Antivirals Flashcards
Viruses depend on what to live?
host cell machinery
Antiviral drugs are only active against what type viruses?
only replicating viruses, not latent viruses
What are 6 sites antiviral drugs work at?
- viral attachment and entry
- uncoating
- nucleic acid synthesis
- transcription/translation
- packaging/assembly
- release
What drugs block viral attachment and entry?
Enfuvirtide
Docosanol
Maraviroc
Palivizumab
What drugs block penetration?
interferon-alfa
What drugs block uncoating?
amantadine and rimantadine
What drugs block nucleic acid synthesis?
NRTIS, NNRTIs, nucleoside/nucleotide analogs
What drugs block integration/transcription?
INSTIs
What drug block viral protein synthesis?
PIs
What drugs block viral release from host cell?
neurominidase inhibitors
How is influenza classified?
antigenic differences
Antigenic variation in influenza occur as?
drift and shifts
Drifts are
epidemics, minor changes like point mutations
Shifts are
pandemics, major genetic changes resulting in alterations of antigen structure usually caused by reassortment
Anti-influenza drugs may work at sites of?
packaging/assembly and release
Neurominidase inhibitors are active against?
Both influenza A and B
What are 3 neurominidase inhibitors?
Oseltamivir
Zanamivir
Peramivir
Oseltamivir
Tamiflu
Zanamivir
Relenza Diskhaler
Peramivir
Rapivab
Oseltamivir formulation and half life
oral, 6-10 hrs
Oseltamivir excretion
kidney
Oseltamivir dose adjustment
renal dysfunction
Oseltamivir adverse effects
GI upset, headache
Zanamivir formulation
inhaler
Zanamivir adverse effects
potential bronchospasms so not recommended for pts with asthma/COPD
Peramivir formulation
single IV dose
Peramivir adverse effects
diarrhea, skin hypersensitivity
All neurominidase inhibitors all have the potential to cause?
neuropsychiatric events like confusion delirium, and hallucinations
What drug blocks influenza endonuclease and prevents cap snatching?
Baloxavir Marboxil
Baloxavir Marboxil
Xofluza
Baloxavir Marboxil approved when and formulation
2018, single oral dose
Baloxavir Marboxil metabolism
UGT1A3 (glucuronidation) and CYP3A4
Baloxavir Marboxil half life and excretion
79.1 hrs and primarily in feces
Baloxavir Marboxil adverse effects and counseling
2 degree bacterial infections and avoid taking with dairy products
Large, double stranded DNA genome, icosahedral capsid and envelope
Herpes viruses
HSV1 is typically associated with?
orolabial ulcers
HSV1 drug treatments
Docosanol OTC, Peniciclovir
Docosanol
Abreva
Docosanol (Abreva) moa
prevents viral entry
Penciclovir
Denavir
Penciclovir moa
triphosphate form competes with dGTP for viral polymerase, inhibits replication
HSV2 is associated with
anogenital ulcers
Commonly known as chickenpox, can later emerge as herpes zoster
Varicella zoster virus
Infects severely immunocompromised/HIV pts, infection often the result of viral reactivation
cytomegalovirus
Guanosine analog that is monophosphorylated by viral TK
acyclovir
Oral nucleoside analog for treatment of HSV2
acyclovir
Acyclovir moa
nucleoside analogs prevent viral replication
Acyclovir
Zovirax
Acyclovir formulation and absorption
topical and IV, poorly absorbed but small doses can improve absorption
Acyclovir half life and excretion
2.5 hrs, excreted in urine
Acyclovir SE and monitoring
GI upset, neurotoxicity, and renal impairment
monitor urinalysis, BUN, SCr, LFTs, CBC
Prodrug of acyclovir used for treatment of HSV2
valacyclovir
Valacyclovir
Valtrex
Valacyclovir metabolism and absorption
converted by 1st pass intestinal or hepatic metabolism and rapid GI absorptions
Valacyclovir formulation, half life and excetion
oral, 2.5 hr, and excreted in urine
Valacyclovir ADE and drug interactions
thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and interacts with cimetidine or probenecid
Does acyclovir or valacyclovir achieve better oral absorption?
