Antiviral drugs are prescription medicines (pills, liquid, an inhaled powder, or an intravenous solution) that fight against flu viruses in your body. Antiviral drugs are not sold over-the-counter. You can only get them if you have a prescription from a health care provider. Antiviral drugs are different from antibiotics, which fight against bacterial infections. If you get sick with flu, antiviral drugs are a treatment option. Check with your doctor promptly if you are at high risk of serious flu complications and you develop flu symptoms. Flu signs and symptoms can include feeling feverish or having a fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills, and fatigue. Your doctor may prescribe antiviral drugs to treat your flu illness. Benefits of Antiviral Drugs Antiviral treatment works best when started soon after flu illness begins. When treatment is started within two days of becoming sick with flu symptoms, antiviral drugs can lessen fever and flu symptoms, and shorten the time you are sick by about one day. They also may reduce the risk of complications such as ear infections in children, respiratory complications requiring antibiotics, and hospitalization in adults.  For people at high risk of serious flu complications, early treatment with an antiviral drug can mean having milder illness instead of more severe illness that might require a hospital stay.  For adults hospitalized with flu illness, some studies have reported that early antiviral treatment can reduce their risk of death. Classification of Antiviral Drugs Drug Mechanism of Action Therapeutic Uses Key Notes Neuraminidase Inhibitors Oseltamivir Zanamivir -Prevent the release of new virions and their spread from cell to cell -Given prior to exposure they prevent infection -Given24-48 hours after onset of infection, they effect intensity and duration of symptoms -Type A and B influenza viruses -Orthomyxoviruses need neuraminidase for life cycle of the virus -Sialic acid analogs -Do not interfere with response immune response to influenza A vaccine -Zanamivir should be avoided in pts with severe reactive asthma or COPD Amantadine Rimantadine -Block the viral membrane matrix protein (M2) which is required for the fusion of viral membrane with cell membrane  Preventing formation of endosome  Interferes with viral uncoating -70 to 90% effective in preventing infection if tx begun at time of or prior to exposure to infection -Given w/in first 48 hours, they reduce duration and severity of systemic symptoms -Influenza A viruses -Amantadine: Parkinson’s disease -Do not impair the response of influenza A vaccine -Amantadine may accumulate to toxic levels in pts with renal failure -Cautious use in pregnant and nursing mothers (embryotoxic and teratogenic) -Cross-resistance occurs between the two drugs Ribavirin -Converted to 5’-phosphate derivative forming ribavirin-triphosphate  Inhibits guanosine triphosphate formation  Prevents viral mRNA capping, blocking RNA-dependent RNA polymerase -Infants and young children: severe RSV infections -Chronic hepatitis C (w/ IFN) -Reduces mortality and viremia of Lassa fever -Guanosine analogs -Contraindicated in pregnancy due Interferon -Interfere with ability of viruses to infect cells -Induce host cell enzymes that inhibit viral RNA translation  Degradation of viral mRNA and tRNA -IFN-α-2b: hepatitis B, C -Condylomata acuminate -Hairy cell leukemia -Kaposi’s sarcoma-IFN-β: MS -Interferes with metabolism of THEOPHYLLINE -Potentiates the bone marrow suppression caused by other agents Lamivudine -Inhibitor of both HBV DNA polymerase and HIV reverse transcriptase -Must be phosphorylated by host cell enzymes to active form (triphosphate) -HBV -HIV -Cytosine analog -Chronic treatment reduces hepatic inflammation -Dose reductions required in moderate renal insufficiency Adefovir dipivoxil -Phosphorylated to adefovir diphosphate  Incorporated into viral DNA  Termination of further DNA synthesis and prevents viral replication -Causes decreased viral load and improved liver function -Nucleotide analog -Cautious use in pts with existing renal disease Entecavir -Intracellular phosphorylation to triphosphate  Competes for viral reverse transcriptase -LAMIVUDINE-resistant HBV -Guanosine analog -Improves liver scarring and inflammation -Drugs that have renal toxicity should be avoided Telbivudine -Phosphorylated intracellularly to triphosphate  Competes with endogenous thymidine triphosphate for incorporation into DNA  Terminates further elongation of DNA -HBV -Thymidine analog -Dose should be adjusted in renal failure -Can be combined with LAMIVUDINE Acyclovir -Monophosphorylated in cell by thby thymidine kinase -Acyclovir triphosphate: competes with deoxyguanosine triphosphate as a substrate for viral DNA polymerase  Incorporates into viral DNA  Premature DNA-chain termination -HSV 1 and 2 -Varicella-Zoster virus -EBV -DOC: HSV encephalitis -Prophylactic to sero+ pts before BM or heart transplant Accumulates in pts with renal failure -Valacyclovir: hydrolyzed to Acyclovir -Resistance occurs due to altered or deficient to thymidine kinase and DNA polymerase -Cross-resistance to other cyclovirs occurs Cidofovir -Inhibits viral DNA synthesis -CMV-induced retinitis in pts w/ AIDS -Nucleotide analog -Eliminates the permanent venous access used for GANCICLOVIR therapy -CI in pts with renal impairment or taking nephrotoxic drugs -PROBENECID can be given to reduce risk of nephrotoxicity Fomivirsen -Directed against CMV mRNA -CMV retinitis -Antisense oligonucleotide -Should be used 2-4 weeks after CIDOFOVIR to reduce toxicity Foscarnet -Reversibly inhibits viral DNA and RNA polymerases  Interferes with viral DNA and RNA synthesis -CMV retinitis in immunocompromised pts -ACYCLOVIR-resistant HSV and Herpes Zoster infections -Phosphonoformate Ganciclovir -Activated through conversion to nucleotide triphosphate  Nucleotide competitively inhibits viral DNA polymerase -CMV retinitis in immunocompromised pts -CMV prophylaxis in transplant pts -Analog of ACYCLOVIR -Accumulates in pts with renal failure-Valganciclovir: rapid hydrolysis in intestine and liver Peniciclovir -Triphosphate inhibits HSV DNA polymerase -Pain and healing are shortened -HSV 1 and 2 -Varicella Zoster -Acyclic guanosine nucleoside Famciclovir -Prodrug metabolized to active PENCICLOVIR -Acute herpes zoster -In animals: increased mammary adenocarcinomas and testicular toxicity Vidarabine (ara-A) -Converted in cells to ara-ATP  Inhibit viral DNA synthesis -Tx of immunocompromised pts with herpetic and vaccinial keratitis -HSV kerato- conjunctivitis -Adenosine analog Trifluridine -Converted to triphosphate  Competitively inhibits incorporation of thymidine triphosphate into viral DNA  Defective DNA -Irreversible inhibitor of viral thymidine HSV 1 and 2 -Vaccina virus -DOC: HSV keratoconjunctivitis and recurrent epithelial keratitis -Fluorinated pyrimidine nucleoside analog NRTIs Zidovudine Stavudine Didanosine Tenofovir Lamivudine Emtricitabine Zalcitabine Abacavir -After entering a cell, they are phosphorylated to corresponding