Antivirals Flashcards
What’s mechanism of action of acyclovir?
Guanine analog requiring 3 phosphorylation steps for activation; 1st step occurs in infected cells by a viral thymidine kinase. 2nd/3rd steps by host cell kinases, accumulates only inside infected cells. It is a Competitive inhibitor viral DNA polymerase. Incorporated into viral DNA >chain termination
What are clinical indications of acyclovir?
Topical, cream-cold sores, ointment for initial genital herpes
Oral for primary/recurrent/suppressive genital herpes; acute VZ (chickenpox), HZ (shingles)
IV use: for severe infections: HSV / HSV encephalitis; VZ / HZ in immunocompromised patients
What are PK of Acyclovir?
PO bioavailability 10-30%, adm. 3-6X/day; CSF levels 50% of Cp
What are ADRs acyclovir?
PO ADRs: nausea / diarrhea, rash, headache, decreased renal function
IV-ADRs: phlebitis, nephrotoxicity/ (crystallization) usu. dose-limiting, CNS disturbances: tremor, delirium, seizures
Topical-ADRs: limited to local skin irritation
Valacyclovir– valine ester prodrug, increases acyclovir oral bioavailability 5X, adm. BID, same indications
What are PKs of famiciclovir?
Prodrug, converted 1st-pass metabolism to active metabolite>penciclovir; MA = acyclovir but no chain termination action
PO bioavailability 70-80%, adm BID
Indications of famciclovir
Use: genital herpes, acute HZ (shingles), recurrent HSV1 / HSV2 in AIDS patients
Penciclovir– topical cream for recurrent herpes labialis
ADRs famciclovir
ADRs: headache, nausea-diarrhea, rash, fatigue, pruritus (i.e., heptocellular dysfunction)
What’s mechanism of Trifluridine & vidarabine?
Trifluridine: Thymidine derivative activated by cellular phosphorylation to inhibit thymidylate synthetase\DNA polymerase
Vidarabine: Adenosine analog activated in viral-infected cells, inhibits DNA polymerase/causes chain termination
What are ADRs TRIFLURIDINE & VIDARABINE
Local burning\stinging, edema
Drug toxic to mammalian cell DNA synthesis, topical use only
burning, irritation, keratitis, uveitis, photophobia
What are indications of TRIFLURIDINE & VIDARABINE
Topical ophthalmic drops for HSV 1 & 2 keratoconjunctivitis and recurrent epithelial keratitis
What are different outcomes of CMV in normal person, seronegative mother, and AIDs?
In normal people - mononucleosis
Seronegative mother - CMV inclusion
AIDS - Multiple Sypmtomatic disease
What is the mechanism of ganciclovir?
Guanine analog, MA similar to acyclovir, triphosphorylation, inhibits viral DNA polymerase
What are indications and PK of ganciclovir?
CMV retinitis/GI-colitis/pneumonia
IV for acute infection; PO for maintenance & prophylaxis; intraocular implant sustained-release for 5-8 months
What are some ADRs of ganciclovir?
Dose-limiting toxicity - myelosuppression (anemia, neutropenia, thrombocytopenia)
ADRs: liver/renal dysfunction, fever, rash, mental changes, rare seizures, pancreatitis
What is mechanism of action , clinical indication, and ADRs of valganciclovir?
Valine ester prodrug of ganciclovir indicated for CMV in AIDS. Adm. PO, with food, increased PO bioavailability of Valcyte provides plasma levels = to IV ganciclovir. Rapidly converted > ganciclovir by intestinal/hepatic esterases. ADRs same as ganciclovir
What’s mechanism of action of cidofovir ?
inhibitor of viral DNA polymerases, cytosine nucleotide analog, broad activity > HSV 1&2, CMV, VZV
Doesn’t require viral enzymes for activation, still requires host cell phosphorylation conc = in infected and noninfected cells
Probenecid adm. to block uptake into renal PT to decrease nephrotoxicity
What are indications and ADRs of cidofovir?
Adm IV for ganciclovir-resistant CMV infection, initial once weekly then biweekly
ADRs – nephrotoxicity (esp. PT), neutropenia, metabolic acidosis, iritis, uveitis
What’s mechanism of action of foscarnet?
Inorganic pyrophosphate, doesn’t require phosphorylation activation
Blocks pyrophosphate binding site viral DNA / RNA polymerase & HIV reverse transcriptase
What are indications and ADRs of foscarnet?
Adm. IV CMV retinitis; ganciclovir/cidofovir -R; acyclovir-R HSV / VZ infections in AIDS
Nephrotoxicity dose-limiting: electrolyte disturbances- loss Mg/K, hypo- or hyperphosphatemia, hyper- or hypocalcemia (tetany, arrhythmias, seizures)
ADRs: headache, GI disturbances, tremors, seizures, genital ulcerations, anemia/BMS
What’s mechanism of action of Fomivirsen?
Antisense oligonucleotide, binds/inhibits mRNA protein synthesis & virus replication
What are indications and contraindications of Fomivirsen? (CMV)
Intravitreal injection in CMV retinitis in HIV-infected patients who can’t tolerate or have no response to other drugs
Initial injections for 2 weeks, maintenance for 4
Contraindicated in patients treated with cidofovir in previous 2-4 weeks, causes increased ocular toxicity
What are ADRs fomivirsen? (CMV)
ADRs - eye inflammation, iritis, vitreitis, inc intraocular pressure, vision changes
What are indication, ADRs, and contrindications of Amantadine? (influenza/rsv)
Prophylactic use in high risk patients for influenza A, provides ~ 70% protection.
ADRs: GI, CNS: confusion/ dizziness/ nervousness, releases dopamine, hypotension, anticholinergic effects
Contraindicated in pregn/ nursing mothers
RIMANTIDINE - 2-4 X more potent, less CNS, less ADRs, no longer in use due to high resistance
What is mechanism of action of amantadine?
Treatment: adm within 48 hr viral exposure
Blocks viral M2 protein/proton channel essential for viral entry/uncoating/release of viral genome into host’s cell. RIMANTIDINE - 2-4 X more potent, less CNS, less adrs