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Infectious Disease > Antivirals > Flashcards

Antivirals Flashcards

1
Q

The basic process of viral infection and virus replication occurs in 6 main steps:

A 
Absorption
Penetration
Viral genome replication
Assembly
Maturation
Release
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2
Q

To be effective, antiviral agents must either?

2

A

Block viral entry into or exit from the cell

Be active inside the host cell

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3
Q

Name the kind of drugs most antivirals are?

1 and 2

A

Purine or Pyrimidine analogs.

They are prodrugs –must be phosphorylated by viral or cellular enzyme

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4
Q

One step do anti-viral drugs work on of the viral attack?

A

Anti-viral agents inhibits active replication so the viral growth resumes after drug removal (when you stop them the virus will not be coontrolled anymore)
–nucleic acid synthesis specifically

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5
Q

What is needed for antiviral drugs to work?

3

A
  1. Current anti-viral agents do not eliminate non-replicating or latent virus (if they go into a latent stage)
  2. Effective host immune response remains essential for the recovery from the viral infection
  3. Clinical efficacy depends on achieving inhibitory concentration at the site of infection within the infected cells
  4. Must be actively replicating
  5. Host must have effective immune response
  6. Clinical efficacy = achieving inhibitory concentration
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6
Q

What are the Anti-HSV/VZV ((Herpes/Varicella/Zoster) agents?

3

A

Acyclovir (Zovirax)
Famciclovir (Famvir)
Valacyclovir (Valtrex)

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7
Q

MOA of Anti-HSV/VZV (Herpes/Varicella/Zoster) agents

2

A

The analog inhibits viral DNA-polymerase

Only actively replicating viruses are inhibited

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8
Q

What is Acyclovir (Zovirax®) used to treat?

mostly 2 and sometimes two others

A

Herpes simplex 1 (mouth) and 2 (genital)

varicella-zoster virus, possibly the Epstein-Barr Virus

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9
Q

Acyclovir (Zovirax®) is treatment of choice for?

4

A
  1. HSV Genital infections,
  2. Herpes labialis/orolabial (cold sores),
  3. HSV encephalitis,
  4. HSV infections in immunocompromised and pregnant patient
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10
Q

What dosage forms does it come in?

3(one main one)

A

Topical, ORAL, and intravenous formulations

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11
Q 
Pharmacokinetics of Acyclovir :
Oral  bioavailability:
Distribution in:
Renal excretion:  
Half life: 
Administration:
A 
~ 20-30% 
all body tissues including CNS 
> 80%
2-5 hours
Topical, Oral , IV
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12
Q

Acyclovir safety/monitoring:
Renal Dosing?
Hepatic dosing?

A
  1. IV route CrCl 25-50 give q 12hrs: CrCl
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13
Q

Acyclovir Mechanism of Action?

2

A

Inhibition of viral synthesis of DNA

  1. Uptake by infected cell
  2. Competes with deoxyguanosine triphosphate for viral DNA polymerases (Chain termination)
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14
Q

Acyclovir is thus selectively activated in cells that are?

A

infected with herpes virus.

Uninfected cells do not phosphorylate acyclovir.

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15
Q

Acyclovir Adverse effects ?
3 big ones
5 others

A 
Reversible renal toxicity
Neurological symptoms
TTP/HUS
GI symptoms
Headache
Rash
Photosensitivity
Anemia
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16
Q

WHat kind of patient does Acyclovir Resistance most often occur in?

Three basic resistance mechanism exist?

What drugs are cross resistant to acyclovir?2

A

Mostly occurs in immunocompromised host
MIC > 2-3 mcg/mL

Reduced or absent thymidine kinase
Altered TK substrate specificity
Alterations in DNA polymerase

Cross resistance to famciclovir and valacyclovir

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17
Q 
Acyclovir (Zovirax®)
Why treat with it?
Primary genital herpes:3
Recurrent genital herpes:1
Long term treatment:3
Varicella Zoster:2
A
  1. Shortens duration of symptoms, time of viral shedding and time to resolution of lesions by approximately 5 days.
  2. Shortens time course by 1-2 days
  3. Decreases frequency of both symptomatic recurrences and asymptomatic viral shedding, thus decreasing sexual transmissions
  4. Decreases total number of lesions and duration of varicella (if begun within 24 hours after the onset of rash)
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18
Q

What do we treat with Famciclovir (Famvir®)?

