2. Obligate intracellular parasites
Consist of a core genome in a protein shell
and some are surrounded by a lipoprotein
lack a cell wall and cell membrane
do not carry out metabolic processes
Replication depends on the host cell
machinery
3. Steps for Viral Replication
1) adsorption and penetration into cell
2) uncoating of viral nucleic acid
3) synthesis of regulatory proteins
4) synthesis of RNA or DNA
5) synthesis of structural proteins
6) assembly of viral particles
7) release from host cell
4.
5. Block viral entry into the cell or must work
inside the cell
Most agents are pyrimidine or purine
nucleoside analogs
8. an acyclic guanosine derivative
Phosphorylated by viral thymidine kinase
Di-and tri-phosphorylated by host cellular
enzymes
Inhibits viral DNA synthesis by:
1) competing with dGTP for viral DNA polymerase
2) chain termination
9. Alteration in viral thymidine kinase
Alteration in viral DNA polymerase
Cross-resistance with valacyclovir, famciclovir,
and ganciclovir
10. Oral, IV, and Topical formulations
Cleared by glomerular filtration and tubular
secretion
Uses:
Herpes Simplex Virus 1 and 2 (HSV)
Varicella-zoster virus (VZV)
Side Ef fects: nausea, diarrhea, headache,
tremors, and delirium
11. L-valyl ester of acyclovir
Converted to acyclovir when ingested
M.O.A.: same as acyclovir
Uses:
1) recurrent genital herpes
2) herpes zoster infections
Side Ef fects: nausea, diarrhea, and
headache
12. Prodrug of penciclovir (a guanosine analog)
M.O.A.: same as acyclovir
does not cause chain termination
Uses: HSV-1, HSV-2, VZV, EBV, and hepatitis B
Side Ef fects: nausea, diarrhea, and
headache
13. Trifluridine- fluorinated pyrimidine
inhibits viral DNA synthesis same as acyclovir
incorporates into viral and cellular DNA
Uses: HSV-1 and HSV-2 (topically)
14. An adenosine analog
inhibits viral DNA polymerase
incorporated into viral and cellular DNA
metabolized to hypoxanthine arabinoside
Side Ef fects: GI intolerance and
myelosuppression
16. An acyclic guanosine analog
requires triphosphorylation for activation
monophosphorylation is catalyzed by a
phosphotransferase in CMV and by thymidine
kinase in HSV cells
M.O.A.: same as acyclovir
Uses: CMV*, HSV, VZV,and EBV
Side Ef fect: myelosuppression
17. Monovalyl ester prodrug of gancyclovir
Metabolized by intestinal and hepatic
esterases when administered orally
M.O.A.: same as gancyclovir
Uses: CMV*
Side Ef fect: myelosuppression
18. Aphosphorylation cytosine analog
not dependent on viral enzymes
Uses: CMV*, HSV-1, HSV-2, VZV, EBV, HHV-6,
adenovirus, and human papillomavirus
Side Ef fects: nephrotoxicity (prevented by
admin. of probenecid)
Resistance: mutation in DNA polymerase
gene
19. An inorganic pyrophosphate
inhibits viral DNA polymerase, RNA polymerase, and
HIV reverse transcriptase
does not have to be phosphorylated
Uses: HSV, VZV, CMV, EBV, HHV-6, HBV, and HIV
Resistance due to mutations in DNA polymerase gene
Side Ef fects: hypo- or hypercalcemia and
phosphotemia
20. An oligonucleotide
M.O.A.: binds to mRNA and inhibits protein
synthesis and viral replication
Uses: CMV retinitis
Side ef fects: iritis and increased intraocular
pressure
24. A deoxythymidine analog
enters the cell via passive diffusion
must be converted to the triphosphate form by
mammalian thymidine kinase
competitively inhibits deoxythymidine
triphosphate for the reverse transcriptase
enzyme
causes chain termination
25. Due to mutations in the reverse
transcriptase gene
more frequent after prolong therapy and in
persons with HIV
26. Available in IV and oral formulations
activity against HIV-1, HIV-2, and human T cell
lymphotropic viruses
mainly used for treatment of HIV, decreases
rate of progression and prolongs survival
prevents mother to newborn transmission of
HIV
27. Myelosuppression, including anemia and
neutropenia
