Antiviral Flashcards
Influenza
Amantidine
Rimantidine
Oseltamivir
Zanamivir
Amantidine MOA:
Inhibit uncoating of the viral RNA within infected host cells, preventing replication
Rimantidine MOA
Inhibit uncoating of the viral RNA within infected host cells, preventing replication
Oseltamivir MOA
Inhibit neuraminidase of influenza a and b; preventing the release of virons from the host cell and prevents entry into the cell
Zanamivir MOA
Inhibit neuraminidase of influenza a and b; preventing the release of virons from the host cell and prevents entry into the cell
Amantidine
Crosses BBB –> parkinson’s Disease
Pregnancy category C
CDC DOES NOT recommend use
Rimantidine
Pregnancy category C
CDC DOES NOT recommend use
Oseltamivir
Pro drug, oral
Indicated: prevention and treatment of Influenza A and B
BEGIN within 2 days of onset (renally dosed)
Pregnancy category C
Zanamivir
Oral inhalation
Indicated: prevention and treatment of Influenza A and B
Avoid in Dairy allergy - contains milk protein
Pregnancy category C
Nucleoside analogs MOA
synthetic analogs of purines or pyrimidines that inhibit the viral replication through
competitive inhibition of DNA polymerase
incorporation and termination of viral DNA chain
inactivation of viral DNA polymerase
Trifluridine
Pyrimidine analogs
Ophthalmic solution
Indications Ocular HSV
Refrigerate
Cidofovir
Pyrimidine analogs
IV formulation ONLY
Indication CMV infections, HSC activity (systemic, organs, meningitis)
Renally Toxic –> HYDRATE prior to therapy
Acyclovir
Guannine Analogs
ONLY effective against activiely replicating virus
Indications HSV and VZV
Oral, IV (renally toxic), topical
Poor bioavailability –> multiple dosing/day (5X)
Pregnancy category B
Monitor renal function
Valacyclovir
Prodrug of acyclovir
Better bioavailability
Indications HSV and VZV
Oral formulation only (1 x day)
Famciclovir
Prodrug of penciclovir guanine analog Inhibits viral DNA polymerase Better bioavailability Indications: prevention and treatment of HSV and VZV Pregnancy category B Oral agent
Penicilovir
Guanine analog
Inhibits viral DNA polymerase
Topical formulation ONLY
Indication: treatment of HSV infections (Herpes labialis and facialis)
Ganciclovir
Guanine analog
Indications: treatment and prevention of CMV infection
IV formulation renally toxic –> HYDRATE
Monitor: CBC w/ diff, LFTs, Renal function, serum electrolytes
Pregnancy category: C
Valganciclovir
prodrug of ganciclovir Oral table take with food renally excreted Indications: Prevention and treatment of CMV infections Monitor CBC w/ diff, renal function
Foscarnet
Inorganic pyrophosphate analog
inhibits viral-specific DNA polymerases and reverse transcriptase at the pyrophosphate binding site –> preventing DNA synthesis
Indications: prevention and treatment of CMV, treatment of refractory HSV and VZV
Monitor: chem 10 (renal function and electrolyte loss), CBC w/ diff (bone marrow suppression), EKG (AV block, ST wave changes)
Pregnancy category C
HAV Vaccines
Vaqta
Havrix
Twinrix
Vaqta
HAV only
Indications >12months of age
2 doses series - 1st dose then 2nd dose 6-18 months later
Havrix
HAV only
Indications >12 months
2 dose series - 1st dose then 2nd dose 6-12 months later
Twinrix
HAV/HBV combination
Indicated >18y/o
3 dose series - 1st dose, then 2nd dose @ 1month, then 3rd dose @ 6months
HBV Agents
Adefovir Entecavir Lamivudine Interferon/peg-interferon Tenofovir Telbivudine
Interferon MOA
signaling proteins that are released by host cell in response to pathogens; triggering protective defense mechanisms within the immune system.
