Non-retroviral antiviral drugs Flashcards
(106 cards)
1
Q
- Viruses are (…) pathogens, therefore they are not living
- Viruses contain (…) and (…)
- What code for enzymes necessary for viral replication?
- What forms protective coats around the genetic materia of virusesl?
- What is the only goal of viruses?
A
- obligate intracellular pathogens
- nucleic acids and proteins
- nucleic acids and proteins
- nucleic acids
- proteins
- to multiple to ensure species survival
2
Q
What are some different ways of viral replication?
A
- DNA to DNA via replication by DNA polymerase
- DNA to RNA via transcription by RNA polymerase
- **RNA to RNA via replication by RNA polymerase
- **RNA to proteins via translation by ribosomes
- RNA to DNA via transcription by reverse transcriptase
3
Q
What is the process of replication for DNA viruses (how they enter the host cell, etc)?
A
- enter host cell
- uncoating of virus
- viral DNA enters nucleus
- viral DNA transcribed to mRNA by host cell polymerase
- translated into virus proteins
4
Q
What are examples of DNA viruses?
A
- herpesvirus family (chickenpox, shingles, oral herpes-HSV1, genital herpes-HSV2)
- adenovirus family (conjuctivitis, sore throat, papillomaviruses)
5
Q
- Are the two replication strategies of RNA viruses?
- Most RNA viruses replicate in (…), but influenza is transcribed in the (…)
A
- rely on own viral enzymes to synthesize mRNA; viral RNA serves as its own mRNA
- host cell cytoplasm; host cell nucleus
6
Q
What are some examples of RNA viruses?
A
- influenza
- rubella
- rhabdovirus
- coronavirus
7
Q
What should an antiviral drug do (at least)?
A
- interfere with virus-specific function, OR
- interefere with a cellular function that dirupts virual replication
8
Q
An ideal antiviral drug should have what properties?
A
- have no or low resistance potential
- have good pharmacokinetic properties
9
Q
Currently there are 4 main antiviral drug groups, what are they?
A
- herpes (HSV1, HSV2, VZW, CMV, EBV)
- influenza (A, B, C)
- hepatitis (A, B, C)
- HIV
10
Q
Herpes viruses are (…) viruses
(type of DNA)
A
dsDNA
11
Q
What are the different Herpes viruses?
A
- herpes simplex virus
- varicella zoster virus (VZV)
- epstein-barr virus (EBV)
- cytomegalovirus (CMV)
12
Q
What are some examples of what the herpes simplex virus can do (and the associated virus type)?
A
- cold sores → HSV-1, HSV2
- genital herpes → HSV-2
- herpes keratitis (eye infection) → HSV-1
- HSV encephalitis → HSV-1
13
Q
What are examples of varicella zoster virus illnesses?
A
- chickenpox (varicella zoster)
- shingles (herpes zoster)
14
Q
What does the epstein-barr virus cause?
A
infectious mononucleosis
15
Q
Cytomegalovirus (CMV) causes infections in what individuals?
A
immunocompromised individuals
16
Q
Anti-herpes antivirals are divided into two main groups, what are they?
A
- nucleoside analogues
- non-nucleoside analogues
17
Q
Which anti-herpes antivirals inhibit viral DNA replication but are ineffective against the latent virus (many are highly specific)?
A
nucleoside analogues
18
Q
What drugs are anti-herpes antiviral nucleoside analogues?
A
- acyclovir
- valacyclovir
- penciclovir
- famciclovir
- cidofovir
19
Q
What drugs are anti-herpes antiviral non-nucleoside analogues?
A
- foscarnet
- docosanol
20
Q
What are the goals of using anti-herpes antivirals for herpes virus treatment?
A
- accelerate lesion healing
- prevent transmission of virus
does not cure herpes, just suppresses symptoms
21
Q
- Aciclovir is a (…) analogue
- It is activated by (…); before this, it is (…)
A
- guanosine
- viral thymidine kinase (TK); inactive→doesn’t have any affect
22
Q
In guanosine, a (…) is needed to add more nucleosides to a DNA backbone
A
3’ hydroxyl group
23
Q
What are the 2 steps in acyclovir MOA?
