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Pharm 2 Undergrad > Anti-Viral Drugs > Flashcards

Anti-Viral Drugs Flashcards

1
Q

Structure of Viruses:

A

-Contain a nucleic acid core surrounded by a protein capsid- some viruses contain an envelope

  • Attach to host cell receptors & then enter the cell, by mechanisms such as endocytosis and penetration (they hijack the host cell machinery)
  • Most RNA viruses form their mRNA in the cytoplasm- influenza virus is an exception.

-Viruses assemble visions within the host cell, released during either cell lysis (non-enveloped viruses) or budding (enveloped viruses)

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2
Q

What is the difference between a normal DNA virus and an RNA retrovirus?

A

-DNA viruses use their DNA to enter host cell nucleuses and begin making viral mRNA.

RNA retroviruses contain reverse transcriptase, which make cDNA into DNA and mRNA.

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3
Q

What is the difference between lytic, patent and chronic viral infections?

A
  • Lytic (phagocytosis)
  • Latent (quiescent stage of infection)
  • Chronic (on-going)
  • All contain incubation periods
  • Usually introduced into the cell primarily by cell- mediated immunity.
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4
Q

Overview of the treatments for treating viral infections?

A
  • Blocking viral attachment to cells
  • Block un-coating of virus
  • Inhibit viral DNA/ RNA synthesis
  • Inhibit viral protein synthesis
  • Inhibit specific viral enzymes
  • Inhibit viral assembly
  • Inhibit viral release
  • Stimulate host immune system
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5
Q

What is the Prodromal Phase of a Viral Infection?

A

A Prodrome is an early sign or symptom which often indicate the onset of a viral infection.
–It is difficult to discern the presence of a viral infection at this phase.

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6
Q

True or False: Antiviral drugs are virustatic (temporarily halt viral replication).

A

True.

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7
Q

True or False: Anti-viral drugs can eliminate a virus in latency.

A

False.

-Anti-virals rely on a comportment host immune system to eliminate or effectively halt virus replication.

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8
Q

Oseltamivir, Zanamivir, Peramivir Drug Class

A
  • Neuraminidase Inhibitors
  • -All inhibit influenza type A and B viruses, and prevent the release of new virions.

Mechanism: Neuraminidase inhibitors remove sialic acid receptors from viral particles from the cell surface- thus preventing self- aggregation and gluing to the infected cell surface.

  • Given 24-48 hours after the onset of the illness.
  • Decreases the duration of symptoms, risk of complications such as pneumonia, shortens hospitalization and decreases risk of death.
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9
Q

Oseltamivir:

A
  • Neuraminidase Inhibitor
  • Orally active prodrug, hydrolyzed by the liver into its active form.
  • ->Safe and effective for prophylaxis (60-80% effective) after exposure to influenza A and B
  • Viral resistance can occur, but is uncommon.
  • AE’s include GI upset & nausea
  • Preferred treatment for Pregnant Women
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10
Q

Zanamivir:

A
  • Neuraminidase Inhibitor
  • IV Zanamivir is also available
  • Safe and effective for prophylaxis (60-80% effective) after exposure to influenza A and B
  • Viral resistance can occur but is uncommon.
  • AVOID in patients with severe respiratory disease or asthma.
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11
Q

Peramivir:

A
  • New injectable neuraminidase inhibitor (IV only)
  • Approved in Dec 2014
  • AE’s include serious skin reactions.
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12
Q

True or False: Neuraminidase Inhibitors (Oseltamivir or Zanamivir) remain the drug of choice in treating Influenza A and B in individuals at high risk in developing complications, including the elderly.

A

True!
-Healthy people normally do not require antiviral prophylaxis or treatment for influenza.

-Oseltamivir and Zanamivir are used for treatment of the Avian Flu.

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13
Q

Un-coating inhibitors, Amantadine and Rimantadine may have activity against some avian strains of influenza, but not against H1N1 subtype strains.

A

Un-coating inhibitors, Amantadine and Rimantadine may have activity against some avian strains of influenza, but not against H1N1 subtype strains.

