Antivirals

Question 1

What are the 3 parts to a virus?

Answer 1

o Nucleic acid

o Protein coat
protects genetic mater.

o Envelope
→ Can have receptors to help enter the host

Question 2

What are the four steps of viral replication?

Answer 2

1. ) Attachment and entrance→ Hemagglutinin (“glu is sticky, that is how it attaches”)
2. ) Synthesis of proteins
3. ) Assembly of new virus

4.) Release of new virus particles
→ Lytic or lysis to enter new host cells-Neuraminidase

Question 3

What is the MOA of anti viral agents?

What type of viruses are the most effective at killing? least effective?

Answer 3

• Virustatic (won’t kill but stop from replicating)
• Most effective against rapidly replicating virus
  → Not effective against latent virus

Question 4

Influenza virus causes ?

What are the three types?/Describe influenza A?

Answer 4

-Causes acute respiratory illness

3 Types: A, B, and C

o Influenza A

• Most common/pathogenic→ can cause epidemics

→ M2 protein on coat

Question 5

What are the different surface antigens of the subtypes for influenza A? Describe them?

Answer 5

• Different subtypes based on surface antigen
• Hemagglutinin (H)

o Holds sialic acid of host

• Neuraminidase (N)

o Cuts sialic acid once the cell replicates

Question 6

Amatadine:

1. ) Indication?
2. ) MOA?

Answer 6

1.)Treatment and Prophylaxis of Influenza A
→ If started within 48 hrs., duration of symptoms are cut in half

2.) MOA:
→ Blocks viral particle uncoating and nucleic acid release into host cell
→ Inhibits viral replication
→ Works on the M2 proteins

Question 7

Amatadine:
1.) Monitor:

2. ) Considerations
3. ) Additional info

Answer 7

1.) -Monitor SCr at baseline

2. ) Considerations:
   - Avoid in Pregnancy and Breast Feeding

3.) Additional Info:

• Can be used in PKD
  → Crosses BBB and increases CNS dopaminergic responses (hallucinations psychosis)

-CDC recommends against use in Influenza A in the US due to high level of amantadine resistance among currently circulating strands

Question 8

Rimantadine:
1.) Indication?

2.) MOA?

Answer 8

1.) Treatment and prophylaxis of influenza A
→Within 48 hours of sxs onset

2.)MOA:
-Inhibits viral uncoating and replication
→ Works on M2 proteins

Question 9

Rimantadine:

1. ) Monitor
2. ) Considerations

Answer 9

1.) Monitor:
→ Monitor SCr at baseline
→ LFTs

2. ) Considerations
   - CDC recommends against use in Influenza A in the US due to high level of amantadine resistance among currently circulating strands

-Avoid in Pregnancy and Breast Feeding

Question 10

1. ) Influenza Drugs we utilize?/What are their purposes?

2. ) MOA?

Answer 10

1.)
-Oseltamivir (Tamiflu)
→ Both tx and ptx of influenzas A and B

-Zanamivir
→ Both tx and ptx of influenzas A and B

-Peramivir
→ Only treatment of influenzas A and B

2.) MOA: Inhibits neuraminidase of influenza A and B
→ Prevents the release of virions from the host cell and prevents entry into the cell

Question 11

Oseltamivir (Tamiflu)

2. ) Treatments vs. Prophylaxis
3. ) Considerations?

Answer 11

2.)
Treatment: 75mg po bid x 5 days
Prophylaxis: must be given within 48 hours of exposure- to be effective

3.) Considerations:
-Renal adjustment required
→ Dosed renally (renal dose adjustments required)
→ CrCl < 60 ml/min

Question 12

Oseltamivir (Tamiflu)

1.) Additional Info:

Answer 12

1.) Additional Info:
→ DOC for pregnancy and breast feeding
→ Prodrug, converted to oseltamivir carboxylate

**98% currently circulating influenza virus in US is Oseltamivir-susceptible

Question 13

Zanamivir

1. ) Administred via ?
2. ) Treatment vs. Prophylaxis

Answer 13

1.) Administered via Oral Inhalation
→ Co-administered with a bronchodilator (albuterol)

2.)
T: Start within 48 hours of onset (2 puffs Q 12hrs X 5 days)
P: 2 puffs daily

Question 14

Zanamivir:

1.) Considerations?

Answer 14

1.)Considerations:
-Avoid in Milk Allergy
→ Contains milk proteins as vehicles

-Caution with Asthma/COPD

***99% of currently circulating influenza virus in US is Zanamivir-susceptible

Question 15

Peramiver

1. ) Administred via ?
2. ) Monitor?