A
- phosphorylation
- chain termination by inhibiting viral DNA polymerase
24
Q
What happens in the first step (phosphorylation) of acyclovir’s mechanism of action?
A
- acyclovir is phosphorylated by viral thymidine kinase to form acyclovir monophosphate
- host kinase further phosphorylates acyclovir monophosphate to form acyclovir biphosphate
- host kinase then further phosphorylates acyclovir bisphosphate to form acyclovir triphosphate which is the active drug
25
What happens in the second step (chain termination) of acyclovirs mechanism of action?
1. herpes DNA polymerase releases two phosphate groups from acyclovir triphosphate which then competes with deoxyguanosine triphosphate as a substrate for viral DNA polymerase and is incorporated into the viral DNA
2. there is no 3' position for another connection to growing a deoxy ribose-PO4 backbone
3. premature chain termination occurs
26
With normal guanine, the (...) allows for the next connection to the DNA backbone
3' hydroxyl group
27
- Acyclovir is used for the treatment of what viruses?
- This drug has limited efficacy against which two viruses?
- This drug is inactive against what?
- HSV infections, varicella zoster, and herpes zoster
- EBV and CMV
- latent viruses in nerve ganglia (such as shingles before it becomes active)
28
What is the descending order of activity for acyclovir in treating herpesviruses?
- Herpes simplex virus type I (HSV-1)
- Herpes simplex virus type II (HSV-2)
- Varicella zoster virus (VZV)
- Epstein-Barr virus (EBV)
- least active against cytomegalovirus (CMV)
29
Acyclovir is approved for the treatment of what?
VZV
30
Topical or oral acyclovir is used for what?
- treat genital herpes (reduces incidence of recurrence)
- for severe orolabial herpes
- immunocompromised patients
31
What is IV acyclovir used for?
- severe cases
- **first-line treatment for HSV ensephalitis**
- viral meningitis
32
Acyclovir is the first-line treatment for (...)
HSV encephalitis
33
Acyclovir resistance is due to two types of viral mutations, what are they?
1. mutations that render due to **viral TK dysfunction**
2. mutations that reduce the **affinity of viral DNA polymerase to acyclovir triphosphate**
34
Cross resistance with acyclovir is possible with (...) and (...)
- famciclovir
- valacyclovir
35
- What type of water solubility and oral bioavailability does acyclovir have?
- When does peak plasma concentration from an oral dose of acyclovir occur (time frame)?
- IV acyclovir provides what type of tissue/penetration?
- What is the protein binding range of acyclovir?
- How is acyclovir excreted?
- poor water solubility and oral bioavailability
- after 2 hours
- excellent tissue/fluid penetration including cerebrospinal fluid (why its useful in viral meningitis)
- 9-33%
- renally excreted
36
- Acyclovir is mostly (...) tolerated
- What can occur with IV formulations of acyclovir in 5-10% of patients?
- What are some rare and reversible effects of acyclovir?
- What are some other adverse effects?
- well tolerated
- reversible nephrotoxicity
- neurological symptoms such as delirium and seizures in those with renal impairment
- GI symptoms (N/V/D), myelosuppression, rash
37
- How can you reduce the risk of nephrotoxicity with IV acyclovir?
- Acyclovir can (...) in the kidney due to (...) properties of the drug
- adequate hydration, slower infusion rate, dosing based on renal function
- crystallize; poor water-soluble properties
38
- Valacyclovir is a (...) of acyclovir
- It is hydrolized almost completely to acyclovir by (...) and (...)
- The mechanism of action on spectrum of activity are (...) of acyclovir
- prodrug
- first-pass intestinal and hepatic metabolism
- identical of acyclovir
39
Valacyclovir has a (...) added to it which makes it more stable than acyclovir
valine group
40
- Valacyclovir is approved to treat which viruses?
- It may reduce what?
- VZV, HSV-1, HSV-2
- transmission to sexual partners
41
- Valacyclovir is approved for prevention of CMV disease in which individuals?
