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38 Cards in this Set

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define therapeutic index.
ratio of treatment efficacy totoxicity
potential targets for antivirals?
adsorption and penetration, uncoating, DNA synth, RNA synth, integration, viral morphogenesis(assembly) and release
differntiate bw the conventional and rational approach to new drug development.
conventional is mass screening procedures to test thousands of compounds for useful whereas the rational approach is due to knowledge of proteins, viruses, and malfunctioning structure via Xray crystalography and NMR it has been possible to design potential drugs on computers, these drugs can be synthesized and then tested.
describe docosanol (abreva)
alcohol that inhibits virus entry into cells, topical cream for herpes, no Rx, shortens healing by one day
describe the drug fuzeon (enfuvirtide)
designed by rational approach, peptide, SQ injection, blocks fusion bw viral envelop and plasma membrane. Combine with other ant HIV drugs, can cause severe allergic rxn, increased frequency of bacterial pneumonia
describe amantadine and rimantadine.
amantadine has bad side effects like nauseas, anorexia, anxiety, loss of concentration, rimantadine may be more effective, with less side effects. Flu is resistant to this recently, except one strand that is not seen now, so CDC says do not give it for now. block M2 channel and prevent uncoating, not effective against influenza type B
the DNA synthesis inhibitor drugs are all what? How do they discriminate between viral and host cell DNA synth?
they are base analogs that can be incorporated into growing SNA strand, discrimination occurs via pi-ing of the drug by a viral not cellular kinase enzyme, or incorporation of pi-ed drug into viral DNA only by a pol enzyme
describe idoxuridine and trifluridine.
both DNA analogs use to treat herpes keratoconjunctivivtis, too toxic for systemic use bc pi-ed by cellular enzymes as well
describe acyclovir (zorivax).
a DNA analog that is poorly pi-ed by cellular kinases, relatively non toxic, treats herpes simplex, herpes varicella, and EBV by inhibiting replication, pi-ed by viral thymidine kinase to mono pi, then cellular kinases make it tri-pi, competes with guanosine, lacks a OH group at 3' thus it is a chain terminator, topical (modest benefit), oral (good effect against primary episodes but little effect in recurrent infections, but long term prophylatic administration -oral- prevents recurrences), IV. no effect on oral HSV1. good in chicken pox in immunosuppressed, oral hairy leukoplakia from EBV, generic oral formulas available, IV for serious issues like immunosuppressed, resistant HSV infections developing in AIDS - mutant strand with decreased thymidine kinase activity, low bioavailability and fast clearence therefore large doses, valacyclovir and famciclovir are replacing oral acyclovir bc of greater bioavailability, but are not good when IV is needed.
Describe valacyclovir (valtrex)
DNA analog similar to acyclovir for herepes treatment, higher bioavailability, turns into acyclovir in liver, can be used for cold sores too and herpes vozter lesions
describe famciclovir (famvir)
DNA analog similar to acyclovir for herpes treatment, greater oral availability, converted to penciclovir in the liver, same mechanism as acyclovir, good prophylaxis for genital herp, treats zoster, chicken pox
describe denavir.
penciclovir cream for topical treatment of cold sores, does not need to be absorbed from the gut
describe ganciclovir.
DNA analog against herpes and zoster, more toxic than acyxlovir thus not used for previous two viruses. Used for HCMV (cytamegalovirus) due to pi-ing by an HCMV kinase, used in HCMV retinitis and pneumonia, too toxic for less serious conditions, not a chain terminator, slows down elongation, treat retinitis with IV then prophlax with iv or oral (low bioavailability), side effects are neutropenia and thrombocytopenia (less platelets and neutros), neutropenia can be reversed via GCSF (neupogen), less serious side effects are rash, anemia, nausea, vomiting, dizziness, headaches, no preggers should take it, AZT is discontinued during high dose gangciclovir therapy
describe valganciclovir (valcyte)
valine ester of ganciclovir, increase bioavailability, treats retinitis in AIDS, prevents HCMV in kidney/heart transplants, NOT in liver transplant patients, side effects are similar to ganciclovir
describe cidofovir (vistide)
nucleotide analog (mono pi analog)thus no pi-ing by viral kinase, cellular kinases make it tri. IV, can cause kidney damage so give with probenecid and saline. Treats HCMV
describe foscarnet (foscavir)
pyrophosphate analog that binds to a binding site on viral DNA pol, used against HSV, VZV, and HCMV. Also effects hep B and HIV. IV route, side effects are hypocalcemia and kidney damage, less sever ones are fever, nausea, anemia, diarrhea. distinguishing bw which drugs to use for HCMV retinitis depends on what toxicities the patient wants, can treat acyclovir resistant HSV mutants but resistance to foscarnet has been seen
most hiv side effects include?
