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Pharmacology Block 3 > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What are one of the biggest challenges with treating viruses?

A

Most drugs work best when the virus is replicating, however most symptoms don’t appear until the virus load has already peaked in the blood.

  • viral latency integrated into genome, can’t target
  • virus uses host cellular machinery, limited targets
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2
Q

What are the most important keys in using antivirals?

A
  • unable to target latent infections

- all drugs are viralstatic, requires competent immune system

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3
Q

What are two drugs that are used to prevent Influenza A and B adsorption/penetration of cells?

A
  • Amantadine

- Oseltamivir

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4
Q

What drug is used to prevent and treat Influenza A?

A

Amantadine - blocks uncoating by inhibiting M2 protein from lowering the pH in the vesicle.
(Becoming more resistant every year)

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5
Q

What is the key in administering Amantadine and Oseltamivir?

A
  • Must be started within 48 hours of the illness to effectively reducing fever and duration of the illness by several days.
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6
Q

What antiviral can be used to prevent infection of Influenza A and B?

A

Oseltamivir - Prodrug

–used as prevention in children under the age of 1–

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7
Q

What are the common side effects of Amantadine and Oseltamivir?

A

Amantadine - CNS Effects - slurred speech, anxiety, confusion
Oseltamivir - n/v/d, bronchitis

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8
Q

What antiviral can be used to treat occular herpes simplex 1 and 2?

A

Trifluridine - Thymidine Analog, inhibits virus DNA synthesis
–OPHTHALMIC only. Too toxic for systemic.

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9
Q

What are unique enzymes encoded by herpes virus family?

A
  • *- Thymidine Synthase -**
  • DNA Polymerase
  • Ribonucleotide Reductase
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10
Q

How does Acyclovir selectively target infected cells?

A

Herpes Virus encodes Thymidine Synthase, which phosphorylates Acyclovir activating it.
- Targets Viral DNA Polymerase, preventing chain elongation by becoming incorporated into DNA

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11
Q

What are the uses for different modes of administering Acyclovir?

A

IV use - systemic herpes simplex, HSV encepholitis
Oral use - primary genital herpes, recurrent HSV1
topical - primary genital herpes
–Overall, well tolerated with n/v/ and HA

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12
Q

How is Famciclovir different from Acyclovir?

A

Famciclovir has similar mechanism of activation and targeting DNA Polymerase, but has a higher bioavailability. Tolerated Well.

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13
Q

What is used for treating acute herpes zoster?

A

Famciclovir.

Also used for treatment and suppression of recurrent genital herpes.

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14
Q

What antiviral is used topically to prevent recurrent oral herpes simplex?

A

Penciclovir, same mechanism as Acyclovir

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15
Q

What kind of people should be concerned with CMV infection?

A
  • HIV - 80% of the time = Retinitis
  • Organ transplant patients
  • Most common infection in both patient populations, depends on CD4+ count.
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16
Q

What drug is used to treat CMV retinitis in AIDs patient and prevention of CMV in transplant patients?

A

Ganciclovir

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17
Q

How does Ganciclovir work and what are the adverse effects?

A

Activated my CMV Kinase, works like Acyclovir

Adverse Effects: Bone Marrow Suppression - enhances suppression of Zidovudine

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18
Q

What drug would be used if a herpes virus is resistant to Acyclovir?

A

Foscarnet - mimics pyrophosphate binding CMV DNA Polymerase

Also used for CMV Retinitis

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19
Q

What is the most concerning adverse side effect of Foscarnet?

A

Renal Damange and electrolyte imbalances. (30-50% of pts)

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20
Q

What is the best CMV Retinitis treatment?

A

HIV Treatment to elevate CD4+ counts, Foscarnet and Ganciclovir only slow progression of the retinitis causing many side effects.

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21
Q

What drugs are approved for treating Hepatitis B?

A

Lamivudine - nucleoside analog - inhibits HBV Reverse transcriptase
Tenofovir - AMP analog, inhibiting HBV Reverse Transcriptase

22
Q

What drug is phosphorylated in vivo to treat RSV and Hep C?

A

Ribavirin -

  • interferes with viral mRNA synthesis
  • inhibits GTP Synthesis
  • Inhibits GTP-capping of mRNA
23
Q

How is Ribavirin used to treat Hepatitis C?

A

Ribavirin is used in combination with interferon-alpha and Boceprevir

24
Q

What is the risk associated with Ribavirin?

A
  • aerosol can clog airways and tubings while treating RSV

- IV/PO versions can cause Bone Marrow Suppression

25
Q

How does Alpha-Interferons work and what are they used for?

