Summary MOA Block viral penetration/ uncoating Inhibit viral DNA polymerase Inhibit viral RNA polymerase Inhibit

viral reverse transcriptase Inhibit viral aspartate protease Inhibit viral neuramidase

  Major Drugs Aman.tadine, Riman.tadine Foscarnet, Acyclovir, Ganciclovir Foscarnet, Ribavirin AZT, DDI, DDC, D4T, 3CT Ritonavir Indinavir Saquinavir Zanamivir Oseltavimir

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VIRAL PENETRATION INHIBITORS Amantadine & Rimantadine
    MOA: (-) attachment, penetration & uncoating of influenza A virus Use: PROPHYLAXIS ONLY! o Can decrease duration of symptoms by 1-2 days Form: ORAL only! AE: CNS effects o Nervousness o Insomnia o Hallucination o Seizure in OD With RESISTANCE!

thymidine kinase of host cell  ACYCLOVIR TRIPHOSPHATE  inhibit  DNA polymerase (DNA chain) DNA polymerase seen in HSV & VZV Use: o ↓ viral shedding in genital herpes o ↓ Acute neuritis in shingles o ↓ Symptoms in early chickenpox (only lessen the lesion)  *given on the early stage (few lesions) o Prophylactic in immunocompromised MOT of chickenpox: Respiratory droplet AE: in IV (crystalluria & Neurotoxic) Resistance: o due to changes in DNA polymerase o decrease activity of TK Treated/ lessens the ff diseases: o Herpes lesion – painful vesicular lesion o Herpes/ Cold sore – reactivation of herpes infection o Chickenpox  Shingles – reactivated form; prone in immunocompromised

o

Seizures in OD

o o o

↑CD4 cells
 Only prevent damage; NOT to inhibit!

Foscarnet
    MOA: NOT an antimetabolite, but still (-) viral DNA & RNA polymerases USE: identical to Ganciclovir (HSV, VZV, CMV), but > activity versue acyclovir-resistant strains of HSV Form: IV AE: Dose-limiting nephrotoxicity with ATN, electrolyte calcium imbalance  tremors & seizures

↓Viral RNA ↓Opportunistic infection

Non-Nucleoside RTIs
   NOT given alone! Resistance emerges if used individually Additive/ Synergistic against HIV

Examples of NRTIs

Zidovudine (Azidothymidine, ZDV, AZT)
 MOA: Zidovudine triphosphate  RT (viral chain termination)  Form: Oral  AE: Dose-limiting hematotoxicity (PMN, RBC, Platelet) – may require blood transfusion, HA, Asthenia, myalgia, myopathy, peripheral neuropathy, lactic acidosis  Resistance: mutation in the gene that codes RT *All NRTIs – cause peripheral neuropathy Other NRTIs  MOA: Same as AZT  Resistance: Same as AZT  AE: *different Didanosine, DDI Pancreatitis (major, dose-limiting) – peripheral neuropathy, hyperuricemia, liver dysfunction Peripheral neuropathy (major, dose-limiting) – GI distress, pancreatitis, neutropenia, rash Peripheral neuropathy (major, dose-limiting) – myelosuppression < ZDV Least toxic of NRTIs, but some GI effects & neutropenia >this can give to hepatitis >both antiviral & antihepatitis

VIRAL NUCLEIC SYNTHESIS INHIBITORS
 Anti-myxovirus

Ribavirin
 MOA: o Ribavirin monophosphate  IMP dehydrogenase o Ribavirin triphosphate  viral RNA polymerase & end capping of viral RNA Form: Aerosol, Topical USE: o RSV, Influenza A&B o Lassa fever o Hantavirus o Adjuncts to alpha-interferons in Hepa C AE: o Hematotoxic, o Upper airway irritation o Teratogenic

 

Famicyclovir & Valacyclovir
   MOA: same as acyclovir Activity against strains resistant to acyclovir, but NOT TK-strains Against DNA polymerase 

Ganciclovir
     MOA: same as Acyclovir (NOT DNA chain termination) Resistance: same as acyclovir USE: HSV, VZV, CMV (prophylaxis & tx) o CMV – can cause retinitis, IMI Form: Oral, IV, & Retinal implant AE: o Dose-limiting hematotoxicity (↓WBC) o Mucositis o Fever, rash, crystalluria

Zalcitabine, DDC

VIRAL NUCLEIC ACID SYNTHESIS INHIBITORS
  (-) polymerase/ reverse transcriptase Protease inhibitor o Protease – used to mature protein

REVERSE TRANSCRIPTASE INHIBITORS (RTIs)
 Anti-retrovirus drugs

Stavudine, D4T Lamivudine, 3CT

Nucleoside RTIs (NRTIs)
   Components of most combination drug regimens used in HIV infection Used (2) NRTIs + (1) Protease inhibitors Use in Highly active antiviral reactive therapy (HAART) to:

