Term
| What are the Nucleoside Analogs? |
|
Definition
Acyclovir
Valcyclovir
Famciclovir
Ganciclovir
Cidofovir
Foscarnet |
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|
Term
| How do the Nucleoside Analogs Block DNA synthesis? |
|
Definition
Inactivation of viral DNA polymerase through direct binding and competition for dNTPs
Inducing viral DNA chain termination |
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Term
| How can resistance develop to the Nucleoside analogues? |
|
Definition
Mutated viral DNA polymerase
Absence of viral TK
(also decreases effectiveness of virus)
Altered viral TK substrate specificity |
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Term
| How are Nucleoside analogues selective for virus infected cells? |
|
Definition
The virus activates the drug to a toxic form
Uninfected cell does not
Preferential affinity of acyclovir triphosphate for viral DNA polymerase rather than cellular |
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Term
| How is Valacyclovir converted to Acyclovir? What is the advantage of this? |
|
Definition
Hydrolyzed by hepatic metabolism after oral administration
Increased Bioavailability
Reaches plasma levels 3-5 x greater than acyclovir |
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|
Term
| What are Acyclovir/Valacyclovir Indicated for? |
|
Definition
Herpes simplex keratitis
Latent HSV
Fever Blisters (H. labialis)
Genital herpes
HSV encephalitis
VZV
CMV-positive bone marrow transplant recipients |
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|
Term
| What adverse effects can occur following high IV doses of Acyclovir? |
|
Definition
Reversible renal dysfunction
Neurologic toxicity |
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|
Term
| What Acyclic Purine Nucleoside Analogues are indicated for CMV retinitis in AIDS patients? |
|
Definition
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|
Term
| What is the most common side effect of Ganciclovir? |
|
Definition
|
|
Term
| What antiherpesvirus agent can achieve higher intracellular levels and effect then acyclovir and is an oral alternative to acyclovir? |
|
Definition
|
|
Term
| What is Famciclovir indicated for? |
|
Definition
Oral alternative to acyclovir
(HSV, VZV, EBV, HBV)
Effective against HBV following liver transplant |
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|
Term
| What antiviral is an acyclic guanine analog? |
|
Definition
|
|
Term
| What Antiherpesvirus Agent is a Cytidine nucleotide analog? |
|
Definition
|
|
Term
| What form of Cidofovir is the active form? |
|
Definition
the Diphosphate form
It is Not phosphorylated by viral TK |
|
|
Term
| What is Cidofovir indicated for? |
|
Definition
| Acyclovir resistant HSV and VZV strains |
|
|
Term
| What is IV Cidofovir used for? |
|
Definition
| delay progression of CMV in HIV+ patients |
|
|
Term
| What is the major Adverse Effect of Cidofovir? How can this be avoided? |
|
Definition
Nephrotoxicity
Must administer with probenecid and IV saline pre-hydration |
|
|
Term
| What is a Non-nucleoside Anti-HSV Agent? |
|
Definition
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|
Term
| What is Foscarnet an analog of? |
|
Definition
| Inorganic pyrophosphate analog |
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|
Term
| What is the Mechanism of Foscarnet? |
|
Definition
Inhibits HSV DNA polymerase and HIV-1 RT
Binds to pyrophosphate binding site of polymerase
Inhibits cleavage of pyrophosphate from dNTP
Blocks viral DNA synthesis |
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|
Term
| What drug can be used for Nucleoside-resistant HSV, VZV, and CMV infections? |
|
Definition
Foscarnet
Effective in CMV retinitis
Effective against HIV by inhibiting RT |
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|
Term
| What adverse effects can Foscarnet cause? How can these be avoided? |
|
Definition
Renal failure or dysfunction
Titrate Dose to Creatinine Clearance |
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|
Term
| Which Antiherpesvirus agent has a Plasma T1/2 greater than the intracellular T1/2? |
|
Definition
|
|
Term
| How are all of the Antiherpesvirus agents Excreted mostly? (Acyclovir, Famciclovir, Ganciclovir, Cidofovir, Foscarnet) |
|
Definition
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|
Term
| What are the Anti-Hepatitis Agents? |
|
Definition
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|
Term
| What anti-hepatitis agent is a Nucleoside analog of guanosine? |
|
Definition
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Term
| What is the mechanism of Ribavirin? (Guanosine analog) |
|
Definition
Interference with synthesis of GTP
Competitively inhibits GTP 5' capping of viral mRNA |
|
|
Term
| How is Ribavirin's bioavailabilty increased? Where does it concentrate? |
|
Definition
Oral Bioavailability increased with fatty meals
Ribavirin triphosphate concentrates in RBC |
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|
Term
| What adverse effect developes in 10-20% of people taking Ribavirin? |
|
Definition
Dose dependent hemolytic anemia with systemic use
Extravascular hemolysis
Bone morrow suppression |
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|
Term
| What form of Ribavirin is well tolerated but can cause possible conjunctival irritation? |
|
Definition
Aerosolized Form
(Reversible deterioration in pulmonary function) |
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|
Term
| What are the Antiinfluenza Agents used? |
|
Definition
Uncoating inhibitors:
Amantadine
Virus release Inhibitors:
Zanamivir |
|
|
Term
| How do the Uncoating Inhibitors work? (Amantadine) |
|
Definition
Act on Maturation of influenza HA glycoprotein
Binds ion channel formed by M2 transmembrane protein in envelope of virus --> Inhibits H+ ion transport that acidifies the interior of the virion |
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Term
| How do the Virus relase inhibitors work? (Zanamivir) |
|
Definition
Inhibits flu Neuraminidase
Which cleaves terminal sialic acid residues, destroying the receptors recognized by viral HA present on cell surface, which is essential for release of virus from infected cell
**Inhibits neuraminidase activity promoting viral aggregation and reducing viral spread** |
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|
Term
| What are the uncoating inhibitors indicated for? (Amantadine) |
|
Definition
Oral prophylaxis against Influenza A
Good alternative to vaccine in immunocompromised patients and the elderly |
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Term
| How can resistance develop to the uncoating inhibitors? (Amantadine) |
|
Definition
| Single amino acid substitution at the level of the transmembrane region of M2 |
|
|
Term
| What Antiinfluenza agents are effective against both influenza A and B? |
|
Definition
Virus release inhibitors:
Zanamivir |
|
|
Term
| Where can resistance develop to the virus release inhibitors? (Zanamivir) |
|
Definition
| HA or neuraminidase mutations |
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|
Term
| What are the adverse effects of the uncoating inhibitors? (Amantadine) |
|
Definition
anorexia
nausea
CNS effects in the Elderly |
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|
Term
| Which virus relase inhibitor is orally inhaled and can cause nasal and throat discomfort? |
|
Definition
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