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Pharmacology II > Exam 3: Antivirals > Flashcards

Exam 3: Antivirals Flashcards

1
Q

Describe the mechanisms of Antivirals

A
  1. Alter uncaring of virus
    • virus uncoats to begin replication
    • drugs prohibit this phase, so cannot penetrate host
  2. Polymerase inhibitors
  3. Inhibit viral protein synthesis
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2
Q

What antiviral drugs are indicated for Influenza A?

A

amantadine (Symmetril)

rimantidine (Flumadine)

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3
Q

Mechanism of amantadine and rimantidine

A

Blocks uncaring of virus preventing penetration into host

- rimantidine is significantly more active than amantadine

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4
Q

Side effects of amantadine and rimantidine

A
  1. CNS stimulation
    • enhanced by antihistamines and caffeine
  2. Insomnia
  3. Grand Mal Seizures
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5
Q

Indications for Tamiflu

A

Influenza A or B

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6
Q

What drug is considered the classic prodrug?

A

Tamiflu

- hydrolyzed to active form

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7
Q

Action of Tamiflu

A

Neuraminidase inhibitor
- drug is an enzyme inhibitor that cleaves the budding viral progeny from its cellular envelope attachment point just prior to release

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8
Q

Indications for ribavirin (Rebetol, Virazole)

A

Treatment of respiratory syncytial virus

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9
Q

Mechanism of ribavirin

A

prevents synthesis of viral proteins encoded by viral mRNA

  • inhibits virus RNA polymerase
  • Disrupts transcription, translation or promotes degradation of viral RNA
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10
Q

Side effects of ribavirin

A

mutagenic
teratogenic
carcinogenic

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11
Q

Indications for trifluridine (Viroptic)

A

herpes simplex keratitis (in eye)

keratoconjunctivitis

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12
Q

Mechanism of trifluridine

A

interferes with viral replication by incorporating into viral DNA in place of thymidine, causing formation of defective proteins

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13
Q

What is the IV drug of choice for HSV encephalitis?

A

acyclovir (Zovirax)

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14
Q

Action of acyclovir (Zovirax)

A

Inhibits viral DNA polymerase preferentially (Cell cycle specific)

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15
Q

Indications for acyclovir

A

IV drug of choice for HSV encephalitis

- primary and recurrent herpes in immunocompromised patients

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16
Q

How often does acyclovir need to be used?

A

Every 3 hours, which is consistent with cycle phases of viruses

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17
Q

Indication of ganciclovir (Cytovene)

A 
human cytomegalovirus (CMV)
- treats CMV retinitis
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18
Q

Action of ganciclovir (Cytosine)

A

inhibits viral DNA synthesis

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19
Q

Which drugs are indicated to treat recurrent genital herpes

A

famciclovir and valacyclovir

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20
Q

T or F, famciclovir and valacyclovir are classic prodrugs

A

true

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21
Q

What are interferons?

A

a family of naturally occurring, inducible glycoproteins that interfere with the ability of viruses to infect cells
- antiviral, cytotoxic, immunomodulatory actions

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22
Q

3 types of interferons?

A

alpha
beta
gamma

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23
Q

How are interferons administered?

A

intralesionally
subcutaneously
IV

24
Q

Mechanism of Interferons

A

Not completely understood…
- Induction of host cell enzymes that inhibit viral RNA translation, ultimately leading to the degradation of viral mRNA and tRNA

25
Q

Most common indications of Inteferons

A

Hepatitis B and C
Multiple Sclerosis

  • Also used for some cancers
26
Q

Adverse effects of Inteferons

A
  1. Flu-like symptoms
  2. bone marrow suppression
  3. neurotoxicity
  4. CNS effects
  5. Severe fatigue
  6. Severe weight loss
  7. Autoimmune disorders
  8. Cardiovascular
  9. Oral
27
Q

Name the new drugs for Hepatitis C

A
  1. ledipasvir + sofosbuvir (Harvoni)
  2. simeprevir (Olysio)
  3. sofosbuvir (Sovaldi)
  4. boceprevir (Victrelis)
  5. telaprevir (Incivek)
28
Q

What is the challenge with antiretrovirals

A

To kill the virus, host cells are often harmed

- Antivirals that alter viral replication processes are often toxic to host cells

29
Q

Explain the mechanism of Antiretrovirals

A
  • Inhibiting viral attachment and entry limits spread of virus within body
  • Alter genome replication = polymerase inhibitors
  • Immunization = provides antibodies against viral envelop proteins
30
Q

Name the drug that was the first antiviral HIV agent that inhibits viral entry into host cells

A

enfuvirtide (Fuzeon)

31
Q

Target of antiretrovirals for Retrovirsuses?

