lasting over a few months and self limiting

VACCINE VACCINE VACCINE- Hepatitis A virus ag 25 units/0.5 ml, inactivated
Ig vacc= for short term prevention

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14
Q

Hepatitis B

A

DNA virus infects hepatocytes
DX of acute HBV infxn= HBsAG and antiHBc
DX of chronic HBV= persistence of HBsAG for greater than 6 months
Goal of therapy: NOT CURABLE, suppress hbv replication to prevent progression to CIRRHOSIS AND HEPATOCELLULAR CARCINOMA or prevent reactivaiton

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15
Q

Cirrhosis

A

Hepatocellular injury-> fibrosis and regenerative nodules
Causes: Chronic viral hep, alcohol, drug toxicity, non alcoholic fatty liver disease
End stage chronic liver disease
SXS: ascites, jaundice, variceal hemorrhage, hepatic encephalopathy- altered mental status

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16
Q

Hepatocellular carcinoma

A

another progressionof Hep B

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17
Q

When should we treate Hepatitis B?

A

Active HBV + altered liver function +/- cirrhosis

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18
Q

Pharmacologic therapy for Hep B

A

1.immune mediating-Pegylated interferon alpha
2.Antiviral agents- BBW for lactic acidosis= preferred agents due to barrier of resistance
* entecavir, tenofovir, diprovoxil

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19
Q

Original therapy for HBV

A

Interferons- Peginterferon alfa
compensated disease- favorable liver biopsy to show compensated
SE: flu like sx (give nsaid), bone marrow suppression, anxiety/depression, thyroid, autoimmune
Pegylated interferons: increase half life

20
Q

Vaccination of Hep B

Most EFFECTIVE STRATEGY

A

requires multiple doses for improved response
3 single ag products:
1. Recombivax
2. Engerix b
3. Heplisav-b

combination vaccine:
1.twinrix- A and B
2.Pediarix- dtap and hbv- kids
3.Vaxelis: HPV, DTap, IPV

Heplisav b vaccine- novel adjuvant for immunogenicity

21
Q

whom should be given and why should you DEFINITELY get the vacc

A
  1. Hep BV- to all household and sexual contacts who are not known to be immune
  2. likelihood of progression to chronic HBV infection <5%
  3. loss of IgG>10 yrs post vaccine but memory still up to 30 yrs past
22
Q

Hepatitis C

A

Goal: eradicate virus
Testing: Recent infxn may not have AB so still RNA test
test AB-> RNA-> acute or past

Acute: hcv is a single stranded RNA virus lacking a proofreading polymerase
Clearance w/out therapy= 25-30%
new guidelines= tx immediately to decrease transmission of HCV
TX regimens are same as chronic hep

23
Q

Direct actign antiviral Agents

HCV

A

Targets 1 of 3 on hcv virion-> MUST BE IN COMBO WITH ATLEAST 2 DRUGS ACTING ON OTHER TARGETS

Drug drug interactions in general: Carbamazepine, phenobarbital, phenytoin, oxcarbazepine, rifampin, st. john’s wort

