viruses Flashcards
viruses
obligate intracellular parisites
adsorption, uncoating, multiplication, assembly, release
immunization
most effective option
Active: vaccination
Passive- injection of immune globulin often blocks viral penetration, lasts a few weeks
palivizumab
humanized monoclonal Ab to prevent sever RSV in high risk pediatric patients
MOA: binds to fusion protein of RSV to prevent fusion to host cells
amantadine and rimantadine
Amantadine and rimantadine
Use: prophylaxis against influenza A but not influenza B
primary use: prophylaxis of influenza A
therapeutic use: for influenza A, reduces fever in 50% of pts and illness duration by 1-2 days if given within first 2 days of illness, for the last several years flu strains have been amantadine-resistant
MOA: blocks viral uncoating by interfering with influenza A M2 protein (an ion channel)
admin oral and well distributed
metabolism: rimatidine- liver metabolism, amantidine, renal (avoid in renal diseasE)
toxicity: amantadine: CNS - slurred speech anxiety
oseltamivir
MOA: prodrug, competitive inhibitor of influenza neuraminidases, interferes with viral release and viral penetration
Uses: treatment of uncomplicated influenza A and B, given within 48 hours of symptom onset, influenza prophylaxis, admin- oral
SE: nausea/vomiting/diarrhea, bronchitis, cough
trifluridine
MOA: interferes w/DNA synthesis, thymidine analog
Use: ophthalmic- herpes simplex types 1 and 2 (conjunctivis)
SE: burning stinging, hypersensitivity
acyclovir
MOA: phosphorylated form is produced 40-100x faster in infected cells by herpes thymidine kinase, inhibits herpes DNA polymerase 10-30x more than host cell DNA polymerase, acts as a competitive inhibitor of dGTP and as a DNA chain terminator
Use: intravenous drug of choice for serious systemic herpes simplex virus (HSV), disseminated neonatal HSV, severe initial genital herpes
Oral: primary genital herpes, primary herpetic gingivostomatosis
Topical: some effect when applied early to primary genital herpes
Rash, itch, headache and fatigue
famcyclovir
MOA: Similar to acyclovir, prodrug converted to peniciclovir phosphorylated, inhibits viral DNA polymerase
Use: acute herpes zoster (shingles) 3 days duration, treatment and suppression of recurrent genital herpes
Admin/excretion: prodrug absorbed better than acyclovir,
Peniciclovir
MOA: very similar to acyclovir
Use: recurrent herpes of the lips and face
adminL topical
Ganciclovir
MOA: same as acyclovir, but monophosphorylation is catalyzed by CMV protein kinase
Use: CMV retinitis in aids pts, CMV prophylaxis for transplant ptss
Toxicity: bone marrow suppression, leukopenia, thrombocytopenia, anemia
Foscarnet
MOA: inhibits CMV DNA polymerase by binding to its pyrophosphate-binding site
Does not require conversion to triphosphate form to be active
Use: AIDS pts with CMV retinits, approved for acyclovir-resistant herpes simplex
SE: renal damage, electrolyte imbalances, seizures
Lamivudine
MOA: nucleoside analog converted by cell enzymes to the triphosphate form, that competitively inhibits the reverse transcriptase domain of the HBV polymerase, causes DNA chain termination
Use: approved for hepatitis B
Toxicity: nausea, diarrhea, rash and vomiting
tenofovir
MOA: monophospate prodrug, phosphorylated by cell enzymes to triphosphate form that completitively inhibits the reverse trascriptase domaine if the HBV polymerase, causes DNA chain terminateion
Use: approved for hepatitis B
Toxicity GI upset, rash, headache
interferon a general information
most cells produce IFN a and B in response to viral infections
They are potent cytokines that have multiple antiviral effects both directly and indirectly. stimulate cytotoxic lymphocytes and natural killer cells, activate proteins that block viral mRNA transcription. Block viral mRNA protein translation in many ways (decrease mRNA cap methylation, activate oligoadenylate synthase, activates protein kinase P1, activates phosphodiesterase). Inhibits glycosyltransferase , blocks viral release
Therapeutic use relies on large scale production of recombinant human interferon
approved antiviral uses for recombinant alpha-interferons
Condyloma acuminata (venereal warts, papilloma virus)
Hepatitis B and C (used in combination with other drugs)
Pegylation decreases clearance
SE: flulike syndrome, leukopenia, bone marrow suppression, neurotoxicity, myalgia
Ribavirin
MOA: interferes with viral mRNA synthesis, inhibits inosine 5-P dehydrogenase and thus GTP synthesis (mono form), Tri form inhibits GTP-dependent capping of viral mRNA
Use: aerosol use in infants and young children with documented severe lower respiratory syncytial virus (RSV), hepatitis C in combo with PEG-interferon a and other drugs
SE: Aerosol use (drug may precipitate in and clog respiratory equipment), pulmonary function deterioration, rash
IV or oral use: hemolytic anemia, bone marrow suppression
Simeprevir
MOA: reversibly inhibits hepatitis C NS3/NS4A protease and blocks cleavage of the polyprotein and formation of infectious virus
Use: hepatitis C genotype 1 in combo with other drugs
Toxicity: Rash, nausea itching, inhibitor CYP3A
sofosbuvir
MOA: nucleoside analog prodrug, converted to triphosphate form that inhibits HCV NS5B RNA polymerase, causes chain termination
Use: all hepatitis C genotypes, given with other genotype-specific drugs
Toxicity: avoid potent inducers of p-glycoprotein (Pgp)
ledipasvir
MOA: inhibits HCV NS5A phosphoprotein
use: hep C genotypes 1 4 5 6 in combo with sofosbuvir
SE: avoid potent inducers of P-glycoprotein (Pgp)
HCV (hep c virus) drug regimen
use 2 or more drugs with different mechanisms, avoid IFNa when possible, genotype-appropriate therapy, look at side effects
Zidovudine AZT
MOA: nucleoside analog, AZT triphosphate competitively inhibits reverse transcriptase (RT) also acts as DNA chain terminator
Use: nucleoside RT inhibitor for treatment of HIV in adults and children
Toxicity: bone marrow suppression, neutropenia, anemia, drugs that inhibit glucuronyl transferase increase hematologic toxicity of AZT and should be avoided, myopathy
tenofovir
MOA: adenosine monophosphate prodrug –> tiphosphate form that competitively inhibits RT, causes DNA chain termination
Use: combination therapy for HIV-infected patients
lamivudine
MOA: nucleoside analog to triphosphate form that cometitively inhibits reverse transcriptase, causes DNa chain termination
Use: synergistic with AZT, its difficult for HIV to become resistant to both drugs
emtricitabine
MOA: analog of lamivudine, samee MOA as lamivudine
Use: combo therapy for HIV
