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Antivirals Flashcards

(52 cards)

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1
Q

6 Steps in viral infection and replication

A
  1. Adsorption
  2. Penetration
  3. Viral Genome Replication
  4. Assembly
  5. Maturation
  6. Release
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2
Q

What do the guanine nucleoside analogs do and what are they?

A

Anti-HSV and Anti VZV
Acyclovir (Zovirax)
Valacyclovir (Valtrex)

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3
Q

Guanine nucleoside analog MOA

A

Drugs phosphorylated by viral thymidine-kinase, then metabolized by host cell kinases to nucleotide analogs
The analog inhibits viral DNA-polymerase
Only actively replicating viruses are inhibited

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4
Q

Acyclovir (Zovirax) Indications and ROA

A 
Topical, oral, IV
HSV1 and 2
VZV
Maybe EBV
DOC for HSV lesions, HSV encephalitis, HSV infx in immunocompromised or pregnant
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5
Q

Acyclovir (Zovirax) PK, Saftey, and monitoring

A 
20-30% oral bioavailability
Wide distribution including CNS
Renal excretion > 80%
Half-life: 2-5 hrs
Preg Cat B
Lactation Safe
IV: CrCl 20-25 give q12h, CrCl <25 q24hr
Hepatic: no change needed
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6
Q

Acyclovir (Zovirax) MOA

A

Inhibits viral synthesis of DNA
Phosphorylated to acyclovir monophosphate
Cellular enzymes convert to acyclovir triphosphate
Competes with viral deoxyguanosine triphosphate for viral DNA polymerases
Lacks 3’ hydroxyl group to prevent further nucleoside attachment - chain termination
Inactivates viral DNA polymerase

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7
Q

Acyclovir (Zovirax) Dose

A 
Varies with infection and severity
200, 400, 800 mg tablets, 200/5mL liquid, IV
VZV: 800 mg PO 4-5/day x 7-10 days
HSV:
1st: 400 mg PO 3-4/day x 7-10 days
Recurrence: 400 mg PO TID x 5 days
Suppression: 400 mg PO BID
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8
Q

Acyclovir (Zovirax) Adverse Effects

A

Reversible renal toxicity - crystallization in tubules
Neuro Sx: encephalopathic somnolence, halluc, confus, coma
TTP/HUS in immunocompromised
GI, HA, rash, photosensitivity, Anemia

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9
Q

Acyclovir (Zovirax) Resistance

A 
Defined as MIC >2-3 mcg/mL
Mostly occurs in immunocompromised
Reduced or absent thymidine kinase
Altered TK substrate specificity
Alterations in DNA polymerase
Cross resistance to famciclovir and valacyclovir
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10
Q

Famciclovir (Famvir) MOA

A

Converted to penciclovir triphosphate in liver and intestines, which has a lower affinity for viral DNA polymerase, but a longer intracellular half-life

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11
Q

Famciclovir (Famvir) Use and Spectrum

A

PO only

HSV 1 & 2, VZV, lesser EBV, invitro HBV

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12
Q

Famciclovir (Famvir) PK

A

77% oral bioavailability
1st pass = conversion to penciclovir
renal excretion > 80%
Half-life 2-3 hours

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13
Q

Famciclovir (Famvir) Saftey and Monitoring

A

Preg Cat B
Lactation: safety unknown
Renal: adjust if CrCl < 40
Hepatic: no adjustment needed

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14
Q

Famciclovir (Famvir) Dose

A 
125, 250, 500 mg tablets
Zoster: 500 mg TID x 7 days
HSV: 
1st: 250 mg PO TID x 7-10 days
Recurrence: 1000 mg PO bid x 1 day w/in 6 hrs of Sx
Suppression: 250 mg PO bid
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15
Q

Famciclovir (Famvir) Adverse Effects

A

Neutropenia, thrombocytopenia
Neuro Sx: somnolence, halluc, delirium
GI, HA, fatigue
elevated LFTs

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16
Q

Famciclovir (Famvir) Resistance

A

Mutations in TK or DNA polymerase
Cross resistance with acyclovir in TK negative strains - may still have activity
Resistance to HBV due to L528M point mutation in viral DNA polymerase

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17
Q

Valcyclovir (Valtrex)

A

Prodrug of Acyclovir
rapidly and almost completely converted to acyclovir via 1st pass metabolism
Same MOA, SOA, and mech of resistance as acyclovir

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18
Q

Valcyclovir (Valtrex) Advantage

A

better oral bioavailabiltiy = 55%

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19
Q

Valcyclovir (Valtrex) PK

A 
55% oral bioavailability
1st pass metabolism to acyclovir
Food does not affect absorption
> 50% renal excretion
Half-life 2-3 hours
ORAL
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20
Q

Valcyclovir (Valtrex) Safety and Monitoring

A

Preg Cat B
Lactation Safe
Renal: adjust if CrCl < 30
Hepatic: none

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21
Q

Valcyclovir (Valtrex) Dose

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A 
500, 1000 mg tabs
Zoster: 1000 mg PO tid x 7-10 days
HSV:
1st: 1000 mg PO bid x 7-10 days
Recurrence: 500 mg PO bid x 3-5 days
Suppression: 1000 mg PO qday
22
Q

Valcyclovir (Valtrex) AE

Study These Flashcards
A

Reversible renal toxicity - crystallization in tubules
Neuro Sx: encephalopathic somnolence, halluc, confus, coma
TTP/HUS in immunocompromised
GI, HA, rash, photosensitivity, Anemia