Interfere with viral replication and activate natural killer cells and macrophages
Peg-Interferon
SQ once weekly
ADEs: Anemias (cbc w/ diff), infections (CXR),
arrhythmias (ekg), LFTs, Hypothyrodism (TSH), psych changes (moods), renal function
REFRACTORY HBV
Interferon
IV, IM, SQ once daily for 16 weeks
ADE:Anemias (cbc w/ diff), infections (CXR),
arrhythmias (ekg), LFTs, Hypothyrodism (TSH), psych changes (moods)
REFRACTORY HBV
Adefovir
Adenosine analog prodrug metabolixed by cellular kinases preventing DNA synthesis
Indications HBV, effective against Lamivudine- resistant HBV
Renally dosed when CrCl<50ml.min
Monitor: Renal function, LFTs, HBV labs (viral load and serologies
NO CO INFECTION COVERAGE
DO NOT USE WITH TENOFOVIR
Entecavir
inhibit HBV reverse transcriptase –> suppressing DNA replication (weak toward HIV)
Co-infectioon, lamivudine resistance on tenofovir
Renally dosed when CrC<50ml/min
Monitor: Renal function, LFTs, T.bili, Blood glucose
Lamivudine
nucleoside reverse transcriptase inhibitor Resistance via M184V and M184I mutations
Indications: HIV-1, HIV-2: 300mg po 1xday
HBV: 100mg po 1xday
Well tolerated (mostly GI/HA)
Monitor: Blood glucose, CBC with diff, HIV VL/CD4 count
Telbivudine
MOA: inhibits DNA polymerase --> preventing DNA replication Thymidine analog Renally dosed when CrCl<50ml/mn ADE: LFTs TOO EXPENSIVE
NS5B Polymerase Inhibitor MOA
Nucleoside/nucleotide analogs that incorporate into HCV RNA leading to chain termination –> stop HCV replication
NS3/4A Protease Inhibitor MOA
Inhibits the cleavage of polyproteins into nonstructural proteins that are essential in HCV replication
Lower barrier of resistance Q80K
NS5A Inhibitor MOA
Inhibits the phosphorylation of proteins required for HCV RNA replication –> preventing HCV RNA replication
* need to do genetic resistance testing
Non-Nucleoside NS5B palm Polymerase Inhibitor MOA
Inhibits the activity of the NS5B to inhibit HCV RNA replication
NS5B Polymerase Inhibitor Agents
Sofosbuvir
NS3/4A Protease Inhibitor Agents
Glecaprevir Grazoprevir Paritaprevir Simeprvir Voxilaprevir
NS5A Inhibitors Agents
Daclatasvir Elbasvir Ledipasvir Ombitasvir Pibrentasvir Velpatasvir
Non-Nucleoside NS5B palm Polymerase Inhibitor Agents
Dasabuvir
3A4 PK Booster Agents
Ritonavir
Sofosbuvir
NS5B RNA nucleotide polymerase inhibitor for Genotype 1,2,3,4 Pro drug Pangenotypic No CYP Interactions Substrate of pgp efflux pump and BCRP *Tenofovir --> Increase renal toxicity associated with Tenofovir Pregnancy: Sofosbuvir ONLY - Category B otherwise Category X
Sofosbuvir/Ledipasvir (Harvoni)
Ledipasvir - NS5A inhibitor
metabolism via oxidation - no DDI via CYP
elimination via pgp efflux pump and BCRP
ADE: Asthenia, Hyperbilirubinemia, fatigue/headache, GI effects, No hepatic dosing, No renal dosing - caution CrCl<30ml/min
DDI: acid suppressants, Tenofovir –> nephrotoxicity, Amiodarone –> Symptomatic bradycardia
Velpatasvir/Sofosbuvir (Epclusa)
NEW GOLD Standard in HCV management Velpatasvir NS5A inhibitor Pangenotypic for genotype 1-6 metabolized CYP 2B6, 2C8, 3A4 Eliminated via feces