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14
Q

Oseltamivir for H5N1 Strains:

A

-Has been active against avian strains of influenza in animal studies, and is an option for treatment of suspected influenced A (H5N1) in humans.

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15
Q

Zanamivir for H5N1 Strains:

A

-Has been active in animal models, but hasn’t been studied in human infections with influenza A (H5N1).

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16
Q

Amantadine (Symmetrel) and Rimantadine (Flumadine):

A
  • Viral Un-Coating Inhibitors:
  • Block the viral membrane matrix protein M2 (H+ ion channel- important for viral uncaring)
  • Both orally administered and used to treat Influenza A strain viruses.
  • No longer effective for prophylaxis of Influenza A due to resistance.
  • Resistance has increased substantially

*Amantadine has been shown to relieve some symptoms of Parkinson’s Disease.

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17
Q

Ribavirin:

A
  • Synthetic guanosine analog effective against RNA and DNA viruses.
  • Used for the treatment of Respiratory Syncytial Virus (RSV) in infants and young children, as well as for treating influenza.
  • Can also be used for treating Hep. C infections (in combination with IFN-alpha-2B) –inhibits GTP formation, viral mRNA capping, and thereby inhibits viral protein synthesis.
  • Available in oral, IV and aerosol (inhaled) forms.

-If a patient has developed resistance to neuraminidase inhibitors, Ribavirin is an acceptable second line drug.

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18
Q

Treatment of Hepatitis B and C:

A
  • Most commonly contracted from chronic hepatitis, cirrhosis and hepatoceullar carcinoma.
  • Chemotherapy is available for Hep. B (INF-alpha or Lamivudine) and Hep C. (INF-alpha and Ribavirin).

-Other drugs for HBV (Hep. B) include Adefovir, Entecavir, Telbivudine and Tenofovir

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19
Q

Interferon (IFN):

A

Mechanism of Action:

  • Induction of host cell enzymes that inhibit viral RNA translation, degradation or viral RNA, and stimulation of the immune system.
  • ->pegIFN–2a and pegIFN–2b require once a week dosing
  • -Pegylation involves attachment of IFN proteins to large inset polyethylene glycol (PEG) molecules which slows absorption, decreases clearance and provides higher and more prolonged serum concentrations.
  • Administered Intralesionally, Subcutaneously or IV
  • ->AE Include Flu- Like Symptoms, Barrow Marrow Suppression, Neurotoxicity and Autoimmune Disorders.
20
Q

Lamivudine:

A

(3TC-deoxythiacytidine)

  • Inhibits both HBV DNA polymerase and HIV reverse transcriptase.
  • Administered orally and is generally well tolerated.
  • Used for treatment of HBV and HIV.
21
Q

Treatment of Herpes Simplex Virus Info:

A

Type 1- Oral
Type 2- Genital
Varicella- zoster virus (VZV); chickenpox; shingles
*Ubiquitous to humans and most infections are asymptotic (latent phase)
-The drugs are only effective during the acute phases of infection- and can’t prevent reoccurrences.

22
Q

Acyclovir:

A
  • Viral DNA requires deoxyguanosine to synthesize and replicate DNA (inhibits DNA synthesis)
  • Drug of choice in treating HSV 1, 2 and VZV
  • Is the analog of the endogenous substrate deoxyguanosine
  • Most common use is for the treatment for genital herpes.
  • Administered IV, orally or topically.

Mechanism of Action: Competitive inhibitor of dGTP for viral DNA polymerases.

  • Binding of the DNA template causes termination of premature viral DNA. Trapping the viral DNA polymerase on acyclovir terminates the viral DNA.
  • -Viral reisstance changes in either viral thymine kinase or viral DNA polymerase.

AEs: Depend on the route of administration.
Topical: Local irritation
Oral: GI upset & headache
IV: Transient renal dysfunction at high doses.