- Valacyclovir has not be proven effective in preventing CMV in which individuals?
- kidney transplant recipients
- heart, liver, lung, pancreas, and small bowel transplant recipients
42
- Valacyclovir resistance is identical to (...)
- However, achieving higher serum acyclovir levels with valacyclovir could reduce to the risk of (...) compared with oral acyclovir
- acyclovir
- resistance
43
If a drug is renally metabolized, (...) may need to be adjusted if patient has renal disease or failure
dosage
44
- Valacyclovir has what type of bioavailability compared to oral acyclovir?
- Serum acyclovir levels are (...) with valacyclovir than with oral acyclovir
- Valacyclovir achieves peak serum concentration in how many hours?
- Adverse effects are similar to those of (...)
- higher bioavailability (55%)
- higher
- 1-3 hours
- acyclovir
45
- What type of analogue is penciclovir?
- What is the MOA of penciclovir?
- What is the polarity/water solubility of penciclovir compared to acyclovir?
- acyclic guanine analogue, similar to acyclovir
- identical to acyclovir
- more polar, more water soluble
46
What are the advantages of penciclovir over acyclovir?
- no nephrotoxicity
- more stable in infected cells
- more recent than acyclovir (less resistance potential)
47
Penciclovir is effective against which viruses?
HSV-1, HSV-2, VZV, and to a lesser extent, EBV
48
- What is the oral bioavailability of penciclovir compared to acyclovir?
- How is penciclovir available and for what?
- What is the oral prodrug of penciclovir and what is it used for?
- poor oral avialability, why it is not an oral drug
- topical therapy for mucocutaneous herpes
- famciclovir for systemic use
49
What are the adverse effects of penciclovir?
mild application site irritation (because it's topical)
50
- What type of analogue is famciclovir?
- Famciclovir is converted in the liver to (...)
- How is this done (what processes)?
- What is the MOA of famciclovir
- diacetyl 6-deoxy analogue of penciclovir
- penciclovir
- hydrolysis followed by oxidation
- through penciclovir
51
- What is famciclovir active against?
- Famciclovir is used for the oral treatment of (...) in (...) patients
- Famciclovir is used for the treatment of (...) and (...)
- It is used as (...) to reduce the risk of recurrent genital herpes
- How it famciclovir excreted?
- HSV-1, HSV-2, VZV, and to a lesser extent, EBV
- varicella in HIV patients
- herpes zoster and recurrent genital and oral herpes
- suppression therapy
- renally excreted
52
- How is oral famciclovir absorbed (rate) and what bioavailability does it achieve?
- What is famciclovir metabolized into?
- Famciclovir reaches peak plasma (...) concentrations within (...)
- Famciclovir is excreted renally as (...) and (...)
- rapidly absorbed, 77% bioavailability
- penciclovir
- penciclovir; 1 hour
- penciclovir and its 6-deoxy precursor
53
- What are the most common adverse effects of famciclovir?
- What are the rare adverse events of famciclovir?
- What has occurred in patients taking high doses of famciclovir (and technically all other antivirals)?
- headache and nausea
- jaundice, rash, pruritis, confusion
- renal failure
54
- What type of analogue is foscarnet?
- Foscarnet is administered (...) for the treatment of (...)
- What is the MOA of foscarnet?
- non-nucleoside pyrophosphate analogue
- intravenously for treatment of herpes virus
- it **selectively** inhibits viral DNA polymerase, thus suppressing viral replication
55
- Foscarnet is active mostly against which viruses?
- It is also active against resistant (...) with (...) mutation or (...) virus with (...)
- Foscarnet is approved for the treatment of (...) in patients with AIDS but is not used often
- HSV-1, HSV-2, CMV
- herpes viruses with TK mutation or CMV viruses with UL97 kinase mutation
- CMV retinitis
56
Foscarnet can be used for treatment of which viruses in which individuals (there's 2, technically 3)?