Answer 15

1.) IV = available as IV
→ Administered by healthcare provider
→ Pts unable to take PO

2.) Monitor: → Monitor renal function at baseline

Question 16

Peramiver
1.) Considerations?

2.) Treatment vs. Prophylaxis

Answer 16

1.) Considerations:
-Requires renal adjustment if:
→ CrCl < 50 ml/min

2.) Treatment only, no PTX

Question 17

Baloxavir marboxil:
1.) Indication?

2. ) MOA?
3. ) Excretion?

Answer 17

1. ) Indication:
   - Txs of influenza A and B

2.) MOA:
-Inhibits viral polymerase acidic protein endonuclease activity
→ Inhibits viral replication

3. )Excretion:
   - Feces

Question 18

Baloxavir marboxil:
1.) Half-life?

2. ) Considerations?
3. )Additional info?

Answer 18

1.) Half-Life:
-80 hours!
→ Allows for 1-time (weight based) dose
→ Within 48 hrs. Of sxs

2.) Considerations:
-Weight based dosing
-Separated from dairy products and calcium-fortified beverages
→ Cation interaction

3. )Additional Info:
   - about $150 (brand name only)

Question 19

Special Populations and Influenza Drugs:

Pregnancy:
-Oseltamivier→ ?

Children:
-Oseltamivir→ Tx vs. Ptx?

• Zanamivir→ Tx vs. Ptx?
• Peramivir→ Tx vs. Ptx?
• Baloxavir→ Tx vs. Ptx?

Answer 19

Pregnancy:
o Oseltamivir
→ Treatment is important, high risk of developing pneumonia post—influenza

Children:

o Oseltamivir
 Tx: any age
 Ptx: > 3 m.o.
→ No vaccine until 6 m.o. → look for CNS SEs

o Zanamivir
 Tx: > 7 y.o.
 Ptx: > 5 y.o.

o Peramivir
 Tx: > 2 y.o.

o Baloxavir
 > 12 y.o.

Question 20

Herpesvirus Family:

Large family of DNA viruses → Name each subtype virus (1-8) and describe its correlating disease/manifestation?

Answer 20

Large family of DNA viruses:
→ Stay latent

• HHV-1
o Herpes Simplex Virus 1 (HSV-1)
→ Oral lesions

• HHV-2
o Herpes Simplex Virus 2 (HSV-2)
→ Genital lesions

• HHV-3
o Varicella Zoster Virus (VZV)
→ Chicken pox/shingles

• HHV-4
o Epstein-Barr Virus (EBV)
→ Chicken pox/Shingles

• HHV-5
o Cytomegalovirus (CMV)
→ IC patients

• HHV-6a/6b/7
o Roseolavirus

• HHV-8
o Kaposi’s Sarcoma (treat their HIV)
→ AIDs patients

Question 21

What non-specific types of antiviral agents (broad categories) do we have available to treat HHV?

Answer 21

• Nucleoside Analogs
-Synthetic analogs of pyrimidines and purines
→ Inhibit viral replication
→Competitive inhibition of DNA polymerase
→Incorporation and termination of viral DNA chain
→Inactivation of viral DNA polymerase

• Miscellaneous Agent
-Won’t cure HHV
→Can prevent if taken early
→Can suppress sxs

Question 22

Trifluridine:

1. ) What type of drug is it?
2. ) Indication?
3. ) Forumulation avaiable?

Answer 22

1.) Pyrimidine Analog

2.) Indication: (tri rhymes with eye)
-Ocular HSV
→ HSV keratoconjunctivitis
→Epithelial keratitis

3.)Formulation:
- Opthalmic solution
→Negligible systemic absorption
→Refrigeration required

Question 23

Cidofivir:

1. ) What type of drug is it?
2. ) Indication?
3. ) Caveat of its metabolism?

Answer 23

1.) Pyrimidine Analog

2.) Indication
-Tx of CMV retinitis in AIDS patients
→ Not a first line option

3.) Active metabolite → toxic

Question 24

Cidofivir:

2. )Half-Life?
3. )Considerations in regards to administering the drug ?

Answer 24

2.) Half life:
-Parent drug
→ 3 hours
-Active metabolite
→ 17 hours

3.) Considerations:
-Induction and maintenance dosing
-Patient needs to be hydrated + coadministration of Probenecid
→ Limits renal toxicity
→ Increases bioavailability

Question 25

Cidofivir: 1.)Monitor? 2.)Side Effects?

