antiviral rubella picorna 2011
TRANSCRIPT
8/3/2019 Antiviral Rubella Picorna 2011
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ANTIVIRALS
Mary Joyce Saborrido- Teoxon, RMT, MD
FEU-NRMF Institute of Medicine
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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.
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Steps inViral
Replication
Adsorption. The virus attaches to the host
cell to specific binding of its spikes to cell
receptors.
1
Penetration. The virus is engulfed into a
vesicle and its envelope is
Uncoated, thereby freeing the viral RNA
into the cell cytoplasm.
2
3
Synthesis. Replication
and Protein Production.
Under the control of viral
genes, the cell synthesizes
the basic components of
new viruses: RNAmolecules, capsomers,
spikes.
4
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.
6
5
Assembly. Viral spike proteins are insertedinto the cell membrane for the viral envelope;
nucleocapsid is formed from RNA and
capsomers.
5
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Viral penetrationinhibitors
• Amantadine
• Rimantadine
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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
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Viral nucleic acid
synthesis inhibitors
• Antiherpetics
•
Antimyxovirus• Antiretrovirals
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Acyclovir- MOA
AcyclovirThymidine
Kinase
Acyclovir
monophosphateThymidine
Kinase
DNA Polymerase
(DNA chain termination)
Acyclovir
triphosphate
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Acyclovir- HSV & VZV
ViralShedding
Primary
Infection
andRecurrence
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Acyclovir
• Propyhlactic in immunocompromised
• Form: Topical, Oral, IV
• AE: IV (Crystalluria & Neurotoxic)
•
Resistance: due to changes in DNApolymerase
: activity of TK
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Famciclovir &
Valacyclovir
•MOA: same as Acyclovir
• Activity against strains
resistant to acyclovir, but notTK - strains
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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
OD
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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.
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Viral nucleic acid
synthesis inhibitors
Anti-myxovirus drugs
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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
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Reverse TranscriptaseInhibitors (RTIs)
Anti-retrovirus drugs
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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)
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Nonnucleoside RTIs
• Resistance emerges if used
individually
• Additive/ Synergistic agaisnt HIV
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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
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Other NRTIs
• MOA: Same as AZT
• Resistance: same as AZT
• AE: Different
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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
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ProteaseInhibitors (PIs)
Anti-retrovirus drugs
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PIs
• 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)
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Viral
neuramidase
inhibitors
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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)
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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
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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.
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•
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
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• What is the probable causative agent?
• VIRAL EXANTHEM?
• Rubeola ?• Rubella ?
• Roseola ?
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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
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• 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?
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• What precaution could the patient
have taken to prevent this infection?
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MMR Vaccine
•Measles: Schwartz/ Moratensubstrains of Edmonston B strain
• Mumps: Jeryl Lynn strain
• Rubella: RA/ 27-3 strain
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PICORNAVIRIDAE
• Small ss(+) RNA viruses
• Naked
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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
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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)
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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