Antiviral Drugs Flashcards
RNA Virus: Influenza
3 types of influenza virus:
Type A: pandemics & epidemics (e.g. Spanish flu 1918, subtypes based on hemagglutinin & neuraminidase: H1N1, H3N2)
Type B: epidemics
Type C: neither (mild illness)
Large animal reservoirs (e.g. birds, pigs)
Clinical m(x): Uncomplicated influenza, Sinusitis, Ear infections
Complications: Viral pneumonia, 2o bacterial pneumonia, Cardiac complications (e.g. myositis), CNS complications (e.g. transverse myelitis, encephalitis, Reye
Penciclovir adverse events?
None
Pandemics and Epidemics are caused by
Influenza Type A
Peramivir dosage?
600 mg IV 1 dose
NAI’s are useful for patients who…
- Require hospitalization
- Have complicated/progressive influenza
- Have high risk of flu like complications
Oseltamivir dosing?
75 mg BID 5 days
Acyclovir MOA?
Inhibits viral DNA polymerase by competing with Guanosine
Monitoring for Ribavirin?
- CBC
- INR
- BUN/SCr
- Pregnancy
Ribavirin administration route?
PO, inhaled, or IV
- Large animal reservoirs
- Transmitted via respiratory route
- Manifests as flu, sinusitis, ear infection
- Complications include viral and bacterial pneumonia, cardiac complications, CNS complications
Influenza (RNA virus)
Palivizumab route of administration?
IM (max of 5 doses)
MOA of Foscarnet and Cidofovir?
Direct inhibition of viral DNA polymerase (don’t need first phosphorylation, makes them helpful for resistant strains)
Which drugs have antimicrobial activity on CMV?
Gangciclovir and Valganciclovir
Ganciclovir adverse effects?
Bone marrow suppression (anemia, thrombocytopenia, leukopenia)
Valganciclovir will have same effects
What do Amantadine and Rimantadine treat?
Just don’t use them for influenza okay
Famciclovir route of administration?
PO
Foscarnet adverse effects?
Electrolyte imbalances –> renal impairment (direct), seizures, anemia
T(x): monitor electrolytes at least 2x/week and use replacement therapy when necessary
Valcyclovir metabolism?
Metabolized first by viral thymidine kinase then by host enzymes (same as Acyclovir)
Ganciclovir and Valganciclovir adverse events?
- Bone marrow suppression (anemia, platelets, WBC)**
- Fever
- Creatine levels; hydrate
- Neuropathy; D/C
- Pruitis; D/C
Mild influenza symptoms are caused by?
Influenza Type C
Suspect acyclovir resistance if lesions do not improve in ______ days
4-5 days
Antigenic Shift
Influenza A only
Virus acquires new hemagglutinin (H) and/or neuraminidase (NA) via genetic reassortment
Results in novel influenza virus
No prior immunity
Can potentially cause a pandemic
Occurs less often**
What are the appropriate dosages (all PO) for Acyclovir, Valaciclovir, and Famciclovir for Herpes Zoster (Shingles)?
Acyclovir: 800 mg PO 5xdaily x 7 d (800mg PO QID x 5 d for Chicken Pox/Varicella)
Valaciclovir: 1 Gm PO TID x 7 d
Famciclovir: 500mg PO TID x 7 d
Penciclovir treats?
HSV and VZV
Ganciclovir MOA?
Inhibits CMV DNA polymerase via CMV UL97
Foscarnet adverse events?
- Renal impairment from damage to tubules
- Electrolyte imbalance
- Seizures (D/C)
- Anemia
- Granulocytopenia
–> Hydrate with 2 L saline prior
Which drugs have antimicrobial activity on HSV and VZV?
Acyclovir, Valaciclovir, Penciclovir, and Famiciclovir
Acyclovir adverse effects?
Drug can crystallize in renal tubues –> renal impairment/damage
T(x): give fluids to dilute concentration or infuse slower
Valacyclovir will have same effects
Famiciclovir MOA?
Prodrug converted to pencyclovir and then inhibits viral DNA polymerase
Which drugs are Adamantanes? Should we use them?
Amantadine, Rimantadine
Nah, they really high influenza resistance
Influenza drug of choice and their MOA
Neuraminidase Inhibitors (NAIs= Oseltamivir (Tamiflu), Zanamivir, Peramivir)
MOA:
- Binds to the surface glycoprotein, neuraminidase (NA)
- Prevents the enzymatic cleavage of sialic acids from cellular receptors on the cell membrane (virions can’t leave the cell to spread infection)
Hepatic impairment with Famiciclovir Tx?
In severe hepatic impairment, prodrug conversion may decrease, leading to an increase in Famiciclovir concentrations
Cidofovir + ______ decreases renal absorption and decreases nephrotoxicity?
Probenecid and saline prehydration
Oseltamivir adverse events?