valacyclovir
CMV treatments
Ganciclovir
Valganciclovir
Foscarnet
Cidofovir
Ganciclovir formulation
IV, solution for injection or ophthalmic use
For refractory cases of CMV
Foscarnet
Cidofovir
CMV prophylaxis
Letermovir
Foscarnet
Foscavir
Letermovir
Prevymis
Valganciclovir
Valcyte
monophosphorylated by viral kinase (UL97 gene). Di- and tri- phosphorylated by host enzymes. Competes with dGTP for viral DNA polymerase incorporation into viral DNA
Ganciclovir
Ganciclovir half live and excretion
4 h, excreted in urine
Ganciclovir ADE
GI upset, myelosuppression, infection, fever, increased serum creatinine
Ganciclovir boxed warnings
hematologic toxicity, impairment of fertility, feta toxicity, mutagenesis/carcinogenesis
Ganciclovir monitoring
CBC with differential and platelet count, SCr, ophthalmic exams
Valganciclovir formulation, elimination and counseling
once daily tab, renal elimination and take with food
Noncompetitive inhibitor of viral DNA polymerase
Foscarnet
Foscarnet formulation, half life and excretion
IV and 3-7 hrs, can remain in bone for several months, renal excretion
Foscarnet boxed warning
renal impairment, seizures
Foscarnet ADE
HA, fever, GI upset, electrolyte imbalance, anemia, QTc prolongation
Foscarnet monitoring
CrCl, ECG/EKG, electrolyes, CBC
Selective inhibitor of viral DNA synthesis
Cidofovir
Cidofovir formulation, half life and excretion
IV, 2.6 hrs, renal excretion
Cidofovir boxed warning
nephrotoxicity, neutropenia, carcinogenic/teratogenic
Vaccine preventable liver infection found in the stool and blood of people who are infected and spread when someone unknowingly ingests the virus
Hepatitis A
Serious liver infection that’s easily preventable by a vaccine and spread sexually or by contaminated needles/blood
Hepatitis B
Infection that attacks the liver and leads to inflammation; virus is spread by contact with contaminated blood from sharing needles or from unsterile tattoo equipment
Hepatitis C
Occurs in people who are also infected with the hepatitis B virus to supply envelope proteins (HBsAgs) for assembling a virion; “Delta hepatitis”
Hepatitis D
Found in stood and spread when someone unknowingly ingests the virus; common is east and south Asia, vaccine licensed in China
Hepatitis E
Can be calledGBV‐C‐ namedaftersurgeon,G.Barker,whofellillwithanon‐Anon‐Bhepatitis); single‐ strandedRNAvirusclassifiedintheFlaviviridaefamily.Noconclusiveevidencetoindicatecauseoffulminantorchronic liverdisease.Transmittedbybloodandsexualcontact.
Hepatitis G
Both HBV and HDV utilize what for cell entry?
NTCP, sodium taurocholate cotransporting polypeptide
Medication only available in EU
Bulevirtide
Bulevirtide moa
entry inhibitor that binds to NTCP, blocking the ability of HDV to enter hepatocytes , so high barrier to resistance is anticipated
Which infection is acute and self limiting
HAV
Which infection is can be both acute and lead to a chronic infection, cirrhosis, liver cancer or death
HBV and HCV
Non-enveloped, single stranded, positive sense RNA virus, acute, usually self-limiting, infection. Supportive care.
HAV
Enveloped, partially double-stranded DNA (circular) virus, acute (supportive care) and chronic infection. Rates of chronic infections 2 to >10% of acute infections. Viral DNA can insert into human chromosome and later REACTIVATE (primary concern)!
HBV
Enveloped, single stranded, positive sense HAV and HBV are RNA virus, chronic infection. Curable.
HCV
Vaccine preventable infections
HAV and HBV
Hepatitis A vaccine, doses and recommended in?