3

A

HSV 1 and 2, VZV,

to a lesser extent, EBV, in vitro activity to HBV

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19
Q 
Pharmacokinetics of Famciclovir:
Oral  bioavailability:
Metabolism:
Renal excretion: 
Half life: 
Administration:
A 
~ 77% 
First-pass metabolism in the intestine and liver results in conversion to penciclovir. 
> 80% 
2-3 hours
 Oral
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20
Q

Famciclovir safety/monitoring:
Pregnancy Category?
Lactation?

Renal dosing?
Hepatic dosing?

A 
B
Safety Unknown (inadequate literature to assess risk: caution advised)

Adjust dose for CrCl

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21
Q

Famciclovir MOA?

how does it compare to acyclovir?

A

famciclovir is converted to penciclovir triphosphate and compared to acyclovir triphosphate,

penciclovir triphosphate has a lower affinity for viral DNA polymerase but a longer intracellular half-life.

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22
Q

Famciclovir Adverse effects
3 serious
4 general symptoms

A

Neutropenia
Thrombocytopenia
Neurological symptoms

GI symptoms
Headache
Fatigue
Abnormal LFT’s

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23
Q

Famciclovir Resistance mechanism?

Cross resistance with what drug and in what strains?

A

Mutations in viral TK or DNA polymerase

Cross resistance with acyclovir in TK negative strains

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24
Q

Valacyclovir (Valtrex®)
is what?

Dosage forms?

A

Valacyclovir is a prodrug of Acyclovir

Rapidly and almost completely converted to acyclovir

Orally only

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25
Q

WHat makes Valacyclovir different then from Acyclovir?

Why is it not used as often then?

A

Advantage: better oral bioavailability (55%)
More convenient dosing

Expensive

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26
Q 
Valacyclovir (Valtrex®)
Pharmacokinetics of Valacyclovir:
Oral bioavailability?
Metabolism?
Renal excretion?
Half life?
Administration?
A
  1. ~ 55%
  2. undergoes rapid and extensive first-pass intestinal and hepatic hydrolysis to yield acyclovir
    Food does not affect absorption
  3. > 50%
  4. 2-3 hours
  5. Oral
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27
Q

Valacyclovir safety/monitoring
Pregnancy Category?
Lactation?

Renal Dosing?
Hepatic Dosing?

A

B
Safe

Adjust dose for CrCl

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28
Q

Valacyclovir (Valtrex®) adverse affects?
3 major

5

A

Reversible renal toxicity
Neurological symptoms
TTP/HUS

GI symptoms
Headache
Rash
Photosensitivity
Elevated LFT’s
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29
Q 
What disease is acyclovair only used for and not  Valacyclovir or
Famciclovir?
A. Primary Genital
B. Recurrent Genital
C. Encephalitis
D. Chronic Suppressive
A

C

30
Q

What do we use to treat varicella?

A

Acyclovir

31
Q

What can we use to treat herpes zoster/

A

Valacyclovir
Famciclovir
Acyclovir

32
Q

What can we use to treat Varicella or Zoster in Immunocompromised?

A

Acyclovir

33
Q

What other Topicals for HSV do we treat orolabial herpes with?
2

A
  1. Penciclovir (Denavir® 1% cream)
    -Topical guanine analog similar to acyclovir
  2. Docosanol (Abreva® OTC)
    Active against a broad range of lipid-envelop viruses
    MOA: interferes with viral fusion to host cell
34
Q

What do we use to treat HSV Keratoconjuctivitis?

A

Trifluridine (Viroptic® 1% ophthalmic)
1 drop q2h (max 9 drops/day)
Active against acyclovir resistant strains
Also active against vaccinia virus and smallpox

35
Q

What is our antiCMV agent?

