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87 Cards in this Set
- Front
- Back
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How many inhibitors of nucleic acid synthesis are there?
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10
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What is an acronym for all the inhibitors of nucleic acid synthesis?
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Tend a flower pot garden for fun and rake leaves
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What is Tend A Flower Pot Garden? What virus does each act against?
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-Trifluridine - HSV 1/2
-Acyclovir - HSV/VZV -Famciclovir - HSV/VZV -Penciclovir - HSV -Ganciclovir - CMV |
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What is "For Fun"? What virus does each act against?
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-Foscarnet - CMV/HSV
-Fomivirsen - CMV |
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What is "And Rake Leaves"? What virus does each act against?
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-Adefovir - Hep B
-Ribavirin - RSV/Hep C -Lamivudine - HIV/Hep B |
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What is the mechanism of Trifluridine?
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It acts as a competitive inhibitor of DNA synthesis by acting as a Thymidine analog
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What is the use of Trifluridine?
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Opthalmic treatment of
-Primary keratoconjunctivitis -Recurrent epithelial keratitis |
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What virus that causes these ophthalmic diseases is inhibited by Trifluridine?
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Herpes simplex types 1 and 2
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What are 3 toxic side effects of Trifluridine?
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-Burning
-Stinging -Hypersensitivity |
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What is Trifluridine not useful for?
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Preventing ophthalmic infection
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What is Acyclovir's mechanism of action?
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Inhibits DNA polymerase by acting as a competitive inhibitor of dGTP to terminate DNA chain extension.
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What has to happen to Acyclovir first in order for it to be active?
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Has to be phosphorylated
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What phosphorylates Acyclovir?
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Viral Thymidine Kinase
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How do we know that Acyclovir is predominantly phosphorylated by viral TK instead of host?
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Bc the virus infected cells produce the phosphorylated form of Acyclovir 40-100X faster than host cells.
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What is the product of viral TK phosphorylation of Acyclovir? What happens to it?
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Acycloguanosine Monophosphate - gets converted to the active form Acycloguanosine triphosphate
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How does Acycloguanosine triphosphate terminate DNA elongation?
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It lacks a 3' OH
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What virus is Acyclovir active against?
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HSV and VZV
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Why isn't Acyclovir active against CMV?
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Bc CMV lacks Thymidine Kinase
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What is the major mechanism of resistance by Herpes?
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Mutation of its genes encoding Thymidine Kinase
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What are 4 methods of administering Acyclovir?
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-IV
-Oral -Topical -Other |
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What are the 2 uses for IV administration of Acyclovir?
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-Serious systemic HSV - encephalitis, neonatal.
-Severe initial genital herpes |
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What is the most common method of administering Acyclovir and for what reason?
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-Oral
-For primary genital herpes |
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What is a downside to oral application of Acyclovir?
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It is absorbed poorly and slowly so it takes multiple doses to reach steady state.
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What is the use of Topical application of Acyclovir?
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Treatment of MILD primary genital herpes when applied early
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Which type of application of Acyclovir is effective against recurrent genital herpes?
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Oral - not topical
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What is another use of Acyclovir other than treating HSV?
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Chickenpox in children
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What is the main advantage of Acyclovir?
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It is well tolerated because it is very selective for HSV infected cells that have TK
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What is the main disadvantage of Acyclovir?
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Its poor bioavailability so that it takes many doses to reach effective steady state concentrations.
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What drug has a similar selectivity and mechanism to Acyclovir but better bioavailability?
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Famciclovir
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What is Famciclovir's mechanism?
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-Prodrug
-Converted to Penciclovir -Then phosphorylated by TK to inhibit viral DNA polymerase |
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What are 3 uses of Famciclovir?
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-Acute herpes zoster (shingles) that is localized and <3 days
-Tx/suppress recurrent genital herpes -Tx recurrent herpes cold sores |
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What is the mechanism of Penciclovir?
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Very similar to Acyclovir - phosphorylated by TK, then stops DNA pol chain elongation.
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What is the method of administration of Penciclovir?
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Topical
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What is Penciclovir used for?
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Recurrent herpes of the lips/face
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What are 2 toxic effects of Penciclovir?
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-Skin irritation
-Rash at application site |
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How is Ganciclovir's mechanism different from Acyclovir?
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It is phosphorylated by a protein kinase of CMV instead of the TK of HSV
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What are the 2 main uses of Ganciclovir?
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-CMV retinitis in AIDS patients
-CMV prophylaxis in transplant recipient patients |
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How is Ganciclovir administered and excreted?
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Admin: IV/oral
Elimin: in urine unchanged |
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What are the 2 main side effects of Ganciclovir?
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-Bone marrow suppression
-Liver dysfunction |
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When does Ganciclovir especially cause bone marrow suppression?
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When given along with Zidovudine (AZT)
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What is the mechanism of action of Foscarnet?
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Inhibits CMV DNA pol by binding its Pyrophosphate-binding site to inhibit DNA synthesis
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What is not required for Foscarnet to be active?
