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Antiviral
 

Antiviral

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    Antiviral Antiviral Presentation Transcript

    • Antiviral Medications
    • Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which actively destroy virus particles outside the body. Most of the antivirals now available are designed to help deal with HIV, herpes viruses (best known for causing cold sores and genital herpes, but actually causing a wide range of diseases), the hepatitis B and C viruses, which can cause liver cancer, and influenza A and B viruses. Researchers are now working to extend the range of antivirals to other families of pathogens. Designing safe and effective antiviral drugs is difficult, because viruses use the host's cells to replicate. This makes it difficult to find targets for the drug that would interfere with the virus without harming the host organism's cells.
    • Agents for Influenza A and Respiratory viruses
      • Influenza A and other respiratory viruses, including influenza B and respiratory syncytial virus (RSV), invade the respiratory tract and cause the signs and symptoms of respiratory “flu.” there are many agents used to combat such threats. A few are listed as follows:
      • Amantadine
      • Oseltamivir
      • Ribavirin
      • Rimantadine
      • Zanamivir
      Agents
    • Pharmacodynamics Although the exact mechanism of action of drugs that combat respiratory viruses is not known, it is believed that these agents prevent shedding of the viral protein coat and entry of the virus into the cell. This action prevents viral replication, causing viral death. These antiviral drugs are indicated for prevention of influenza A infection, which is especially important in health care workers and other high-risk individuals, and for reducing the severity of infection if it occurs.
    • Pharmacokinetics Amantadine is well absorbed orally and maximum drug concentrations (Cmax) are directly dose-related for doses of up to 200 mg/day. Doses above 200 mg/day may result in disproportional increases in Cmax. In healthy volunteers, peak concentration were reached after 3 hours and the half-life was 17 hours (range: 10 to 25 hours). Amantadine is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. In individuals older than 60 years, the plasma clearance of amantadine is reduced and the plasma half-life and plasma concentrations are increased. The clearance is also reduced in patients with renal insufficiency: the elimination half-life increases two to three fold or greater when creatinine clearance is less than 40 ml/min and averages eight days in patients on chronic haemodialysis. Amantadine is not removed by haemodialysis. As the excretion rate of amantadine increases rapidly when the urine is acidic, the administration of urine acidifying drugs may increase the elimination of the drug from the body.
    • Use of these antiviral agents is frequently associated with various adverse effects that may be related to possible effects on dopamine levels in the brain. These adverse effects include light-headedness, dizziness, and insomnia; nausea; orthostatic hypotension; and urinary retention. Another possible side-effect of amantadine is livedo reticularis, the dermatological reaction that results in skin mottling and purpurish mesh network of blood vessels. Organs Affected
    • Agents for Herpes and Cytomegalovirus
    • Agents
      • Herpes viruses account for a broad range of conditions, including cold sores, encephalitis, shingles, and genital infections. Cytomegalovirus (CMV), although slightly different from the herpes virus, can affect the eye, respiratory tract, and liver and reacts to may of the same drugs. A number of antiviral drugs are used to combat these infections.
      • Acyclovir (Zovirax) is specific for herpes virus infections. It is excreted unchanged in the urine and therefore must be used cautiously in the presence of urine and therefore must be used cautiously in the presence of renal impairment. Acyclovir crosses into breast milk and exposes the neonate to high levels of the drug, so extreme caution must be used during lactation.
      • Others to be noted are:
      • Cidofovir
      • Famciclovir
      • Foscarnet
      • Ganciclovir
      • Valacyclovir
      • Valganciclovir
    • Drugs that combat herpes and CMV inhibit viral DNA replication by competing with viral substrates to form shorter, noneffective DNA chains. This action prevents application of the virus, but it has little effect on the host cells of humans because their DNA uses different substrates. These antiviral agents are indicated for treatment of the DNA viruses herpes simplex, herpes zoster, and CMV. Research has shown that they are very effective in immuno-compromised individuals, such as patients with AIDS, those taking immunosuppressant, and those with multiple infections.
    • Pharmacokinetics Of the agents used in the treatment of herpes and CMV, Cidofovir (Vistide) has proved embryotoxic in animals. For many of the other agents, no adequate studies have been completed during human pregnancy and lactation, but because of the toxicities of all of these drugs, they should be used during pregnancy and lactation only if the benefits clearly outweigh the potential risks to the fetus or neonate.
    • The adverse effects most commonly associated with these antiviral include nausea and vomiting, headache, depression, rash, and hair loss. Rash, inflammation, and burning often occur at sites of IV injection and topical application. Renal dysfunction and renal failure also have been reported. Organs Affected
    • Agents for HIV and AIDS
    • Agents Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that can lead to acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Previous names for the virus include human T-lymphotropic virus-III (HTLV-III), lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV). HIV primarily infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: firstly, direct viral killing of infected cells; secondly, increased rates of apoptosis in infected cells; and thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections.
