Antivirals Flashcards
Drugs that affect (3):
Attachment and penetration
- Enfuviritide (HIV)
- Docosanol (HSV)
- Palivizumab (RSV)
- Maraviroc
Drugs that affect (2):
Uncoating
- Amantadine
- Rimantadine (Influenza)
Drugs that affect (5):
Synthesis of viral components
- NRTIs (HIV)
- NNRTIs (HIV)
- Acyclovir (HSV)
- Foscarnet (CMV)
- Entecavir (HBV)
Drug that affects (1):
Packaging and assembly of virus particle
- Protease inhibitors (HIV)
Drug that affects (1):
Release of virus
- Neuraminidase inhibitors (Influenza)
Virus attaches to specific receptors on host cell and becomes internalized
Attachment and penetration
Protein coat of the virus is dissolved by viral enzymes to liberate viral RNA or DNA
Uncoating
Virus takes over host cell nucleus and replicates its DNA or RNA, then makes proteins
Synthesis of viral components
Viral genome may be encapsulated by viral protein, multiple membranes, or no protein
Packaging and assembly of virus particle
Some viruses are released rapidly and kill the host cell; others are released slowly and allow the cell to survive
Release of virus
Herpes Drugs (4)
- Acyclovir (Zovirax)
- Valacyclovir (Valtrex)
- Famciclovir (Famvir)
- Docosanol (Abreva)
Acyclovir MOA (3)
- Guanosine analoge
- Activated by viral thymidine kinase
- Inhibits DNA synthesis by competing with dGTP
Acyclovir Admin and t 1/2
- Oral
- Topical
- IV
- Short half life, dose 3-4qd
Acyclovir Elimination
Kidney
- Decreased renal fxn will affect drug significantly
Prodrug of Acyclovir
Valacyclovir
- Higher biavail
- Food does NOT affect absorption
DOC Herpes
Acyclovir
Acyclovir Tx (3)
- Genital herpes, herpes keratitis, herpes zoster, herpes encephalitis, varicella zoster
- Prophylaxis in organ transplant
- Chronically to immunocomp
Acyclovir SE (3)
Well tolerated
- N/V, HA
- Nephrotoxic with high IV dose (hydrate)
- Somnolence/lethargy with Zidovudine in HIV pts
- Safe in pregnancy
Famciclovir (Famvir) / Penciclovir MOA and features
t 1/2, elimination
- Phosphorylated by viral thymidine kinase
- Similar to acyclovir
- Longer t 1/2
- Renal elimination
Docosanol MOA
- Inhibits viral fusion to cell membrane
Docosanol Tx
- OTC cold sores
CMV/Herpes Drugs (5)
- Ganciclovir
- Valganciclovir
- Cidofovir
- Foscarnet
- Fomvirsen
Ganciclovir & Valganciclovir MOA (3)
- Inhibits CMV DNA replication
- Activated by viral kinase in cells infected with herpes or CMV
- Less selective than acyclovir (more toxic)
Ganciclovir Admin
IV
Valganciclovir Admin
Oral
Ganciclovir & Valganciclovir Tx (3)
Tx or prophylaxis of CMV/Herpes
- Immunocomp
- Transplant pts
- CMV retinitis
Ganciclovir & Valganciclovir SE (5)
- Neutropenia, thrombocytopenia (mainly when high doses given IV, especially when combined with Zidovudine)
- Nausea, fever (most common)
- Rash
- Phlebitis
- Confusion, headache, seizures
- Abnormal liver function tests
Other drugs for CMV/Herpes that do NOT req activation (2)
- Cidofovir
- Foscarnet
Cidofovir Tx
- Resistant CMV/Herpes
Cidofovir SE
- Renal tox (use probenecid/hyrate)
Foscarnet MOA
- Inhibits DNA and RNA polymerase, reverse transcriptase
Foscarnet Admin
IV
Foscarnet Tx
- Resistant CMV/Herpes
Foscarnet SE (1)
- Renal toxicity
Fomvirsen MOA
- Antisense compound to viral mRNA
Fomvirsen Tx
- CMV retinitis (intraocular)
Fomviersen SE (2)
- Ocular inflammation
- Visual haze
Influenza Drugs (4)
- Oseltamivir
- Zanamivir
- Amantadine
- Rimantadine
Neuraminidase Inhibitors (2)
- Oseltamivir
- Zanamivir
Oseltamivir & Zanamivir MOA (2)
- Neuraminidase Inhibitors
- Block release of virus
Oseltamivir Tx (2)
- Influenza Type A and B
- Bird flu
Zanamivir Tx
- Influenza A and B
Oseltamivir Admin and SE
- Oral
- NAUSEA/VOMITING (take with food)
Zanamivir Admin and SE
- Inhaled or intranasal
- May worsen RESPIRATORY fxn in COPD
- Bronchospasm in asthmatics
Amantadine MOA
- Inhibits uncoating of virus
Amantadine Tx
