Anti-virals - Flu, RSV, HBV, HCV Flashcards
Oseltamivir (Tamiflu)
Zanamivir (Relenza)
Flu tx
MOA: neuroaminidase (cleaves sialic acid) inhibitor selective for influenza A and B –> therefore virus cannot bud off the host cell
Oseltamivir:
-given orally, activated in gut and liver, and excreted in the kidney
- may cause vomiting
- used for bird flu tx
Zanamivir
- intranasal spray
- may cause a bronchospasm in asthmatics or worsen respiratory function in COPD pts
Amantadine and Rimantadine
Flu
Oral absorption, plasma half life 20hrs, excreted in kidney unchanged
MOA: block the uncoating the virus and inhibit the release of viral particles into the cell cytoplasm
Uses:
- prevention and treatment of flu type A in high risk pts
- prophylactic use reduces the incidence and severity of sx
- tx may dec. duration of sx by 1-2 days
SE:
- dopamine agonist: CNS effects: hallucinations etc. (amantidine only- rimantiadine does not x the BBB)
- N/V/Dizziness
- teratogenic in animals
Ribavarin
RSV tx
MOA: Phosphorylated by cellular enzymes to ribavirin 5-triphosphate –> inhibits mRNA synthesis, protein synthesis and viral replication
Uses
- RSV in infants and children (aerosol admin)
- lassa fever (IV)
- Hepatitis C (orally with interferon alfa 2b or 2a)
Toxicity
- Teratogenic
*** absorbed passively by staff working with the aerosols pregnant women should not administer it
- Dyspnea, chest soreness, cardiac arrest, and hypotension
- HA/GI problems, insomnia, lethargy with oral use
- anemia, depression, and suicide with oral use
- declining pulmonary function in pts with preexisting pulmonary disease
Lamivudine
HBV
MOA: inhibits HBV DNA polymerase and reverse transcriptase- doses lower than for tx of HIV
* resistance can develop- x resistance with entecavir but NOT ADEFOVIR
- well tolerated
Adeofovir
HBV
Similar to lamivudine
may cause renal toxicity and lactic acidosis
Entacavir
HBV
similar to Lamivudine
Higher rate of HBV suppression- and improvement of liver function
well tolerated
Telbivudine
HBV
MOA: competitive inhibitor of HBV DNA polymerase
SE: inc. creatine kinase, N/V/D, fatigue
resistance common
Interferon alfa 2B, alfa 2A
HCV
administerd SQ- long acting depot shots
MOA:
- inhibits virus replications and viral protein synthesis
- induces cell host to produce enzymes that inhibit translation and transcription of viral messenger RNA adn thus dec. the viral replication
- inhibits processing and release of virus
- Inhibits penetration of virus as well as uncoating
Uses
- when previous tx not effective, tx for 6 months if genotype 2 and 3
- alfa 2b can also be used with chronic hep B
- tx warts and herpetic keratitis
Toxicity
- flu like sx
- GI sx: N/V
- Muscoloskeletal effects: myalgia, and arthralgia
- Hematological: Neutropenia, anemia, and thrombocytopenia
- Hepatic effects: inc. serum ALT
- CV effects: edema and hypotension
Boceprevir, Telaprevir, Simeprevir
HCV
*absorbed best if taken with fat containing food
*combined with interferon
MOA: block the activity of a serine protease required fro production and processing of viral proteins- mature proteins are essential for viral replication
SE:
- strong inhibitors of CYP3A4
* SIMEPREVIR should not be taken with any drugs that inhibit CYP3A4
- anemia, leukopenia, neutropenia
- rash
- dyspnea
- fatigue
Sofobuvir
Sofobuvir/ledipasvir
HCV
MOA:
1. Sofobuvir: converted to uridine triphosphate –> corporated into the viral RNA –> chain termination
* inhibits replication of hep. C by inhibiting NS5B RNA polymerase
2. Ledipasvir : inhibts HCV NS5A protein –> prevents replicationp by blocking viral hyperphosphorylation which is needed for optimal function
Uses
- HCV genotype 1 with compensated hepatic disease, HCC awaiting liver transplant, and pts coinfected with HIV o
Dasabuvir
HCV
non-nucleoside inhibitor of HCV NS5B RNA polymerase
Ombitasvir
HCV
inhibits HCV NS5A - essential for viral replication and viron assembly
* in cell cultures
Paritaprevir
HCV
HCV NS3/4A protease inhibitor - needed for proteolytic cleavage of HCV encoded polyprotein into mature forms and is essential for viral replication
Ritonivir
HCV
protease inhibitor
inhibitor of CYP3A therefore used to increase the peak and trough levels of other drugs
