Acyclovir

Class: Antiviral / Anti-Herpetic Agent

MOA: blocks DNA replication (competes w/dGTP and is incorporated into DNA where it causes premature chain termination) plasma 1/2L 2.5 hrs.

Resistance: altered or deficient viral thymidine kinase or polymerase  

USE: DOC for Herpes; VZV 

Toxicity: Oral admin - N/V/D, HA; IV admin (high doses, dehydrated pts) transient renal dysfunction

Ganciclovir

Class: antiviral / anti-CMV agent

MOA: blocks DNA replication (competitively inhibits viral DNA polymerase and may be incorporated into DNA to block elongation) 1/2L > 24 hrs

Use: cytomegalic retinitis in immunocompromised pts, CMV disease in transplant pts.

Toxicity: myelosuppression, dose-dependent neutropenia, CNS effects (HA, behavior changes, convulsion, coma),  carcinogenic

Foscarnet

Class: Antiviral / anti - CMV agent

MOA: Reversibly inhibit viral DNA and RNA polymerases 

Use: IV Tx of cytomegalic retinitis in imm. comp. HIV pts resistant to gangciclovir; herpes pts who are resistant to acyclovir

Toxicity: nephrotoxicity, anemia, N/F, HA, genital ulcerations

Trifluridine

Class: Antiviral

MOA: inhibits viral DNA synthesis / blocks DNA replication

Use: primary keratoconjunctivitis recurrent epithelial keratitis from HSV infection

Toxicity: inflammation of the cornea

Idoxuridine

Class: Antiviral 

MOA: inhibits viral DNA synthesis, is incorporated into viral and cellular DNA - making it more susceptible to breaks

Use: Topical tx of HSV keratitis

Toxicity: Pain, inflammation or edema of the eye

Zanamivir

Class: Anti-influenza A and B agent / viral respiratory infections

MOA: inhibit neuraminidases, decreased release of virus from infected cells

Use: decrease duration of the illness, decrease the incidence of resp complications; prophylaxis against the flu - also H1N1

Toxicity: nasal and throat discomfort; HA/bronchospasms in asthmatic pts. 

Oseltamivir 

(tamiflu)

Class: Anti-influenza Type A and B agent / viral respiratory infections

MOA: inhibit neuraminidases, decreased release of virus from infected cells

Use: shorten the duration of flu and decrease incidence of respiratory complications; prophylaxis of flu - also H1N1

Toxicity: N/V/HA - take w/food for less N

Interferon (IFNs) Alpha

Class: Antiviral - tx of viral herpetic infections

MOA: IFN bind to cellular receptors and activate the JAK-STAT signal transduction pathway.  Induce protein 2'-5'-oligoadenylate synthetase and a kinase that inhibit protein synthesis 

Use: Genital warts, chronic hep B and C, Kaposi's sarcoma in HIV infected pts, MS Peg-interferon 2A w/Ribavirin is the tx for chornic hep C.

Toxicity: IM or SC may produce flu-like sx.  High dose/chronic - bone marrow suppression, fatigue, susceptibility to bact. inf., anorexia, diarrhea, depression/anx.  

Ribavirin

Class: Anti Hep C Agent

MOA: alters the intracellular nucleotide pools; inhibits viral mRNA synthesis 

Use: Hep C (esp when combined with pegIFN), aerosol to treat infants and children with RSV infections.  (also - influ-A and B, parainfluenza, paramyxovirus, and HIV)

Toxicity: aerosol - conjunctival irritation and wheezing; systemic - anemia and bone marrow suppression.  Teratogenic

Zidovudine

(AZT)

Class: NRTI (nucleoside reverse transcriptase inhibitor)

MOA: Thymidine kinase converts drug to AZT-TP which is incorporated into viral DNA and terminates chain elongation.  

Use: HIV, protects fetus from becoming infected in HIV-infected preg. women

Resistance: reverse transcriptase becomes mutated and has lower affinity for AZT-TP

Toxicity: Bone marrow (anemia and leukopenia) HA  

Interactions: PAL I CARE - Probenecid, acetaminophen, lorazepam, indomethacin, cimetidine

Didanosine

(ddI)

Class: Nucleoside Reverse Transcriptase Inhibitor

MOA: inhibits reverse transcriptase; terminates DNA chain elongation

Use: pts. w/ AZT-resistant HIV infections

Resistance: reverse transcriptase becomes mutated

Toxicity: Pancreatitis, non-cirrhotic portal HTN, GI disturbances, dose-limiting peripheral neuropathy. Increased tox. with Stavudine. 

