Exam III Antivirals Flashcards
What are Viruses?
Microscopic parasite that replicates inside another organism’s cells.
3 structural parts
Nucleic acid (RNA or DNA)
Protein Coat - Protects genetic material
Envelope - Fatty protective shield, liposomal surface of the cell
Steps of Viral replication
- Attachment and entrance
- Synthesis of proteins
- Assembly of new Virus
- Release of new virus particles
Repeat
Antiviral Agent MOA
Antivirals are virustatic, toxic to host cell, most effective against rapidly replicating virus, not effective against a latent virus.
Locations of action
Block at Vitral attachment/entrance
Blocked while attempting penetration
Blocked from uncoating
Block Nucleic Acid synthesis
Blocked Late protein synthesis
Blocked Packaging/assembly
Influenza Virus
Causes acute respiratory illness
3 types
Influenza A
- Most common*
- Most pathogenic (epidemics)*
- Different subtypes (based on surface antigen H/N etc)*
Influenza B
Influenza C
Special considerations regarding Influenza Drugs
Pregnancy
Oseltamivir
Children
Oseltamivir - Any age for treatment/ >3month old for prevention
Zanamivir: treatment > 7y.o. / prevention > 5y.o.
Peramivir: treatment > 2y.o.
Baloxavir: treatment > 12 y.o.
Herpesvirus Family
Large Family of DNA viruses
HHV-1: Herpes Simplex Virus 1 (HSV 1) -> Oral Lesions
HHV-2: Herpes Simplex Virus 2 (HSV 2) -> Genital Lesion
HHV-3: Varicella Zoster Virus (VZV) -> Chicken Pox / Shingles
HHV-4:Epstein-Barr Virus (EBV) -> mononucleosis/ lymphoma
HHV-5: Cytomegalovirs (CMV)
HHV6a/6b/7: Roseolavirus
HHV-8: Kaposi’s Sarcoma
HHV: Antiviral agents
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 DNA Polymerase
Miscellaneous agents
Amantadine
Used for Prevention/treatment of Flu A - If started within 48 hours shortens duration of symptoms by half.
MOA - Blocks viral particle uncoating and nucleic acid release into host cell -> inhibits viral replication
50-90% excreted unchanged in urine
Half-life 16-17 Hrs
Dose: 200mg/day or 100mg bid x3-5 days, initiate within 48 hrs of symptom onset - 100mg PO daily in elderly PTs - D/C within 24-48 Hrs of symptom resolution
Pregnancy - Cat C avoid in breastfeeding
Monitor SCr at baseline
Used in Parkinsons - Crosses BBB -> increases CNS dopaminergic response
CDC recommends against use in Flu A in the US due to high level of amantadine resistance among currently circulating strands.
Rimantadine
Treatment and prophylaxis of Flu A
MOA: Inhibits Viral uncoating and replication
Excreted in Urine
Half-Life: 25 Hrs, longer in PTs > 70 y.o., 50 Hrs in PTs w/ severe hepatic impairment
Dose: 100mg bid x3-5 days, initiate within 48 Hrs of Symptom onset - 100mg PO in elderly PTs - D/C within 24/48 Hrs of symptom resolution
Pregnancy: Cat C avoid use in Breastfeeding
Monitor: SCr at baseline/ LFTS
Available in Tabs or Syrup
CDC recommends against use in Flu A in the US due to high level of rimantadine resistance among currently circulating strands.
Currently used Influenza Drugs
Oseltamivir (tamiflu)
Zanamivir (Relenza)
Peramivir (Rapivab)
Indicated for treatment and prevention of Flu A & B (Peramivir only for treatment)
MOA: Inhibits neuraminidase of Flu A&B -> Prevents release of virions from the host cell and prevents entry into the cell.
Bolaxavir marboxil (Xofluza)
Newest Flu A&B drug.
