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Disease & Defense > LEC 29 Antivirals > Flashcards

LEC 29 Antivirals Flashcards

1
Q

How does Acyclovir work?

What does it treat?

A
  • Guanosine derivative that inhibits DNA synthesis
  • Activated only in infected cells, bc it requires a viral kinase for the first of three phosporylation steps

Tx of HSV. Reduces symptoms and transmission d/t reduced viral shedding

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1
Q

What other HSV/CMV drugs have the same MOA as Acyclovir?

A
  • Valacyclovir
  • Penciclovir
  • Famciclovir
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2
Q

What DNA synthesis drugs work better for CMV?

A
  • Gancyclovir, Valganiclovir, Cidofovir - Slightly diff MOA; more active against CMV DNA Polymerase
  • Foscarnet - different; works when resistance to gancyclovir is seen
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3
Q

How do nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) work?

A
  • They inhibit reverse transcription
  • NRTIs lack a 3’ OH group so the attachment of the next nucleotide is impossible
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4
Q

What do you know about Abacavir?

A
  • NRTI
  • Good oral F
  • 12-24 h half life
  • Resistance requires several mutations
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5
Q

What do you know about Didanosine?

A
  • NRTI
  • Good oral F
  • Cellular metabolism and renal clearance
  • Pancreatitis can be a problem - limit use in alcoholics
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6
Q

What do you know about Emtricitabine?

A
  • NRTI
  • Good oral F
  • AE: hyperpigmentation of palms and soles
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7
Q

What do you know about Lamivudine?

A
  • NRTI
  • 80% F
  • Well tolerated and possibly safer than didanosine
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8
Q

What do you know about Stavudine (d4T)?

A
  • NRTI
  • Good CNS penetration
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9
Q

What do you know about Tenofovir?

A
  • NRTI
  • Works well for HBV also
  • Often co-administered with emtricitabine
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10
Q

What do we know about Zalcitabine?

A
  • NRTI
  • Can cause dose-dependent neuropathy (slowly reversible)
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11
Q

What do we know about Zidovudine (AZT)?

A
  • NRTI
  • First anti-retroviral
  • Often co-administered with lamivudine
  • Admin to preg women in late stage preg and neonates has been shown to reduce vertical transmission of HIV by 23%
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12
Q

What are the general adverse effects of NRTIs?

A
  • Lactic acidosis
  • Hepatomegaly, steatosis
  • Not generally metabolized by CYP450 in liver
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13
Q

Which two NRTIs should NOT be co-administered?

A

Stavudine and Didanosine

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14
Q

How do NNRTIs work?

A
  • Bind to a different site on the viral reverse transcriptase
  • Result is the same – blocking RNA to DNA
  • Highly susceptible to resistance through mutations in the pol gene - combine with other therapies
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14
Q

What do you know about Efavirenz?

A
  • NNRTI
  • can be given once daily d/t long half life
  • has shown teratogenicity - avoid giving to preg pts in first trimester
15
Q

What do you know about Nevirapine?

A
  • NNRTI
  • A single dose is effective in prevention of transmission of HIV from mother and child
  • Given during labor and to the neonate
16
Q

What are the adverse effects of NNRTIs?

A
  • Multiple drug interactions
  • Metabolized by liver
  • Some induce and some inhibit CYP450
  • Must know what meds the pt is taking
17
Q

How do protease inhibitors work?

A
  • In late stage of the life cycle
  • Precursors of coat proteins Gag-Pol are made
  • Must be cleaved at specific points by proteases to assemble correctly
  • Specific protease inhibitors target this process

HIV/AIDS Tx

18
Q

Protease inhibitors are usually combined with what other antiretroviral drug class as a part of HAART?

A

Reverse Transcriptase Inhibitors

19
Q

All PIs are substrates and inhibitors of what?

A

CYP3A4

20
Q

What do you know about Ritonavir?

A
  • PI
  • Good oral F
  • Metabolized by CYP3A4
  • Strong inhibitor of CYP3A4
  • Subtherapeutic levels of ritonavir can inhibit the CYP3A4-mediated metabolism of other PIs
21
Q

What do you know about Atazanavir?

A
  • PI
  • 12 h half life - QD dosing
  • Less effect on pt’s lipid profile than other PIs
  • Potent inhibitor of CYP3A4 CYP2C9
22
Q

What are the adverse effects of protease inhibitors?

A
  • Use in HAART has led to carb and lipid metabolism disorders
  • Cross inhibits endogenous lipid-regulating proteins
  • Leads to “buffalo hump” and gynecomastia
  • Hyperglycemia and Insulin resistance
23
Q

How do entry inhibitors work?

A
  • Attachment of many HIV strains requires to receptors on human cells
  • Drugs bind to this receptor or the proteins that can block attachment and entry of HIV into the cell
24
Q

What do you know about Maraviroc?

A
  • Entry Inhibitor
  • Good oral F
  • Good tissue penetration
  • Binds specifically to CCR5
  • No x-reactivity with other entry inhibitor (enfuvirtide)
  • Substrate of CYP3A4 - watch use with PIs and other 3A4 inhibitors
25
Q

What do you know about Enfuvirtide?

A
  • Entry Inhibitor
  • Synthetic 36-aa peptide
  • Binds to the gp41 subunit of the virus and inhibits conformational changes required for entry
  • Is not a P450 substrate
26
Q

How do Oseltamivir and Zanamivir work?

A
  • Anti flu drugs
  • Inhibit neuraminidase A and B
  • Reduce viral spreading
27
Q

How is Oseltamivir administered?

A
  • Orally
  • Prodrug that is activated in the gut

Can cause GI upset

28
Q

How is Zanamivir delivered?

A

Intranasally

can cause bronchospasms

29
Q

When must Tamiflu and Relenza be administered in order to be effective?

A
  • EARLY - replication of the virus peaks 24-72 hours after infxn
  • Can shorten duration of symptoms by 1-2 days
  • Once daily prophylaxis is 70-90% effective
30
Q

How does Baloxavir maboxil (Xofluza) work?

A
  • Targets virus polymerase complex
  • enzyme inhibitor
  • targeting of cap-dependent endonuclease activity
  • reduces ability to make viral RNA needed for replication
31
Q

When must Xofluza be administered?

A
  • w/i first 48 hrs of symptoms
  • can reduce length and severity of symptoms and viral shedding
  • One dose orally
  • Really long half life - >80 hrs
32
Q

How does INF-α work?

A
  • HBV and HCV tx
  • Host cytokine that exerts complex antiviral, immunomodulatory, and antiproliferative actions
  • Enhances phagocytic activity of macrophages
  • Augmentation of the proliferation and survival of cytotoxic T cells
  • Must be delivered parenterally
33
Q

How does PEGylating INF-α make it a better drug?

A

Dramaticallly increases half life - from QD dosing to once weekly dosing

33
Q

What is the main route of clearance of INF-α and what are its adverse effects?

A
  • Proteolytic degradation in the kidney
  • AE: GI irritation, flu-like syndrome, fatigue, severe depression, alopecia, thyroid dysfunction, mental confusion
34
Q

What do you know about Ribavirin?

A
  • Prodrug - when active, represents RNA nucleotide
  • Used in combo with INF-α for HCV
  • Exact MOA unknown - inhibits GTP formation, mRNA capping, and blocks RNA-dep polymerases
  • Inhibits many DNA and RNA viruses including: HCV, Flu A and B, RSV, HIV
  • Monotherapy not effective - must combine with other antivirals

Disease & Defense (37 decks)

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