Stavudine

(d4T)

Class: Nucleoside Reverse Transcriptase Inhibitor

MOA: inhibits reverse transcriptase, terminates DNA chain elongation

Use: HIV(d4T)

Toxicity: peripheral neuropathy, potentially fatal lactic acidosis, peripheral lipoatrophy, central fat accumulation, hyperlipidemia

Lamivudine

(3-TC)

Class: Nucleoside Reverse Transcriptase Inhibitor

MOA: inhibits reverse transcriptase and terminates DNA chain elongation

Use: delays resistance to AZT when used in combo; Chronic Hep B infections

Toxicity: Pancreatitis often develops in pediatric pts. 

Abacavir

(ddl)

Class: Nucleoside Reverse Transcriptase Inhibitor

MOA: inhibits reverse transcriptase and terminates DNA chain elongation

Use: HIV infected adults and children in combo with AZT and Lamivudine or a protease inhibitor

Toxicity: hypersensitivity - fever, GI distress, malaise, and rash

Zalcitabine

(ddc)

Class: Nucleoside Reverse Transcriptase Inhibitor

MOA: inhibits reverse transcriptase and terminates DNA chain elongation

Use: combo with AZT or alone for those who cannot tolerate AZT

Toxicity: peripheral neuropathy, rash, and stomatitis on initial tx

Tenofovir

Class: Nucleotide Reverse Transcriptase Inhibitor

MOA: Inhibits reverse transcriptase and terminates DNA elongation

Use: HIV, chronic Hep B infections

Toxicity: Flatulence, some renal toxicity.  

Interactions: don't give as didanosine, lamivudine, or abacavir combo

Efavirenz 

Class: Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

MOA: alters the conformation of reverse transcriptase

Use: in combo with Zidovudine and Lamivudine

Toxicity: Dizziness HA insomnia rash, nightmares, hallucinations, don't give to pt w/chronic hep b

Interactions: decreases conc. of Phenobarbital, Phenytoin, Carbamazepine, Methadone, Rifabutin. Coadministration with Rifampin will reduce the levels of Efavirenz.

Nevirapine

Class: Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

MOA: alters the conformation of reverse transcriptase 

Use: in combo with Didanosine and Stavudine

Toxicity: rash, fever, nausea, severe dermatologic effects, and fatal hepatotoxicity

Interactions: St. John's Wort, Rifampin, and Ketoconazole. (induces CYP3A4)  Ethinyl estradiol - alt methods of Birth control. 

Delaviridine

Class: Non-nucleoside reverse transcriptase inhibitors

MOA: binds and inhibits reverse transcriptase

Use: used in combo with Zidovudine and Didanosine to treat HIV

Toxicity: Rash is less frequent and severe than other NNRTIs

Drug Interactions: inhibits CYP3A4, inhibits CYP2C9

Atazanavir

Class: Protease Inhibitors

MOA: interfere with proteolysis of the gag-pol precursor and thereby lead to nonfunctional virions

Use: HIV, taken in combo with AZT and Lamivudine, or other NRTIs.  May be taken once per day

Toxicity: N/V/D; lipodsytrophy, hyperglycemia

Drug Interactions: Atazanavir has less of an effect on lipid profiles

Lopinavir

Class: Protease Inhibitors

MOA: interfere with proteolysis of the gag-pol precursor and thereby lead to nonfunctional virions  Metabolized by P450 CYP3A

Use: HIV, taken in combo with AZT and Lamivudine, or other NRTIs Given in combo with Ritonavir

Toxicity: N/V/D; lipodystrophy and hyperglycemia

Ritonavir

Indinavir

Nelfinavir

Amprenavir

Saquinavir

Enfuvirtide

Class: HIV Fusion/Entry Inhibitors

MOA: HIV viral envelope glycoprotein undergoes a conformational change when it binds to the host cell surface.  Enfuvirtide binds to the glycoprotein and prevents the conformational change. 

Use: injected twice daily in HIV pts. 

Toxicity: pain, erythema, nodules and cyst formation at the site of injection

Maraviroc

Class: HIV Fusion/Entry Inhibitor

MOA: chemokine receptor 5 (CCR5) inhibitor 

Use: in adults with CCR5-tropic HIV-1.  CCR5 is a co-receptor for viral entry into the cell

Toxicity: Respiratory infection, rash, musculoskeletal symptoms, abd pains, and postural dizziness.  Hepatotoxicity.

Drug Interactions: Inducers and inhibitors of CYP3A