Non-HIV Antivirals Flashcards
1
Q
CMV
A
Cytomegalovirus
2
Q
HSV
A
Herpes Simplex Virus
3
Q
VZV
A
Varicella Zoster Virus
4
Q
HAV/HBV/HCV
A
Hepatitis A/B/C Virus
5
Q
Antiviral Target Sites
A
- Crucial for viral infection
- Intracellular organisms whose replication depends on host cell machinery
- Antivirals only work on active, replicating viruses
- Antivirals work at site of viral attachment/entry, uncoating, nucleic acid synthesis, transcription/translation, packaging/assembly, and release
6
Q
Influenza
A
- Single-stranded RNA virus
- Antigenic differences: A (pandemic causing) and B
- Frequent antigenic variation: Drifts and Shifts
- Drifts (epidemics) - minor changes like point mutations
- Shifts (pandemic): major genetic change resulting in alterations of antigen structure cause by reassortment
7
Q
Neuraminidase Inhibitors
A
- Interfere with viral release from host cells
- Activate against Influenza A and B
- Work at site of packaging/assembly and release
- Potential neuropsychiatric events (confusion, delirium, hallucination)
8
Q
Neuraminidase Inhibitor Examples
A
- Oseltamivir (Tamiflu): activated by hepatic estrases, excreted by kidney, AE: GI upset/HA
- Zanamivir (Relenza Diskhaler): concentrated in respiratory tract, AE: bronchospasm (Not recc for asthma/COPD)
- Peramivir (Rapivab): single IV dose, AE: diarrhea, skin hypersensitivity
9
Q
Xofluza
A
- Baloxavir Marboxil
- First influenza drug approved by FDA
- MoA: Endonuclease inhibitor, inhibits endonuclease cleavers from influenza, no viral mRNA leads to no infection
- Single oral dose
- Hepatic metabolization and excretion
- Avoid dairy products
- AE: secondary bacterial infections
10
Q
Herpes Virus
A
- Large, double-stranded DNA genome with icosahedral capsid/envelope
- HSV1: typically oral
- HSV2: anogenital ulcers
11
Q
Varicella Zoster Virus
A
- Commonly known as chickenpox
- Later emerges as herpes zoster (shingles)
12
Q
Cytomegalovirus
A
- Infects severely immunocompromised patients (organ transplants)
- Infect often results in viral reactivation
13
Q
Nucleoside Analogs + HSV 2
A
- Acyclovir and Valacyclovir
- MoA: prevent viral replication, incorporated into growing DNA strands and acts as chain terminators
14
Q
Acyclovir
A
- Zovirax
- Topical or IV
- Activation by viral kinase
- Host enzymes convert to di- then tri-phosphate form where it competes for viral DNA polymerase
- Resistance occurs by alteration of viral TK or DNA polymerase
- Poorly absorbed (several small doses), excreted by urine
- AE: GI upset, neurotoxicity, renal impairment
- Monitoring: Urinalysis, BUN, SCr, LFTs, CBC
15
Q
Valacyclovir
A
- Valtrex
- Prodrug of acyclovir
- Converted by 1st pass or hepatic metabolism
- Higher [plasma] than acyclovir
- Rapid GI absorption
- Excreted by urine
- AE: thrombotic thombocytopenic purpura, hemolytic uremic syndrome, renal impairment
- DDI: cimetidine, probenecid
16
Q
Nucleoside Analogs + CMV
A
- Ganciclovir (Cytovene)
- Valganciclovir (Valcyte)
- Refractory options: Foscarnet (Foscavir), Cidofovir
- Prophylaxis: Letermovir (Prevymis)
17
Q
Ganciclovir
A
- Cytovene
- MoA: completes with dGTP for viral DNA polymerase incorporation into viral DNA
- Resistance: mutations in viral DNA polymerase
- Excretion: urine
- AE: GI upset, myelosuppresion, infection, fever, increased SCr
- Boxed warning: hematologic toxicity, impairment of fertility, fetal toxicity, mutagenesis/carcinogenesis
- Monitoring: CBC with differentials/platelet counts, SCr, ophthalmic exams if retinitis
18
Q
Valganciclovir
A
- Valcyte
- Prodrug of ganciclovir
- Once daily tablet
- 60% bioavailability when taken with food
- Renally eliminated
19
Q
Foscarnet
A
- Foscavir
- Used for refractory cases of CMV
- MoA: noncompetitive inhibitor of viral DNA polymerase
- IV
- Excretion: renally
- Boxed warning: Renal impairment, seizures
- AE: HA, fever, GI upset, electrolyte imbalance, anemia, QTc prolongation
- Monitoring, CrCl, ECG, electrolytes, CBC
20
Q
Cidofovir
A
- Used for refractory cases for CMV
- IV
- MoA: selective inhibitor of viral DNA synthesis
- Renally eliminated