GI intolerance, headaches, and insomnia
28. Didanosine- synthetic deoxy-adenosine
analog; causes pancreatitis*
Lamivudine- cytosine analog
Zalcitabine- cytosine analog; causes
peripheral neuropathy*
Stavudine- thymidine analog;causes
peripheral neuropathy*
Abacavir- guanosine analog; more effective
than the other agents; fatal hypersensitivity
reactions can occur
30. An acyclic nucleoside phosphonate analog of
adenosine
M.O.A.- competively inhibits HIV reverse
transcriptase and causes chain termination
after incorporation into DNA
Uses – in combination with other
antiretrovirals for HIV-1 suppression
31. An analog of adenosine monophosphate
Phosphorylated by cellular kinases
M.O.A. - Competitively inhibits HBV DNA
polymerase and results in chain termination
after incorporation into viral DNA
Uses - Hepatitis B
Side ef fects - nephrotoxicity
33. Bind to site on viral reverse transcriptase, different
from NRTIs
results in blockade of RNA and DNA dependent
DNA polymerase activity
do not compete with nucleoside triphosphates
do not require phosphorylation
these drugs can not be given alone
substrates and inhibitors of CYP3A4
34. Nonnucleoside Reverse
Transcriptase Inhibitors
(NNRTIs)
Nevirapine- prevents transmission of HIV
from mother to newborn when given at onset of
labor and to the neonate at delivery
Delavirdine- teratogenic, therefore can not
be given during pregnancy
Efavirenz- teratogenic, therefore can not be
given during pregnancy
36. The protease enzyme cleaves precursor
molecules to produce mature, infectious virions
these agents inhibit protease and prevent the
spread of infection
These agents cause a syndrome of altered
body fat distribution, insulin resistance, and
hyperlipidemia
37. M.O.A.: Specific inhibitors of the HIV-1 protease
enzyme
M.O.R.: mediated by expression of multiple and
variable protease amino acid substitutions
Side Ef fects:hyperbilirubinemia
Contraindications:inhibitor/substrate for
CPY3A4, do not give with antifungal azoles
38. A synthetic peptide-like substrate analog
inhibits HIV-1 protease
prevents cleavage of viral polyproteins
39. M.O.A.: Specific inhibitors of the HIV-1 protease
enzyme
M.O.R.: mediated by expression of multiple and
variable protease amino acid substitutions
Less cross-resistance with Amprenavir
Side Ef fects: diarrhea and flatulence
Amprenavir can cause Stevens-Johnson syndrome
Contraindications:inhibitor/substrate for
CPY3A4
40. Enfuvir tide (T-20)- binds to the gp41 subunit of
the viral envelope glycoprotein, preventing the
conformational changes required for fusion of the
viral and cellular membranes
By blocking fusion (entry into cell), FUZEON
prevents HIV from infecting CD4 cells
43. Inter feron Alfa
Endogenous proteins
induce host cell enzymes that inhibit viral RNA translation
and cause degradation of viral mRNA and tRNA
Bind to membrane receptors on cell surface
May also inhibit viral penetration, uncoating, mRNA
synthesis, and translation, and virion assembly and
release
44. Pegylated inter feron Alfa
A linear or branced polyethylene gylcol
(PEG) moiety is attached to covalently to
interferon
Increased half-life and steady drug
concentrations
Less frequent dosing
Tx chronic hepatitis C in combination with
ribavirin
45. A guanosine analog
phosphorylated intracellularly by host enzymes
inhibits capping of viral messenger RNA
inhibits the viral RNA-dependent RNA
polymerase
inhibits replication of DNA and RNA viruses
48. cyclic amines
inhibit the uncoating of viral RNA therefore
inhibiting replication
resistance due to mutations in the RNA
sequence coding for the structural M2
protein
used in the prevention and treatment of
Influenza A
49. Inhibits the enzyme neuraminidase
inhibit the replication of influenza A and
Influenza B
treats uncomplicated influenza infections
administered intranasally
50.