Vaqta, 2 doses, 1 yr or older
Hepatitis B vaccine that is 3 doses for birth to adult
Recombivax and Engerix
Hepatitis B vaccine that is 2 doses for >18yoa
Heplisav
Hepatits B vaccine that is 3 doses for >18yoa
TwinRix
Treatment goals of HAV infection
no specific treatment, self limiting, supportive care
Treatment goals of chronic HBV infection (3)
- suppression of HBV DNA to undetectable levels
- seroconversion of HBeAg from positive to negative
- reduction in elevated serum aminotransferase levels
Treatment goals of chronic HCV infection
viral eradication
First line treatment for HBV
nucleoside reverse transcriptase inhibitors: TDF, TAF, and Entecavir
Tenofovir disproxil fumarate
Viread
Tenofovir alafenamide
Vemlidy
Entecavir
Baaraclude
What are treatments used for HBV but use is limited because of resistance?
Adefovir and Lamivudine
Adefovir
Hepsera
Lamivudine
Epivir
Why should patients be tested for HIV prior to HBV therapy (2)
- HBV drugs have activity against HIV
- HBV can be treated with 1 drug bit it is not acceptable to treat HIV with 1 drug (partial drug exposure = increased potential for reisistance)
TDF moa
AMP analog inhibits HBV polymerase and HBV replication
TDF boxed warning
post-treatment acute exacerbation of HBV
TDF ADE
GI upset, potential renal toxicity and bone loss
TDF metabolism
intracellular hydrolysis to tenofovir then phosphoylated to active tenofovir diphosphate
TDF half life and excretion
17 hrs and excreted in urine
TAF moa
tenofovir prodrug, allows slow delivery into lymphoid cells and hepatocytes, reduced dosing and toxicity
TAF DI
P-gp substrate, avoid use with phenytoin, rifampin and St. John’s wort
Entecavir
Baraclude
Entecavir moa
guanosine nucleoside analog that competitively inhibits all three functions of HBV DNA polymerase; 1. base priming 2. reverse transcription of negative strand and 3. synthesis of the positive strand of HBV DNA
Entecavir boxed warning
severe, acute HBV exacerbations; HIV/HBV coinfection, lactic acidosis, and hepatomegaly
Entecavir half life and counseling point
128-149 hrs and take with food
Entecavir metabolism
minor hepatic glucuronide/sulfate conjugation
Entecavir excretion
kidneys so needs to be renally adjusted
Entecavir ADE
hepatic impairment, ALT elevation, peripheral edema, ascites, hematuria, nephrotoxicity, increased SCr
Boxed warning of direct acting antivirals
Risk of HBV reactivation upon DAA cessation in co-infected pts so test for HBV before starting DAA for HCV
DAA contraindications
CI with CYP3A5 inducers
Mavyret
Glecaprevir/Pibrentasivir
Mavyret moa
combination of NS3/4A PI and NS5A inhibitors
Mavyret ADE
HA, fatigue, GI upset, hypoglycemia in diabetes pts
Mavyret half life, excretion and counseling points
6 and 13 hrs, excreted in feces and should be taken with food
Epclusa
Sofosbuvir/Velpatasvir
Epclusa moa
combinationof NS5B and NS5A inhibitors
Epclusa ADE
HA, fatigue, GI upset, hypoglycemia in diabetics
Epclusa half life, excretion and counseling points
0.5 and 15 hrs, excreted in urine and feces and can be taken with or without food but do not take with PPIs
Ribavirin
Ribatol, Ribashere
Ribavirin moa
Guanosine analog, phosphorylated intracellularly by host enzymes; may interfere with the synthesis of GTP, inhibit capping of viral mRNA, and inhibit viral RNA–dependent polymerase
Ribavirin boxed warning
Do not use alone for HCV, hemolytic anemia,
Ribavirin ADE
CNS effects, GI upset, dermatologic effects, hematologic effects (neutropenia, anemia), muscle weakness, hepatic toxicity (can increase hepatotoxic effects of all NRTIs).
Ribavirin half life and excretion
44-298 hrs and excreted in urine/feces
Ribavirin bioavilability
increases with high-fat meals and decreased when co-administered with antacids
Vosevi moa
Combination of protease inhibitor (Voxilaprevir) NS5A (Velpatasvir) and NS5B (Sofosbuvir) inhibitors
Vosevi boxed warning
HepB reactivation
Vosevi counseling point
take with food
Vosevi ADE
fatigue, HA, nausea, diarrhea, insomnia