- acyclovir-resistant HSV and VZV in immunocompromised patients
- gancyclovir-resistant CMV disease in immunocompromised patients
57
Foscarnet resistance is through mutations in (...); this drug has a (...) resistance threshold
- viral DNA polymerase
- lower resistance threshold
58
- Foscarnet has a complicated pharmacokinetic profile due to its high incidence of (...) and its deposition and subsequent gradual release from (...)
- What is the plasma half-life of foscarnet?
- A terminal half-life up to (...) may occur when it has accumulated in the (...)
- How is foscarnet excreted?
- nephrotoxicity; bones
- 2-4 hours
- 8 days; bones
- through glomerular filtration (kidneys)
59
- When giving patients foscarnet, you should make sure patients are (...) due to it causing nephrotoxicity
- Foscarnet can cause (...) resulting in (...)
- It can (...) bivalent metal ions which may reduce (...) ions in circulation
- Electrolyte disturbances can cause (...) and (...)?
- well hydrated
- myelosuppression; anemia
- chelate; calcium
- neurological symptoms and cardiac arrythmias
60
What are some examples of electrolyte disturbances that foscarnet can cause?
- hypokalemia
- hypomagnesemia
- hypophosphatasemia
61
What are some examples of neurological symptoms that can be caused by foscarnet use due to electrolyte disturbances?
- paresthesis
- seizures
62
Describe the structure of docosanol?
it's a saturated 22-carbon aliphatic alcohol
63
What does docosanol do?
blocks viral entry and subsequent replication (prevents lipid enveloped virus from entering cells)
64
- What is docosanol active against?
- How it applied (and to treat what)?
- Docosanol is available (...)
- a wide range of **lipid enveloped** viruses including herpes virus
- applied topically to treat recurrent oral-facial herpes simplex episodes (cold sores/fever blisters)
- available OTC
65
- CMV is a member of the (...) family
- Transmission of the virus occurs through (...)
- Healthy individuals who are infected with CMV usually are (...)
- However, it can cause severe complications in (...) patients
- herpes
- exposure to body fluids
- non-symptomatic
- immunocompromised patients
66
CMV can be fatal in which individuals?
- newborns
- people w/ compromised immune systems
67
- What are some CMV complications in newborns?
- What are some CMV complications in immunocompromised individuals?
- hearing/vision loss, mental disability, autism
- GI tract (fever, abdominal pain, blood stool), liver (abnormal function), CNS (encephalitis), and lungs (pneumonia)
68
- How to anti-CMV drugs work?
- What are names of anti-CMV drugs?
- interfere with viral replication by inhibiting viral DNA polymerase
- ganciclovir, valganciclovir
69
- What type of analogue is ganciclovir and what is it used for?
- What is ganciclovir's MOA?
- Ganciclovir triphosphate is a competitive inhibitor of (...) which leads to (...)
- acyclic guanosine analogue for management of CMV
- it is first phosphorylated by viral UL97 kinase and subsequently cellular kinase to the triphosphate form
- viral DNA polymerase; chain terminator
70
What is ganciclovir approved for?
| (don't forget what IV formulation does)
treatment of:
- CMV retinitis in pts with AIDS
- CMV prophylaxis in transplant recipients
- IV ganciclovir may be used to treat other forms of CMV disease such as colitis or esophagitis
71
If a patient has CMV disease and is either a bone marrow or organ transplant recipient, what is the first-line treatment that will be used?
ganciclovir
72
- Ganciclovir resistance is most common in which individuals?
- What is ganciclovir resistance due to?
- most common in immunocompromised patients with prolonged exposure to the drug
- due to mutations in UL97 gene (deficiency in viral kinase necessary for drug activation)
- a less common resistance mechanism is a mutation of the UL54 gene (viral DNA polymerase)
73
- What are the different formulations of ganciclovir?
- How is ganciclovir orally absorbed and what is its bioavailability?
- How is ganciclovir excreted?
- oral and IV formulations
- poorly absorbed orally, 5% bioavailability
- renally excreted
74
What are the adverse effects of ganciclovir?
