LEC 29 Antivirals Flashcards
(37 cards)
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
1
Q
What other HSV/CMV drugs have the same MOA as Acyclovir?
A
- Valacyclovir
- Penciclovir
- Famciclovir
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
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
4
Q
What do you know about Abacavir?
A
- NRTI
- Good oral F
- 12-24 h half life
- Resistance requires several mutations
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
6
Q
What do you know about Emtricitabine?
A
- NRTI
- Good oral F
- AE: hyperpigmentation of palms and soles
7
Q
What do you know about Lamivudine?
A
- NRTI
- 80% F
- Well tolerated and possibly safer than didanosine
8
Q
What do you know about Stavudine (d4T)?
A
- NRTI
- Good CNS penetration
9
Q
What do you know about Tenofovir?
A
- NRTI
- Works well for HBV also
- Often co-administered with emtricitabine
10
Q
What do we know about Zalcitabine?
A
- NRTI
- Can cause dose-dependent neuropathy (slowly reversible)
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%
12
Q
What are the general adverse effects of NRTIs?
A
- Lactic acidosis
- Hepatomegaly, steatosis
- Not generally metabolized by CYP450 in liver
13
Q
Which two NRTIs should NOT be co-administered?
A
Stavudine and Didanosine
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
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
How do entry inhibitors work?
* 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
What do you know about Maraviroc?
* 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
What do you know about Enfuvirtide?
* 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
How do Oseltamivir and Zanamivir work?
* Anti flu drugs
* Inhibit neuraminidase A and B
* Reduce viral spreading
27
How is Oseltamivir administered?
* Orally
* Prodrug that is activated in the gut
| Can cause GI upset
28
How is Zanamivir delivered?
Intranasally
| can cause bronchospasms
29
When must Tamiflu and Relenza be administered in order to be effective?
* 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
How does Baloxavir maboxil (Xofluza) work?
* Targets virus polymerase complex
* enzyme inhibitor
* targeting of cap-dependent endonuclease activity
* reduces ability to make viral RNA needed for replication
31
When must Xofluza be administered?
* 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
How does INF-α work?
* 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
How does PEGylating INF-α make it a better drug?
Dramaticallly increases half life - from QD dosing to once weekly dosing
33
What is the main route of clearance of INF-α and what are its adverse effects?
* Proteolytic degradation in the kidney
* AE: GI irritation, flu-like syndrome, fatigue, severe depression, alopecia, thyroid dysfunction, mental confusion
34
What do you know about Ribavirin?
* 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