ADE: anemia, GI, Headache, Fatigue, no hepatic dosing, no renal dosing - caution in GFR<30ml/min
LOTS OF DDI
Voxilaprevir/Velpatasvir/Sofosbuvir (Vosevi)
Voxilaprevir NS3/4A protease Inhibitor via CYP3A4 –> DDI
Significant DDI with acid suppressants (Antacid, H2Blockers, PPIs)
Renal issues: do not use when GFR<30ml/min
ADE: headache, fatigue, GI, Rash, Depression, Elevated lipase, CPK, t. bili
Elbasvir/Grazoprevir (Zepatier)
Elbasvir - NS5A Inhibitor
Grazoprevir - NS3/4A Protease Inhibitor
ADE: GI, Fatigue, headache, Anemia, elevated LFTs, Hyperbilirubinemia, No renal or hepatic dosing
LOTS OF DDI
Viekira Pak
Paritaprevir (NS3/4A protease inhibitory)
- Metabolism 3A4 - MAJOR DDIs
Ritonavir (CYP3A4 Booster)
Ombitasvir (NS5A Inhibitor)
- Metabolized via hydrolysis
+
Dasabuvir (non-nucleoside NS5B palm polymerase inhibitor
- Metabolism via 2C8, 3A4 (possible DDIs)
Must be taken eith food
No renal or hepatic dosing
ADE: GI, rash, LFTs
TO COMPLICATED
Viekira XR
Genotype 1a and 1b
Paritaprevir/ritonavir/Ombitasvir/Dasabuvir
Must be taken with food - cannot be chewed, crushed, or split
TOO MANY DDI
ADE: GI, rash, LFTs
3 pills once a day
Simeprevir
NS3/4A Protease Inhibitor for Genotype 1 ONLY
- Q80K resistance mutation –> reduction in efficacy based on SVR
- more effective in 1b
Metabolized via 3A4 & 1A2 –> interactions
Take with food
Sulfonamide Allergy
ADE: Rash, LFTs, GI, Hyperbilirubinemia
MUST BE GIVEN WITH Sofosbuvir
Daclatavir
NS5A Inhibitor
Indications: HCV genotype 3
Must be co-administered with Sofosbuvir
Metabolism
- CYP3A4 - substrate –> DDI
Co-administered with 3A4 inhibitor –> reduce to 30mg QD
Co-administered with 3A4 inducer –> increase to 90mg QD
ADE: Anemia, Fatigue, GI effects, Headache
Glecaprevir/Pibrentasvir (Mavyret)
Glecaprevir - NS3/4A Protease Inhibitor Pibrentasvir - NS5A Inhibitor Pangenotypic for genotypes 1-6 Dose: 3 tablet once daily with food Glecaprevir: CYP3A4, eliminated pgp efflux pumps Pibrentasvir: Biliary-fecal route
No renal dosing
ADE: Headache, Fatigue, GI, Elevated t.bili
Pef-Interferon + Ribavirin
Refractory HCV
Ribavirin
MOA: Increase mutation frequency and inhibits HCV polymerase activity
Indications: in combination with PEG-IFN therapy
ADE: pruritus, weight loss, GI symptoms, Neutropenia, Headache, Insomnia, Fatigue, Fever
BBW: hemolytic anemia + Teratogenicity
Recommendations for patients with CKD stage 1, 2, or 3
Daclatasvir Elbasvir/Grazoprevir Glecaprevir/Pibrentasvir Ledipasvir/Sofosbuvir Sofosbuvir/Velpatasvir Simeprevir Sofosbuvir/Velpatasvir/Voxilaprevir Sofosbuvir
Recommendations for patients with CKD stage 4 or 5 (GFR<30ml/min)
Elbasvir/Grazoprevir
Glecaprevir/Pibrentasvir
When to initiate HIV Therapy
any time end organ damage, pregnant, co-infection (HBV/HCV)
DO NOT INITIATE THERAPY IF PATIENT IS NOT READY or WILLING
What to initiate
Integrase inhibitor based Antiretroviral therapy:
- Raltegravir + Emtricitabine/Tenofovir DF or Tenofovir AF
- Elvitegravir/c/TDF/Emtricitabine
- Elvitegravir/c/TAF/Emtricitabine
- Dolutegravir + Emtricitabine/Tenofovir DF or Tenofovir AF
- Dolutugravir/abacavir/lamivudine