- Boxed Warning: nephrotoxicity, neutropenia, carcinogenic/teratogenic
21
Q
Hepatitis Types
A
- Type A is acute and self-limiting
- B and C can be acute and can lead to chronic infection, cirrhosis, liver cancer, and death
- HAV/HBV are vaccine preventable
22
Q
HAV
A
- Non-enveloped
- Single stranded positive sense RNA virus
- Supportive Care
23
Q
HBV
A
- Enveloped
- Partially double-stranded DNA virus
- 2-10% of acute infections lead to chronic infections
- Viral DNA can insert into human chromosome and reactivate later
- Use reverse transcription
24
Q
HCV
A
- Enveloped
- Single stranded positive sense RNA virus
- Chronic infection
- Curable
- Untreated HCV clearance believed to be 20-35%
- Treatment goal: Viral eradication
25
Q
HBV Chronic Treatment Goals
A
- Suppression of HBV DNA to undetectable levels
- Seroconversion of HBeAg from positive to negative (present when HBV is replicating)
- Reduction in elevated serum aminotransferase levels (ALT, AST)
26
Q
HBV First-line Treatment Options
A
- Nucleoside Reverse Transcriptase Inhibitors (NRTI)
- EX: Tenofovir (TDF/Viread and TAF/Vemlidy) and Entecavir (ETV/Baraclude)
27
Q
NRTIs+ HIV
A
- Test all patients for HIV before starting therapy
- Most HBV drugs have activity against HIV
- HBV can be treated with 1 drug but HIV must have multiple
28
Q
Viread
A
- Tenfovoir disproxil fumarate (TDF)
- Potent adenosine nucleotide analog
- MoA: AMP analog inhibits HBV polymerase and therefore its replication
- Boxed warning: post-treatment acute exacerbation of HBV
- Resistance: low rate of emergence, mutation of HBV’s polymerase/reverse transcriptase
- AE: GI upset, potential renal toxicity, bone loss
- Eat with high fat meals
- Excreted renally
29
Q
Vemlidy
A
- Tenofovir alagenamide (TAF)
- Prodrug
- Allows delivery to lymphoid cells and hepatocytes
- Reduced dosing and toxicity
- P-gp substrate: don’t use with St. John’s wort, rifampin, or phenytoin
30
Q
Baraclude
A
- Entecavir (ETV)
- Cyclopentyl guanosine nucleoside analog that competitively inhibits HBV polymerase
- MoA: Inhibits all three functions of HBV DNA polymerase (base priming, reverse transcription of negative strand, and synthesis of positive strand of HBV DNA)
- Boxed warnings: severe/acute HBV exacerbations, HIV/HBV coinfection, lactic acidosis, hepatomegaly
- Hepatic metabolism, renally eliminated
- AE: hepatic impairment, ALT elevation, peripheral edema, pyrexia, ascites, hematuria, nephrotoxicity, increased SCr
31
Q
DAA + Suffix
A
- Direct-acting Antivirals
- previr: NS3/4A protease inhibitor
- asvir: NS5A
- buvir: NS5B
- Preferred to use two drugs with different sites of actions
32
Q
DAA Similarities
A
- Boxed warning: risk of HBV reactivation upon DAA cessation in coinfected patients (test for HBV before starting DAA for HCV)
- Significant DDI: CI with CYP3A4 inducers, most increase [statin] and myopathy risk
33
Q
Mavyret
A
-Glecaprevir/pibrentasvir (G/P)
-Covers all HCV genotypes
-MoA: combination of NS3/4A PI and NS5A inhibitors
AE: HA, fatigue, GI upset, hypoglyceia in diabetics
-Take WITH food
-Hepatically metabolized and excreted
34
Q
Epclusa
A
- Sofosbuvir/Velpatasvir
- Covers all HCV genotypes
- MoA: combines NS5B and 5A inhibitors
- AE: HA, fatigue, GI upset, hypoglycemia in diabetics
- Take with or without food
- No PPIs!!! (CI)
- P-gp and CYP metabolized
- Urine and fecal elimination
35
Q
Ribavirin
A
- RBV (Ribatol)
- Given with Epclusa to improve cute rates in those with decompensated cirrhosis
- MoA: guanosine analog, interferes with GTP synthesis, inhibits viral RNA-dependent polymerase and mRNA capping
- Boxed Warning: Don’t use alone for HCV, hemolytic anemia, teratogenic, embryocidal
- AE: CNS effects, GI upset, dematologic/hematologic effects, muscle weakness, hepatic toxicity
- Don’t give with antacids
- Hepatic and intracellular metabolism
- Excreted in urine and feces
36
Q
Vosevi
A
- MoA: Combination of PI, NS5A, and 5B inhibitors
- Boxed warning: HepB reactivation
- Administer with food
- AE: Fatigue, HA, Nausea, diarrhea, insomnia
- PKPD specific to each component