Nausea
Vomiting
Conjunctivitis
Epistaxis
Take with food
Foscarnet and Cidofovir administration route?
IV/Topical
Which antiviral prodrugs turn into which antiviral drugs once metabolized in the body?
Valaciclovir –> Acyclovir
Valganciclovir –> Ganciclovir
Famciclovir –> Penciclovir
Penciclovir MOA?
inhibits viral DNA polymerase
Foscarnet and Cidofovir treat?
ALL 3! HSV, VZV, and CMV
HSV-2
Transmitted via direct exposure to genital skin or fluids
Very expensive drug to treat CMV?
Valganciclovir
Topical Antivirals for HSV
Idoxuridine (HSV-1)
Trifluridine (HSV)
Docosanol (Abreva) –> treats herpes labialis (cold sores), only OTC option
Antigenic Drift
Influenza A or B
Virus acquires point mutations in surface antigens
- Hemagglutinin (H)
- Neuraminidase (NA)
Human antibodies no longer confer immunity to antigenic variants
Results in need for:
- Annual vaccination
- Updates in combo of antigenic variants in each annual vaccine
Occurs more frequently**
NAI’s MAY be considered for patients who…
- Desires to shorten duration of illness
- Therapy can be initiated within 48 hr of symptoms
Ribavirin
Used for: Hep C Virus (in combination), RSV, Influenza
Adverse effect: hemolytic anemia
Foscarnet and Cidofovir used most commonly in?
- AIDS patients
- Patients with resistance to acyclovir MOA
Shingles:
Acyc- 800 mg 5X 7 days
Valacyc- 1 g TID 7 days
Famicyc- 500 mg TID 7 days
Chicken Pox:
Acyc- 800 mg QID 5 days
VZV Dosing
Valcyclovir adverse events?
- Headache
- GI
- Phlebitis (inflamed vein)
- Rash/itching
- Renal impairment
- CNS effects; reduce dose or D/C
Palivizumab
Used for: RSV prophylaxis in pediatric patients
Administration route: IM
3 topical for Herpes Viruses?
Idoxuridine
Trifluridine
Doconasol (OTC)
Penciclovir metabolism?
First metabolized by viral thymidine kinase then by host enzymes
** no systemic absorption so no dosage adjustments
Which guanosine analogue antiviral drug is preferred for use in pregnant women?
Acyclovir
Ganciclovir treats?
CMV
Oseltamivir (Tamiflu)
Most commonly used NAI (oral)
Oseltamivir is a prodrug
Preferred treatment in pregnant women
Dose: 75 mg PO BID x 5 days
Antiviral drugs that are acyclic guanosine analogues?
Acyclovir, Valaciclovir, Penciclovir, Famiciclovir, Ganciclovir, Valganciclovir
Zanamivir adverse events?
- Headache
- Throat and tonsil pain
- Nasal sxs and cough
Ribavirin adverse events?
- Anemia- Needs close monitoring (CBC)
- Other blood dycrasias
- Fatigue, headache, insomnia, depression
- GI
- Alopecia, rash, itching
- Hyperbilirubinemia
Peramivir adverse events?
- GI problems
- Neutropenia
- Hyperglycemia
- High creatnine
- High hepatic enzymes
- Insomnia
- Hypertension
Antivirals with Pregnancy Risk Factor C (do not use these with pregnant women)
Ganciclovir, Valganciclovir, & Cidofovir
Use contraception while on these drugs!
Ribavirin MOA?
Thought to target viral RNA polymerase to inhibit mRNA synthesis
Penciclovir administration route?
Topical cream
Valacyclovir administration route?
PO
Pregnancy Risk Factor C?
Ganciclovir
Valganciclovir
Foscarnet
Cidofovir
Palivizumab
All 3 influenza drugs
Acyclovir metabolism
Metabolized first by viral thymidine kinase then by host enzymes
Ganciclovir administration route?
IV
Acyclovir administration route?
Topical, oral or IV
Palivizumab adverse events?
- Fever
- Rash
- Antibody development
- Anaphylaxis
Cidofovir adverse events?
- Renal impairment
- Neutropenia; reduce dose
- Metabolic acidosis; D/C
- Ocular complications; D/C
Zanamivir dosage?
10 mg BID 5 days (inhaled)
Ribavirin pregnancy risk factor?
Category X- do NOT use with pregnant women or their partners
Herpes Simplex Virus (HSV)
Human a-herpevirus has 2 types= HSV-1 & HSV-2
140-417 million infected worldwide between 15-49 years ol
Clinical Mx:
- Herpes labialis or cold sores (mainly HSV-1)
- Genital herpes (mainly HSV-2)
- Other: keratitis, encephalitis, disseminated disease
Only epidemics are caused by?