23
Q

Other drugs for treating Herpes Virus:

A
  • Valacyclovir: L-valvy ester of acyclovir which converts to acyclovir after oral administration
  • Famciclovia: An analog of acyclovir which is converted to penciclovir by first pass metabolism.
  • Penciclovir: An acyclic guanosine nucleoside derivative which can be used for topical application only
  • Ganciclovir: For treatment of CMV retinitis in AIDS patients, and for CMV prophylaxis in transplant patients.
  • Foscarnet: For the treatment of CMV retinitis in immunocompromised hosts, and for acyclovir- resistance HSV and herpes zoster infections
24
Q

Treatment of Retroviral Infections:

A
  • ->Retroviruses: Use RNA template to create new viral DNA
  • HTLV Groups: HTLV-1 and HTLV-2
  • Lentiviruses: HIV-1 & HIV-2
25
Q

HIV Mechanism of Action:

A
  • Attaches to CD4+ cells (via CD4 receptor to co-receptor)
  • ->2 co- receptor types: CCR5 and CXCR4 (chemokine receptors)
  • ->Contains a reverse transcriptase to make cDNA , which is incorporated into the host genome and forms a provirus.
  • -This inactivates CD4+ cells, leading to deficient cell- mediated immunity.
  • Release (Buds Off) without killing the host cell. After budding, the viral protease cleaves the viral protein precursors (maturation).
26
Q

Therapeutic Regimen for HIV:

A

-Use a combination drugs to suppress HIV replication and to restore a degree of immune competency in the host.

  • Commonly referred to as HAART therapy- Highly active anti-retroviral therapy.
  • The current standard of care is to use 3 drugs or more simultaneously for the entire duration of treatment.
  • ->Maximizes viral inhibition and minimizes drug toxicity.
27
Q

NRTI’s:

A

Nucleotide and Nucleoside Reverse Transcriptase Inhibitor (NRTI)

  • Convert to the triphosphate in the cell.
  • -Are preferentially incorporated by viral reverse transcriptase into viral DNA into terminate it’s elongation.

–Have a much lower efficacy to host cells DNA polymerase, but affects mitochondrial DNA polymerase in certain tissues- explains some of the side effects.

28
Q

Zidovudine (AZT: Azidodeoxythymidine)

A

-Converted by mammalian thymidine kinase to triphosphate, and it introduced by viral reverse transcriptase into viral DNA.

  • Used in HAART- decreases viral load and increases CD4+ cells (also used for prophylaxis)
  • Orally administered and glucuronylated by the liver & excreted in the urine (DDI’s are common)

AE’s: Toxic to bone marrow, headaches and toxicity can be potentiated by other drugs.
-Toxicity is potentiated if glucuronylation is decreased by co-administration of other medications such as probenecid, acetaminophen, indomethacin and cimetidine

29
Q

Which drugs should not be given with AZT as they are activated by the same intracellular pathways?

A

Stavudine

Fibavirin

30
Q

Other common NRTIs:

A
  • Didanosine (ddI, dideoxyinosine)
  • Zalcitabine (ddC, dideoxycytidine)
  • Lamivudine (3TC, deoxy-thiacytidine)
  • Abacavir (FTC, a cytidine analogue)
  • Tenofovir (for HIV and HBV infections)

*Enofovir/ Emtricitabine combination (Truvada) is used as prophylaxis for HIV infection.

31
Q

Non-Nucleotide Reverse Transcriptase Inhibitors (NNRTI’s):

A
  • Highly selective, non- competitive inhibitors of HIV-1 reverse transcriptase
  • -Lacks affinity against HIV-2
  • Do not require activation of cellular enzymes.
  • Lack of effect on bone marrow, and lack of cross resistance with NRTI’s
  • Can develop resistance, DDI’s and hypersensitivity reactions.
32
Q

Nevirapine:

A
  • Used with other anti-retroviral agents.
  • Used as a substitute for AZT
  • INDUCES CYP450 enzymes and metabolism of oral contraceptives, ketoconazole, methadone, metronidazole, quinidine, theophylline and warfarin.

