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Pharm: Pre Midterm 2 > Antivirals: Flu and Hepatitis > Flashcards

Antivirals: Flu and Hepatitis Flashcards

1
Q

The current available antiviral drugs target three main groups of viruses, what are they?

A

Influenza
Hepatitis
Herpes

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2
Q

First lets start with the antiviral drugs for influenza. First up are the Neuraminidase inhibitors (Oseltamivir and Zanamivir). What are the general features?

A

Neuraminidase is a essential enzyme in the replication of influenza A and B viruses

  • -cleaves sialic acid residues from viral proteins and surface proteins of infected cells, functioning to promote virion release and to prevent clumping of newly released virions.
  • -by giving these drugs there is interference with these actions, thus impede viral release and viral spread
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3
Q

What are the pharmacokinetics for the Neuraminidase Inhibitors?

A

Oseltamivir: prodrug. activated in the gut and liver. orally taken and excreted renally
Zanamivir: intranasally and 4-20% is absorbed systemically (excreted in urine)

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4
Q

Neuraminidase inhibitors are approved for what use?

A

Oseltamivir: tx of children greater than 1 year and adults with A or B influenza.
Zanamivir: tx of children greater than 7 and adults with A or B influenza.
–tx needs to be started within 48h of disease onset
–reduce the febrile period during infection

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5
Q

What are the AE of Neuraminidase inhibitors?

A

Oseltamivir: n/v/d/abd pain/ neuropsychiatric
Zanamivir: acute bronchospasm

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6
Q

What is the resistance pattern for the Neuraminidase Inhibitors?

A

Oseltamivir resistant influenza A has been reported

Normally if resistance to oseltamivir occurs then zanamivir is also resistant

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7
Q

What is the recommendation of Neuraminidase Inhibitors and pregnancy?

A

Recommended for the tx or prophylaxis of influenza in pregnant women and women up to 2 weeks postpartum
–also should get the vaccine if prego

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8
Q

Next influenza drug are the M2 Inhibitors (Amantadine and Rimantadine). What are some features?

A

Inhibit replication of influenza A virus by impairing the function of the membrane protein M2
–M2 is an acid activated ion channel required for viral uncoating and nucleocapsid release

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9
Q

What are the pharmacokinetics for M2 inhibitors?

A

Amantadine: well absorbed after oral admin and is excreted by glomerular filtration
Rimantadine: well absorbed orally but undergoes hepatic metabolism

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10
Q

What are M2 inhibitors used for?

A

Susceptible Influenza A infection

  • -need to be given within 48 hours of disease onset
  • reduce duration of symptoms by 1 day
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11
Q

What has limited the use of M2 inhibitors in the clinical setting?

A

Resistance

  • -Amantadine resistance: emerges within 2-4 day of tx
  • -Rimantadine: M2 mutation confers cross resistance
  • -no longer used due to resistance
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12
Q

What are the AE of M2 inhibitors?

A

Amantadine: well tolerated.

  • -mild neurologic symptoms, esp in old ppl taking neuroaffective drugs
  • -neuro symptoms are less severe and frequent with rimantadine
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13
Q

Can M2 inhibitors be used in pregnancy?

A

NOPE

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14
Q

Next antiviral drugs will focus on Hepatitis. What are the goals of antiviral tx?

A

Hep B: suppressive

Hep C: viral eradication

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15
Q

First antiviral used for Hepatitis is Interferons. What are some features?

A

Natural occurring proteins produced in response to viral infection.
–alpha, beta and gamma
Only available in parenteral formation, either SQ or IM
Administered daily or 3 times a week
Extensive renal metabolism

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16
Q

What is pegylation in terms of Interferon tx for Hepatitis?

A

Attachment of IFN to a large inert polyethylene glycol

  • -reduces the rate of absorption and excretion of IFN and therefore increases plasma concentration
  • -administered once a week
17
Q

What is the MOA for interferon?