nausea, vomiting, diarrhea, myositis, rash, headaches, asthenia and redistribution of fat
describe zidovudine (AZT)
nucleoside analog for HIV that is pi-ed by cellular kinases then RT will use it, has no 3' OH and is a chain terminator, side effects are macrocytic anemia (big RBC's), granulocytopenia, and liver function abnormalities
describe didanosine (videx) and zalcitabine (hivid)
nucleoside analogs for HIV, must be pi-ed by cellular kinases, chainterminators (lackboth OH's), pancreatitis, peripheral neuropathy (painful)
describe stavudine (zerit)
nucleoside analog for HIV, peripheral neuropathy
describe lamivudine (epivir)
HIV treatment, nucleoside analog, pancreatitis also can be used for Hep B but use is declining due to resistance
describe emtriva (emtricitabine)
HIV treatment, nucleoside analog.
describe tenofovir
nucleotide analog used for HIV, damages liver, kidneys, pancreas
describe the HIV nucleoside/nucleotide analog combination drugs.
combivir (lamivudine and zidovudine), epzicom (lamivudine and abacavir), trizivir (lamivudine, zidovudine, and abacavir), truvada (emtricitabine and tenofovir)
describe atrpla.
combo of two nucleoside/nucleotide analogs (emtricitabine and tenofovir) and an NNRTI (efavirenz) lactic acidosis, liver damage
describe delaviridine (rescriptor).
NNRTI for HIV
describe efavirenz (sustiva)
NNRTI for HIV, not for pregnant women
describe nevirapine (viramune)
NNRTI for HIV
describe the two aproaches to treating hep B
use interferon alpha or modified, longer acting pegylated interferon alpha via a SQ injection, can cause fever, muscle ache, fatigue, depression and irritability. Rare psychosis, renal or cardiac failure. Other approach is nucleoside/tide analogs that target the RT/DNA pol but can cause liver disease if pt. stops taking them
describe entecavir (baraclude)
nucleoside analog for Hep B
describe adefovir (hepsera)
less expensive nucleoside analog for hep B
describe ribavirin
broad spectrum antiviral that inhibits IMP dehydrogenase reducing intracellular GTP and inhibiting RNA synth, use against respiratory syncytial virus (RSV) in complicated kids (aerosol), hep C (oral) in combo with pegylated IFN alpha (PEG intron plus rebetol or pegasys plus copegus), and lassa fever (oral or IV).
how do the HIV anti protease drugs work?
HIV protease is an aspartyl protease that has different speceficity than any mammalian protease, used rational design to predict which non peptide compounds would fit into enzymes active site and inhibit it. Side effects include normal anti HIV drug side effects and hyperglycemia or hyperlipidemia (got to monitor these blood levels)
describe ritonavir (norvir)
HIV protease inhibitor, given in combo with other anti proteases, supresses break down via lliver of many other drugs, take it with ex and you die, but this side effect boosts blood levels of other co admnistered inhibitors which is a good thing.
describe kaletra
ritonavir plus lopinavir, combo HIV protease inhibitor, but can casuse pancreatitis
describe indinavir (crixivan)
HIV protease inhibitor, can cause nephrolithiasis, need to drink lots of liquids with each dose
describe atazanavir (reyataz)
HIV protease inhibitor, less likely to cause increased lipid levels, do not use with drugs for acid reflux
how do the two drugs against influenza A and B work? Side effects, names?
inhibit NA enzyme causing binding and sticking to sialic acid on cell surface, aggregation to other virus particles, and possibly bind to the components of mucus in the respiratory tract and never reach the host cells. Zanamivir (relenza) is inhaled, given wi 36 hrs of onset, can cause bronchospasm, and is a treatment and prophylatic agent. oseltamvir (tamiflu) is oral rout, converted in liver to active for thus higher bioavailability, give wi 36 hrs of symptom onset, mild GI effects, prophylactic and treatment