51. Viral Replication
A virus cannot replicate on its own.
It must attach to and enter a host cell.
It then uses the host cell’s energy to synthesize protein, DNA,
and RNA.
52. Viruses are difficult to kill because they live
inside our cells.
Any drug that kills a virus may also kill our cells.
53. Competent immune system:
Best response to viral infections
A well-functioning immune system will eliminate
or effectively destroy virus replication
Immunocompromised patients have frequent viral
infections
Cancer patients, especially leukemia or lymphoma
Transplant patients, due to pharmacological therapy
AIDS patients, disease attacks immune system
54. Key characteristics of antiviral drugs:
Able to enter the cells infected with virus.
Interfere with viral nucleic acid synthesis and/or regulation.
Some agents interfere with ability of virus
to bind to cells.
Some agents stimulate the body’s immune system.
55. Viruses killed by current antiviral therapy:
cytomegalovirus (CMV)
herpes simplex virus (HSV)
human immunodeficiency virus (HIV)
influenza A (the “flu”)
respiratory syncytial virus (RSV)
56. Inhibit viral replication
Inhibit viral attachment
Prevent genetic copying of virus
Prevent viral protein production
57. Two types of nucleosides:
Purine nucleosides
guanine
adenosine
Pyrimidine nucleosides
thymine
cytosine
58. Agent Antiviral Activity
guanines
acyclovir HSV 1 & 2, VZV
ganciclovir (DHPG) CMV retinitis and systemic
CMV infection
ribavirin (RTCD) Influenza types A and B,
RSV, LV, HV
adenosines
didanosine (ddl) HIV
vidarabine (Ara-A) HSV, herpes zoster
59. Agent Antiviral Activity
cytosines
lamivudine (3TC) HIV
zalcitabine (ddC) HIV
thymine
idoxuridine (IDU) HSV
stavudine (d4T) HIV
trifluridine HSV
zidovudine (AZT) HIV
60. amantadine
(Symmetrel) and rimantadine
(Flumadine)
influenza A
foscarnet (Foscavir)
CMV (retinitis and systemic)
Neuraminidase Inhibitors: oseltamivir (Tamiflu)
and zanamivir (Relenza)
influenza types A and B
63. Before beginning therapy, thoroughly
assess underlying disease and medical history,
including allergies.
Assess baseline VS and nutritional status.
Assess for contraindications, conditions
that may indicate cautious use, and potential drug
interactions.
64. Be sure to teach proper application technique for
ointments, aerosol
powders, etc.
Emphasize hand washing before and after administration
of medications to prevent site contamination and spread
of infection.
Patients should wear a glove or finger cot when applying
ointments or solutions to affected areas.
65. Instruct patients to consult their physician before
taking any other medication, including OTC
medications.
Emphasize the importance of good hygiene.
Inform patients that antiviral agents are not cures,
but do help to manage symptoms.
66. Instruct patients on the importance of taking these
medications exactly as prescribed and for the full
course of treatment.
With zidovudine:
Inform patients that hair loss MAY occur so that they
are prepared for this rare adverse reaction.
This medication should be taken on an empty stomach.
67. Monitor for side effects:
effects are varied and specific to each agent
68. Monitor for therapeutic effects:
effects will vary depending on the type of viral infection
Effects range from delayed progression of AIDS
and ARC to decrease in flu-like symptoms, decreased frequency
of herpes-like flare-ups,
or crusting over of herpetic lesions.