Viral Agents

Front 1

Abacavir

Back 1

- Oral NRTI (HIV drug)
- Used in HAART
- Guanosine analog that targets RT and terminates DNA chain polymerization
- Resistance develops rapidly when given alone
- Causes hypersensitivity in 8% of patients

Front 2

Acyclovir

Back 2

- Oral/IV/topical guanosine analog (herpes family)
- Used for HSV (encephalitis, suppression of genital herpes, and mucocutaneous prophylaxis for immunosuppressive therapy) and severe VSV (ocular infection)
- Guanosine prodrug that is selectively mono-Pi by viral thymidine kinase → converted to GTP by cellular enzymes → selectively incorporated into DNA by viral DNA polymerase → terminates viral DNA replication
- Resistance via thymidine kinase deficiency or DNA polymerase mutation
- Renally secreted with 2.5 hour half-life
- Well tolerated, may cause minor discomfort upon application
- High IV doses can cause encephalopathy
- Probenacid decreases clearance
- Decreases clearance of methotrexate

Front 3

Efavirenze

Back 3

- Oral NNRTI (HIV drug)
- Used in HAART to slow replication of HIV
- Non-competitive inhibition of RT (does not bind active site)
- Can cause rash, drowsiness, insomnia, dizziness, and confusion

Front 4

Emtricitabine

Back 4

- Oral NRTI (HIV drug)
- Used in HAART
- Cytodine analog that inhibits RT and terminates DNA chain polymerization
- Resistance develops rapidly when given alone
- Can cause fatty liver

Front 5

Enfuvirtide

Back 5

- SC viral FI (HIV drug)
- Used in HAART
- Synthetic peptide that blocks conformational change in viral coat protein gp41, which is necessary for viral entry into host cell
- 98% incidence of local reactions at injection site
- Must be given twice daily, it is expensive, and supply is limited

Front 6

Foscarnet

Back 6

- IV phosphate analog (herpes family)
- Treat CMV retinitis, CMV prophylaxis, ganciclovir-resistant CMV, and acyclovir-resistant HSV
- Phosphate analog → binds pyrophosphate binding sites of viral DNA polymerase/reverse transcriptase → prevents viral DNA replication
- No observed resistance
- Renal excretion with 3-6 hour half-life
- Accumulates in bone
- Dose-limiting nephrotoxicity and electrolyte disturbances (hypocalcemia)
- Occasional paresthesias, penile ulcers, and GI intolerance
- Rare CNS toxicity

Front 7

Ganciclovir

Back 7

- IV/intraocular guanosine analgo (herpes family)
- Treat CMV, especially in immunocompromised patients
- 5'-GMP analog → converted to GTP by cellular enzymes → selectively incorporated into DNA by viral DNA polymerase → terminates viral DNA replication
- Resistance via DNA polymerase mutation
- Renal excretion of unchanged drug with 3-4 hour half-life
- Commonly causes bone marrow suppression (neutropenia/thrombocytopenia)
- Occasionally causes CNS toxicity, anemia, rash, and GI intolerance
- Rarely causes coma and hepatotoxicity

Front 8

Indinavir

Back 8

- Oral PI (HIV drug)
- Used in HAART to decrease replication of HIV
- Inhibits viral-encoded acid protease to prevent cleavage and assembly of protiens
- Must be taken every 8 hours and in fasting state
- Metabolized by CYP450 3A system but 20% is secreted unchanged in urine
- GI intolerance and retinoid-like effect in 30% of patients
- Nephrolithiasis in 5% of patients; prevent through good hydration
- Elevates bilirubin levels, but does not cause hepatitis/hepatic damage
- Drugs that interact with CYP450 3A system should be avoided (rifampin, terfenadine, benzodiazepines, etc.)

Front 9

Lamivudine

Back 9

- Oral NRTI (HIV drug)
- Used in combination therapy with zidovudine (synergistic) and PI for HAART
- Used alone for chronic hepB treatment
- Deoxythymidine analog → binds with high affinity to RT and terminates DNA polymerization (lacks 3'-OH)
- Rapid resistance due to RT mutation, but lowers resistance to zidovudine (and rarely reverses zidovudine resistance)
- Rarely causes pancreatitis
- Other adverse effects are similar to, but less frequent than zidovudine (bone marrow suppression, lactic acidosis, etc.); adverse effects are not additive

Front 10

Maraviroc

Back 10

- CCR5 antagonist
- Twice daily for multi-drug resistant CCR5-tropic HIV-1 strains
- Resistance via CXCR4-tropic strains
- Substrate for CYP 3A and P glycoprotein (Pgp)