    • Reverse Transcriptase Inhibitors
      • The reverse transcriptase inhibitors bind directly to HIV reverse transcriptase, blocking both RNA- and DNA- dependent DNA polymerase activities. They prevent the transfer of information that would allow the virus to replicate and survive.
      • These are some of its samples:
      • Delavirdine
      • Efavirenz
      • Emtricitabine
      • Nevirapin
      Pharmacokinetics There are no adequate studies about reverse transcriptase inhibitors in pregnancy, so use should be limited to situations in which benefits clearly outweigh any risks. It is suggested that women not breastfeed if they are infected with HIV.
    • Protease Inhibitors
      • The protease inhibitors block protease activity within the HIV virus. Protease is essential for the maturation of the infectious virus; without it, an HIV particle is immature and noninfective.
      • The protease inhibitors that are available for use include the following:
      • Amprenavir
      • Atazanivir
      • Fosamprenavir
      • Indinavir
      • Lopinavir
      • Tipranivir
      • Nelfinavir
      • Ritonavir
      • saquinavir
      Of the protease inhibitors listed, saquinavir is the only agent that has not been shown to be teratogenic; however, as mentioned, its use during pregnancy should be limited. Saquinavir crosses into breast milk and women are advised not to breast-feed while taking this drug. For the other agents listed, there are no adequate studies in pregnancy, so use should be limited to situations in which benefits clearly outweigh any risks. It is suggested that women not breastfeed if they are infected with HIV. Pharmacokinetics
    • Nucleosides
      • Nucleosides interfere with HIV replication by inhibiting cell protein synthesis, leading to viral death.
      • Examples of these are:
      • Didanosine
      • Lamivudine
      • Stavudine
      • Tenofovir
      • Zalcitavine
      • Zidovudine
      Of the protease inhibitors listed, zidovudine is the only agent that has been proven to be safe when used during pregnancy. For the other agents listed, there are no adequate studies in pregnancy, so use should be limited to situations in which benefits clearly outweigh any risks. It is suggested that women not breastfeed if they are infected with HIV. Pharmacokinetics
    • Fusion Inhibitors Entry inhibitors, also known as fusion inhibitors, are a class of antiretroviral drugs, used in combination therapy for the treatment of HIV infection. This class of drugs interferes with the binding, fusion and entry of an HIV virion to a human cell. By blocking this step in HIV's replication cycle, such agents slow the progression from HIV infection to AIDS. The drug Enfuvirtide works by disrupting the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected. A biomimetic peptide, enfuvirtide was rationally designed to mimic components of the HIV-1 fusion machinery and displace them, preventing normal fusion. Drugs that disrupt fusion of virus and target cell are termed entry inhibitors or fusion inhibitors.
    • Pharmacodynamics The viral agents used to treat HIV and AIDS operates at various points in the life cycle of the virus and results in its death or inactivation. Use of these drugs in in combination can affect more viral particles and reduce the number of mutant viruses that are formed and spread into the non-infected cells. These antiviral agents are indicated for the treatment of patients with documented AIDS orARC who have decreasd numbers of T-cells and evidence of increased opportunistic infections
    • Agents for Hepatitis B
    • Hepatitis B virus infects the liver of hominoidae, including humans, and causes an inflammation called hepatitis. It is a DNA virus and one of many unrelated viruses that cause viral hepatitis. Adefovir and entecavir are indicated for the treatment of adults and chronic hepatitis B who have evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases or histologically active disease. Both drugs decrease the viral load of hepatitis B by preventing viral replication through the blocking of reverse transcriptase. Pharmacodynamics
    • Pharmacokinetics These drugs are rapidly absorbed from the GI tract with peak effects occurring in 0.5 to 1.5 (entecavir) and 0.5 to 4 hours (adefovir). They are metabolized in the liver and excreted in the urine. The half-life of adefovir is 7.5 hours; entecavir has a half-line of 128 to 149 hours. It is not known if either of these drugs crosses the placenta or enters breast milk.
    • The adverse effects most frequently seen with these drugs are headache, dizziness, nausea, diarrhea, and elevated liver enzymes. Severe hepatomegaly with steatosis, sometimes fatal, has been reported with adefovir use. Lactic acidosis and renal impairment have been reported with both drugs. There is a risk that hepatitis B exacerbation could occur when the drugs are stopped. Organs Affected
    • Locally Active Antiviral Agents
      • Some antiviral agents are given locally to treat local viral infections.
      • These agents include the following:
      • Idoxuridine
      • Imiquimod
      • Fomivirsen
      • Docosanol
      • Ganciclovir
      • Penciclovir
      • Trifluridine
      • Vidarabine
      • These antiviral agents act on viruses by interfering with normal viral replication and metabolic processes. They are indicated for specific, local viral infections.
      Pharmacodynamics
    • Locally active antiviral drugs are not absorbed systemically, but caution should be used in patients with known allergic reactions to any topical drugs. Because these drugs are not absorbed systemically, the adverse effects most commonly reposted are local burning, stinging, and discomfort. These effects usually occur at the time of administration and pass with time. Notes: