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Multi-Systems: Antiviral Agents Flashcards

1
Q

(2) Anti-herpes-viral drugs that are Guanosine analogs that
inhibit Nucleic Acid Synthesis?

A

Acyclovir (HSV, VZV)

Ganciclovir (CMV)

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2
Q

Mechanism of Acyclovir and Ganciclovir?

A
  • Acts as a Chain terminator and Viral DNA Polymerase Inhibitor (HSV-enzyme required to activate)
  • Guanosine analog w/ Acyclic Sugar
  • Phosphorylated by Viral Thymidine Kinase
  • -> acylcoGMP –> acycloGTP
  • Valacyclovir + H2O –> Acyclovir + Valine
  • Valganciclovir + H2O –> Ganciclovir + Valine
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3
Q

Clinical use of Acyclovir and Ganciclovir?

A
  • Acyclovir
    • HSV-1, HSV-2
    • VZV
    • EBV
  • Ganciclovir
    • CMV
    • HHV-6, HHV-7
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4
Q

Resistance to Acyclovir and Ganciclover?

A
  • Deleted or Mutated - Viral Tyrosine Kinase
  • Resistant - Viral DNA Polymerase
  • No effect during latent infection because Viral Tyrosine Kinase is not expressed
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5
Q

Drugs that work on CMV?

A
  • Ganciclovir (Guanosine analog)
  • Foscarnet (Viral DNA polymerase inhibitor)
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6
Q

(2) Anti-herpes-viral, Viral DNA polymerase inhibitors that stop Nucleid Acid Synthesis?

A
  • Foscarnet (CMV)
  • Cidofovir (HSV* - Acyclovir resistant)
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7
Q

Mechanism of Foscarnet?

A
  • An inorganic pyrophospate analog that Inhibits Viral DNA polymerase w/out requireng activation via Phosphorylation by Viral Kinases.
  • Effective against resistant strains of HSV, VSV, and CMV
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8
Q

Clinical use of Foscarnet?

A
  • Acyclovir-resistant HSV and VZV
  • Ganciclovir-resistant CMV
    • ​Produces less Bone Marrow suppression than Ganciclovir
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9
Q

SEs of Foscarnet?

A
  • Nephrotoxicity
  • Foscarnet acts as a Potent Chelator of divalent Cations
  • -> decreased ionized Ca2+, Mg2+
  • -> Symptomatic Hypocalcemia w/ normal Serum Ca2+
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10
Q

Resistance to Foscarnet?

A
  • Foscarnet binds to the pyrophosphate binding site of the DNA polymerase
  • -> Mutations in DNA Polymerase that prevent binding
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11
Q

(2) Antiviral drugs that Block the
Influenza A M2 Protein Channel
–> Preventing Uncoating of Influenza virion
–> Req’d for Infection

A
  • Amantadine
  • Rimantadine
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12
Q

Mechanism of Amantadine and Rimantadine?

A
  • M2 channel conducts Protons from the Endosome into the Virion
  • -> Acidification of the Interior and Dissociation of the Matrix protein from Viral ribonucleoproteins (RNPs)
  • Amantadine / Rimantadine prevent Virion from fusing w/ the Endosomal membrane and stops from Releasing contents into Cytoplasm
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13
Q

Clinical use of Amantadine and Rimantadine?

A
  • Influenza A infections
  • No longer used though due to increased Resistance
  • Resistance arises rapidly via Single-point mutation of M2 protein
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14
Q

(1) Hepatitis Anti-viral, Guanine nucleotide Synthesis that Inhibits Nucleic Acid Synthesis?

A
  • Ribavirin
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15
Q

Mechanism of Ribavirin?

A
  • Guanosine analog that is Phosphorylated by Cellular enzymes
  • Inhibits Syn. of Guanine Nucleotides by competitively inhibiting Inosine Monophosphate Dehydrogenase
  • Inhibits IMP dehydrogenase
  • -> Impaired Purine synthesis
  • Inhibits Viral RNA polymerase and 5’ cap formation on mRNAs
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16
Q

Clinical use of Ribavirin?

A
  • Chronic HCV Infection (in combination w/ IFN-α)
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17
Q

SEs of Ribavirin?

A
  • Hemolytic anemia when administered IV
  • Severe Teratogenic
  • Oncogenic
  • Gonadotoxic
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18
Q

Small polypeptide (18 kd) that binds to a cellular receptor
and Induces a Antiviral Cellular State?

A
  • IFN-α
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19
Q

Mechanism of IFN-α?

A
  • Binds to Cellular Receptor and Induces a Antiviral Cellular State
    1. ​​Phosph. of EF 2 –> Inhibit Peptide Chain Initiation
    2. Ribonuclease Activation –> degrade Viral mRNA
    3. Phosphodiesterase exp –> degrade tRNAs
  • -> inhibit Peptide Chain Elongation
    1. Increase Natural killer cell lytic function
    2. Increase exp. of MHC Class I molecules
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20
Q

Clinical use of IFN-α?

A
  • Chronic Hepatitis B and Hepatitis C Infections
  • Anti-tumor effect on various cancers
    • Melanoma
    • Hairy cell leukemia
    • Kaposi’s Sarcoma
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21
Q

SEs of IFN-α?

A
  • Flu-like Symptoms
    • Fever
    • Myalgias
    • Malaise
  • Neutropenia
  • Thrombocytopenia
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22
Q

(2) Drugs that Reversibly Inhibit Neuraminidase (NA)
of Influenza A and B and impairs budding of Virions?

A
  • Zanamivir
  • Oseltamivir
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23
Q

SEs of Zanamivir and Oseltamivir?

A
  • Bronchospasm
  • Oseltamivir (Tamiflu) is a prodrug that is converted by the Liver to an Active neuraminidase Inhibitor after Oral Administartion
    • Used for Treatment and Prophylaxis of Influenza A and Influenza B Infections.
24
Q

Mechanism of Enfuvirtide?

