Term
| When a virus comes into contact with a host cell, it can insert its |
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Definition
| genetic material, taking over host's functions |
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Term
| An infected cell produces more viral |
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Definition
protein n genetic material
instead of normal products |
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Term
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Definition
| Some viruses may remain dormant inside host cells for long periods, causing no obvious change in their host cells |
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Term
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Definition
a dormant virus is stimulated,
: new viruses are formed, self-assembled, and burst out of the host cell, killing the cell and going on to infect other cells. |
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Term
| The Baltimore classification |
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Definition
| based on genetic contents and replication strategies of viruses. |
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Term
| virus carry genetic material as |
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Definition
double stranded DNA
RNA
single stranded DNA |
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Term
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Definition
binding
engulfment
transport
fusion
delivery of viral RNA/DNA into nucleus
synthesis of viral proteins
Assembly n budding |
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Term
| 2nd cause of human viraL DISEASE |
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Definition
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Term
| # of herpes virus types to infect humans |
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Definition
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Term
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Definition
core
capsid
tegument
envelope |
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Term
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Definition
| single linear molecule of dsDNA |
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Term
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Definition
| It consists of viral enzymes, some of which are needed to take control of the cell's chemical processes and subvert them to virion production, some of which defend against the host cell's immediate responses |
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Term
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Definition
| the outer layer of the virion and is composed of altered host membrane and a dozen unique viral glycoproteins. |
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Term
chemotherapy of antivirals
the first active agents were |
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Definition
| LOW specificity for inhibiting viral vs host DNA synthesis |
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Term
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Definition
| Acyclic guanosine derivative |
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Term
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Definition
Requires 3 phosphorylation steps for activation to the monophosphate by virus specific thymidine kinase
Then converted to the di- and tri-phosphates by host kinases in the infected cell |
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Term
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Definition
Competes with deoxy GTP for viral DNA polymerase resulting in incorproation into viral DNA.
Acts as a chain terminator |
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Term
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Definition
| activity against HSV-1 = HSV-2 >(10x) VZV |
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Term
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Definition
topical-herpetic lesions, but no detectable systemic activity.
oral-varicella and cutaneous zoster if begun 24 or 72 hr respectively after the onset of rash.
Effective against genital herpes; shortens duration and healing time.
iv-Treatment of choice for herpes encephalitis, neonatal HSV infections and serious HSV and VZV infections |
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Term
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Definition
-Bioavailability from oral formulations < 20%, but is unaffected by food.
-Diffused readily into most tissues and fluids
-[CSF] half that of serum.
-Half life 2-3 hr in normal patients, up to 20 hr in patients with kidney disorders.
-Cleared by glomerular filtration and tubular secretion |
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Term
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Definition
-Occurs via alteration on either the viral thymidine kinase or viral DNA polymerase enzymes.
-Cross resistance to analogs working through the same mechanism can occur |
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Term
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Definition
-Generally well tolerated but adverse effects can include N, D, HA.
-Following IV dosing can experience some reversible renal or neurological toxicity.
-Concurrent therapy with other nephrotoxic agents can enhance the potential for nephrotoxicity. |
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Term
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Definition
-The L-valyl ester “prodrug” of acyclovir.
-Rapidly converted to acyclovir following oral administration via first-pass enzymatic hydrolysis in the liver and intestines resulting in blood levels equivalent to IV dosing |
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Term
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Definition
Used to treat recurrent genital herpes and suppression of frequently recurring genital herpes (which markedly decreases the risk of transmission), also used as a 1-day treatment for orolabial herpes and as a treatment for herpes zoster.
-shown to be effective against CMV after organ transplant |
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Term
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Definition
acyclovir analogs with he following properties
Similar mechanism of action as acyclovir except penciclovir cannot cause chain termination.
It has lower affinity for viral DNA polymerase but it does achieve higher intracellular concentrations so the effect is the same.
-uses similar to acyclovir |
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Term
| Penciclovir/Famciclovir resistance crosses over to |
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Definition
acyclovir
(thymidine kinase deficiency) |
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Term
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Definition
A 22-carbon saturated aliphatic alcohol that acts as a viral fusion/entry inhibitor.
Available as a 10 % AI topical cream without a prescription (Abreva). |
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Term
| Trifuridine (Triflurothymidine) |
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Definition
inhibits viral DNA synthesis in HSV-1, HSV-2, CMV, vaccina and some adenoviruses.
It is phosphorylated by intracellular host enzymes, and then competes with thymidine triphosphate at the viral DNA polymerase active site for incorporation into viral DNA.
However it also can be incorporated into host DNA preventing its systemic use, therefore it is only used topically. |
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Term
| Trifuridine (Triflurothymidine) uses |
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Definition
| Keratoconjunctivitis and recurrent epithelial keratitis from HSV 1 and 2. |
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Term
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Definition
RNA genome
capsid
lipid envelope |
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Term
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Definition
-Orally bioavailable cytosine analog
-Absorption from gut decreased in presence of food and/or antacids
-Phenotypic resistance is rare. |
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Term
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Definition
-Azidothymidine, AZT is an azido analog of deoxythymidine.
-Again, relatively short T1/2 in serum and intracellularly.
-Eliminated by glucuronidation followed by renal excretion.
-Co-administered with lamivudine.
-Resistance is generally seen is strains with three or more mutations in the RT genes.