23
Q

Topicals for HSV

Study These Flashcards
A

Penciclovir (Denavir 1% cream) - HSV1
Docosanol (Abreva OTC) - HSV1
Trifluridine (Viroptic) - HSV keratoconjunctivitis

24
Q

Penciclovir (Denavir 1% cream)

Study These Flashcards
A

For orolabial HSV
topical guanine analog similar to acyclovir
apply every 2 hrs while awake

25
Docosanol (Abreva OTC)
For orolabial HSV Active against broad range of lipid-envelop viruses MOA: interferes with viral fusion to host cell Apply 5 times/day until healed (10 days) Shortens healing by 0.7 days
26
Trifluridine (Viroptic)
For HSV keratoconjunctivitis 1 drop q2h (max 9 drops/day) Active against acyclovir resistant strains Active against vaccinia virus and smallpox
27
Anti-CMV Agents
Ganciclovir (Cytovene)
28
Ganciclovir (Cytovene) - ROA and Spectrum
``` ROA: oral, IV, intraocular Spectrum: CMV/EBV - 10x potency of acyclovir HSV/VZV - equal to acyclovir Human Herpes Virus 6 ```
29
Ganciclovir (Cytovene) DOC
DOC for CMV retinitis in immunocompromised | Prevention of CMV disease in transplant pts
30
Ganciclovir (Cytovene) PK
50% oral bioavailability Excreted unmodified in the urine Renal excretion >90% Half-life: 2-4 hrs
31
Ganciclovir (Cytovene) Safety and Monitoring
Preg Cat C Lactation unsafe Renal: adjust if CrCl < 50 Hepatic: not defined
32
Ganciclovir (Cytovene) MOA
Competes with deoxyguanosine triphosphate In CMV, viral phosphotransferase converts to ganciclovir triphosphate Contains 3'-hydroxyl group allowing for DNA to continue
33
Ganciclovir (Cytovene) Adverse Effects
``` Reversible pancytopenia Fever Rash Phlebitis (IV) Confusion Renaly Dysfxn Psych disturbances Seizures ```
34
Influenza Agents
Oseltamivir (Tamiflu) Zanamivir (Relenza) Amantadine Rimantadine
35
Neuraminidase Inhibitors
Oseltamivir and Zanamivir Neuraminidase - flu enzyme essential for viral replication Neuraminidase inhibitors prevent release of new virions and their spread from cell to cell Effective against flu A and B Do not interfere with flu A vaccine For prophylaxis and treatment
36
Oseltamivir (Tamiflu) - Class and MOA
Oral neuraminidase inhibitor Cleaves terminal sialic acid residue on glycoconjugates and destroys receptors newly formed virions adhere to cell surface and limit spread
37
Oseltamivir (Tamiflu) Spectrum and AE
Flu A and B in adults and peds Avian influenza H5N1 disease AE: N/V, HA
38
Oseltamivir (Tamiflu) Dosing
A&B Tx: 75 mg PO bid x 5 days w/in 48 hrs of Sx onset | Prophylaxis: 75 mg PO bid x 5 days w/in 48 hrs of exposure
39
Zanamivir (Relenza)
Neuraminidase inhibitor Given via inhalation: 2 puffs bid x 5 days Spectrum: uncomplicated flu A&B, some avian flu AE: nasal and throat discomfort, bronchospasm Not recommended in pts with severe flu, asthma or COPD
40
Amantadine (Symmetrel) & Rimantadine (Flumadine) | MOA, Spectrum, AE
MOA: prevents release of viral nucleic acid into host cell Spectrum: Flu A (resistance is frequent) AE: seizures, anticholinergic, CNS, edema, blurry vision Much resistance - not recommended in US
41
Amantadine PK and off-label
50-90% bioavailability Crosses BBB (Rimantadine does not) Oral administration Used for extrapyramidal Sx and Parkinsonism
42
Ribavirin Class and MOA
Purine nucleoside analog | MOA: inhibits RNA polymerase - not well understood
43
Ribavirin Spectrum
DNA and RNA viruses: flu, HCV, parainfluenza, RSV, lassa virus
44
Ribavirin Uses
DOC: RSV bronchiolitis and pneumonia in hospitalized children via aerosol Alternative for: flu, parainfluenza, measles in immunocompromised pts Used in combo with interferons or sovaldi for HCV
45
Ribavirin ROA and Special Pops
``` IV through CDC Oral and inhalation Preg Cat X Lactation unsafe BBW: hemolytic anemia ```
46
Ribavirin AE
Resp. deterioration Depression, suicidal ideation, psych effects, anxiety Bacterial Infxs Fatigue, dizziness
47
Causes of Hepatitis
``` Refers to swelling of liver in response to: Drugs Toxins Excessive alcohol Infx from bacteria or viruses ```
48
Hep A
typically spreads when infected individuals improperly handle food or water
49
Hep B
transmitted via sexual intercourse, needle sharing, or contact with contaminated blood Vaccine since 1980's Chronic Tx: interferon, NRTI, liver transplant
50
Hep C
More likely to cause permanent liver damage Genes mutate fast New genotypes make vaccine impossible Tx: interferon plus ribavirin
51
NRTI
Nucleoside Reverse Transcriptase Inhibitors Emtricitabine Tenofovir Entecavir - guanosine analog - lamivudine resistant strains Lamivudine - cytosine analog HBV
52
Hepatitis Anti-viral Drugs
``` Interferons Lamviudine - cytosine analog HBV Entecavir - guanosine analog - lamivudine resistant strains Ribavirin - Hep C with interferons Sofosbuvir (Sovaldi) - Hep C Simeprivir (Olysio) - Hep C Ledipasvir-Sofosbuvir (Harvoni) - Hep C ```

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