A
  • Polypeptide Fusion inhibitor
  • Binds to the First Heptad-repeat (HR1) in the
  • *gp41** subunit of the HIV envelope glycoprotein and
  • *Prevents** the Conformational changes Req’d for the Fusion of Viral and Cellular membranes
  • HIV is prevented from establishing infection in the Target Cell.
25
Clinical use of Enfuvirtide?
* **HIV infection** * Salvage regimens to treat *Multi-drug-resistant HIV*
26
(3) Drugs that are Fusion Inhibitors?
1. **Maraviroc** (HIV - CCR5 as a co-receptor) 2. **Enfuvirtide** (HIV - gp41 HRI region) 3. **Palivizumab** (RSV)
27
Mechanism of Maraviroc?
* This entry inhibitor **Binds** to the **CCR5 Receptor** on * *Macrophages**, **T cells,** and **Dendritic cells** * **Prevents HIV from using CCR5 as a co-Receptor** * Blocks entry of CCR5-trophic HIV into cells
28
Clinical use of Maraviroc?
* HIV Infection * Primarly to salvage regiments of multi-drug-resistant HIV * Prior to intiation of Therapy, a Viral tropism assay should be done to Exclude **CXCR4** or **dual trophic HIV Infection**
29
SEs of Maraviroc?
* Cardiovascular * Myocardial Ischemia * Myocardial Infarction
30
Mechanism of Raltegravir?
* An **Integrase inhibitor** that reversibly * *Inhibits HIV Integrase** --\> **Preventing** the HIV genome from being **inserted** into the Host cell Chromosome.
31
Clinical use of Raltegravir?
* HiV infection
32
(5) Drugs used for HSV?
1. **Acylovir** 2. Ganciclovir 3. Foscarnet 4. Cidofovit 5. Trifluridine
33
(1) Drug used for EBV?
* **Acyclovir** - **Oral Hairy Leukoplakia only** * **Anti-viral** therapy is not indicated for **Infectious Mononucleosis - -\>**They will break out in a Full-Body Head to Toe Rash
34
(4) Drugs used for VZV?
1. **Acyclovir** 2. Ganciclovir 3. Foscarnet 4. Cidofovir
35
(3) Drugs used for CMV?
1. **Ganciclovir** 2. Foscarnet 3. Cidofovir
36
(5) Drugs used for HBV?
* **Tenofovir** * **Entecavir** * **Telbivudine** * **Lamivudine** * **INF-α**
37
(2) Drugs used for Influenza A?
* **Zanamivir** * Amantadine
38
(1) Drug used for Influenza B?
1. **Zanamivir**
39
(1) Drug for RSV?
* **Ribavirin**
40
(2) Drugs for HCV?
* **Ribavirin** * **IFN-α**
41
(6) Drugs that **Inhibit HIV's Reverse Transcriptase (RT): AZT (Azidothymidine) - ?** (Nucleoside RT Inhibitors - NRTIs) "SEAL-DZ"
* Stavudine (d4T) * Emtricitabine (FTC) * Abacavir (ABC) * Lamivudine (3TC) * Didanosine (ddl) * Zidovudine (ZDV) --\> Used for general Porphylaxis and During **Pregnancy** to decrease risk of Fetal Transmission
42
Mechanism of AZT?
* Nuclear analog of **Thymidine** --\> **Phosphorylated** by **Cellular Enzymes** --\> **Zidovudine Triphosphate** - -\> **Inhibits HIV's Reverse Transcriptase** (RT) * NRTI's lack the Hydroxyl group at 3' Position req'd for addition of Further Nucleotides - -\> **Chain Termination** when **Incorporated into DNA**
43
Clinical use of AZT?
* **HIV-1** and **HIV-2** * Decrease incidence of **Maternal-fetal HIV** Transmission (w/ combination treatment) * **Post-HIV exposure** Prophylasix (needlestick, sexual)
44
SEs of AZT?
* **Myelosuppression** * Increased MCV --\> used to verify compliance * **Mitochondrial toxicity - -\> Lactic acidosis - -\> Hepatic acidosis** - -\> Peripheral **Fat Wasting**
45
(3) Drugs that **Inhibit HIV** and **HBV Reverse Transcriptase?** And acts as a **Chain Terminator** when **Incorporated into Viral DNA**? "CAdT"
* Cidofovir * Adelovir Dipivoxil * Tenofovir (TDF)
46
Mechanism of Tenofovir?
* Nucleotide analog of Adenosine * Addition of Two more Phosphate groups by Cellular enzymes - -\> **Inhibitor of HIV** and **HBV** **Reverse Transcriptase** * **Also,** acts as a **Chain Terminator** when incorporated into **Viral DNA**
47
Clinical use of Tenovir?
* HIV Infection * Chronic HBV infection * Including HBV strains resistant to Lamivudine
48
SE of Tenovir?
* **Nephrotoxicity** * Especially w/ **Adefovir** and **Cidofovir** * Nucleotide analogs (NOT nucleoside analogs) are actively secreted by and are Toxic to the PCVT (Kidney) * Co-administration of **Probenecid** decreases Toxicity (by preventing drug accumulation in Renal tubular cells) and Increases Serum Drug levels * **Severe**"Rebound" **Heptatitis** can occur upon discontinuation if **HBV** infection persists * **CONTRAINDICATED:** Pregnancy (development and Bone abnormalities)
49
(4) Drugs that **Inhibit HIV's Reverse Transcriptase (RT)**? (Non-nucleoside Reverse Transcriptase Inhibitor - NNRTI) "NEED"
* Nevirapine * Efavirenz * Etravirine * Delaviradine
50
Mechanism of NNRTI's?
* Binds w/ High Affinity to and **Inhibits HIV's Reverse Transcriptase (RT)** * Does not require Phosphorylation to be active or complete w/ Nucleotides * **HIV-2 RT is not inhibited**
51
Clinical use of NNRTI's?
* HIV-1
52
SEs of NNRTI's?
* **Neuropsychiatric effects** * **​**Feeling "Hung-over" * Bizarre and Vivid Dreams * **CONTRAINDICATED - Pregnancy (Teratogenic)**
53
(9) Drugs that **Inhibit the HIV Protease** that is responsible for **Cleaving** the t**wo polyprotein products of HIV mRNA**? (gag and gag-pol polyproteins) "F-SALT-RIND"
* **Fosampre**navir * **Saqui**navir * **Ataza**navir * **Lopi**navir * **Tipra**navir * **Rito**navir * **Indi**navir * **Nelfi**navir * **Daru**navir
54
SEs of HIV protease inhibitors?
* **GI Distress** * **Lipodystrophy** * Glucose Intolerance * Hyperlipidemia * **Myocardial Infarction** (small)
55
What is special about Ritonavir?
* Ritonavir is a PI that potentially **inhibit CYP450** - -\> multiple drug interactions * **Co-administered** w/ other **Protease Inhibitors** give w/ Ritonavir to **"Boost"** their serum levels
56
Used topically for HSV-1 and HSV-2 Eye Infections?
* Trifluridine * Thymidine analog * Phosphorylated by both Viral and Cellular Thymidine Kinases * Breackage and Faulty protein production * Inhibits DNA Synthesis

Pharmacology (29 decks)

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