-Most common adverse effect is myelosuppression. |
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Term
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Definition
-Orally bioavailable cytosine analog
-Absorption from gut decreased in presence of food and/or antacids
-Phenotypic resistance is rare. |
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Term
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Definition
-Azidothymidine, AZT is an azido analog of deoxythymidine.
-Again, relatively short T1/2 in serum and intracellularly.
-Eliminated by glucuronidation followed by renal excretion.
-Co-administered with lamivudine.
-Resistance is generally seen is strains with three or more mutations in the RT genes.
-Most common adverse effect is myelosuppression. |
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Term
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Definition
-Anti-HIV thymidine analog
-Major toxicity is dose related peripheral neuropathy. But symptoms revolve upon withdrawal.
-Other adverse effects include include pancreatitis and arthralgias, lactic acidosis with hepatic steatosis. |
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Term
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Definition
-An acyclic nucleoside phosphonate analog of adenosine.
-Two rather than three phosphorylations are require for activity.
-Also given as the prodrug, tenofovir disopoxilfumarate to enhance solubility
-Resistance is via mutation of the K65R gene (HIV-1 reverse transcriptase).
-Adverse effects. Many |
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Term
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Definition
-nrti
-Analog of deoxyadenosine
-can be inactivated by stomach acid so buffered formulations are necessary.
-Major adverse effect is dose dependent pancreatitis
-Can interfere with the absorption of other antivirals and antibiotics. |
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Term
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Definition
-nrti
-Orally bioavailable fluorinated analog of lamivudine with an extended serum (10h) intracellular (24h) half life.
-Low penetration into CSF.
-Kidney elimination.
-Resistance occurs frequently via mutation in HIV-RT gene M184V/I.
-Adverse effects are minor |
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Term
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Definition
-nrti
-Anti-HIV Guanosine (purine) analog
-Well absorbed orally.
-Metabolized by hepatic glucuronidation and carboxylation.
-[CSF] = 1/3 [serum].
-Resistance develops slowly.
-Hypersensitivity reactions to Abacavir in 3-5% of patients that may be fatal. |
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Term
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Definition
-orally bioavailable anti-HIV agent based on the pyrimidine cytosine.
-Used synergistic with a variety of antiretroviral nucleosides such as abacavir and zidovudine. |
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Term
| Nucleoside/nucleotide reverse transcriptase inhibitors (NRTI’s) chemistry |
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Definition
| Analogs of endogenous 2′-deoxy-nucleosides and nucleotides |
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Term
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Definition
-Requires intracellular phosphorylation to the triphosphate to be active.
-competitively inhibiting viral reverse transcriptase.
-Incorporate into newly synthesized vDNA leading to premature chain termination |
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Term
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Definition
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Term
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Definition
| Mutations in RT genes (single aa substitution) results in decreased affinity |
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Term
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Definition
-inhibition of mitochondrial DNA polymerase
-Some degree of non-specific toxicity
Lactic acidosis
Hepatic steatosis (fatty liver)
Dyslipidemia (high lipids)
Insulin resistance
Myocardial infarct |
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Term
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Definition
RNA genome
capsid
lipid envelope
reverse transcriptase |
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Term
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Definition
| polypeptide chains including receptor binding proteins |
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Term
| retrovirus particles also contain the enzyme reverse transcriptase (or RTase), which catalyzes |
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Definition
| the synthesis of a complementary DNA molecule (cDNA) using virus RNA as a template. |
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Term
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Definition
Dose dependent proximal tubular nephrotoxicity
-Proteinuria.
-Azotemia (a medical condition characterized by abnormally high levels of nitrogen-containing compounds, such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood. It is largely related to insufficient filtering of blood by the kidney
-Mutagenic, carcinogenic, gonadotoxic and embryotoxic |
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Term
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Definition
-cmv infection
-IV Cidofovir’s half life is 3h, but its active metabolites half life is 15-70h allowing for infrequent dosing
-Cidofovir phosphocholine that acts as a reservoir of active drug.
-Poor CSF penetration.
-Elimination is via active renal tubular secretion. |
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Term
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Definition
-mutations in the viral DNA polymerase gene
-Cidofovir is unaffected by mutations in CMV phosphotransferase which confer resistance to ganciclovir |
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Term
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Definition
-treat cmv infection
-An acyclic nucleoside phosphonate, that is not dependent on activation by a virus-encoded enzyme for activity |
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Term
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Definition
| Cidofovir diphosphate acts as both a potent inhibitor and an alternative substrate for vDNA polymerase, competitively inhibiting vDNA synthesis and becoming incorporated into the vDNA chain. |
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Term
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Definition
-to point mutations in viral DNA polymerase gene associated with prolonged use of the drug.
-in HIV with mutations in reverse transcriptase gene
-Some cross resistance with ganciclovir and related compounds |
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Term
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Definition
-Renal impairment
-Hypo/hyper calcemia, phosphatemia, kalemia and magnesemia
-Possible genotoxicity |
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Term
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Definition
-treat cmv infections
-Functions by blocking the pyrophosphate binding site of these enzymes inhibiting the cleavage of pyrophosphate from deoxyribonucleotide triphosphates.
-It is effective against both DNA and RNA viruses |
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Term
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Definition
treat cmv infection
-Phosphonoformic acid, an inorganic pyrophosphate analog that directly inhibits viral DNA polymerase, RNA polymerase and reverse transcriptase |
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