Dosage forms?3

A

Ganciclovir

Oral, intravenous, and intraocular

36
Q

Ganciclovir is the drug of choice for?

2

A
  1. CMV retinitis in immunocompromised patient

2. Prevention of CMV disease in transplant patients

37
Q 
Ganciclovir (Cytovene®)
Pharmacokinetics of Ganciclovir:
Oral Bioavailability
Excretion? 
Renal excretion?
Half life?
A
  1. 50%
  2. Is excreted unmodified in the urine
  3. > 90%
  4. 2-4 hours
38
Q

Ganciclovir Safety/Monitoring
Pregnancy Category?
Lactation?

Renal Dosing?
Hepatic Dosing?

A

C (animal studies show adverse fetal effects)
Unsafe

Adjust dose for CrCl

39
Q

Ganciclovir MOA?

A

Competes with deoxyguanosine triphosphate similar to acyclovir

However in CMV, viral-encoded phosphotransferase converts to ganciclovir triphosphate

Unlike acyclovir, ganciclovir contains a 3’-hydroxyl group, allowing for DNA to continue

40
Q

Ganciclovir

Adverse affects?

A 
LOTS OF THEM(only used for CMV)
reversible pancytopenia
Fever
Rash 
Phlebitis (IV)
Confusion
Renal dysfunction
Psychiatric disturbances
Seizures
41
Q

Influenza Agents?

4

A

Oseltamivir
Zanamivir
Amantadine
Rimantadine

42
Q

Neuraminidase inhibitors are which influenza agents?

A

Oseltamivir / Zanamavir

43
Q

What makes influenza virus suceptible to antivirals?

A

Influenza contains an enzyme neuraminidase which is essential for the replication of the virus.

44
Q

How do Neuraminidase inhibitors, Oseltamivir / Zanamavir, work against influenza?

A

Neuraminidase inhibitors prevent the release of new virions and their spread from cell to cell.

45
Q

What types of influenza do Oseltamivir / Zanamavir work against?

Will it interact with the vaccine?
What can it be used for?

A

These are effective against both types of influenza A and B.

Do not interfere with immune response to influenza A vaccine.

Can be used for both prophylaxis and acute treatment.

46
Q

What is the brand name for Oseltamivir?

A

Tamiflu

47
Q

What is the spectrum of activity for Tamiflu?

3

A

Infuenza A and B in both children and adults,
avian influenza,
H5N1 disease

48
Q

Tamiflu adverse effects?

A

NV, headache

49
Q

Zanamivir (Relenza®) spectrum of activity?
2

MOA?
Dosage form?
Adverse effects?

A

Uncomplicated influenza A and B, some strains of avian influenza

Neuraminidase inhibitor
Given via inhalation
Adverse effects: nasal and throat discomfort, bronchospasm

50
Q 
Amantadine (Symmetrel®)
Rimantadine (Flumadine®)
MOA?
Spectrum of activity?
Adverse effects? 5

What do we really need to know about these??

A

NOT CURRENTLY RECCOMENDED IN THE US

MOA:
Prevents the release of viral nucleic acid into host cell
SPectrum of Activity: Influenza A, however resistance is frequent
Adverse effects: Seizures, anticholinergic, CNS, edema, blurry vision

Used for extrapyramidal sx and parkinsonism

51
Q

Whats the difference b/w Amantadine (Symmetrel®) and

Rimantadine (Flumadine®)?

A

Amantadine cross extensively BBB whereas Rimantadine does not cross extensively.

52
Q

MOA for Ribavirin?

Antiviral spectrum for ribavirin?
5

A

Purine nucleoside analog
Mechanism of action not fully understood
-Inhibition of RNA polymerase

Antiviral spectrum:
DNA and RNA viruses are susceptible,

including

influenza, HCV, parainfluenza viruses, RSV, Lassa virus

53
Q

Ribavirin is the drug of choice for?
3

Ribavirin is an alternative drug for?

Dosage forms?

