Inhibits viral DNA synthesis:

1) competition with deoxyGTP for the viral DNA polymerase, resulting in binding to the DNA template as an irreversible complex

2) chain termination following incorporation into the viral DNA

Only activated in infected cells – requires viral kinase

Renal: crystalline nephropathy,

interstitial nephritis

Neuro: tremors, delirium, seizures

Rx: HSV-1, HSV-2, VZV

(Varicella Zoster virus)

Long-term suppression of

genital herpes (↓ recurrency

freq. & viral shedding)

Inhibits viral DNA synthesis:

L-valyl ester of acyclovir.  Rapidly converted to acyclovir via first-pass enzymatic hydrolysis in liver and intestine → 3-5 times greater serum levels

Confusion, hallucinations, seizures (at high doses); AIDS patients have ↑risk of GI interolerance, thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome

First or recurrent herpes, orolabial herpes, herpes zoster

Inhibits viral DNA synthesis:

Competes with thymidine triphosphate for incorporation by the viral DNA polymerase

Incorporation of trifluridine triphosphate into both viral and host DNA prevents its systemic use

HSV-1, HSV-2, CMV,

vaccinia, some adenoviruses

Competitively inhibits viral DNA polymerase; causes termination of viral DNA elongation

Myelosuppression, insomnia,

peripheral neuropathy

blood dyscrasias

implants → cataracts

Rx: CMV, HSV, VZV, EBV,

Rx (CMV): retinitis, colitis,

esophagitis, pneumonitis

Inhibits viral DNA polymerase, RNA polymerase, & HIV reverse transcriptase. Blocks the pyrophosphate binding site of these enzymes and inhibits cleavage of pyrophosphate

from deoxynucleotide triphosphates

Renal impairment, hypo/hyper

calcemia & phosphatemia,

hypokalemia, hypomagnesemia,

penile ulcerations, CNS

(hallucinations, seizures)

Rx: HSV, VZV, CMV, EBV,

HIV-1

Rx (CMV): retinitis, colitis,

esophagitis

Inhibits viral DNA polymerase, competitively inhibiting DNA synthesis and becoming incorporated into the viral DNA chain.

Nephrotoxicity (proteinuria,

azotemia, metabolic acidosis, Fanconi’s syndrome), uveitis,  neutropenia (15-24%)

Rx: CMV, HSV-1, HSV-2,

VZV, EBV, HPV

CI: renal insufficiency

Blocks translation of viral mRNA by binding to the complementary sequence of the mRNA transcribed from the coding segment of a key CMV gene

CMV in immunocompromised patients, (e.g. AIDS)

Analog of deoxyadenosine

Pancreatitis, peripheral sensory

neuropathy, hepatitis, CNS toxicity (irritability, insomnia), retinal changes & optic neuritis

CI: risk factors for pancreatitis

(alcoholism, other drugs)

Guanosine analog

Hypersensitivity, occasionally fatal; Respiratory problems

(dyspnea, pharyngitis); skin rash in about 50% of patients

CI: patients w. existing cardiac

risk factors

Deoxythymidine analog

Myelosuppression (→ macrocytic

anemia, neutropenia), extremity fat loss

Rx: slows disease progression

and prolongs survival, HIV associated dementia, prevents

mother-child transmission

Cytosine analog

Peripheral neuropathy, pancreatitis oral/esophageal ulcerations

CI: taking w. stavudine,

didanosine, isoniazid

Cytosine analog

Hepatotoxicity, headache,

insomnia, fatigue, GI discomfort

CI: taking w. zalcitabine

Cytidine analog

Headache, diarrhea, nausea,

Asthenia, hyperpigmentation of the palms and/or soles

Rx: HBV (hep B virus)

CI (oral form): children, pregnant women, renal or hepatic failure

Thymidine analog

Peripheral sensory neuropathy,

pancreatitis, lactic acidosis w. steatosis, lipoatrophy

CI: taking w. didanosine or

zidovudine

Bind directly to HIV-1 reverse transcriptase → inhibit RNA- and DNA-dependent DNA polymerase.