Acyclovir
 MOA: ACYCLOVIR  thymidine kinase  ACYCLOVIR MONOPHOSPHATE 

Prepared by: EGBII; 09-18-11

PROTEASE INHIBITORS (PIs) Ritonavir, Indinavir, Saquinavir
 MOA: Aspartate protease is a viral enzyme that cleaves precursor polypeptides in HIV buds to form the proteins of the mature virus core USE: In combination with (2) NRTIs AE: o Ritonavir (Gi distress, asthenia, paresthesia, (-) P450) o Indinavir (GI distress, Nephrolithiasis platelet, (-) P450) o Saquinavir (LEAST toxic, has very LOW oral bioavailability) Differences Rubeola
.Hard measles .Red measles *child Infants adults Fever rash 3 Cs: .cough .colds .conjunctivitis .koplik’s spot – grayish white on 2nd molar .complications

o

Rubella -togaviridae
.German .3-day *adult Infants  adult Fever rash .lymphadeno pathy .arthralgia

Roseola -HHV-6
.Exanthem subitum

o o

Measles: Schwartz/ Moratem substrains of Edmonston B strain Mumps: Jeryl Lynn strain Rubella: RA/27-3 strain

MMR-given @ 15 mos of age CONGENITAL RUBELLA  Transplacental if mom is infected (1st trimester)  *Presentation: o Microencephaly o MR o Sensorineural deafness o Cataract o Pulmonary stenosis o PDA, VSD, TOF o Small patiens (sometimes) o +IUGR  Prevention o Don’t expose pregnant to infected person o One strain (95%)  Protect via vaccine  Diagnostic test o Heme agglutination inhibition o For congenital rubella  Known IgM – cannot be transmitted via placenta  If IgM present = infection

 

Infants <1yr Fever rash .fever–40’C .fever subside & rash appear

VIRAL NEURAMIDASE INHIBITORS Zanamivir & Oseltamivir
    MOA: (-) neuramidase of influenza A&B enzymes that prevent clumping of virions USE: Prophylaxis, duration of flu symptoms by 2-3 days Form: o Zanamivir – intranasal, aerosol o Oseltamivir – Tamiflu, oral AE: N&V, Zanamivir (nasal & throat irritation)

RUBELLA  Can cause German measles/ 3 day measles/ Post natal rubella  Under Togaviridae  Classified: Rubiviruses (only member)  Transmission: o Inhalation of respiratory droplets o Transplacental (congenital rubella)  Morphology: spike-like, hemaglutinincontaining surface projections POST-NATAL RUBELLA  Non-specific signs & symptoms o Fever, cough, colds  Specific signs & symptoms o 7-14 days incubation period Maculopapular rash (3days rash) o 1st day – face o 2nd day – trunk o 3rd day – lower extremities  NO more in face & trunk  Tx: Supportive & MMR (live attenuated)

Prepared by: EGBII; 09-18-11

POLIOVIRUS
PEECORnA Includes:  P – polio  E – entero  E – echo  CO – coxsackie  R – rhino  A – hepatitis A Picornaviridae  Smallest ss(+) RNA virus  Naked o Resistant to detergent/ alcohol o Survive in acidic pH/ salty water PicoRNAviridae  Multiply in CYTOPLASM  Icosahedral  ALL virus here are: o Fecal-oral transmission EXCEPT RHINO – respiratory  Acid-labile      3 strains (1,2,3) Most infections are 90% asymptomatic, small % cause fever (viremia) Smaller % cause ASEPTIC meningitis Poliomyelitis (flaccid paralysis) even 12% results from viral damage to anterior horn (causing atrophy Prevented by vaccine: need TRIVALENT vaccines, 2 types: o SALK (Killed/ injectable) or inactive, can give to:  Immunocompromised  Pregnant mom  But NOT lifelong immunity o SABIN (live/oral/best gut immunity) or activated  OPV, with lifelong immunity  Prob: can be reactivated in immunocomp’  NOT given in preggy For paralytic – NO treatment

COXSACKIE
COXSACKIE A
Diseases 1. Herpangina (vesicles on soft pa fauces)  Vesicular – same with chickenpox with blisters only in hand & foot 2. Hand-foot & mouth disease (oral lesions primarily in the anterior buccal mucosa) 3. *Aeptic meningitis – absence bacterial culture BUT with symptoms of meningitis 4. Acute lymphoglandular pharyngitis 5. Common cold/ Rhinovirus

COXSACKIE B
     Bornhomn’s disease (AKA pleurodyna or Devil’s grip; severe intercostal pain, fever *with Aseptic meningitis Severe systemic illness of newborns Possible link to acute-onset, insulindependent diabetes in young children Myocarditis

ENTEROVIRUS
     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

RHINOVIRUSES
   The common cold  #1 cause Not stable under acidic conditions Peaks summer & fall

HEPATITIS
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A VIRUS

ECHOVIRUSES & MOST
ENTEROVIRUSES  Aseptic meningitis  Respiratory infections

Ss (+) RNA Infectious hepatitis Inactivated vaccine Hyperimmune serum for post-exposure prophylaxis

Prepared by: EGBII; 09-18-11

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