A

RSV bronchiolitis and pneumonia in hospitalized children (given by aerosol)
Lassa Fever

Influenza, parainfluenza, measles virus infection in immunocompromised patients
Used in combination with interferons for HCV

Available orally and via inhalation
Intravenous and available through the CDC

54
Q

Ribavirin pregnancy cat?

Lactation?

A

Pregnancy Category: X (teratogenic/embryocidal effects in all animal species)
Lactation: Probably Unsafe

55
Q

Adverse affects for ribavirin?

A

BBW-Hemolytic anemia!!

56
Q

Hepititis is a general term that refers to swelling or inflammation of the liver in response to?
4

A

Drugs
Toxins
Excessive alcohol
Infections from bacteria or viruses

57
Q

How do we treat Hep A?

A

Clears on its own with rest and adequate hydration

58
Q

How do we treat Hep B?

3

A
  1. May clear on its own
2. Chronic cases may be treated with:
Interferon
Nucleoside Reverse Transcriptase Inhibitors (NRTI) such as:
Emtricitabine
Tenofovir
Entacavir
Lamivudine
  1. Some patients may need liver transplant
59
Q

Standard treatment for Hepatitis C has long been what?

BUt what is the downside?
2

A

a synthetic, injectable version of interferon plus the antiviral drug ribavarin

Side effects are intolerable
Virus can become resistant to the meds

60
Q

Hepatic Viral infections?

4

A
  1. Interferons
  2. Lamivudine – cytosine analog – HBV
  3. Entecavir – guanosine analog – HBV Lamivudine resistance strains
  4. Ribavirin – Hepatitis C (with interferons)
61
Q

Researchers learned that to stop hepatitis C any effective drug had to do what?
2

What was the new medication that met this formula?
3

A
  1. incorporate itself in the virus’s genetic code so as to halt replication
  2. To avoid potentially debilitating side effects the medication needs to enter the liver quickly and directly, avoiding as many other organs as possible

sofosbuvir (Sovaldi)
Sofosbuvir paired with ledipasvir cured at least 94% of patients with genotype 1 disease
This combination mixed in a single daily pill (Harvoni) heralded a new curative treatment for patients with hepatitis C….consistent cure rates >90%

62
Q

Flu A virus causes what disease?
What is our drug of choice?
What is our alternative drug?

A
  1. Influenza
  2. Oseltamivir and Zanamivir
  3. Amantidine and Rimantadine
63
Q

RSV caues what diseases?

Drug of choice?

A
  1. Pneumonia and Bronchitis

2. Ribavirin (aerosol)

64
Q

HSV can cause genitial herpes. What is the drug of choice and the alternative drugs?

A

Acyclovir

Valacyclovir and Famciclovir

65
Q

HSV can cause Keratitis conjunctivitis. What is the drug of choice and the alternative drugs?

A

Trifluridine

Idoxuridine and Acyclovir

66
Q

HSV can cause encephalitis. What is the drug of choice and the alternative drugs?

A

ONLY IV acyclovir

67
Q

HSV can cause Neonatal HSV infection. What is the drug of choice and the alternative drugs?

A

ONLY IV acyclovir

68
Q

WHat is the drug of choice and alternative drugs for HSV in an immunocomprimised host?

A

Acyclovir

Valacyclovir and Famciclovir

69
Q

How do we treat VZV is a normal host?

How do we treat VZV in an immunocomprimised host, during pregnancy or shingles?
Alternative drugs?

A

No therapy

Acyclovir

Valacyclovir and Famciclovir

70
Q

What disease does CMV cause?
What is our drug of choice?
What is the alternative drug?

A

Retinitis
Ganciclovir
IV Foscarnet

71
Q

HBV and HCV cause what disease?
What drugs do we have to treat them?
7

A

Hep B and Hep C

Ribavirin
Interferons
Lamivudine
Entecavir
Sofosbuvir (Sovaldi)
Simeprivir (Olysio)
Ledipasvir-sofosbuvir (Harvoni)

Infectious Disease (29 decks)

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