Influenza Type B
Acyc- 200mg 5x 7-10d or 400 mg TID 7-10d
Valacyc- 1 g BID 7-10d
Famicyc- 250 mg TID 7-10d
HSV Dosing
Acyclovir treats?
HSV and VZV
The clinical manifestations of herpes include…
Cold sores
Genital herpes
Keratitis, encephalitis, disseminated disease
Which drugs have antimicrobial activity on all 3- HSV, VZV, and CMV?
Foscarnet and Cicofovir
Pregnancy Risk Factor B?
Acyclovir
Valacyclovir
Famiciclovir
Penciclovir
Monitoring for Palivizumab?
- Hypersensitivity rxns
- CBC (esp with bleeding at injection site)
NAIs MOA?
- Prevent viral release from the infected host cell
- Keeps the varion stuck on the cell membrane
Famiciclovir adverse events?
- Headache; reduce dose
- Drug interaction; reduce dose
Valacyclovir MOA?
Prodrug converted to acyclovir by enzyme in GI tract and liver; then inhibits viral DNA polymerase
Palivizumab treats?
RSV in pediatric patients
Ganciclovir and Valganciclovir metabolism?
metabolized by CMV UL97 phosphotransferase
Varicella Zoster Virus (VZV)
Infects ~30% of humans in their lifetime
Trasmitted by respiratory route
Clinical manifestations: chickenpox, shingles, neuralgia/cranial nerve palsies, pneumonia, encephalitis
Valacyclovir treats?
HSV and VZV
*prodrug for Acyclovir*
Doconosal MOA?
May interfere with binding of viral envelope proteins to cell membrane
What are the appropriate dosages for Acyclovir, Valaciclovir, and Famciclovir for 1st episode of genital HSV?
Acyclovir: 400 mg PO TID x7-10 d, 200 mg PO 5xdaily x7-10 d
Valaciclovir: 1 Gm PO BID x 7-10 d
Famciclovir: 250 mg PO TID x 7-10 d
Very expensive drugs to treat VZV/HSV?
Valacyclovir
Penciclovir
Famiciclovir
Famciclovir treats?
HSV and VZV
Acyclovir Resistance?
Resistance can emerge due to mutations in viral thymidine kinase or viral DNA polymerase
Foscarnet and Cidofovir MOA?
Inhibits viral DNA polymerase with no prior phosphorylation needed for binding to the DNA strand
Ribavirin treats?
Influenza, RSV, Hep C
HSV-1
Transmitted via contaminated aerosols or droplets
Famciclovir metabolism?
First metabolized by viral thymidine kinase then host enzymes (just like Penciclovir)
Factors that make patients HIGH risk for influenza complications
- Children < 5 yr (especially those < 2 yr)
- Adults ≥ 65 yr
- Pregnant women (and those up to 2 wk postpartum)
- Residents of nursing homes or long-term care facilities
- American Indians and Alaskan Natives
- Individuals ≤ 18 yr receiving long-term aspirin therapy (d/t risk of Reye syndrome)
- Individuals with the following chronic medical conditions: Chronic pulmonary disorders (e.g., asthma), Neurologic or developmental disorders (e.g., stroke, cerebral palsy, epilepsy, spinal cord injury, intellectual disability), Heart disease (e.g., congestive heart failure [excluding hypertension alone]), Blood disorders (e.g., sickle cell disease), Kidney disorders, Liver disorders, Endocrine disorders (e.g., diabetes mellitus), Metabolic disorders (e.g., mitochondrial disorders), Morbid obesity (BMI ≥ 40 kg/m2), Immunocompromising conditions (e.g., HIV/AIDS, chronic corticosteroid use)
Guanosine analogue antivirals MOA?
Halts viral DNA replication by inhibiting DNA polymerase (compete with dGTP)
Phosphorylated 3 times to be incorporated into DNA replication, second and third phosphorylation is by host
Acyclovir, Valaciclovir, Penciclovir, and Famiciclovir: HSV thymidine kinase for first phosphorylation
Ganciclovir and Valganciclovir: UL97 for first phosphorylation
Valganciclovir administration route?
PO
Palivizumab MOA?
Antibody neutralizes glycoprotein F of RSV inhibiting the fusion of RSV to the host cell
Acyclovir adverse events?
- Renal impairment (crystallization); hydrate
- Phlebitis; ensure IV intact
- GI; reduce does
- Headache; reduce dose
- Rash, itching; D/C
Cytomegalovirus (CMV)
Worldwide prevalence 30-95%
Exclusively human reservoir (transmitted via blood, sexual contact, body fluids)
High morbidity and morality in immunocompromised (transplant patients)
Clinical manifestations: retinitis, esophagitis, colitis, pneumonitis, CNS disease
DNA Viruses
Herpes Simplex Virus (HSV)
Varicella Zoster Virus ( VZV)
Cytomegalovirus (CMV)
