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Acyclovir (general info)
- Active against: HSV-1, HSV-2, VZV, CMV and EBV
- Guanine nucleoside analog: (only difference is in deoxyribose moiety, cant get 5'3' synthesis, get chain termination)
- selective drug: accumulated only in infected cells
- affects synthesis of viral DNA
- Oral Bio; 15-20%
- T1/2: 2-3 hr
- cleared by glomerular filtration and tubular secretion
- Used for: genital herpes, herpes proctitis, varicella, zoster, herpes encephalitis severe herpes (IV), herpes labialis(topical)
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Acyclovir (Mechanism of action)
Acyclovir --> monophosphate derivative --> di-triphosphate analogs--> blocks viral DNA polymerase
- Enzyme 1: viral thymidine kinase
- Enzyme 2: cellular kinase
- (mutation in either enzyme can cause resistance to acyclovir)
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Acyclovir (side effects)
- Well tolerated in general
- Common: pain, swelling, reddness at place of injection
- Uncommon: stomach pain, diarrhea, renal insufficiency(crystalline nephropathy), headache
- Rare: coma, seizure, neutropenia, leukopenia, anorexia, fatigue, hepatitis
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Valacyclovir
- Pro drug converted into acyclovir
- serum conc 3-5 times higher than acyclovir
- oral bio: 54% about 1/2 in CSF
- no other advantage over acyclovir, same mechanism, same side effects
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Famciclovir
- Prodrug converted to penciclovir
- guanosine analog
- Active against HSV1,2, VZV, EBV, and HBV
- Actived by viral TK (phosphorylation)
- Competitive inhibtion of DNA polymerase ONLY, no chain termination
- Has lower affinity for viral TK than acyclovir but achieves higher intracellular conc
- T1/2: 7-20 hr
- Well tolerated
- headache and gi intolerance uncommon
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Penciclovir
- active metabolite of famciclovir
- available for topical application against recurring herpes labialis
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Ganciclovir (general info)
- Treats CMV and CMV retinitis
- Guanosine analog
- prodrug activated by viral PK phosphotransterase
- available in oral or IV forms
- T1/2: 2-4 hr
- resistance: mutation in drug target (phosphotransferase)
- Cross resistnace with strains resistant to acyclovir (TK deficiency)
- excreted by renal system
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Ganciclovir (side effects)
- Common: bone marrow suppression (neutropenia and thrombocytopenica occur in 20-40% and 5-20% respectively)
- Uncommon: renal insufficiency (crystallization of drug), fever, headache, pain at injection, tremor, tiredness, weakness
- Rare: skin rash and encephalopathy
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Valaganciclovir
- Ganciclovir prodrug
- hydrolyzed in intestine and liver
- 900mg qd
- plasma protein binding <2%
- renal ilimination
- Same ADR and MOA as ganciclovir
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Foscarnet
- Active against HSV, VZV,CMV, EBV, HHV-6, KSHV AND HIV-1.
- Also used for CMV retinitis (effective as ganciclovir)
- poor oral bio so IV only
- CSF is 1/2 of plasma
- T1/2: 3-7 h but 30% deposit in bond with T1/2 of months
- Nephrotoxicity (hypo or hyper phosphatemia, hypo magnesemia)
- N/v, anemia, high LFT
- CNS toxicity:headache, hallucinations, seizure
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Cidofovir
- cytosine analog
- active for: CMV retinitis and acyclovir resistant herpes, also HPV, poxvirus, adenovirus, and polyomavirus
- Cidofovir converts to cidofovir-diPO4
- Effective against TK strains cuz phosphrylation is independent of viral enzymes
- bindes to viral DNA polymerase and blocks DNA synthesis
- T1/2: cidofovir 2-6 h, dipo4 17-65h, cidofovir phosphocholine >87 h
- Nephrotoxic : give probenecid with it to protect kidney
- Uveitis, oxular hypotony, neutropenia, acidosis
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Lamivudine
- For Hep B
- potent NRTI
- lower dose that when used for HIV
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Adefovir
- For Hep B
- NRTI
- failed for HIV
- nephrotoxic at higher doses
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Entecavir
- For Hep B
- guanosine nucleoside analog
- Oral
- well tolerated
- side effects: HA, fatigue, dizziness, nausea
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Interferon a-2b
For Hep B
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Ribavirin
- For Hep C
- guanosine nucleoside analog
- oral used in combo therapy with IFN-a
- inhibits capping of viral mRNA but mech unknown
- teratogenic so contradicted to pregnant and anemic
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Interferon a-2A and IFN-a2B
subq or intramuscular
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Zanamivir
- sialic acid analog
- prodrug activated by esterases in GI or liver
- Selective inhibitor of influ A and B virus neuraminidases
- Prevents release of virus from infected cells (causes viral aggregation at the cell surface)
- resistance through mutations in neuraminidase and hemagglutinin
- oral bio: <5%
- renal excretion: 100%
- Inhaled or IV
- T1/2: 2.5-3 hr
- for treatment and prophylaxis
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Osteltamivir
- Prodrug activated by esterases in gi and liver
- selective inhibitor of influ A and B virus neuraminidases
- Mech of Action and resistance same as Zanamivir
- Oral bio: 80%
- Effect of meal is negligible
- renal excretion 95%
- For treatment and prophylaxis
- ADR: mild Gi complain, HA
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Amantadine and Rimantadine
- Tricyclic amines
- target M2 protein with influ A
- inhibit uncoating of viral RNA
- oral bio: 90%
- rimantadine is 4-10x more active than amantadine
- Amantadine excreted unmetabolized in urine
- rimantadine undergoes extensive metabolism, reduce dose in renal or hepatic insufficiency
- Common side effects: GI (no appetite, nausea) and CNS(light headedness and insomnia)
- Cross resistance with each other
- decrease the symptoms of flu by 1-2 days, speed recovery and decrease the duration of virus shedding.
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