A 
Reverse transcriptase (1st class to be used)
- main enzyme used by virus to copy genome into DNA
32
Q

3 primary classes of Antiretroviral drugs for HIV

A
  1. Nucleoside reverse transcriptase inhibitors
  2. Protease inhibitors
  3. Nonnucleoside reverse transcriptase inhibitors
33
Q

What are the drug concepts for HIV?

A
  • Drugs target structural and functional differences between viral and human proteins
  • Treatment of HIV infection requires combination therapy = HAART (Highly Active AntiRetroviral Therapy)
  • “cocktails”
34
Q

Define a typical cocktail

A

all of the primary classes of antiretroviral drugs

  1. nucleoside reverse transcriptase inhibitor
  2. non-nucleoside reverse transcriptase
  3. protease inhibitors
35
Q

When are antiretrovirals started in a patient?

A

when immunosuppression becomes pronounced

- CD4

36
Q

What is a Triple Cocktail?

A

2 nucleoside reverse transcriptase inhibitors

1 Protease inhibitor

37
Q

Side effects of Antiretrovirals

A
  1. Anemia (toxic to bone marrow and blood cells)
  2. Leukopenia and granulocytopenia
  3. Hepatotoxicity
  4. Peripheral neuropathy
  5. Pancreatitis
38
Q

T or F, Nucleoside Reverse transcriptase inhibitors are not classified as prodrugs

A

False,

Must be biotransformed/bioactivated to work

39
Q

Action of Nucleoside Reverse transcriptase inhibitors

A

Drug is integrated into DNA polymerase so that synthesis of viral DNA is terminated

  • Inhibits viral enzyme reverse transcriptase
  • **Drugs have no effect on cells already containing HIV
40
Q

T or F, Reverse transcriptase of HIV is 1100 times less susceptible to inhibition than are normal human cells making them harder to target

A

False,

1100 times more susceptible

41
Q

List the Nucleoside reverse transcriptase inhibitors

A 
abacavir (Ziagen)
(B) didanosine (Videx)
emtricitabine (Emtriva)
lamivudine (Epivir)
stavudine (Zerit)
zalcitabine (Hivid)
(B) zidovudine (Retrovir) = AZT
42
Q

Action of AZT

A

Inhibits HIV synthesis and reduces morbidity/mortality from AIDS and AIDS-related complex

43
Q

Side effects of AZT

A
  1. Very toxic = bone marrow depression
  2. CNS effects
  3. Nausea
  4. Oral effects = altered taste, tongue edema, bleeding gingiva
44
Q

What drugs have interactions that inhibit metabolism of AZT

A

NSAIDS

Aspirin

45
Q

List the Non-nucleoside reverse transcriptase inhibitors

A

delavirdine (Rescriptor)
efavirenz (Sustiva)
etravirine (Intelence)
nevirapine (Viramune)

46
Q

Action of Non-nucleoside reverse transcriptase inhibitors

A

block reverse transcriptase

- Drugs inhibit the catalytic reaction of reverse transcriptase that is independent of nucleotide binding

47
Q

T or F, Non-nucleoside reverse transcriptase inhibitors are classified as prodrugs

A

false, Do not require bioactivation

48
Q

Action of Protease Inhibitors

A

Drugs suppress viral replication by inhibiting protease, the enzyme responsible for cleaving viral precursor peptides into infective virions
- Prevents maturation of HIV-infected cells

49
Q

What is the primary difference of protease inhibitors vs the other 2 classes of antiretrovirals

A

Interfere with the action of HIV-infected cells

50
Q

List the Protease inhibitors

A 
atazanavir (Reyataz)
darunavir (Prezista)
fosamprenavir (Lexiva)
(B) indinavir (Crixivan)
(B) nelfinavir (Viracept)
ritonavir (Norvit)
(B) saquinavir (Invirase)
tipranavir (Aptivus)
51
Q

Action of Nucleotide Reverse transcriptase inhibitors

A

Interferes with HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication

52
Q

Name the Nucleotide Reverse Transcriptase inhibitor drug

A

tenofovir (Viread)

53
Q

Action of Integrase Inhibitors

A

Inhibits integrase, the enzyme that helps to insert the viral cDNA strand produced by reverse transcriptase into the human genome
- prevents integration of proviral gene into human DNA

54
Q

Name the Integrase Inhibitor drugs

A

raltegravir (Isentress)

dolutegravir (Tivicay)

55
Q

What is complera

A

A NEW combination drug used for initial treatment of HIV-infected individuals

56
Q

Complera contains what 3 medications

A

emtricitabine
rilpivirine
tenofovir disoproxil fumarate

Pharmacology II (24 decks)

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