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

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

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 .kopliks spot grayish white on 2nd molar .complications

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 Dont 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 .fever40C .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
Bornhomns disease (AKA pleurodyna or Devils 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

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