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Flashcards in antivirals Deck (42):
1

interferons

One of the best known agents of the class of drugs which inhibit viral synthesis in infected cells.
One form of human interferon, named interferon alpha, is well-established as a treatment for hepatitis B and C,

2

viricides

actively deactivate virus particles outside the body.

3

ffective anti-viral treatment is limited to a small number of viruses:

influenza types A and B and respiratory syncytial virus (R.S.V.).
○ Herpesviruses
○ Cytomegalovirus
○ Human immunodeficiency virus
○ Viral hepatitis B and C

4

Influenza A

known to occur only in humans. It is often referred to as seasonal flu.
• H1N1 and H3N2 are the most common
strains of influenza A.

• Swine flu, originally designated as novel
influenza A (novel A H1N1), is now most often referred to as simply H1N1.

5

influenza A and B treatment

Tamiflu (Oseltamivir) or Relenza (Zanamivir)

Ribaviran/ Virazole - for both influenza A and B and R.S.V.

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Oseltamivir/ Tamiflu

Indication: Treatment (and prevention) of
infections due to influenza A and B virus in adults and in children at least one year of age -- when given within 48 hours of symptoms of infection--.
Tamiflu has also shown effectiveness for H5N1 also known as avian flu.

• MOA: Neuramidase inhibition. Tamiflu was the first orally active neuraminidase inhibitor to be commercially developed.

• Char: Oral route. !!!Must be started within 48 hours of onset of symptoms in order to be effective.!!!!

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Neuramidase

viral enzyme that allows for the release of viral progeny (virons) from the host cell. If inactivated the virus cannot leave the host cell and eventually dies due to exhausting the cell’s metabolism

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Oseltamivir/ Tamiflu dosage

The usual adult dosage for the treatment of influenza is 75 mg twice daily for 5 days, beginning within 2 days of the appearance of symptoms.

• Standard prophylactic dosage is 75 mg once daily for patients aged 13 and older.

• Doses are decreased for children and patients with renal impairment.

9

Oseltamivir/ Tamiflu SE

• Side effects: Abdominal pain, nausea, vomiting and headache.
• There is concern about potential adverse neurologic effects including delirium, hallucinations, depression and increased suicidal ideation but the data are not definitive.
• As with all anti-microbials, the risk of creating medication-resistant influenza is not only likely, it’s certain.

10

Zanamivir/ Relenza MOA

• Zanamivir was the first neuraminidase inhibitor to be commercially developed.

• Mode of action consists of blocking the function of the viral neuraminidase protein, thus preventing the virus from budding off from the host cell.

• Relenza has proven to act against both influenza A and influenza B and avian flu, when given within 48 hours of infection.

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methods of antiviral action

1. interfere with the ability of a virus to attach to the host cell and/ or inhibit entry into the host cell.
2. selectively target the processes that allow for the virus to shed its protein coat within the host cell thus blocking release of the virus.
3. inhibit viral genome replication by blocking the synthesis of viral components after a virus has invaded the host cell.
4. block viral release from a host cell.


***additional treatment option involves stimulation of the body's immune system to respond to the virus rather than attacking the virus directly.

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Zanamivir/ Relenza dosage

Relenza is formulated as a powder that is delivered via the respiratory tract by an oral inhaler.

• The recommended dose of Relenza for the treatment of influenza in adults and pediatric patients 7 years of age and older is 10 mg (two puffs) twice daily for 5 days.

• Two doses should be taken on the first day of treatment whenever possible, provided there is at least 2 hours between doses.

• On subsequent days, doses should be about 12 hours apart (i.e. morning and evening) at approximately the same time each day.

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Zanamivir/ Relenza CI

• Relenza is not recommended for the treatment or prophylaxis of influenza in individuals with a history of asthma or COPD due to risk of serious bronchospasm

• Relenza has not been proven effective for prophylaxis of influenza when tested in nursing home settings.

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Zanamivir/ Relenza info and se

• Class: Anti-viral
• Indication: Influenza treatment and/or
prophylaxis
• MOA: Neuramidase inhibitor
• Char: Inhaled route only
• Side effects: Nausea and vomiting. As an
anti-viral medication, the incidence of post-treatment diarrhea, vaginal Candidiasis and thrush is negligible.

15

Amandatine/ Symmetrel

• Amandatine is an anti-viral agent that was recommended as prophylaxis against influenza A or for treatment of influenza A before 2009 but is no longer indicated due to resistant strains.