Answer 25

1. ) Monitor: - SCr - Urine protein w/in 48 hours before each dose - WBC + diff before each dose 2.) Side Effects: -*Black Box Warning → Renal Impairment resulting in HD → Neutropenia → Carcinogen/Teratogen

Question 26

Acyclovir: 1. ) What type of drug is it? 2. ) Indiction ? 3. ) When is this drug most effective? 4. ) This drug is "dependent" on?

Answer 26

1.) Purine analog 2.) Indication: -HSV -VZV -Limited benefit → CMV → EBV 3.) -Only effective against actively replicating virus → Not effective in latent phase -Kinase Dependent Must be activated in cell by viral pathways → Highly selective to infected cells →Reduces the toxicity of the drug

Question 27

Acyclovir: 1.) What 3 reasons affect dosing AND frequency? 2. )Formulations? 3. ) Monitor?

Answer 27

1.) Dosing based on stage of disease → Ideal body weight → Frequency based on CrCl to prevent accumulation of toxic renal crystals -Poor bioavailability = Complex Dosing → ~ 20% → Dosed up to 5x/day 2.) Formulations: Oral and Topical → IV – must be hydrated/stable BP → Bolus saline first 3.) Monitor: → Renal Function (can cause AKI)

Question 28

Valacyclovir: 1. ) What type of drug is it? 2. ) Indiction? 3. ) What is special about this drug?

Answer 28

1.) -Prodrug of Acyclovir → Better bioavailability 2.) Indication: -DOC** → HSV → VZV 3.) (crosses BBB- option for HSV Encephalitis)

Question 29

Valacyclovir: 1. ) Monitoring? 2. ) Formulation available? 3. )Dosing based on?

Answer 29

1. ) Monitoring: - SCr @ baseline 2.) Formulation? -Oral formulation only 3.) → Dosing based on stage of disease → Less frequent than Acyclovir (2x daily)

Question 30

Famciclovir: 1. ) What type of drug is it? 2. ) Indication?

Answer 30

1.) Prodrug of Penciclovir 2.)Indication: -TX and Ptx of: → HSV → VZV

Question 31

Famciclovir: 1.) What is its bioavailability like compared to acyclovir ? 2. ) Dosed based on? 3. ) Monitor?

Answer 31

2.) Considerations: -Dosed based on stage -Better bioavailability than Acyclovir →Reduced frequency required 3. ) Monitor: - SCr

Question 32

Penciclovir: 1. )What type of drug is it? 2. ) Indication? 3. ) Formulation?

Answer 32

1.)Active metabolite of Famciclovir 2. ) Indication to use drug: - Recurrent herpes labialis → think pen as in penis which can give WOMEN herpes because men suck. 3.) Available as topical formulation only "like a pen top"

Question 33

Valganciclovir: 1. ) What type of drug is it? 2. ) Indications?

Answer 33

1.) Prodrug of Ganciclovir 2.) Indications: -Tx and Ptx of CMV infections → Ptx – transplant patients, IC patients

Question 34

Valganciclovir: 1. ) What formulations are available? 2. ) How would you advise you patient to take this drug? 3. ) Monitor?

Answer 34

1. ) Oral formulation only 2.) Considerations: → Administer with food -Dose varies based on disease 3.)Monitor: -SCr -Pregnancy test -CBC with Diff → Bone marrow toxicity

Question 35

Ganciclovir: 1. ) What type of drug is it? 2. ) Indication?

Answer 35

1.) Acyclovir analog 2.)Indication: → Tx and Ptx of CMV infections

Question 36

Ganciclovir: 1. ) Administration? 2. ) Monitor?

Answer 36

1.) Administration? -IV administration → Administer slowly in a large peripheral or central vein → Hydrate pre/post administration 2. ) Monitor: - SCr → **Renally Toxic** - Pregnancy Test - CBC/Platelets

Question 37

Miscellaneous Agent Foscarnet: 1. ) MOA? 2. ) Indication? 3. )Really effective in?

Answer 37

1.) MOA: -Inhibits viral specific DNA polymerases, preventing DNA synthesis → Does not require activation by kinases → Effective for HSV deficient in kinases 2.) Indications: -Tx and Ptx of CMV -Tx of HSV/VZV → Not first line 3.) → Effective in Acyclovir resistant HSV/VZV

Question 38

Miscellaneous Agent Foscarnet: 1. ) Where can this drug accumulate in the body? 2. )Administration?

Answer 38

1.) Accumulate in bone and cartilage 2.) Administration: -IV only → Proper hydration

Question 39

Miscellaneous Agent Foscarnet: 1. ) Monitoring? 2. ) If possible avoid giving this drug to ?

Answer 39

3. ) Monitoring: - SCr - Electrolytes - CBC + diff - EKG → avoid giving in cardiac patients if possible