Antiviral Rubella Picorna 2011

8/3/2019 Antiviral Rubella Picorna 2011

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ANTIVIRALS

Mary Joyce Saborrido- Teoxon, RMT, MD

FEU-NRMF Institute of Medicine

What to expect?

• To review the viral replication.

• To site the effects of each antiviral drugs.

• To enumerate the different antiviral drugs.

• To identify the uses of each antiviral drugs.

• To discuss the different adverse effect of

each to human.

Steps inViral

Replication

Adsorption. The virus attaches to the host

cell to specific binding of its spikes to cell

receptors.

Penetration. The virus is engulfed into a

vesicle and its envelope is

Uncoated, thereby freeing the viral RNA

into the cell cytoplasm.

Synthesis. Replication

and Protein Production.

Under the control of viral

genes, the cell synthesizes

the basic components of

new viruses: RNAmolecules, capsomers,

spikes.

Released. Enveloped viruses bud off of the

membrane, carrying away an envelope with

the spikes. This complete virus or virion isready to infect another cell.

Assembly. Viral spike proteins are insertedinto the cell membrane for the viral envelope;

nucleocapsid is formed from RNA and

capsomers.

Viral penetrationinhibitors

• Amantadine

• Rimantadine

Amantadine & Rimantadine

• MOA: (-) attachment, penetration & uncoating of Influenza A virus

• Use: PROPHYLAXIS only (but can duration of symptoms by 1-2 days)

• Form: PO

• AE: CNS effects (nervousness, insomnia,hallucination, seizure in OD)

• Resistance: Documented

Viral nucleic acid

synthesis inhibitors

• Antiherpetics

Antimyxovirus• Antiretrovirals

Acyclovir- MOA

AcyclovirThymidine

Kinase

Acyclovir

monophosphateThymidine

Kinase

DNA Polymerase

(DNA chain termination)

Acyclovir

triphosphate

Acyclovir- HSV & VZV

ViralShedding

Primary

Infection

andRecurrence

http://slidepdf.com/reader/full/antiviral-rubella-picorna-2011 9/39Acyclovir- HSV & VZV

Acyclovir

• Propyhlactic in immunocompromised

• Form: Topical, Oral, IV

• AE: IV (Crystalluria & Neurotoxic)

Resistance: due to changes in DNApolymerase

: activity of TK

Famciclovir &

Valacyclovir

•MOA: same as Acyclovir

• Activity against strains

resistant to acyclovir, but notTK - strains

Ganciclovir

• MOA: same as Acyclovir (not DNA chain

termination)

• Resistance: same as Acyclovir

• Use: HSV, VZV, CMV (prophylaxis & Tx)

• Form: Oral, IV and retinal implant

• AE: Dose-limiting hematotoxicity ( WBC,plt),

mucositis, fever, rash, crystalluria, Seizures in

Foscarnet

• MOA: Not an antimetabolite, but still (-) viral

DNA & RNA polymerases

• USE: identical to Ganciclovir, but > activity versus

acyclovir-resistant strains of HSV

• Form: IV

• AE: Dose-limiting nephrotoxicity w/ ATN,

electroltre imbalance Ca+2 tremors and

seizures.

Viral nucleic acid

synthesis inhibitors

Anti-myxovirus drugs

Ribavirin

• MOA: Ribavirin monophosphate IMPdehydrogenase

Ribavirin triphosphate viral RNApolymerase and end-capping of viral RNA

• Form: Aerosol, Topical

• Use: RSV, Infleunza A & B, Lassa fever,

Hantavirus, adjuncts to alpha-interferons inHepa C

• AE: Hematotoxic, Upper airway irritation,Teratogenic

Reverse TranscriptaseInhibitors (RTIs)

Anti-retrovirus drugs

Nucleoside RTIs (NRTIs)

•Components of most combination drugregimens used in HIV infection

• Used 2 NRTIs w/ PI

• Use in HAART ( viral RNA, CD4 cells,opportunistic infxn)

Nonnucleoside RTIs

• Resistance emerges if used

individually

• Additive/ Synergistic agaisnt HIV

Zidovudine (Azidothymidine, ZDV, AZT)

• MOA: Zidovudine triphosphate RT (Viral chain

termination)

