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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
WHat makes Valacyclovir different then from Acyclovir? Why is it not used as often then?
Advantage: better oral bioavailability (55%) More convenient dosing Expensive
26
``` Valacyclovir (Valtrex®) Pharmacokinetics of Valacyclovir: Oral bioavailability? Metabolism? Renal excretion? Half life? Administration? ```
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
27
Valacyclovir safety/monitoring Pregnancy Category? Lactation? Renal Dosing? Hepatic Dosing?
B Safe Adjust dose for CrCl
28
Valacyclovir (Valtrex®) adverse affects? 3 major 5
Reversible renal toxicity Neurological symptoms TTP/HUS ``` GI symptoms Headache Rash Photosensitivity Elevated LFT’s ```
29
``` What disease is acyclovair only used for and not Valacyclovir or Famciclovir? A. Primary Genital B. Recurrent Genital C. Encephalitis D. Chronic Suppressive ```
C
30
What do we use to treat varicella?
Acyclovir
31
What can we use to treat herpes zoster/
Valacyclovir Famciclovir Acyclovir
32
What can we use to treat Varicella or Zoster in Immunocompromised?
Acyclovir
33
What other Topicals for HSV do we treat orolabial herpes with? 2
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
What do we use to treat HSV Keratoconjuctivitis?
Trifluridine (Viroptic® 1% ophthalmic) 1 drop q2h (max 9 drops/day) Active against acyclovir resistant strains Also active against vaccinia virus and smallpox
35
What is our antiCMV agent? Dosage forms?3
Ganciclovir Oral, intravenous, and intraocular
36
Ganciclovir is the drug of choice for? | 2
1. CMV retinitis in immunocompromised patient | 2. Prevention of CMV disease in transplant patients
37
``` Ganciclovir (Cytovene®) Pharmacokinetics of Ganciclovir: Oral Bioavailability Excretion? Renal excretion? Half life? ```
1. 50% 2. Is excreted unmodified in the urine 3. > 90% 4. 2-4 hours
38
Ganciclovir Safety/Monitoring Pregnancy Category? Lactation? Renal Dosing? Hepatic Dosing?
C (animal studies show adverse fetal effects) Unsafe Adjust dose for CrCl
39
Ganciclovir MOA?
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
Ganciclovir | Adverse affects?
``` LOTS OF THEM(only used for CMV) reversible pancytopenia Fever Rash Phlebitis (IV) Confusion Renal dysfunction Psychiatric disturbances Seizures ```
41
Influenza Agents? | 4
Oseltamivir Zanamivir Amantadine Rimantadine
42
Neuraminidase inhibitors are which influenza agents?
Oseltamivir / Zanamavir
43
What makes influenza virus suceptible to antivirals?
Influenza contains an enzyme neuraminidase which is essential for the replication of the virus.
44
How do Neuraminidase inhibitors, Oseltamivir / Zanamavir, work against influenza?
Neuraminidase inhibitors prevent the release of new virions and their spread from cell to cell.
45
What types of influenza do Oseltamivir / Zanamavir work against? Will it interact with the vaccine? What can it be used for?
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
What is the brand name for Oseltamivir?
Tamiflu
47
What is the spectrum of activity for Tamiflu? | 3
Infuenza A and B in both children and adults, avian influenza, H5N1 disease
48
Tamiflu adverse effects?
NV, headache
49
Zanamivir (Relenza®) spectrum of activity? 2 MOA? Dosage form? Adverse effects?
Uncomplicated influenza A and B, some strains of avian influenza Neuraminidase inhibitor Given via inhalation Adverse effects: nasal and throat discomfort, bronchospasm
50
``` Amantadine (Symmetrel®) Rimantadine (Flumadine®) MOA? Spectrum of activity? Adverse effects? 5 ``` What do we really need to know about these??
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
Whats the difference b/w Amantadine (Symmetrel®) and | Rimantadine (Flumadine®)?
Amantadine cross extensively BBB whereas Rimantadine does not cross extensively.
52
MOA for Ribavirin? Antiviral spectrum for ribavirin? 5
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
Ribavirin is the drug of choice for? 3 Ribavirin is an alternative drug for? Dosage forms?
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
Ribavirin pregnancy cat? | Lactation?
Pregnancy Category: X (teratogenic/embryocidal effects in all animal species) Lactation: Probably Unsafe
55
Adverse affects for ribavirin?
BBW-Hemolytic anemia!!
56
Hepititis is a general term that refers to swelling or inflammation of the liver in response to? 4
Drugs Toxins Excessive alcohol Infections from bacteria or viruses
57
How do we treat Hep A?
Clears on its own with rest and adequate hydration
58
How do we treat Hep B? | 3
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 ``` 3. Some patients may need liver transplant
59
Standard treatment for Hepatitis C has long been what? BUt what is the downside? 2
a synthetic, injectable version of interferon plus the antiviral drug ribavarin Side effects are intolerable Virus can become resistant to the meds
60
Hepatic Viral infections? | 4
1. Interferons 2. Lamivudine – cytosine analog – HBV 3. Entecavir – guanosine analog – HBV Lamivudine resistance strains 4. Ribavirin – Hepatitis C (with interferons)
61
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
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
Flu A virus causes what disease? What is our drug of choice? What is our alternative drug?
1. Influenza 2. Oseltamivir and Zanamivir 3. Amantidine and Rimantadine
63
RSV caues what diseases? | Drug of choice?
1. Pneumonia and Bronchitis | 2. Ribavirin (aerosol)
64
HSV can cause genitial herpes. What is the drug of choice and the alternative drugs?
Acyclovir Valacyclovir and Famciclovir
65
HSV can cause Keratitis conjunctivitis. What is the drug of choice and the alternative drugs?
Trifluridine Idoxuridine and Acyclovir
66
HSV can cause encephalitis. What is the drug of choice and the alternative drugs?
ONLY IV acyclovir
67
HSV can cause Neonatal HSV infection. What is the drug of choice and the alternative drugs?
ONLY IV acyclovir
68
WHat is the drug of choice and alternative drugs for HSV in an immunocomprimised host?
Acyclovir Valacyclovir and Famciclovir
69
How do we treat VZV is a normal host? How do we treat VZV in an immunocomprimised host, during pregnancy or shingles? Alternative drugs?
No therapy Acyclovir Valacyclovir and Famciclovir
70
What disease does CMV cause? What is our drug of choice? What is the alternative drug?
Retinitis Ganciclovir IV Foscarnet
71
HBV and HCV cause what disease? What drugs do we have to treat them? 7
Hep B and Hep C ``` Ribavirin Interferons Lamivudine Entecavir Sofosbuvir (Sovaldi) Simeprivir (Olysio) Ledipasvir-sofosbuvir (Harvoni) ```

Infectious Disease (29 decks)

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