4.2.2_Pharm

Prevent or reduce transmission (hygiene, public health, nosocomial prevention)
Immunization

Effective against many viruses, directed against surface antigens
Monoclonal: Palivizumab for RSV
Polyclonal: CMV ___ ___, hep B ___ ___, Rabies ___ ___, and varicella-zoster ___ ___ are used to prevent viral infection in exposed Pt's.
Usefulness: acute, serious dz administered w/ nucleoside antiviral to obtain synergistic effect; post exposure prophylaxis
IV-IG to obtain high titer of antiviral antibodies

Lead to rapid secondary immune response
Effective for HPV (Gardacil for HPV 6,11,16,18), Hep A (Havrix) and B, Polio, Rabies, yellow fever, VZV (Varivax); MMR, Flu (effective for 6 mo. or longer)
Side effects: fever, achy muscles, malaise
Administered IV or orally

3 classes of antiviral chemotherapy

Viruses: influenza A & B
Mech: inhibits neuraminidase (enables virus to be released from cell)
Notable ADME: (1) inhalation poorly adsorbed), (2) oral prodrug, hepatic metabolism
Adverse effects: Psychiatric bx, bronchospasm (1), d/n and sinusitis

Viral uncoating inhibitors
Influenza A
Mech: inhibits M2 ion channel; inhibits uncoating of virus endosome
(1) Hepatic clearance; (2) renal clearance
Resistance since 2005 (no longer used)
Adverse effects: GI, CNS
(2) Exhibits some anti-parkinsons activity

Activity: HSV, VZV (limited use for CMV and EBV)
Mech: converted by viral thymidine kinase; Tri-PO₄ cmpd inhibits viral DNA synthesis
higher affinity for viral DNA polymerase, competes w/ guanine, incorporated into growing DNA chain of virus => terminating synthesis
Resistance: Deficient TK, altered TK, altered DNA polymerase
Side effects: n/v, rash, phlebitis, CNS & nephrotoxicity in renal impaired Pt's

Activity: CMV (much greater the acyclovir), HSV, VZV, human herpes virus 6
Mech: less dependent on viral TK
More toxic than acyclovir; myelosuppression

Similar to acyclovir but longer duration of action
cross resistance w/ acyclovir
Side effects: headache, GI

Activity: CMV, HSV, VZV, EBV, HHV-6 (secondary to gancyclovir and acyclovir in compromised Pt's)
Mech: Cytosine analog, inhibits viral DNA synthesis (not dependent on TK)
DLT: nephrotoxicity
Resistance due to mutations in viral DNA polymerase
Administered IV (not orally)

Activity: HSV, VZV, CMV, HHV-6, HIV
Mech: inhibits DNA polymerase (mimics pyrophosphate)
Side effects: many, Headache, tremor, irritability, seizures, hallucinations (due to changes in Ca levels)
DLT: nephrotoxicity and hypocalcemia
ADME: IV, accumulates in bone (but no myelosuppression)

Activity:

First anti-sense therapy for viral infection

Long chain fatty acid alcohol

RNA and DNA viruses

Activity:

Adefovir

FDA approved for HPV infections
Mech: dependent on TLR7, induces secretion of pro-inflammatory cytokines (IFN & TNF & interleukins)
Topical Admin