HLA-B5701 negative
Under special conditions
Darunavir/Ritonavir or Darunavir/c + TDF/Emtricitabine or TAF/Emtricitabine or Abacavir/Lamivudine
- epzicom if HLA-B5701 negative
Atazanavir/ritonavir or Atazanavir/c + TDF/Emtricitabine or TAF/Emtricitabine or Abacavir/Lamivudine
Raltegravir + Abacavir/Lamivudine (baseline HIV VL <100K copies/ml) inferior to truvada/descovy
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir - TDF - TAF Zidovudine
MOA: competitively inhibits of HIV-1 reverse transcriptase
Renally dosed (except Abacavir) Mitochondrial toxicity - due to inhibition of mitochondrial DNA polymerase - lactic acidosis and hepatic steatosis - lipoatrophy --> fat wasting extremities, buttocks, face
Truvada
Emtricitabine/Tenofovir DF
Dsescovy
Emtricitabine/Tenofovir AF
Epzicom
Abacavir/Lamivudine
Combivir
Zidovudine/Lamivudine
Abacavir
ADE: Rash, CVD risk
DO NOT USE baseline HIV VL >100K copies/ml
Testing for HLA-B5701 allele before initiation of abacavir is recommended to identify the patients with an increased risk of an abacavir associated hypersensitivity reaction
Didanosine
ADE: Weight-dosed, pancreatitis, peripheral neuropathy
Emtricitabine
ADE: Hyperpigmentation, well tolerated
Active against HBV
Lamivudine
ADE: well tolerated, headache
Also reactive against HBV infections
Rapidly selects for mutation - M184V
Stavudine
ADE: weight-dosed, pancreatitis, peripheral neuropathy
Tenofovir
TDF - nephrotoxicity, osteomalacia
TAF - Safer, no kidney or bone mineral density
Zidovudine
ADE: bone marrow suppression (anemias, RBC, WBC, platelets)
High level resistance is generally seen
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
1st Generation: - Efavirenz - Nevirapine 2nd Generation: - Etravirine - Rilpivirine
MOA: binds noncompetitively to allosteric site
baseline genotypic resistance testing is recommended
resistance occurs rapidly with monotherapy and results from single mutation
- lowest genetic barrier resistance
- MOST COMMON MUTATION = K103N (resistant to efavirenz & nevirapine)
Efavirenz
1st generation NNRTI
take on empty stomach (take at bed)
ADE: CNS effects - somnolence, fatigue, psych changes, SI/SA - rash, LFTs
Metabolized by CYP3A4; induces and inhibits CYP3A4
Pregnancy category: D
Nevirapine
1st generation NNRTI
DO NOT USE: in female with CD4 > 350cells/mm3; males with CD4 >400cells/mm3
Metavolized by CYP3A4; Induced CYP3A4
ADE: rash, liver toxicity
Etravirine
2nd generation NNRTI
Active against K103N virus
Metabolized by CYP3A4; Induces and Inhibits CYP3A4\
ADE: rash, LFTs, minor CNS effects
Rilpivirine
2nd generation NNRTI
active against K103N virus
Must be taken with food; 900kcals (bad for diabetic, heart disease, obese)
Metabolized by CYP3A4; substrate
ADE: rash, LFTs, CNS effects
Do not use: baseline HIV VL > 100K copies/ml
Complera
Rilpivirine/TDF/Emtricitabine
Odefsey
Rilpivirine/TAF/Emtricitabine
Protease Inhibitors Agents
Atazanavir Fosamprenavir Darunavir Indinavir Lopinavir/ritonavir Nelfinavir Ritonavir Saquinavir Tipranavir
Protease Inhibitors