• Amantadine is also used as a treatment for the early stages of Parkinson's disease.

• It is best used as short-term therapy (range of 6 to 12 months) for people with early stage mild to moderate symptoms of Parkinson's disease.

16

Herpes virus

• There are eight members of the herpes virus family that infect humans.

• These viruses include HSV-1, HSV-2 and VZV (varicella-zoster virus – the cause of chickenpox and shingles).

• Other human herpesviruses include: Epstein- Barr virus (EBV), human cytomegalovirus (CMV), Roseola-associated HHV, Pityriasis Rosea associated virus and Kaposi's sarcoma associated herpesvirus.

17

Ramsay Hunt syndrome

type 2 also known as herpes zoster oticus is a disorder that is caused by the reactivation of pre-existing herpes zoster virus in the geniculate ganglion, a nerve cell bundle, of the facial nerve. Ramsay Hunt syndrome type 2 typically presents with inability to move many facial muscles, pain in the ear, taste loss on the front of the tongue, dry ears and mouth, and the eruption of an erythematous rash.

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Hutchinson’s sign

refers to an outbreak of herpes zoster on or near the of the nose. This sign may precede the development of ophthalmic herpes zoster. This occurs because the nasociliary branch of the trigeminal nerve innervates both the cornea and the tip of the nose.

19

Drugs for herpesvirus infection

• Acyclovir/ Zovirax
• Famciclovir/ Famvir
• Foscarnet/ Foscavir
• Gancyclovir/ Cytovene
• Trifluridine/ Viroptic
• Vidarabine/ Vitravene

20

Acyclovir/ Zovirax

• Class: Anti-viral
• Indication: Herpesvirus infections such as
HSV-1, HSV-2 and Herpes zoster (chicken
pox and shingles).
• MOA: Acyclovir is a guanosine analog
that is incorporated into the virus DNA and inhibits further viral synthesis.

21

Acyclovir/ Zovirax moa

• Acyclovir only works against viruses that are actively replicating and is ineffective against latent virus.

• Char: PO, IV and topical ointment (USELESS)
. Acyclovir can actively cross the blood barrier and can thus be used to treat herpes meningitis and encephalitis. Resistance to Acyclovir is being reported more frequently.

22

Acyclovir/ Zovirax se

• Side effects: Dependent upon route of administration. Headache, nausea and vomiting can occur with oral dose. Transient renal insufficiency can occur with higher IV doses and skin irritation can occur with topical doses.

23

Human immunodeficiency virus

retrovirus that can lead to acquired immunodeficiency syndrome (AIDS), a condition in which the immune system begins to fail, leading to life-threatening opportunistic infections.
• Infection with HIV occurs by the transfer of blood, semen, vaginal fluid or breast milk.

24

HIV moa

When HIV infects a cell, the viral enzyme, reverse transcriptase, copies the viral single stranded RNA genome into a double-stranded viral DNA.

• The viral DNA is then integrated into the host chromosomal DNA which allows the cellular processes of the host, such as transcription and translation, to reproduce the virus.

25

Drugs for HIV /AIDS

• There are 4 main categories of drug used as treatment or prophylaxis against human immunodeficiency virus.

• Reverse transcriptase inhibitors (RTIs)
• Protease inhibitors (PIs)
• Fusion inhibitors
• Integrase inhibitors

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HAART.

highly active antiretroviral therapy or HAART.

• HAART options are combinations (also referred to as “anti-viral cocktails") of anti- viral agents usually consisting of at least three drugs belonging to at least two classes of anti-retroviral agents.

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HAART drug classes

two nucleoside reverse transcriptase inhibitors plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).

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Reverse transcriptase inhibitors (RTIs)

RTIs block enzymatic function of reverse transcriptase and prevent the completion of synthesis of double-stranded viral DNA thus preventing HIV from multiplying.

• RTIs come in three main forms:
• Nucleoside reverse transcriptase inhibitors
• Nucleotide reverse transcriptase inhibitors
• Non-nucleoside reverse transcriptase inhibitors

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Nucleoside reverse transcriptase inhibitors

• Zidovudine (AZT)/ Retrovir
• Didanoside (ddI)/ Videx
• Stavudine (d4T)/ Zerit
• Lamivadine (FTC)/ Epzicom
• Zalcitabine (ddC)/ Hivid
• Lamivadine + Zadovudine/ Combivir

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Zidovudine (AZT)/ Retrovir

• Class: Anti-viral, nucleoside reverse transcriptase inhibitor
• Indication: H.I.V.
• MOA: AZT is a pyrimidine analog that is
incorporated into the viral DNA by reverse transcriptase. Incorporation into viral DNA terminates further replication.
Char: PO. Crosses blood brain barrier. Short half life of approximately 1 hour (0.5 to 3 hrs). Increasing resistance to the drug is occurring.
• Side effects: Headaches are common. Potentially toxic to bone marrow with severe anemia and leukopenia in patients receiving high doses.