- Influenza A tx and prophylaxis
Amantadine Elimination
- Renal
Amantadine SE (2)
- CNS HALLUCINATIONS
- N/V
- Rarely used
Rimantidine vs Amantadine SE
- Rimantidine does NOT enter CNS = NO hallucinations
RSV Drugs (2)
- Ribavirin
- Palivizumab
Ribavirin MOA (4)
- Purine analogue
- Becomes phosphorylated
- Inhibits viral RNA synthesis
- Inhibits RNA polymerase and synthesis of GTP
Ribavirin Tx (3)
- Active against many viruses
- RSV
- Hep C
Ribavirin Admin
- Aerosol (RSV)
- IV (Lassa, SARS)
- Oral
Ribavirin SE (4)
- Pulmonary, dyspnea
- Hypotension
- Anemia
- Depression, lethargy
- GI
Ribavirin CI
- TERATOGENIC (exposure at work)
Palivizumab MAO (2)
- Antibody to RSV
- Passive immunity
Palivizumab Tx
- Prophylaxis in high risk pts
- Injected 1x per month
Drug of Choice for Chronic Hep B
Lamivudine
Lamvudine MOA (2)
- Reverse transcriptase inhibitor (also used for HIV)
- Inhibits HBV polymerase
Adefovir SE (2)
- Renal toxicity
- Lactic Acidosis
Drugs for Hep B (4)
- Lamivudine (DOC)
- Adefovir
- Entacavir
- Telbivudine
- — these drugs replaced interferon a2b for tx HBV
Telbivudine MOA
- similar to Lamvudine
- More effective in some pts
Drugs of Hep C (6)
- Interferon a2b
- Interferon a2a
- Boceprevir
- Telaprevir
- Simeprevir
- Sofosbuvir/Ledipasvir (Harvoni)
- Viekira
Boceprevir, Telaprevir, Simeprevir MOA
- Specific for serine protease needed for replication of HCV
Interferon MOA (4)
Blocks viral entry
- Blocks transcription and translation of mRNA
- Blocks viral replication
- Blocks viral processing
- Blocks viral assembly and release
Boceprevir, Telaprevir, Simeprevir increased effectiveness with _____ (2)
- Interferon
- Ribavirin
Boceprevir, Telaprevir, Simeprevir SE
- Strong inhibitors of CYP3A4 (drug interactions)
- Exacerbate anemia, neutropenia, fatigue
Interferon Toxicity (5)
- Flu-like symptoms
- Musculoskeletal aches and pains
- GI: nausea, anorexia
- CNS: depression, suicide
- Hematologic: neutropenia, anemia (worse when combined with Ribavirin, Teleprevir, Boceprevir)
Sofosbuvir/Ledipasvir (Harvoni) MOA (3)
- Inhibits NS5B RNA polymerase
- Lepidasvir inhibits NS5A
- Halts HCV reproduction
Sofosbuvir/Ledipasvir (Harvoni) SE (3)
- Irritability
- Fatigue
- Lethargy
Sofosbuvir/Ledipasvir (Harvoni) success with genotype ___
Genotype I
Sofosbuvir/Ledipasvir (Harvoni) interesting feature
Possible liver reversal
Dasabuvir, Ombitasvir, Paritaprevir, Ritonavir (Viekira) MOA (4)
- Dasabuvir inhibits HCV NS5B polymerase
- Ombitasvir inhibits HCV NS5A
- Paritaprevir inhibits HCV NS3/4A polymerase
- Ritonavir inhibits CYP3A and increases bioavail
Dasabuvir, Ombitasvir, Paritaprevir, Ritonavir (Viekira) SE (2)
- Fatigue
- Insomnia
Treatments of HIV (5)
- Reverse Transcriptase Inhibitors
- Protease Inhibitors
- Non-nucleotide Reverse Transcriptase Inhibitors
- Fusion Inhibitors
- Integrase Inhibitors
Nucleotide Reverse Transcriptase Inhibitor (4)
- Zidovudine
- Lamivudine
- Emtracitabine
- Tenofovir
- Didanosine
- Zalcitabine
- Stavudine
- Abacavir
Zidovudine MOA (2)
- Thymidine analogue
- Incorporated into DNA, inhibits reverse transcriptase
- Combined with Lamivudine
Zidovudine t 1/2 and penetration
- Short t 1/2
- Gets into CNS
Zidovudine Tx (4)
- Maintains CD4 count
- Prophylaxis post exposure
- Decrease risk of transmission of virus in pregnancy and newborns
- AIDS dementia
- Psoriasis and T cel leukemia
Zidovudine SE (4)
- Anemia, Neutropenia
- CNS
- GI
- Somnolence with ganciclovir
Monotherapy for HBV
- Lamivudine
Drug for HIV and HBV pts
- Lamivudine
Top drug combos for HIV (2)
- Lamivudine & Zidovudine
- Tenofovir & Emtricitabine
Tenofovir & Emtricitabine SE (2)
- Mild GI
- Flatulence
Didanosine SE (2)
- Peripheral neuropathy
- Combined with Zidovudine
Zalcitabine (2)
- Peripheral neuropathy
- Oral ulcers
Stavudine SE
- Peripheral neuropathy
Abacavir SE
- Hypersensitivity (do not use drug again!)