- reversible bone marrow suppression
- rash, N/V/D
- increased serum creatinine levels and liver enzymes
- neurotoxicity may occur occasionally
75
- Valganciclovir is an L-valyl ester prodrug of (...)
- How is this converted to the active drug?
- ganciclovir
- hydrolyzed and converted to ganciclovir
76
Valganciclovir is approved for treating what conditions?
- oral formulation for mild-moderate CMV disease in transplant recipients
- CMV retinitis in AIDS patients
- prevention of CMV disease in pediatric heart and kidney transplant recipients
77
Describe the resistance of valganciclovir?
identical to ganciclovir:
- mutations in viral UL97 kinase and DNA polymerase enzymes
78
- Oral valganciclovir is well-absorbed and hydrolyzed to ganciclovir by (...) or (...) cells
- What is the bioavailability of ganciclovir after valganciclovir?
- When is peak plasma concentration achieved?
- How is valganciclovir eliminated?
- intestinal or hepatic cells
- 60%
- 1-3 hours
- renally eliminated
79
What are the adverse effects of valganciclovir?
- bone marrow suppression (most common)
- N/V/D
80
- The influenza viral is a segmented negative (...) virus with surface antigens
- What are the surface antigens (subtypes?)?
- What are the 4 types of influenza known to exist?
- What are the types of human flu?
- What is the avian flu type?
- ssRNA
- hemagglutinin (H) subtypes 1-16 (human 1,2,3); neuraminidase (N) subtypes 1-9 (human 1,2)
- A, B, C, D
- type A (H1N1, H2N2, H3N2), type B
- H5N1
81
- What is the preferred method for influenza prevention?
- What are the 2 proteins essential for the replication of the flu virus that are targeted by current anti-flu drugs?
- seasonal influenza vaccination
- M2 protein and neuraminidase
82
What is this describing:
- acid-activated ion channel
- present only in influenza A
- drugs inhibiting this protein prevent viral uncoating
the M2 protein
83
What is this describing:
- its inhibitors are structural analogues of sialic acid (protein on host cell membranes)
- its inhibitors prevent viral release
neuraminidase
84
- What influenza antiviral drugs inhibiting viral M2 protein prevent viral uncoating?
- What influenza antiviral drugs inhibit neuraminidase and prevent viral release?
- amantadine, rimantidine
- oseltamivir, zanamavir, peramivir
85
- Which antiviral influenza drugs are potent inhibitors of the M2 ion channel?
- These are only active against which influenza type?
- Both are what type of amines?
- What is the symmetry of these drugs?
- amantadine, rimantadine (adamantanes)
- influenza A
- tricyclic amines
- amantadine is symmetric, rimantadine is asymmetric
86
Resistance to amantadine and rimantadine can develop within how many days?
2-4 days
(both are no longer used as antiviral drugs to treat flu infections because of this)
87
- Amantadine has what type of effects?
- Because of this, it can be used in patients with what conditions?
- domaminergic effects
- parkinson's disease, drug-induced parkinson's, and in traumatic brain injuries
88
What are the different neuraminidase inhibitors (antiviral flu drugs)?
- zanamivir
- oseltamivir
- peramivir
89
- Oseltamivir is the ester form of (...) which is the active form
- How it oseltamivir administered?
- What happens to oseltamivir in the liver?
- What strains of influenza is oseltamivir active against?
- oseltamivir carboxylate
- orally (in capsule and suspension)
- it is hydrolyzed by the liver to oseltamivir carboxylate which inhibits viral neuraminidase
- influenza A and B
90
What is oseltamivir approved to do?
- treatment of influenza A or B viral infections for children (>1 year) and adults
- postexposure prophylaxis against influenza A and B, including pandemic strands
91
- What is oseltamivir resistance caused by?
- Oseltamivir resistance among which influenza strain occurs less frequently?
- Oseltamivir has cross resistance to (...), but little to no cross resistance to (...)
- mutations in the neuraminidase gene
- influenza B
- peramivir; zanamivir
92
- How is oral oseltamivir absorbed and when does it reach peak serum concentrations?