Front 11

Oseltamivir

Back 11

- Oral neuraminidase (anti-influenza)
- Reduces duration of illness caused by influenza A and B when given within 48 hours of symptom onset; works prophylactically in 66% of patients
- Can cause N/V (reduced by taking with food) and headache
- FDA warning about neuropsychiatric events in children/adolescents, including suicide

Front 12

Raltegravir

Back 12

- HIV-1 integrase strand transfer inhibitor
- Used in HAART for multi-drug resistant HIV-1
- Metabolized by UDP glucuronosyltransferase 1A1, so must monitor levels when given with rifampin (UGT 1A1 inducer)
- No interaction with CYP 3A

Front 13

Ribavirin

Back 13

- Aerosol purine analog (HepC drug)
- Mainly used for hepC, but also approved for respiratory syncitial virus in infants
- Aerosol delivery requires special equipment, isolation, and precautions
- Possible teratogen and mutagen
- Aerosol delivery can cause transient wheezing and deterioration of pulmonary funciton
- Systemic delivery causes anemia from bone marrow suppression and hemolysis

Front 14

Ritonavir

Back 14

- Oral PI (HIV drug)
- Used in HAART to decrease replication of HIV
- Inhibits viral-encoded acid protease to prevent cleavage and assembly of viral proteins
- Many drug interactions and side effects, so used in combination with other PIs to prolong their stay in the body
- Many noxious side effects, including GI distress, headaches, asthenia, fatigue, taste disturbances, circumoral parasthesia, elevation of ALT/AST/creatine kinase/triglycerides
- Associated with lipodystrophy (buffalo hump), insulin resistance and elevated blood lipids
- Need to start at low dose and slowly escalate to full dose
- Powerful inhibitor and inducer of CYP450 3A enzymes, so closely monitor levels of concomitant analgesics,antibiotics, anticoagulants, anticonvulsants, antidepressents, antiemetics, antineoplastic, and CCBs
- CI with antiarrhythmics and sedative hypnotics due to CYP450 3A interactions
- CI with disulfiram and metronidazole because it is formulated in ethyl alcohol

Front 15

Telbivudine

Back 15

- Oral HepB polymerase inhibitor
- Used to treat HepB only; no anti-HIV activity
- Half-life of 40 hours
- Excreted unchanged renally
- 21% of patients develop rebound HepB after 2 years of treatment
- High level of cross resistance between telbivudine and lamivudine

Front 16

Tenofovir

Back 16

- Oral NRTI (HIV drug)
- Used in HAART to treat HIV
- Used alone for chronic hepatitis B
- AMP pro-drug → binds with high affinity to RT and terminates DNA polymerization
- Advantages → once daily dosing, taken with/without meals, does not require kinase for it's anti-RT activity
- Resistance develops rapidly
- Nephrotoxicity that manifests as Fanconi's syndrome (wasting of urine metabolites in proximal tubules), not Fanconi's anemia
- CI in children and pregnancy

Front 17

Valcyclovir

Back 17

- Oral guanosine analog (herpes family)
- Used for HSV (encephalitis, suppression of genital herpes, and mucocutaneous prophylaxis for immunosuppressive therapy) and severe VSV (ocular infection)
- Pro-drug of acyclovir → activated by hydrolysis in intestinal wall and liver to provide higher oral serum levels of acyclovir

Front 18

Valgancyclovir

Back 18

- Oral guanosine analog (herpes family)
- Treat CMV, especially in immunocompromised patients
- Pro-drug form of ganciclovir → activated by hydrolysis in intestinal cell wall and liver

Front 19

Zidovudine

Back 19

- Oral NRTI (HIV drug)
- Used with another RTI and a PI in HAART for management of HIV and to reduce HIV transmission during pregnancy
- Deoxythymidine analog → binds with high affinity to RT and terminates DNA polymerization (lacks 3'-OH)
- Rapid resistance due to RT mutation
- 1 hour half-life → four times daily dosing
- Widely distributed, including CNS and semen
- Dose-limiting granulocytopenia and anemia, which are increased by amphotericin B, acetaminophen, aspirin, alpha-interferon, TMP/SMZ, and probenecid → avoid giving with nephrotoxic agents or agents that suppress bone marrow
- Can cause lactic acidosis that leads to hepaticsteatosis/hepatomegaly (may contribute to lipodystrophy)
- Other side effects include severe headache, nausea, myalgia, myopathy, seizures and neurotoxicity