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No phosphorylation to the triphosphate form is needed.
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What are the 2 main uses of Foscarnet?
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-CMV retinitis in AIDS patients
-Acylovir resistant HSV |
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Is it safe to give Foscarnet in conjunction with Acyclovir or Ganciclovir?
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Yes
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How is Foscarnet administered? Why?
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IV - it has poor bioavailability
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How is Foscarnet excreted?
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Unchanged in urine
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What is the downfall of Foscarnet?
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It is pretty toxic
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What are the 3 toxic side effects that Foscarnet can have?
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-Renal damage
-Electrolyte imbalances -Seizures |
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What drug enhances the renal damage caused by Foscarnet?
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Amphotericin B
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What drug increases the risk of fatal hypocalcemia caused by Foscarnet?
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Pentamidine
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What is Pentamidine?
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Prophylactic agent against Pneumocystis
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What is another side effect that causes a lot of intolerance to Foscarnet?
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GI upset - n/v, diarrhea
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What used to be a common problem in treating CMV retinitis in AIDS patients?
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Always flipping back and forth to juggle the BM suppression and liver dysfunction caused by Ganciclovir, with Renal damage due to Foscarnet
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What newer drug has helped in treating CMV retinitis in AIDS patients?
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Fomivirsen
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What is the mechanism of Fomivirsen?
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Antisense nucleic acid - it inhibits gene expression and/or replication in CMV
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What is Fomivirsen's main use?
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Treatment of CMV retinitis in patients that don't respond to other drugs
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Why is Fomivirsen only used for patients that fail to respond to other drugs?
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Bc it has to be given by intraocular injection every week
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What are 3 toxic side effects of Fomivirsen?
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-Increased IOP/inflammation
-Blurred vision -Photophobia |
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What is And Rake Leaves and what are the viruses each is used for?
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-Adefovir (Hep B
-Ribavirin (RSV/Hep C) -Lamivudine (HIV/Hep B) |
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What is Adefovir?
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A prodrug dATP analog
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What is Adefovir's mechanism?
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Inhibits Hep B DNA polymerase by competing for dATP incorporation and causes DNA chain termination when incorporated into DNA.
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What is Adefovir used for?
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Treatment of chronic Hep B
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How is Adefovir administered and excreted?
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Admin: oral
Excretion: renal |
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What are 4 side effects of Adefovir?
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-Asthenia
-Headache -Abdominal pain -Nausea |
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What can happen when Adefovir is discontinued?
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It can cause hep B to flare up
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What is Ribavirin, and how is it activated?
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-A nucleoside analog
-Host enzymes phosphorylate it |
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What is the mechanism of monoP Ribavirin?
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Inhibits Inosine-5'-Phosphate dehydrogenase; inhibits GTP synthesis
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What is the mechanism of triP Ribavirin?
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Inhibits GTP-dependent capping of viral mRNA
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What are 2 methods of administering Ribavirin, and for what patients?
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-Aerosol - for infants/young children with documented severe lower resp RSV infections
-Oral for Hep C patients |
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How is Ribavirin metabolized and eliminated?
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Metabolized: in liver
Eliminated: in both metabolized and unmetabolized forms in urine |
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What are 3 toxic effects that can be seen with aerosol use of Ribavirin?
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-Clog equipment - suffocation
-Deterioration of lung function -Rash |
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What is the main toxic effect that can be seen with Oral administration of Ribavirin in Hep C patients?
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Bone marrow suppression/anemia
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What is the L in And Rake LEaves?
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Lamivudine
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What is Lamivudine's mechanism of action?
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IT is a nucleoside analog inhibitor of the RT domain of the hep B DNA polymerase
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What is required for Lamivudine's activity?
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Phosphorylation by cell enzymes
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What is Lamivudine used for?
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Treating hep B
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How is Lamivudine administered and excreted?
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Administered: orally
Excreted: unchanged in urine |
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What kind of toxic side effects does Lamivudine have?
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Not severe - its very well tolerated!!
But may cause nausea/diarrhea |
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What is the "miscellaneous" antiviral?
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Interferon
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What is required for Interferon to be effective?
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The host has to have endogenous production of interferon in the first place
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What is the general action of Interferon like?
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Nonspecific against viral activities
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What does Interferon induce host cells to do?
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Produce enzymes that block viral mRNA translation
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For what type of interferon has recombinant antiviral use been approved?
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Interferon-alpha
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What are 3 diseases that Inf-a is used in treating?
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-Condyloma acuminata (HPV warts)
-Hep B -Hep C |
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Where does Interferon-a fall in terms of treating Condyloma acuminata?
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2nd to phys/chem disruption of warts
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What is a specific way that IFN-a is used for treating Hep C?
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-PEG-alfa-2a or 2b IFNs, in combo with RIBAVIRIN
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What are 3 toxic side effects of Interferon?
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-Flu-like syndrome
-Suppresses BM, leukopenia -Neurotoxicity/myalgia |