- What is the bioavailability of oseltamivir phosphate carboxylate?
- More than 99% of active oseltamivir carboxylate is excreted (...)
- well absorbed; in 1 hour
- 75%
- renally
93
What are the most common adverse effects of oseltamivir?
- N/V/D
- abdominal pain
- insomnia
- vertigo
94
What are the neuropsychiatric adverse effects of oseltamivir that are more common in children?
- delirium
- abnormal behavior
- hallucinations
95
- How is zanamivir administered?
- Why is it administered this way?
- What are the indications for zanamivir use?
- inhalation
- has poor absorption through the oral route
- used for treatment and prophylaxis of influenza A and B
96
- Inhaled zanamivir produces high concentrations in the (...) where influenza infections occur
- About (...) of inhaled zanamivir is absorbed systemically, producing peak serum concentrations in (...) hours
- How is the absorbed zanamivir drug excreted?
- respiratory tract
- 4-20%; 1-2 hours
- excreted unchanged in urine
97
- How is inhaled zanamivir tolerated?
- What can zanamivir produce?
- What should be given as treatment for patients with pulmonary disease?
- What are some other adverse effects of zanamivir?
- well tolerated
- acute bronchospasm with decline in respirator function
- bronchodilator such as albuterol
- HA, GI symptoms; hypersensitivity and neuropsychiatric adverse effects are rare
98
- How is peramivir administered?
- Peramivir is highly effective against which influenza strains?
- What else is it highly effective against?
- What does peramivir have cross resistance to?
- single dose via IV route
- influenza A and B
- emerging strains with pandemic potention (H5N1, H7N9, H9N2)
- oseltamivir
99
- What is the bioavailability of peramivir?
- Because of this, it is administered via (...)
- Peramivir is not significantly metabolized by the (...) as it is not a substrate of (...)
- Peramivir is almost entirely eliminated by (...)
- (...)% of peramivir is excreted unchanged
- low bioavailability (3%)
- IV
- liver; CYP enzymes
- renal excretion
- 90%
100
- In what populations of people is peramivir well tolerated in?
- Adverse effects are generally (...)
- What are the common side effects of peramivir?
- adult and pediatric populations
- mild to moderate and self limiting
- GIT disorders (N/V/D) and decreased neutrophil count
101
- What is a newer agent approved in 2018 to be used against influenza and is only available as brand name right now so it is very expensive?
- What type of inhibitor is this drug?
- baloxavir marboxil
- endonucleotide inhibitor
102
- Baloxavir marboxil is an oral prodrug converted to (...)
- What is the MOA of this drug?
- baloxavir
- inhibitor of a selective polymerase acidic protein in influenza viral RNA polymerase which prevents viral gene transcription and replication
103
- Baloxavir marboxil of active against which strains of influenza?
- What else it is active against?
- influenza A and B viruses
- strains resistant to standard antiviral agents
104
- How is baloxavir marboxil available?
- What is the indications for using this drug?
- What are the pharmacokinatics of baloxavir marboxil?
- What should you avoid while taking this drug?
- What are the adverse effects of baloxavir marboxil?
- oral formulation as a single dose
- prophylaxis and treatment of influenza A and B
- possibility of chelation with cations
- avoid dairy products, calcium-fortified beverages, or oral supplements containing calcium, iron, magnesium, selenium, or zinc
- GI upset (diarrhea)
105
- Regardless of post-exposure prophylaxis or treatment, antiviral agents for influenza must be started within (...)
- Prophylaxis is best for (...) patients
- What are some examples of patients that fall in this category?
- Which influenza antiviral drugs are not indicated for prophylaxis? Why?
- 48 hours
- high-risk patients
- young children, elderly, persons with chronic diseases, immunocompromised patients
- adamantanes and peramivir due to resistance
106
- Influenza treatment benefits are highly dependent on timing of (..) of treatment
- Which antiviral is generally the best choice?
- Why is this?
- initiation; the sooner the better
- oseltamivir (tamiflu)
- low cost, widely available, pediatric and adult formulations