MOA: Inhibit the activation of immature proteins –> block the GAG-POL region within protease to inhibit the cleavage of proteins
Class Effects: Rash, LFTs, Increases Blood glucose (DM), Increases TG and LDL, Lipodystrophy (central adiposity), Increases CVD risk
All PIs are metabolized by CYP3A4 (most are potent CYP3A4 inhibitors)
High genetic barrier to resistance (difficult to become resistance)
Ritonavir
Most 3A4 Potent inhibitor
ADE: GI
DO NOT give with nelfinavir
Active against HIV –> as a booster
Atazanavir
ADE: PR interval prolongation, Hyperbilirubinemia
GI neutral
Lipid neutral
Darunavir
MUST co-admin w/ ritonavir
Sulfonamide –> cautious with sulfa allergy
GI neutral
Lipid neutral
Fosamprenavir
Sulfonamide –> cautious with Sulfa allergy
ADE: GI
Indinavir
Nephrolithiasis, hyperbilirubinemia
Lopinavir
ADE: GI
Saquinavir
ADE: GI, CVD risk
Tipranavir
Only CYP3A4 inducer
MUST Co-admin w/ ritonavir
Sulfonamide –> cautious with sulfa allergy
ADE: Intracranial hemorrhage
Cobicistat
Similar to ritonavir –> used as 3A4 booster
ONLY with atazanavir and darunavir
NO HIV Activity
DDI/Contraindications = ritonavir
ADE: renal impaitment (don’t use with TDF when CrCl<70ml/min)
Evotaz
Atazanavir/Cobicistat
1 tablet + 2 NRTIs
Prezcobix
Darunavir/Cobicistat
1 tablet + 2 NRTIs
Fusion Inhibitor
Enfuvirtide
ONLY SQ
MOA: inhibits gp41 and prevents the fusion of HIV to CD4 cell surface
ADE: injection site reaction, GI
Entry inhibitor
Maraviroc
MOA: inhibits HIV co-receptor CCR5-tropic HIV-1 infection
MUST test for co-receptor tropism prior to using
With inhibitor: decrease dose
With inducer: increase dose
ADE: LFTs, Rash, Pyrexia, orthostasis
Integrase Inhibitors
Raltegravir
Elvitegravir
Dolutegravir
Bictegravir/TAF/Emtricitabine
Raltegravir
MOA: Blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host
Metabolized by glucuronidation and does not interact with the CYP450 system
Eliminated via pgp efflux pumps
Resistance: virologic failure has been uncommon in vitro resistance requires only a single point mutation at codons 148 or 155
ADE: rash, LFTs, Increase CPK, pyrexia
Quad Pill
Elvitegravir/COBI/TDF/Emtricitabine
MOA: Blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host
3A4 Substrate, glucuronidation
CrCl > 70ml/min
Treatment naive patients
ADE: new or worsening renal function, bone mineral density losses, GI
TOO MANY C/I and DDI
Genvoya
Elvitegravir/COBI/TAD/Emtricitabine
MOA: Blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host
Safe in pt with CrCl > 30
Dolutegravir
MOA: Blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host
Metabolism: UGT-1A1, 3A4
ADE: Hypersensitivity reaction, LFTs (especially in HBV or HCV co-infections), Insomnia, Hyperglycemia (>125mg/dl), hypertriglyceridemia
DDI: Polyvalent cations (Mg, Al, Fe, Ca) Space 2hrs before or 6hrs after cations
Bictegravir/TAF/Emtricitabine
Integrase Inhibitor Treatment naive and as SWITCH regimen Renal issues CrCl<30ml/min Metabolism Glucuronidation and Via CYP3A4 ADE: GI & Headache
SWITCH regimen
a pt on an effective HIV regimen & able to maintain viral suppression for at least 6 months & looking for simple regimen