Osetamivir
Prodrug: Converts to oseltamivir carboxylate
99% eliminated in Urine
Half-Life: 6-10 Hrs
Dose:
- Treatment - 75mg PO BID x5 days (may extend in immunocompromised)*
- Prophylaxis - 75mg PO QD w/ in 48 hours of exposure, give throughout exposure period and x7 days after last known exposure.*
- Renal Adjustments required*
Pregnancy: Drug of choice for Flu treatment - Safe for Breastfeeding
Available in Cap, Susp and Generic
>98% of currently circulating Flu virus in US is Oseltamivir-susceptible
Zanamivir
Administered via oral inhaler
- Co-administer w/ bronchodilator*
- Do not reconstitute in liquid or nebulize*
Eliminated unchanged in Urine
Half-Life: 2.5-5 Hrs, 19 Hrs in severe Renal impairment
Dose:
- Treatment: 10mg (2puffs) inhaled Q12 x 5days - Start within 48 Hrs of onset*
- Prophylaxis: 2 puffs inhaled QD (duration dependent on setting)*
Avoid in milk allergy -> contains milk proteins as vehicles
Caution if asthma/COPD
>99% of currently circulating Flu virus in US
Peramivir
Available as IV -> requires admin by health care provider
Eliminated primarily unchanged in Urine
Half-Life: 20 Hrs
Dose:
- 600mg IV x 1 w/in 48 Hrs of onset*
- CrCl < 50ml/min -> requires adjustment*
- Administer over 15-30 min*
Monitor: renal function at baseline
Baloxavir Marboxil
FDA approved OCT 2018
MOA: Inhibits viral polymerase acidic protein endonuclease activity -> inhibits viral replication
Excreted mostly in feces
Half-Life: 80 Hrs
Dose:
- 40-79kg: 40mg PO x1*
- >80kg: 80mg PO x1*
- Start w/in 48 Hrs of onset*
Separate from dairy products and calcium-fortified beverages
Cost - $150
Trifluridine
Indicated in ocular HSV (HSV Keratoconjunctivitis and epithelial keratitis)
Dose 1 GTT in eye Q2H while awake (max 9GTT/Eye/Day) x 21 days
Ophthalmic solution
Negligible systemic absorption
Refrigeration required
Cidofivir
Only indicated for treatment of CMV retinitis in AIDs PTs (Not 1st line agent)
Has active metabolite
Eliminated 80-100% unchanged in urine
Half-Life:
- Parent drug - 3Hrs*
- Active Metabolite - 17 Hrs*
Dose:
- Induction 5mg/kg IV weekly x 2 Weeks*
- Maintenance 5mg/kg IV Q2 Weeks*
PT needs to be hydrated and co-administer probenecid
Monitor: SCr, Urine protein w/in 48 Hrs before each dose, WBC w/diff before each dose.
Black box warning: renal impairment (resulting in HD), neutropenia, carcinogen/teratogen
Acyclovir
Indicated for HSV, VZV, CMV (limited), EBV (Limited)
Only effective against actively replicating virus -> not effective against latent virus
Eliminated in Urine
Half-Life: 2-3 Hrs
Multiple formulations - IV (hydrate), Oral, Topical
Dosing: Varies based on stage of disease
Poor bioavailability
Monitor renal function
Valacyclovir
Prodrug of acyclovir -> better availability
Indicated in HSV/VZV
Oral formulation only
Dosing depends on stage of disease (less frequent than acyclovir 1-2 QD)
Monitor SCr at baseline
DO NOT CONFUSE with Valcyte/Keflex
Famciclovir
Indicated in prevention and treatment of HSV/VZV infections
Prodrug of penciclovir
Eliminated primarily in Urine
Half-Life: HSV-1: 10 Hrs, HSV-2: 20 Hrs, VZV: 7 Hrs
Dose
- TID-BID (bioavailability is > acyclovir)*
- Dose is dependent on stage of disease*
Monitor SCr
Penciclovir
Indicated in recurrent herpes labialis
Active metabolite of famciclovir
Available as topical formulation only
Dose:
Apply Q2H while awake x4 days
Valganciclovir
Indicated in prevention and treatment of CMV infections
Prodrug of ganciclovir
Eliminated Renally
Half-Life: 4 Hrs (intracellular 18 Hrs)
Dose:
- Available as Oral formulation only*
- Caries based on disease*
- Administer w/food*
Monitor: SCr / pregnancy test / CBC w/diff
Ganciclovir
Indicated in treatment and prevention of CMV infections
Acyclovir Analog
Eliminated in Urine
Half-Life: Oral - 5 Hrs, IV - 3.5 Hrs
Dose:
- IV admin*
- Administer slowly in large peripheral or central vein*
- HYDRATE -> renal toxic*
Monitor: SCr/Pregnancy test/CBC/ platelets
Foscarnet
MOA: inhibits viral specific DNA polymerases -> prevents DNA synthesis
Does not require activation by kinases -> effective for HSV deficient in kinases
Indicated in prevention and treatment of CMV, treatment of HSV/VZV
Effective in acyclovir-resistant HSV/VZV
Eliminated in Urine
Half Life: 3-4 Hrs (plasma), 45-130 Hrs (terminal)
Dose:
- IV formulation only*
- Requires Hydration*
Monitor: SCr/Electrolytes/CBC w/diff/ ECG