A

IFN initiate a cascade of events via Janus Kinases

  • -leads to cellular responses (inhibition of virus replication, suppression of cell proliferation, enhancement of the phagocytic activity of macrophages, and augmentation of the specific cytotoxicity of lymphocytes)
  • -antiviral action is due to activation of a host cell ribonuclease that degrades viral mRNA
  • -IFNalpha promotes formation of NK cells that destroys infected liver cells
18
Q

IFNa have been used in multiple viral infection and are most commonly used for chronic viral hepatitis alone or in combo with other drugs. When used in combo?

A

Combo with ribavirin
—acute HCV infection to chronic HCV is reduced
Pegylated + ribavirin
–superior to standard IFNalpha in chronic HCV

19
Q

What are the AE of Interferon?

A 
Neuropsychiatric disorders (screen for depression) (if depressed can give serotonin reuptake inhibitors)
Neurological disturbances 
Myelosuppression 
Cardiovascular disorders 
Endocrine Disorders 
Pulmonary Disorders
20
Q

The next drug used in the tx of Hepatitis is Ribavirin, what are some features?

A

MOA is diverse and not understood.

Oral (first pass metabolism so only 65% bioavailable), Aerosolized(Some absorbed systemically) and IV formulations

21
Q

Ribavirin is used for what?

A

In combo with IFNalpha for HCV
Tx of RSV in kids (if RSV pneumonia then give via inhalation)
Off label for: HSV, Influenza, Severe acute resp syndrome, Coronavirus, Lassa Fever

22
Q

What are the AE of Ribavirin?

A

Aerosolized: sudden deterioration of resp function and cardio effects. Hemolytic anemia. Depression and relapse of drug abuse
Do not use in patients with past psychiatric disorders
Teratogenic effects: do not give to pregos or their partners (use contraception during therapy and 6 months after)

23
Q

The current tx of HCV is IFNalpha plus ribavirin. Recently two serine protease inhibitors have been approved. The first is Boceprevir. What are some features?

A

HCV protease inhibitor
Used in combo with interferon and ribavirin
Exerts anti-HCV properties by binding reversibly to the HCV nonstructural 3 protein inhibiting viral replication
Orally and metabolized in the liver
AE: Flu like illness and Anemia (can be severe)

24
Q

The second protease inhibitor is Telaprevir, what are some features?

A

Same MOA as Boceprevir
Tx of naive HCV patients and those who do not benefit from tx with IFNalpha and ribavirin
AE: anemia, and rash (can be severe with eosinophilia)

25
Q

In addition to IFN’s several nucelos(t)ide analogs are available for the tx of hepatitis. What is the mechanism of their anti-HBV property?

A

Competitive Inhibition of HBV DNA polymerase

26
Q

Nucleos(t)ide analogs have what additional properties?

A

Additional anti-HIV properties

  • -recommended that HBV patients considered for tx with these drugs be tested for HIV infection, and monotherapy with these drugs be avoided to reduce risk of HIV resistance.
  • -hep B may also develop resistance therefore use of combo drugs is recommended
27
Q

If discontinuation of Nucleos(t)ide analogs what happens?

A

Severe exacerbation of hepatitis

  • -monitoring for hepatotoxicity should be performed after stopping tx.
  • -lactic acidosis may occur and should be withdrawn if there is an increase in ALT levels
28
Q

The first Nucleoside analog is Lamivudine, what are some features?

A

Nucleoside analog of cytosine

  • -phosphorylated intracellularly into its active 5’triphosphate metabolite
  • -active metabolite is incorporated into viral DNA by HBV polymerase
  • -DNA chain termination
29
Q

What are the AE of Lamivudine?

A

AE:
–mild
Clinical utility of lamivudine is limited by the rapid development of antiviral resistance

30
Q

The second Nucleoside analog is Entecavir, what are some feature?

A

Nucleoside guanosine analog
–considered one of the most potent agents for the tx of patients with Hep B
MOA:
–inhibits 3 specific function of HBV polymerase: priming of the HBV DNA polymerase, reverse transcription of the negative strand from the pregenomic mRNA, and synthesis of positive strand HBV DNA
Resistance:
–high barrier to resistance and requires at least 3 mutations for resistance to occur

Pharm: Pre Midterm 2 (37 decks)

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