Acyclovir

Famciclovir

Penciclovir

Trifluridine

Cidofovir

Ganciclovir

Formivirsen

Foscarnet

Interphon alph

Adefovir

Entecavir

Ribavirin

Amantadine

Oseltamivir

Rimantadine

Zanamivir

Miscellaneous Antiviral Agents?

Palivizumab

Imiquimod

Abacavir

Didanosine

Emtricitabine

Lamivudine

Stavudine

Zidovudine

Delavirdine

Efavirenz

Nevirapine

Atazanavir

Indinavir

Lopinavir

Ritonavir

Saquinavir

Enfuvirtide

Maraviroc

Inhibits DNA synthesis 2 ways:

1) Competition w/ deoxyGTP for DNA poly (viral)

2) Chain termination following incorporation into viral DNA

Immunocompromised

Mutations in thymidine kinase, DNA poly (viral)

Thymidine Kinase-deficient strains

Genital herpes - overall shortens symptom duration

Varicella and cutaneous zoster infection- decrease total number of lesions, duration of symptoms, & viral shedding

*Varicella w/i 24hrs

Cut zoster inf w/i 72h

Prophylaxis of HSV in pts undergoing organ transplant

Prophylaxis of HSV infections in pts undergoing organ transplant

Herpes simplex encephalitis (DOC)

Neonatal HSV infection (DOC)

Serious HSV or VZV infectious (DOC) - *in immunonocompromised pts w/ VZV it reduces incidence of cutaneous & visceral dissemination

Nausea, diarrhea, headache

Reversible renal or neurological toxicity with IV admin

*crystalline nephropathy, interstitial nephritis

*tremors, delirium, seizures

Use with nephrotoxic agents

use with probenicid and cimetidine

use with zidovudine (cause somnolence & lethargy)

Competitive inhibition of viral DNA polymerase

*achieves > [intracellular] although lower affinity then acyclovir

1st episode and recurrect genital herpes

Suppression of chronic genital herpes (daily admin)

Herpes labialis (daily admin)

Acute zoster

Keratoconjunctivitis

Recurrent epithelial keratitis caused by HSV1/2

Acyclovir resistant HSV infections

Competitively inhibits viral DNA polymerase

Causes termination of viral DNA elongation

Increases duration of usage

Mutation in UL97

Mutations in DNA poly

Long-term tx diminshes risk of Kaposi sarcoma in Aids (HHV8)

Delay progress of CMV retinitis in AIDS pt (IV admin)

Prophylaxis of CMV infection in organ transplant (IV combo w/ oral)

Prevent end-organ CMV disease in AIDS pt (oral admin)

CMV retinitis (opthalmic admin)

Myelosuppression

nausea, diarrhea, fever, rash, headache, insomnia, peripheral neuropathy

CNS toxicity & hepatotoxicity

Admin with probenecid or trimethprim

Admin with didanosine (increase levels of didanosine)

antisense therapy

Inhibits CMV replicaton through seq-specific and nonspecific mech, including inhibition of binding to cells

Direct inhibition of viral DNA polymerase, RNA poly, & HIV reverse transcriptase

*blocks phosphate binding site & inhibits cleavage of pyrophosphate from deoxy triphosphates

Mutations in HSV and CMV DNA poly

*associated with prolonged or repeated exposure to the drug

CMV retinitis, colitis, and esophagitis

*more effective w/ ganciclovir admin

HSV & VZV acyclovir resistance

Long-term use reduces incidence of Kaposi sarcoma

increased toxicity when used with ganciclovir

Renal impairment, hypophosphatemia, hypokalemia, penile ulceration, and much more

Use w/ potential nephrotoxic drugs

use with zidovudine (inc anemia risk)

Use with imipenem (inc risk of seizures)

Potent inhibitor and alternative substrate for viral DNA poly

*comp inhibit  DNA synthesis

*becomes incorporated into the viral DNA chain

CMV retinitis

Adenovirus infections

Proxy tube nephrotoxicity

proteinuria

met acidosis

Fanconi's syndrome

neutropenia

Renal insufficiency

admin w/ other potential nephrotoxic drugs

Competitive inhibition of HIV-1 reverse transcriptase

*incorporation in the growing viral DNA chain results in premee chain termination due to inhibition of binding w/ the incoming nucleotide

Hypersensitivity rxns

* fever, malaise, n/v, diarrhea, anorexia, elevated serum aminotransferase and CK

Discontinuation reverses the syndrome, but if drug retaking w/i hours symptoms resume and can be fatal

Pts w/HLA-B5701 allele @ risk

Alcoholism, hypertriglyceridemia (risk for pancreatitis)

use with pancreotoxic drugs

existing cardiac risk factors

Headache, diarrhea, nauseau, asthenia

*Hyperpigmentation of the palms and/or soles (esp in blacks)

Young kids

Pregnancy

Renal failure

Hepatic failure

use w/ metronidazole or disulfiram

use with lamivudine

M184 mutation

L180 & M2041 HBV DNA poly mutations w/ chronic therapy

HIV infection

HBV infection

Peripheral sensory neuropathy, pancreatitis, arthralgias, elevation of serum aminotransferases

Lactic acidosis

Advanced immunosuppression

admin w/ neuropathy-inducing drugs (didanosine)

admin w/ zidovudine

M41L, D67N, K7OR, T215F, K219Q are most common mutations

*high resistance w/ 3 or more mutations

dec rate of disease progression and prolongs survival of HIV pts

HIV associated dimentia

HIV associated thrombocytopenia

Vertical transmission of HIV

Myelosuppression resulting in macrocytic anemia

GI intolerane, headaches, insomnia, fat loss, thrombocytopenia, hyperpigmentation of the nails

High doses: anxiety, confusion, tremulousness

Use with probenecid, phenytoin, methadone, etc

use w/ other myelosuppressors (b/c of risk of hematological anxiety)

use with stavudine

High Fat meal (need to be taken empty)

pregnancy

Prevention of HIV from mom-baby - vertical transmission

*admin to mom w/i onset of labor and neonate w/i 3 days of delivery

Redistribution and accum of body fat

Inc triglycerides and LDL levels

hyperglycemia & insulin resistance

increased spontaneous bleeding in hemophiliac pts

What are the contraindications w/ PIs

*Hint one of the main contraindication w/ NNRTIs

GI issue (diarrhea, nausea, ect)

headache, peripheral neuropathy

hepatic enzyme elevation

EKG changes

admin w/ acid reducing agents

severe hepatic insufficiency

Hyperbilirubinemia & nephrolithiasis

Thrombocytopenia, elevated aminotransferase levels, insulin resistance

Enfuvirtide

Maraviroc

Docosanol

Palivizumab

Amantadine

rimantadine