AE: Rash which can be severe and fatal hepatotoxicity can occur (requires the monitoring of transaminases)

33
Q

Efavirenz:

A
  • Has potent activity against HIV-1
  • Is used only in combination with other anti-viral HIV-1 agents.
  • Efavirenz + 2 NRTI’s remains the preferred regimen for treating naive patients.
34
Q

Atripla:

A

Efavirenz + Tenofovir + Embricitabine (once daily co-formulation single pill)

35
Q

Protease Inhibitors:

A
  • Selective, reversible inhibitors of HIV aspartyl protease and block viral maturation.
  • Lead to a significant reduction in AIDS deaths.
  • Can lead to buffalo hump

*Aspartyl protease is responsible for the formation of reverse transcriptase, protease integrate and structural proteins.

  • Protease inhibitors are synergistic with NRTI’s and NNRTI’s
  • Are substrates and inhibitors of CYP450 enzymes
  • DDI’s are common & problematic.

AE’s: GI intolerance, as well as disturbances in glucose and lipid metabolism. Other AE’s include Diabetes, hypertriacylglycerolemia, hypercholesterolemia, and fat redistribution- “buffalo hump” and breast enlargement

36
Q

Potential DDI’s with Protease Inhibitors:

A
  • Excessive sedation from Midazolam and Triazolam (Benzodiazepines)
  • Bleeding from warfarin
  • Respiratory depression from fentanyl
  • Avoid using inducers of CYP450 enzymes (Rifampin, barbiturates, carbamazepine, ect.)
  • ->They will cause failure of protease inhibitor treatment.
37
Q

Ritonavir:

A
  • ->Low in palatability and good in absorption (>60%)
  • Inhibits most cytochrome P450 enzymes, and is one of the most potent inhibitors of CYP34A enzymes (leads to DDI’s)
  • Inhibits the metabolism of all current HIV PI’s, and is frequently used in combinations with most other PI’s (except nelfinavir)
  • At low doses, it is employed as the “pharmacokinetic enhancer” for other protease inhibitors, allowing reduced doses and dosing frequency of co-adnmistered drugs.
38
Q

Saquinavir:

A
  • ->Poor availability (4%) and must be taken with meals.
  • Absorption increases with high- fat meals and grapefruit juice.
  • -Plasma levels can be significantly increased when combined with other agents that inhibit it’s metabolism.

AEs:
-GI upsets are common

39
Q

Atazanvir, Indinavir, Daruanvir

A

Other Protease Inhibitors

40
Q

Enfuviritide:

A

Viral Fusion Inhibitor

  • It is a 36 amino-acid peptide that binds to GP41 and prevents it’s conformational changes that occur when HIV fuses with the host cell membrane.
  • Usually combined with other anti- viral agents.
  • It is costly (because it’s a protein base) and is only given subcutaneously twice a day.
41
Q

Maraviroc:

A
  • Selective CCR5 Antagonist
  • Is restricted to use in adults with CCR5 tropic HIV-1 (R5 virus)
  • ->A commercial assay is available for R5 tropism (CCR-5 is the major co-receptor involved in virall entry into the cell for CCR5- tropic HIV-1 strains–these strains predominate during the early stages of infection, and remain dormant in 50-60% of late-stage disease cases.
42
Q

True or False:

A

CXCR4 viruses can’t be treated with Maraviroc (will be ineffective)
–There is a commercial test to ensure the infection is CCR-5 or CXCR4.

43
Q

Integrase Inhibitors:

A

–Inhibit HIV integrase activity

44
Q

Raltegravir:

A
  • The first in a new class of oral HIV drugs called HIV-1 integrate strand transfer inhibitors (InSTI’s)
  • Inhibits HIV-1 integrate activity, preventing viral DNA from integrating with cellular DNA.
  • it is active against HIV strains resistant to other anti- retroviral drugs.
  • Was approved for use in combination therapy for treatment- experienced adults infected with HIV-1 strains resistant to multiple anti-retroviral agents.

–Resistance occurs in patients not taking any other fully active drugs, and due to the mutation in viral integrate.

45
Q

Dolutegravir/ Elvitegravir:

A

2 newly approved integrate inhibitors for HIV treatment.

Pharm 2 Undergrad (29 decks)

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