A
  • Interferon-alpha is used to induce the host immune system to elicit a great response against viral infections
  • -Used improving disease course of Hep B and C
  • -Genital Warts
26
Q

What is the major drawback of using interferons as therapy?

A

Constant Flu-like symptoms (fatigue/body aches)
Bone Marrow suppression
Myalgias

27
Q

What antiviral blocks NS3 protease of Hepatitis C?

A

Boceprevir - prevents the cleaving of the propeptide, inhibiting formation of virions

28
Q

What are the major side effects of using Boceprevir?

A
  • Bone Marrow Suppression
  • Neutrapenia
  • Induces CYP3A - many drug interactions
29
Q

What is the recommended cocktail for treating Hep C?

A

Boceprevir + Interferon-alpha + Ribavirin

30
Q

What are the most common Nucleoside Reverse Transcriptase Inhibitors used in HIV Therapy?

A
  • Zidovudine
  • Tenofovir
  • Lamivudine
  • Emtricitabine
  • Abacavir
31
Q

What NRTI drug is a thymidine nucleoside analog?

A

Zidovudine - binds RT, prevents elongation

32
Q

What is a common side effect of Zidovudine?

A

Bone Marrow Suppression
Myopathy
–other drugs that reduce glucoronidation cause increased toxicity of Zidovudine

33
Q

What are the common mechanisms of inhibiting Nucleoside Reverse Transcriptase?

A
  • Nucleoside Analogs
  • competitive inhibitors
  • DNA chain termination after incorporation
34
Q

What is the antiviral that is used for HIV treatment that is a prodrug and also treats Hep B?

A

Tenofovir - nucleoside prodrug

–Well Tolerated– Preferred Choice of HIV

35
Q

Why is it a good idea to use Lamivudine and Zidovudine together?

A

They are both nucleoside analogs RT inhibitors, but if the HIV strain becomes resistant to one drug they are always susceptible to the other and vice versa. Synergistic

36
Q

What is another drug that has the same profile as Lamivudine, but is apart of the preferred drug cocktail for HIV?

A

Emtricitabine (analog of Lamivudine)
- longer half life, minimal side effects
“Preferred Choice”

37
Q

What NRTI requires genetic testing prior to starting due to possibly fetal hypersensativity?

A

Abacavir

38
Q

What are common side effects of many NRTIs?

A
  • Lactic Acidosis
  • Hepatic Steatosis
  • *Commonality for most NRTI side effects is Mitocondrial gamma-DNA Polymerase**
39
Q

What is a non-nucleoside reverse transcriptase inhibitor used for HIV treatment?

A

Efavirenz - allosteric inhibitor of RT disrupting active site

40
Q

What are the common side effects of Efavirenz?

A

Overall well tolerated very commonly used

–CNS effects, psychiatric symptoms, nightmares/vivid dreams

41
Q

What are two commonly used protease inhibitors for HIV treatment?

A
  • Lopinavir

- Ritonavir

42
Q

What is the unique use of Ritonavir in treatment?

A

Ritonavir is used with other protease inhibitors, in order to boost their effectiveness due to Ritonavir being a potent inhibitor of CYP3A - preventing the metabolism of other proteases.

43
Q

What is the common mechanism of action for Protease inhibitors?

A

Prevents viral protease from cleaving the Gag-pol polypeptide, competitive inhibitor

44
Q

What are common toxicities of protease inhibitors?

A
  • Can cause or worsen DM
  • changes lipid distribution and increases CV risks
  • changes fat distribution to build up in the gut, thinning of the face/legs
  • inhibit CYP3A many drug interactions
45
Q

What is a common fusion inhibitor for HIV?

A

Enfuvirtide - binds g41 subunit preventing the ‘snap back’ mechanism

46
Q

When would a fusion inhibitor be used for HIV treatment?

A

Enfuvirtide - Last Resort ONLY. When patients have failed other therapies.
No cross reactivity or resistance
Administered SubQ Only (Some local reactions)

47
Q

What is a CCR5 inhibitor and how does it work?

A

Maraviroc, binds CCR5 on host cells preventing HIV from using it as a co-receptor and entering the cells. T-cells and Macrophages.
Adverse: CV events and hepatotoxicty

48
Q

What is an integrase inhibitor of HIV? When is it used?

A

Raltegravir, used when patients have failed previous treatment.
-well tolerated-

49
Q

What are common reason why treatment for HIV fails?

A
  • failure to maintain regimens / compliance
  • resistant strains emerge
  • side effects cause patients to stop drugs
  • missing doses = allowing mutated viruses to replicate
50
Q

What are the ideal combination of antiviral drugs for HIV treatment?

A

Three or more drugs

Commonly 2x NRTI and 1x NNRTI or PI or Integrase inhibitor

Pharmacology Block 3 (19 decks)

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