Unlike NRTI's, NNRTIs do not compete with nucleoside triphosphates or require phosphorylation to be active.

GI intolerance, skin rash (Stevens- Johnson syndrome)

Metabolistm by the CYP450 system = innumberable drug interactions

Rx: HIV-1

CI: pregnancy

Bind directly to HIV-1 reverse transcriptase → inhibit RNA- and DNA-dependent DNA polymerase.

Unlike NRTI's, NNRTIs do not compete with nucleoside triphosphates or require phosphorylation to be active.

GI intolerance, skin rash (Stevens- Johnson syndrome)

Metabolistm by the CYP450 system = innumberable drug interactions

Rx: HIV-1

CI: pregnancy

Bind directly to HIV-1 reverse transcriptase → inhibit RNA- and DNA-dependent DNA polymerase.

Unlike NRTI's, NNRTIs do not compete with nucleoside triphosphates or require phosphorylation to be active.

GI intolerance, skin rash (Stevens- Johnson syndrome)

Metabolistm by the CYP450 system = innumberable drug interactions

Rx: HIV-1

prevents mother-child HIV transmission

Prevent post-translational cleavage of the Gag-Pol polyprotein, thereby preventing the processing of viral proteins into functional conformations. Results in the production of immature, noninfectious viral particles.

Fat redistribution (central obesity,

buffalo hump, peripheral and facial wasting, breast enlargement,

cushingoid)

Rx: HIV-1, HIV-2

Binds to the gp41 subunit of the viral envelope glycoprotein, prevents fusion of the viral and cellular membranes.

Local injection site reactions

(hypersensitivity, eosinophilia)

Rx: HIV-1

Binds to CCR5, one of two coreceptors (the other is CXCR4) necessary for

entrance of HIV into CD4+ cells.

Upper respiratory tract infections,

muscle/joint pain, sleep disturbance, ↑hepatic transaminase

CI: preexisting liver

dysfunction

Binds integrase and inhibits strand transfer.  This interferes with the integration of reverse-transcribed HIV DNA into chromosomes of host cells.

Diarrhea, nausea, dizziness,

headache

Binds to specific cell membrane receptors that cause induction of intracellular signals → inhibits viral penetration, translation, transcription, protein processing, maturation, and release as well as ↑expression of MHC antigens, phagocytic activity of macrophages, and proliferation/ survival of cytotoxic T cells.

Flu-like syndrome, neurotoxicity,

myelosuppression, tinnitus,

retinopathy, pneumonitis,

cardiotoxicity

Rx: HBV, HCV

CI: hepatic decompensation,

autoimmune disease, history

of cardiac arrhythmia

Interferes with synthesis of guanosine

triphosphate, to inhibit capping of viral messenger RNA, and to inhibit the viral RNA-dependent polymerase of certain viruses

Hemolytic anemia, depression,

fatigue, irritability, rash, cough,

insomnia, nausea, pruritus

Fetal abnormalities

Teratogenic, mutagenic!

Rx: hepatitis C, respiratory

syncytial virus, pneumonia

CI: uncorrected anemia, endstage

renal failure, ischemic

vascular disease, pregnancy

Block the M2 proton ion channel of the virus particle and inhibit uncoating of the viral RNA within infected host cells, thus preventing its replication.

Teratogenic, rapid resistance, GI effects, CNS (nervousness, difficulty concentrating, insomnia)

Influenza A only

Block the M2 proton ion channel of the virus particle and inhibit uncoating of the viral RNA within infected host cells, thus preventing its replication.

Teratogenic, rapid resistance, GI effects, CNS (nervousness, difficulty concentrating, insomnia)

Influenza A only

Interfere with release of progeny influenza virus from infected to new host cells, thus halting the spread of infection within the respiratory tract.

GI effects, cough, bronchospasm, reversible ↓pulmonary function, transient nasal and throat discomfort

Influenza A & B viruses

Interfere with release of progeny influenza virus from infected to new host cells, thus halting the spread of infection within the respiratory tract.

GI effects, cough, bronchospasm, reversible ↓pulmonary function, transient nasal and throat discomfort

Influenza A & B viruses