24
Hepatitis C classes of direct acting antiviral agents | may be combo to eradicate
1. Nonstructural protein (NS)5A inhibitors- Pibrentasvir and Velpatasvir 2. NS5B nucleoside polymerase inhibitors- Sofosbuvir 3. NS5B nonnucleoside polymerase inhibitors- Glecaprevir 4. NS3/4A protease inhibitors
25
Nonstructural proetin (NS) 5A inhibitors
NS5A protein assists in both viral replication and assembly of HCV-> exact MOA is unclear 1. Pibrentasvir- avail only with Glecaprevir, NOT REC IN HEPATIC IMPAIRED, excreted: **biliary** 2. Velpatasvir- fixed with Sofosbuvir- no dose adjustment for renal or hepatic- **requires acidic environ for absorption**
26
NS5B RNA polymerase inhibitors
NS5B is an RNA dependent RNA polymerase in post translational processing in rep of HCV 1. Sofosbuvir * nucleoside analogs target catalytic site- RARE CASES OF SYMP BRADYCARDIA W/ AMIODARONE
27
NS3/4A protease inhibitors
inhibits the NS3/4A serine protease necessary for the proteolytic cleavage of HCV encoded polyprotein 1. Glecaprevir: * combo with Pibrentasvir
28
Who is not eligible for simplified tx
1. current or prior episode of decompensated cirrhosis 2. prior hep c tx 3. end stage renal disease 4. HIV or HBsAG positive 5. Current pregnancy 6. known or suspected hepatocellular carcinoma 7. prior liver transplant | bc of hepativ impairment ## Footnote ALL HIGHLIGHTED
29
Child- Pugh score
predict mortality in cirrhosis Portal decompression sxs-> see if candidate Bilirubin albumin INR Ascites Encephalopathy
30
Chronic Hepatitis C | tx for naive adults w/ cirrhosis
1. Mavyret= Glecaprevir/pibrentasvir= 1-6 genotypes 2. Epclusa= Sofosvubir/Velpatasvir= 1,2,4,5, or 6
31
Mavyret drug interactions | glecaprevir/pibrentasvir
inhibit P-glycoprotein, breast cancer resistance protein, and organic anion transporting polypeptide * coadmin with drugs that are substrates of above= INCREASE PLASMA CONC * coadmin drugs that inhibit hepatic of above= increase plasma conc of Glecaprevir or pibrentasvir Carbamazepine, efavirenz, and St. john's wort= significant decrease plasma conc
32
Epclusa regimen | velpatasvir/sofosbuvir
AE: headache, fatigue, nausea, asthenia, insomnia St. John's wort increases interactions w/ meds
33
Ribavirin | Decomp cirrhosis
Decompensated cirrhosis or patients with HC GT3 MOA not well understood AE: **Hemolytic anemia- complaints of fatigue** ***pregnancy category X= 2 forms of contraception during tx and for 6 months after***
34
Testing prior to tx of Hep C
1. Hepatitis B infection- HBV reactivation reported during tx-> fulminant hepatitis, hepatic failure, death 2. Quantitative HCV testing-> to confirm chronic infxn and monitor response to therapy 3. HCV genotyping- affect tx choice and need for pretx resistance testing 4. HIV ag/ab test 5. asses of underlying liver disease- guide tx options 6. General labs w/in 3 mo of starting: CBC, INR, HEPATIC FUNCTION PANEL, eGFR
35
Influenza | sialic acid is key-> removes acid off sugar chains-> modify host respons ## Footnote then contagious
type A-> devided into subtypes of Hemagglutinin H and Neuraminidase N on surface B C
36
Influenza FDA approved tx
1. Oseltamivir phosphate- Tamiflu= neuraminidase inhibitor 2. Zanamivir- Relenza= Neuraminidase inhibitor= inhaled 3. Peramivir- Rapivab= Neuraminidase inhibitor- in hospital 4. Baloxavir Marboxil- Xofluza MOA of tamiflu= doesnt allow exit
37
Oseltamivir- tamiflu
Sialic acid analog interferes with viral release which aborts infxn USE FOR A AND B **ideally given within 48 hours Seasonal H1n1 develop resistance quickly** Children: cdc tec tx from birth american acad of pediatrics - rec 2 wks and older Prego safe Hospitals use SE: NV Headaches
38
Zanamivir- Relenza
inhalation powder- not widely used seasonal h1n15 remain sensitive- dont use if people have breathing issues SE: bronchospasm, sinusitis, dizziness
39
Peramivir- Rapivab
IV single dose SXS allev 21 hrs sooner, Fever resolved 12 hours sooner SE: diarrhea
40
Baloxavir marboxil- Xofluza | endonuclease inhibitor
MOA: prevents RNA cutting enzyme from hijacking host mRNA transcription process for uncomplicated flu pt 12 and older sick <48 hrs potential for rapid development of resistance
41
Respiratory syncytial virus infection | RSV
who is at risk?- premature infants, younger than 6 mo, children suppressed, kids with neuromuscular disorders bc cant cough Prophylax for infants and kids: Palivizumab- Synagis-> monthly IM injxn during season ## Footnote FALL, WINTER, SPRING
42
Coronavirus (Covid 19)
Severe acute resp syndrome- coronavirus Paxlovid- dont use severe renal impairment or hepatic Veklury-dont use severe renal impairment Lagevrio- if prego Outpatient: Veklury
43
National institute of health recommendations for nonhospitalized pts
Dexamethasone or other syst corticosteroids for symptomatic tx
44
NIH rec for hospitalized adults
Symptomatic + Paxlovid and Remdesivir
45
Nirmatrelvir-Ritonavir (Paxlovid)
combo of oral protease inhib nirmatrelvir-blocks activity of sars cov protease-> enzyme req for viral rep ritonavir-> slows metab of nirmatrelvir to remain active for longer | DOSE DEPENDENT ON KINDY FUNCTION
45
Remdesivir (Veklury)
RNA polymerase inhibitor approved emergency IV use in US in hospitalized pt infected with SEVERE DISEASE AE: n, renal tox, diarrha, rash
46
study guide
1. name viruses and antiviral tx 2. clinical use of acyclovir and SE and interactions 3. MOA of acyc and why not effective on others 4. tx of CMV 5. drug classes in Hep B and SE and monitoring 6. classes of Hep c and SE and monitoring 7. Influenza and MOA and why 1 drug is preferred

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