Drugs that cause Peripheral neuropathy
- Didanosine, Stavudine
- Zalcitabine
Drugs that cause Lactic Acidosis
- Zidovudine, Zalcitabine
- Didanosine, Stavudine
Drugs that cause Anemia/granulocytopenia
- Zidovudine, Didanosine
Non-Nucleotide RTIs (3)
- Delavirdine
- Nevirapine
- Efavirenz
Non-Nucleotide RTIs MOA (4)
- Bind directly to inhibit viral reverse transcriptase
- Use ONLY with nucleoside analogues
- Long-acting, well absorbed
- Metabolized by CYP3A/2D6
Non-Nucleotide RTIs preferred drug
- Efavirenz
Non-Nucleotide RTIs used in pregnancy
- Nevirapine (or just take pt off Efavirenz)
“Navir” drugs
Protease Inhibitors
Protease Inhibitors MOA
- Inhibited protease prevents cleavage of the polypeptide and subsequent maturation of the viron
Protease Inhibitors Features (4)
- Mutations and resistance common when used alone (COMBINE with NRTIs)
- Do not interrupt therapy
- Metabolized by CYP3A4
- Drug interactions: St. John’s Wort (always find out about OTC drug use)
Altered body fat distribution
- Buffalo hump
- Abd fat
- THIN face
Protease Inhibitors
Protease Inhibitors Other SE (5)
- Cholesterol/TGs increase
- Atherosclerosis, cerebrovascular incidents, MI
- DM
- Depression
- Abd pain
Protease Inhibitor Drug of First Choice
- Atazanavir
Atazanavir (4)
- Well tolerated
- Once a day dosing
- Less effect lipoproteins
- Increase bilirubin (inhibits uridinediphosphate-glucuronosyl transferase A1)
Protease Inhibitor Drug of Second Choice
- Darunavir
Darunavir Features (2)
- Well tolerated
- Combined with Ritonavir
Darunavir SE (2)
- HA
- Nightmares
Saquinavir bioavailability (3)
- Increased with high-fat food, Grapefruit juice, Ritonavir
- Inducer of CYP3A decreases effectiveness
- Inhibition of CYP3A
Saquinavir (SE)
- GI common
Ritonavir bioavailability (3)
- Inhibit CYP3A4
- Combined with other protease inhibitors to increase their bioavailability
- Many drug interactions
Ritonavir SE (3)
- GI
- Burning, tingling
- Liver enzymes elevated
Used with Ritonavir to increase availability
Lopinavir
Lopinavir/Ritonavir SE (2)
- D/N
- Liver enzymes elevated with hepatic dz
Indinavir Features (2)
- Cross resistance with Ritonavir
- Metabolized by CYP3A4, drug reactions
Indinavir SE (2)
- Kidney stones
- Hyperbilirubinemia
Nefinavir Features
- CYP3A, many drug interactions
Nefinavir SE
- Mostly GI
Amprenavir/Fosamprenavir (2)
- Good oral absorption
- Inhibits CYP3A4 (many drug interactions/metronidazole)
Stevens-Johnson syndrome rash
Amprenavir/Fosamprenavir
Tipranavir MOA
- Non-pepiditic protease inhibitor
Tipranavir Tx (2)
- May work if resistant to other drugs
- Combined with Ritonavir to increase bioavail (metabolized by CYP3A4)
Enfuvirtide MOA (2)
- Binds to viral envelop glycoprotein
- Prevents fusion of virus and entry into cell
Enfuvirtide Tx (2)
- No cross resistance with other drugs
- Advanced dz when other drugs fail
Enfuvirtide SE (2)
- Injection site/rxn
- Pneumonia
Enfuvirtide Admin
SC
Drug used only if there is CCR5 receptor on T cell
- Maraviroc
Maraviroc SE
- Rash
Raltegravir MOA (2)
- Blocks integrase
- Prevents viral replication
Raltegravir Tx
- Used when other drugs stop working
Raltegravir SE
- N/V
- HA
Integrase Inhibitors
Raltegravir
Co-receptor inhibitors
Maraviroc
Atazanavir + Indinavir =
Bilirubin
Didanosine + Stavudine =
Neuropathy
Zidovudine + Stavudine =
antagonism
Drug that affects Adenosine?
Tenofovir
Drugs that affect Guanosine?
Didanosine, Abacavir
What drugs affect Thymidine?
Zidovodine, Stavudine
What drugs affect Cytosine?
Zalcitabine, Emticitabine, Lamivudine