31

Nucleotide reverse transcriptase inhibitors

• Nucleotide analog reverse transcriptase inhibitors are also referred to as NtARTIs or NtRTIs.
• Normally, nucleoside analogs are converted into nucleotide analogs by the body.
• Taking NtRTIs directly allows for conversion steps to be skipped, which usually results in fewer side effects.

32

Non-nucleoside reverse transcriptase inhibitors

• Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA.
• Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs bind within a pocket termed the NNRTI pocket.

33

Protease inhibitors

• Many viruses contain an enzyme known as protease.
• Protease cleaves viral protein chains apart so that they can be assembled into new viral particles (virons).
• Protease inhibitors prevent active viral replication by inhibiting the activity of this enzyme.
• Protease inhibitors are currently used to treat HIV and Hepatitis C.

34

Protease inhibitors

• Saquinavir/ Invirase
• Amprenavir/ Agenerase • Indinavir/ Crixivan
• Nelfinavir/ Viracept
• Ritonovir/ Norvir

35

Saquinavir/ Invirase

• Class: Anti-viral, protease inhibitor • Indication: H.I.V., Hepatitis C
• MOA: Protease enzyme inhibition
prevents viral protein molecules from being cleaved into smaller fragments, which prevents both the replication of the virus within the cell and the release of mature viral particles from an infected cell.

Char: usually administered as part of a multi-drug ‘cocktail” in order to reduce the incidence of drug resistance.

• Side effects: Mostly G.I. i.e. abdominal discomfort, nausea, vomiting and diarrhea.

36

Interferons

• Interferons are cytokines produced by the cells of the immune system in response to foreign agents such as viruses, bacteria, parasites and tumor cells.
• IFN-α and IFN-β are secreted by many cell types including lymphocytes (such as NK cells, B-cells and T-cells) as well as macrophages, fibroblasts, endothelial cells, osteoblasts and other tissue cell types.

37

IFN-α and IFN-β

stimulate both macrophages and NK cells to elicit an anti-viral and anti-tumor response.
• However, interferons also accounts for many of the host symptoms, such as severe myalgias arthralgias, fevers, sore throat and headaches.

very important in fighting RNA virus infections.

secreted by many cell types including lymphocytes (NK cells, B- cells and T-cells),

IFN-α acts as a pyrogenic factor by altering the activity of thermosensitive neurons in the hypothalamus thus causing fever.

It does this by eliciting the release of prostaglandin-E2 (PGE2).

IFN-ω is released by leukocytes at the site of viral infection or tumors.

38

Interferon classes

• There are three main types of interferon utilized as drug treatments:
• Interferon alpha – for hepatitis C
• Interferon beta – for relapsing multiple sclerosis
• Interferon gamma – for chronic granulomatous diseases

39

interferon types

Interferon type I - Interferon beta-1a - Interferon beta-1b
- Pegylated interferon alfa-2a - Pegylated interferon alfa-2b

Interferon type II - Interferon-gamma
Interferon type III - Interleukin 28 - Interleukin 29

40

Interferon alpha

• Class: Anti-viral
• Indication: Chronic hepatitis B and C,
genital warts due to HPV, Kaposi’s sarcoma
and hairy cell leukemia.
• MOA: Interferon is a naturally occurring
glycoprotein that interferes with the ability of a virus to infect cells. Interferon appears to induce host cell enzymes that inhibit viral RNA translation and subsequent viral synthesis within the infected host cell.

41

Interferon alpha se and char

• Char: IM, IV, and intra-lesional injection.
Crosses blood brain barrier. Interferon alpha is obtained via recombinant DNA technology.

• Side effects: Arthralgias, myalgias, fever, lethargy, headache, dizziness, hair thinning and depression.

42

Interferon alpha types

• Pegylated interferon alpha is a form of interferon in which polyethylene glycol is added to make the interferon last longer in the body.

• The pegylated form is injected once weekly, rather than three times per week for conventional interferon-alpha.

• When treating hepatitis C, pegylated interferon is often administered with the drug, !!! Ribavirin !!!