##Antiviral Drugs


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##Antiviral Drugs

  1. 1. AntiViral Drugs
  2. 2. Therapy Difficulties <ul><li>Viruses depend on the host metabolic machinery for replication so selectivity is a problem. </li></ul><ul><li>Late clinical symptoms </li></ul>
  3. 3. Treatment of Respiratory Virus Infections <ul><li>Influenza Type A , B and RSV </li></ul><ul><li>Immunization is a better approach for type A </li></ul><ul><li>Antiviral drugs are used when </li></ul><ul><ul><li>Allergy 2 the vaccine. </li></ul></ul><ul><ul><li>Outbreak due 2 Immunological variant of the viruse not covered by the vaccine </li></ul></ul><ul><ul><li>Outbreak in an unvaccinated group. </li></ul></ul><ul><li>3 groups of drugs </li></ul><ul><ul><li>Neuraminidase inhibitors. </li></ul></ul><ul><ul><li>Inhibitors of viral uncoating. </li></ul></ul><ul><ul><li>Ribavirin. </li></ul></ul>
  4. 4. Neuroaminidase Inhibitors Oseltamivir Zanamivir <ul><li>Effective against type A,B influenza. </li></ul><ul><li>They do not interfere with vaccination process. </li></ul><ul><li>B4 exposure they prevent infection. </li></ul><ul><li>within 24-48 hours they affect the intensity and duration of symptoms. </li></ul>
  5. 5. Neuroaminidase Inhibitors Mode of Action <ul><li>Neuroaminidase help in the release of the virion from the cell after replication. </li></ul><ul><li>Neuroaminidase inhibitors prevent this process and thus preventing the continuing of the virus life cycle </li></ul><ul><li>Virions accumulate at the internal infected cell surface </li></ul>
  6. 8. Neuroaminidase Inhibitors Pharmacokinetics <ul><li>Oseltamivir </li></ul><ul><li>Orally Active </li></ul><ul><li>Metabolized by the liver </li></ul><ul><li>Eleminated in the urine </li></ul><ul><li>Zanamivir </li></ul><ul><li>Inhaled or intranasally. </li></ul><ul><li>Eliminated in the urine. </li></ul>
  7. 9. Neuroaminidase Inhibitors Adverse Effects <ul><li>Oseltamivir </li></ul><ul><li>GI discomfort </li></ul><ul><li>Nausea </li></ul><ul><li>Zanamivir </li></ul><ul><li>Irritation of the RT. </li></ul><ul><li>Avoided in asthma ,chronic obstructive respiratory diseases. </li></ul>
  8. 10. Inhibitors of Viral Uncoating Amantadine Rimantadine <ul><li>Limited to influenza A viruse. </li></ul><ul><li>70-90% effective in the prevention of the infection if used at the time of exposure of before it. </li></ul><ul><li>They reduce the duration and the severity of the symptoms. </li></ul><ul><li>Doesn’t impair the vaccination process but used as a supplement to provide protection till the antibodies r produced. </li></ul>
  9. 11. Inhibitors of Viral Uncoating Mode of Action <ul><li>Blocking the viral membrane protein M2. </li></ul><ul><li>M2 is important as an ion channel for the fusion of the viral membrane with the cell membrane forming the endosome </li></ul>
  10. 12. Inhibitors of Viral Uncoating Pharmacokinetics <ul><li>Amantadine </li></ul><ul><li>A – well absorbed orally </li></ul><ul><li>D – distributes through out the body and crosses the BBB. </li></ul><ul><li>M – not extensively metabolized. </li></ul><ul><li>E – in the urine. </li></ul><ul><li>Rimantadine. </li></ul><ul><li>A – well absorbed orally. </li></ul><ul><li>D – does not cross the BBB as much as Amantadine. </li></ul><ul><li>M – metabolized by the liver. </li></ul><ul><li>E – in the urine. </li></ul>
  11. 13. Inhibitors of Viral Uncoating Adverse Effects. <ul><li>Amantadine </li></ul><ul><li>Neurological symptoms. </li></ul><ul><ul><li>Insomnia,dizziness. </li></ul></ul><ul><li>Carefully employed in patients with </li></ul><ul><ul><li>psychological diseases , cerebral atherosclerosis , renal impairment ,epilepsy. </li></ul></ul><ul><li>GI intolerance. </li></ul><ul><li>Used with caution in pregnant and nursing patients. </li></ul><ul><li>Rimantadine </li></ul><ul><li>Fewer CNS problems. </li></ul><ul><li>GI intolerance </li></ul><ul><li>Used with caution in pregnant and nursing patients. </li></ul>
  12. 14. Inhibitors of Viral Uncoating Resistance <ul><li>Result from a change in one amino acid of the M2 matrix protein. </li></ul><ul><li>Develop in 50% in treated patients </li></ul><ul><li>Can be tranmitted. </li></ul>
  13. 15. Ribavarine <ul><li>Effective against RNA and DNA viruses. </li></ul><ul><li>Used in the treatment of infants with RSV infections. </li></ul><ul><li>Effective in chronic hepatitis C infections when used with IF-alfa-2b. </li></ul>
  14. 16. Ribavirin Mode of Action <ul><li>The drug is converted into 5’-phosphate derivatives (ribovirin triphosphate) </li></ul><ul><li>RTP inhibit GTP formation and interfearing with mRNA formation. </li></ul>
  15. 17. Ribavirin Pharmacokinetics <ul><li>Effective orally and IV </li></ul><ul><li>A – increased when taken with a fatty meal. </li></ul><ul><li>Aersol is used in certain resp. conditions </li></ul><ul><ul><li>Treatment of RSV infection. </li></ul></ul><ul><li>D – Retention in all tissues except for the brain. </li></ul><ul><li>E – in the urine. </li></ul>
  16. 18. Ribavirin Adverse Effects <ul><li>Anemia </li></ul><ul><li>Elevated Billirubin </li></ul><ul><li>Some teratogenic effects </li></ul>