Anti-Virals Flashcards
1
Q
Which anti-viral agents are used to treat viral respiratory infections?
A
Oseltamivir
Zanamivir
Ribavirin
2
Q
Which anti-viral agents are used to treat Herpes viruses/CMV?
A
Acyclovir Famciclovir Valacyclovir Ganciclovir Foscarnet
3
Q
Which classes of drugs are anti-HIV?
A
- Viral fusion inhibitor
- Integrase inhibitor
- NRTs/NNRTs
- Protease inhibitors
4
Q
What respiratory infection do anti-viral primarily treat?
A
Influenza
5
Q
Which anti-viral is also anti-parkinson’s disease?
A
Amantadine
6
Q
Does Rimantadine get into the brain?
A
No
7
Q
Which anti-viral drugs are Nucleoside Reverse Transcriptase Inhibitors?
A
- Didanosine
- Zalcitabine
- Zidovudine
8
Q
Which drugs are anti-viral Protease Inhibitors?
A
- Indinavir
2. Saquinavir
9
Q
T or F: Viruses have ALL cell membranes and walls and are also encapsulated.
A
FALSE:
No cell membrane
No cell wall
Yes encapsulated
10
Q
Why is selective toxicity an issue with anti-viral drugs?
A
Few drugs are selective enough to prevent viral replication without injury to the host
11
Q
What is the structure of most anti-viral drugs?
A
Most are nucleoside analogs
12
Q
Are most drugs virostatic or virocidal?
A
static (they keep the virus in place)
13
Q
T or F: Current antivirals DO NOT eliminate non replicating or latent virus.
A
True
14
Q
Clinical efficacy depends on achieving inhibitory concentrations at the site of infections. Where is the site of infection in this context?
A
usually within host cells
15
Q
What are the 3 steps of initial viron attack?
A
- Adsorption
- Penetration
- Uncoating
16
Q
What are some potential sites of anti-viral action?
A
Replication of the genome & synthesis of viral proteins
- Transcription of viral mRNA
- Replication of viral genome
- Translation of viral proteins—more tricky
- Regulatory proteins (early)—translated by host to help handle the viral replication
- Structural proteins (late) - Posttranslational modification—protease inhib.
- Assembly & Release
17
Q
What are ‘spike proteins’ ?
A
on the surface of the influenza A virus: hemagglutinin [HA] and Neuraminidase [NA] proteins.
18
Q
What does Hemagglutin do?
A
– bind to target cell receptors containing sialic acid, facilitate cell entry
19
Q
What does Neuraminidase do?
A
Facilitate release of new virons from infected cells.
20
Q
What is a controversial adverse effect of the Influenza vaccine?
A
Guillian-Barre Syndrome
21
Q
What are the 2 Neuraminase Inhibitors? And how are these 2 administered?
A
Oseltamivir (Tamiflu) -Oral
Zanamivir (Relenza) - Inhaled
22
Q
What 2 drugs are Inhibitors of viral uncoating?
A
- Amantadine (Symmetrel)
2. Rimantadine (Flumadine)
23
Q
What is the MOA of Amantidine and Rimantidine?
A
prevents viral uncoating (M2 membrane matrix protein)
And
possibly release of new virions
24
Q
What is the limitation of Amantadine and Rimantidine?
A
Activity restricted to RNA viruses – Only influenza A
AND
No longer recommended for prophylaxis or treatment of influenza
25
Which inhibitor of viral uncoating is not extensively metabolized?
Amantidine
26
Insomnia, dizziness, ataxia
Hallucinations, seizure
These are adverse effects for which anti-viral?
Amantadine
27
What are the Contraindications of Amantidine and Rimantidine?
pregnancy & lactation
28
Does Rimantidine have any CNS effects?
Nope--does not get into the brain!
29
What is the preferred anti-viral for subtype unknown or H1N1?
Zanamivir
30
What is the preferred anti-viral for:
H3N2,
influenza B, or
H1N1 if <7 yrs, or Asthma/COPD?
Oseltamavir
31
What can the combination of Oseltamavir plus Rimantadine be used for?
Alternate for HiN1
32
Is there a vaccine for RSV?
Nope
33
What is RSV?
respiratory syncytial virus
34
What is the preferred treatment for severe infections with RSV in infants and young children?
Ribavirin
35
What anti-viral can be used for this conditions:
Acute hepatitis A, Influenza A & B
Lassa hemorrhagic fever
Ribavirin
36
What would you need to add to Ribavirin if you were treating a patient with Hep C?
Plus interferon alfa-2b
| a “broad spectrum antibiotic
37
Which two anti-viral are worthless for RSV?
amantadine and ranantidine
38
What is the MOA of Ribavirin?
inhibition of viral mRNA synthesis
39
What is Ribavirin and what is it used for?
- Synthetic guanosine analog
| - Effective against broad spectrum of RNA & DNA viruses
40
How is Ribavirin administered?
Effective orally,
IV
AND
aerosol inhalation
41
Does Ribavirin get into the CNS?
No--this is dangerous because the virus can hide out in the brain
42
What are the Contraindications of Ribavirin?
Pregnancy
43
Which anti-viral has these adverse effects?
increased bilirubin, transient anemia
Ribivirin
44
Why is transient anemia bad? What agent causes it?
Ribavirin causes it and it is bad because it it caused by drugs interfering with our bone marrow’s ability
45
Which Hepatitis is being treated with this therapy?
interferon-α + ribavirin
Hep C
46
How would you treat Hepatitis B ?
interferon-α + (Lamivudine—HIV drug)
47
What is an Interferon anyway?!
Family of naturally occurring glycoporoteins that interfere with the ability of viruses to infect cells
48
Which interferon has been approved to treat Hep B
Hep C,
Kapok's sarcoma,
Hairy cell leukemia?
-IFN alpha-2b
49
What is the MOA of IFN alpa-2b?
Appears to induce host cell enzymes that inhibit viral RNA translation & ultimately lead to degradation of viral mRNA & tRNA
50
How is IFN alpha2b administered?
Given IV, SC, IM-(into the CSF)
51
How would you treat Chronic HCV?
Rebetron: (interferon alfa-2b + ribavirin)
52
What are the adverse effects of INF alpha2b?
fever,
lethargy,
bone marrow depression,
cardiovascular problems
53
If you wanted to treat chronic HCV, what would you add to IFN alpha 2b?
Ribavirin
54
What is Acyclovir and what is it's MOA?
Guanosine analog
Selectively inhibits viral DNA polymerase & is incorporated into viral DNA where it acts as a chain terminator
55
Which anti-viral agent is:
monophosphorylated in the cell by the herpes virus-encoded enzyme, thymidine kinase--and which cells are most susceptible?
1. Acyclovir
| 2. virus-infected cells most susceptible
56
How is Acyclovir administered?
IV, PO, or topical(??)
57
Does Acyclovir get into the CSF?
Yes
58
What is a caveat to Acyclovir?
Accumulates in renal failure
59
If a virus has resistance due to altered or deficient (cytomegalovirus; CMV) thymidine kinase--which drug will not work?
Acyclovir
60
What is strange about Acyclovir's adverse effects?
Depend on route of administration
61
What are the therapeutic uses for Acyclovir?
Genital & oral herpes (HSV 1 & 2)
62
What is the DOC for Herpes simplex encephalitis? This drug also
accelerates healing of Herpes zoster
and is effective in treating--
Some Epstein-Barr virus (EBV) infections?
Acyclovir
63
What virus does Acyclovir NOT treat?
CMV
64
What drug accelerates healing of Herpes zoster and is effective against some Epstein-Barr virus (EBV) infections?
Acyclovir
65
Which agent is a live attenuated virus vaccine, for the prevention of shingles?
Zostavax
66
What is particular about CMV? So what is it treated with?
lacks viral thymidine kinase
Ganciclovir (iv, topical) – Analog of Acyclovir
DNA/RNA Polemerase inhibitors
67
What is Cidofovir (Foscarnet) used for?
Broad antiviral Activity
CMV,
HSV,
HZV
68
Why should you be careful when prescribing Foscarnet?
Nephrotoxicity
69
In treating HSV 1, HSV 2 & HZV, which agent is topical?
Penciclovir - topical
70
In treating HSV 1, HSV 2 & HZV, which agents are NOT topical?
Famciclovir
| Valacyclovir
71
In treating HIV infection, which drug is an early inhibitor?
GP41
72
In treating HIV infection, what do the integrase inhibitors do?
Viral DNA strand transfer
73
Which anti-viral agents prevent chain elongation?
Nucleotide & Non-Nucleotide Reverse Transcriptase Inhibitors (NRTs &NNRTs)
74
Which anti-viral agents are responsible for cleavage of viral polyprotein?
Or in other words: deal with the Inhibition of viral assembly or maturation of the viral particles?
Protease inhibitors
75
What is Combination Therapy?
Inhibitor of reverse transcriptase plus protease inhibitor
76
What does HAART therapy = ?
highly active anti-retroviral therapy—drugs that are:
| reverse transcription inhib + protease inhib.
77
What do the Fusion Inhibitors do?
prevent HIV from being successfully taken up
78
What is Enfuvirtide?
A viral GP41 fusion inhibitor
79
What is Enfuvirtide used for?
indicated for treatment-experienced patients with ongoing HIV replication despite current antiretroviral use
80
What are the adv effects of Enfuvirtide?
1. Almost all patients develop local injection site reactions with mild or moderate pain, erythema, induration, nodules and cysts.
2. Eosinophilia
3. Systemic hypersensitivity reactions
4. Increased incidence of bacterial pneumonia.
81
What is Maraviroc?
An ORAL viral fusion inhibitor
82
Why is Maraviroc oral?
Because it hits a different receptor
83
What receptor does Maraviroc hit that makes it oral?
CCR5 coreceptor only;
| not CXCR4
84
How do the Integrase inhibitors work? (MOA)
Inhibits integration of viral strand DNA into host DNA
85
What drugs are Integrase Inhibitors?
Raltegravir
86
What are the adverse effects of Raltegravir?
nausea, headache, diarrhea
87
Which drug is most famous bc it is effective to prevent the offspring of HIV women in getting HIV (protects the fetus!) ? What is this drug anyway?
It is a Reverse Transcriptase inhib.
| Zidovudine
88
What are Abacavir and Didanosine?
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors -- NRTI
89
What is Combivir?
Lamivudine + Zidovudine
| NRTIs
90
What drug is
| Abacavir +Lamivudine +Zidovudine
Trizivir
| an NRTI
91
What are NTRIs?
- Analogs of native ribosides (Nucleosides or nucleotides containing ribose)
- All lacking the 3’-hydroxyl group
92
What is the MOA of the NTRIs?
DNA chain elongation is terminated
93
What are the adv effects of NTRIs?
1. Inhibition of mitochondrial DNA polymerase:
--Peripheral neuropathy, pancreatitis, lipoatrophy
--Fatal liver Toxicities :
lactic acidosis hepatomegaly with steatosis
94
What is Zidovudine? and What is its MOA?
--Thymidine analog
--AZT is phosphorylated to the triphosphate, incorporated into the growing viral DNA & thus, causes chain termination during DNA synthesis
95
How is Zidovudine administered?
Orally
96
Does Zidovudine get into the CNS?
Yes (HIV cannot hide here)
97
What is Zidovudine used for?
- -Used in three-drug combination therapy for HIV infection
- -Prophylaxis for exposure
- -Decreases transmission of HIV to fetus of infected mothers
98
What are the adv effects of Zidovudine ?
```
Bone-marrow suppression
HA is common
GI: N/V, anorexia
Avoid or use with caution ( All glucuronidated)
Probenecid
Acetaminophen
Lorazepam
Indomethacin
Cimetidine
```
99
What are the Non-Nucleoside Reverse Transcriptase Inhibitors (NNTRI’s)?
There are 1st gen and 2nd gen:
1st gen:
Efavirenz
2nd gen: Etravirine
100
What is different about these NNTRI's?
Lack effect on blood forming elements
101
Why would you prefer a 2nd get NNTRI over a 1st get?
Used when 1st generation resistance a problem
102
What is the preferred NNTRI?
Efavirenz
103
What are the 2 Protease inhibitors ?
Indinavir
| Ritonavir
104
What is the MOA of the Protease inhibitors?
Inhibit HIV protease enzyme, preventing post-translational processing of viral polyproteins
105
What are the adverse effects of the protease inhibitors?
Well tolerated, GI Sxs most common
106
How are the protease inhibitors given in terms of treatment?
Frequently given in combination with AZT and lamivudine –
HAART therapy = highly active anti-retroviral therapy
107
What is Ritonavir's new job since resistance has emerged against it?
SOLUTION: while the liver is chewing in on Rit. The other drug sneaks in and does the job