• Form: Oral

• AE: Dose-limiting hematotoxicity ( PMN, RBC,

Plt) may require bld transfusion, HA, Asthenia,

myalgia, myopathy, peripheral neuropathy, lacticacidosis

• Resistance: Mutation in the gene that codes RT

Other NRTIs

• MOA: Same as AZT

• Resistance: same as AZT

• AE: Different

Didanosine,DDI

Pancreatitis (major, dose-limiting) – peripheral

neuropathy, hyperuricemia, liverdysfxn

Zalcitabine,DDC

Peripheral neuropathy (major,dose-limiting) – GI distress,pancreatitis, neutropenia, rash

Stavudine,D4T

Peripheral neuropathy (major,dose-limiting) –

myelosuppresion < ZDVLamivudine,3TC

Least toxic of NRTIs, but someGI effects and neutropenia

ProteaseInhibitors (PIs)

Anti-retrovirus drugs

• MOA: Aspartate protease is a viral enzyme thatcleaves precursor polypeptides in HIV buds toform the proteins of the mature virus core.

• Use: In combination w/ 2 NRTIs

• AE: Indinavir (Nephrolithiasis, GI distress, plt, (-P450)

Ritonavir (GI distress, asthenia, Paresthesia,

(-) P450)Saquinavir (one of the least toxic, has very

low oral bioavailability)

neuramidase

inhibitors

Zanamivir & Oseltamivir

• MOA: (-) neuramidase of Influenza A

& B, enzymes that prevent clumpingof virions

• Use: PROPHYLAXIS, duration of flu

symptoms by 2-3 days• AE: N & V, Zanamivir (Nasal & Throat

irritation)

MOA Major Drugs

Block viralpenetration/ uncoating Amantadine,Rimantadine

Inhibit viral DNApolymerase

Acyclovir, Foscarnet,Ganciclovir

Inhibit viral RNApolymerase

Foscarnet, Ribavirin

Inhibit viral reverse

transcriptase

AZT, DDI, DDC, D4T,

3TCInhibit viral asapartateprotease

Indinavir, Ritonavir,Saquinavir

Inhibit viralneuramidase

Zanamivir, Oseltamivir

Case # 1

• A 25-year-old woman had

arthralgia and mild rash on herface and spread to her body. She

recalled that she had felt as if she

had flu a few days before theonset of the rash. The rash

disappeared in 4 days.

What is the probable causative agent?• A 25-year-old woman had arthralgia

and mild rash (FACE BODY)

• (+) FLU symptoms few days beforerash

• Rash disappead on the 4th day

• What is the probable causative agent?

• VIRAL EXANTHEM?

• Rubeola ?• Rubella ?

• Roseola ?

RUBEOLA RUBELLA ROSEOLA

Measles

Hard Measles

Red Measles

German Measles

Three day Measles

Exanthem

subitum

Infants adults Infants Adults Infants

FEVER RASH

• 3Cs

• COUGH

• COLDS

CONJUNCTIVITIS• Koplik’s spots

• COMPLICATION

FEVER RASH

• Lymphadenopathy

• Arthralgia

FEVER RASH

• Describe the causative agent as to:

• Structure

• Site of replication

• What features of the case pointed to

the diagnosis of rubella infection?

• How was the infection transmitted?

• What precaution could the patient

have taken to prevent this infection?

MMR Vaccine

•Measles: Schwartz/ Moratensubstrains of Edmonston B strain

• Mumps: Jeryl Lynn strain

• Rubella: RA/ 27-3 strain

PICORNAVIRIDAE

• Small ss(+) RNA viruses

• Naked

Enteroviruses (group)

• Summer-fall peak incidence

• Fecal-oral transmission but do not cause diarrhea

• Peak age group <9 years for most

• Stable at pH3

• Resistant to alcohol, detergents because there is no

envelope

• Polio - ECHO - Entero

• Coxsackie A & B - Hepa A

Polio virus

• Most infections are asymptomatic, small %cause fever (viremia).

• Smaller % cause aseptic meningitis• Poliomyelitis (paralysis) (even smaller%)

results from viral damage to anterior hornmotor neurons

• Vaccines: both are trivalent

-Salk (killed/injectable)

- Sabin (live/oral/ best gut immunity)

Coxsackie A

• Herpangina (vesicles on soft palate and

fauces)• Hand-foot-and mouth disease (oral

lesions primarily in the anterior buccalmucosa)

• Aseptic meningitis

• Acute lymphoglandular pharyngitis

• Common cold

Antiviral Rubella Picorna 2011

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