Pharm 49 Antivirals

Front 1

Drug of choice for CMV?

Back 1

Ganciclovir, valganciclovir

Front 2

Drug of choice for HSV, VZV?

Back 2

Acyclovir

Front 3

Drug of choice for HBV?

Back 3

IFN-α, lamivudine

Front 4

Drug of choice for HCV?

Back 4

IFN-α

Front 5

Drug of choice for Influenza A/B?

Back 5

Oseltamivir

Front 6

NRTIs?

Back 6

Zidovudine
Abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine

Front 7

NNRTIs?

Back 7

Delavirdine
Efavirenz, nevirapine, tenofovir

Front 8

Protease Inhibitors?

Back 8

Indinavir
Amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir

Front 9

Fusion inhibitors?

Back 9

Enfuvirtide

Front 10

Antiherpes drugs?

Back 10

Acyclovir
Ganciclovir
Cidofovir
Foscarnet
Vidarabine
Idoxuridine, Trifluridine
Fomivirsen

Front 11

general MOA of antiherpes drugs?

Back 11

antimetabolites bioactivated via viral or host cell kinases to form compounds that inhibit viral DNA polymerases

Front 12

MOA of acyclovir?

Back 12

activated to acyclovir triphosphate, which blocks viral DNA synthesis
(competitive substrate for DNA polymerase, also leads to chain termination after incorporation into viral DNA)

Front 13

mechanism of resistance to acyclovir?

Back 13

virus lacks thymidine kinase
(involved in the initial viral-specific phosphorylation of acyclovir)

Front 14

toxic effects of parenteral acyclovir?

Back 14

delirium, tremor, sezures, hypotension, nephrotoxicity

Front 15

which drug is converted to acyclovir by hepatic metabolism, reaches plasma levels 3-5X greater than acyclovir, and has longer duration?

Back 15

Valacyclovir

Front 16

which drug is activated by viral thymidine kinase and inhibits DNA polymerase but doesn't cause chain termination?

Back 16

Penciclovir

Front 17

Which of the acyclovir congeners have activity against TK- strains of HSV?

Back 17

none of them

Front 18

MOA of docosanol?

Back 18

inhibits fusion btwn HSV envelope and plasma membranes (prevents viral entry and subsequent replication)

Front 19

MOA of ganciclovir?

Resistance?

Back 19

guanine derivative, triphophorylated to form a nucleotide that inhibits DNA polymerases of CMV and HSV and causes chain termination.

HSV: absence of TK; CMV: mutations in viral phosphotransferase and viral DNA polmerases

Front 20

Which drug has high oral bioavailability and has decreased usage of IV ganciclovir in CMV?

Back 20

Valganciclovir (prodrug of ganciclovir)

Front 21

Clinical use of ganciclovir and valganciclovir?

Back 21

prophy and tx of CMV retinitis and other CMV infxns in immunocompromised pts

Front 22

toxic effects of ganciclovir?

Back 22

leukopenia, thrombocytopenia, mucositis, hepatic dysfxn, seizures

Front 23

MOA of cidofovir?

Resistance?

Back 23

activated by host cell kinases to diphosphate that inhibits DNA polymerases of HSV, CMV, adenovirus and HPV

mutations in DNA polymerase gene

Front 24

Toxic effects of cidofovir?

Back 24

Nephrotoxicity (IV administered and metabolized by kidneys, adjust dose in proportion to CrCl),

Probenicid decreases tubular secretion and reduces nephrotoxicity

Front 25

MOA of Foscarnet?

Resistance?

Back 25

*Does not require phophorylation for action;
Inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase

point mutations in DNA polymerase gene

Front 26

Clinical use of foscarnet?

Back 26

alternative prophy/tx of CMV, esp. against TK- strains
inhibits TK- HSV, esp. in AIDS pts

Front 27

Toxic effects of foscarnet?

Back 27

*Effects are severe*
Nephrotoxicity w/ electrolyte disturbances (esp hypocalcemia)
GU ulcers
CNS (HA, hallucinations, seizures)

Front 28

Antiherpes drug that is an adenine analog, is active against HSV, VZV, and CMV, used topically for herpes keratitis, is rapidly metabolized and has marked toxicity?

Back 28

Vidarabine

Front 29

Toxic effects of Vidarabine?

Back 29

(with systemic use)
GI upset, paresthesias, tremor, convulsions, hepatic dysfxn

Front 30

Antiherpes drugs that are pyrimidine anaolgs, used topically in herpes keratitis, but are too toxic for systemic use?

Back 30

Idoxuridine and trifluridine

Front 31

MOA of Fomivirsen?

Back 31

antisense oligonucleotide that binds mRNA of CMV, inhibiting early protein synthesis

Front 32

Clinical use of Fomivirsen?

Back 32

injected intravitreally for CMV retinitis

Front 33

current ideal tx regimen for HIV?

Back 33

tx with 3 or more anti-retroviral drugs before onset of sx, if possible

Front 34

MOA of NRTIs?

Back 34

activated by host kinases to triphosphates which competitively inhibit binding of natural nucleotides to dNTP binding site of rev transcriptase and also chain terminate (lack 3'-hydroxyl, preventing attachment of next nucleotide)

Front 35

problem with NRTIs?

Back 35

resistance emerges rapidly if used as single agents (via mutations in pol gene)

Front 36

Features of Abacavir?

Toxic effects?

Back 36

NRTI: guanosine analog; good oral bioavail; 12-24h 1/2 life; resistance develops slowly

Hypersensitivity rxns (sometimes fatal) in 5% of HIV pts

Front 37

Which NRTI causes pancreatitis in alcoholic pts and pts with hypertriglyceridemia?

Back 37

didanosine

Front 38

Toxic effects of didanosine?

Back 38

peripheral neuropathy
diarrhea
hepatic dysfxn
hyperuricemia
CNS effects

Front 39

Which NRTI has once-daily dosing but is contraindicated in pregnancy, children, and pts with hepatic or renal dysfxn?

Back 39

Emtricitabine

Front 40

Toxic effects of Emtricitabine?

Back 40

asthenia
GI upset
HA
hyperpigmentation of palms and/or soles

Front 41

which NRTI is used in HBV infection in addition to HAART?

Back 41

Lamivudine

Front 42

toxic effects of Lamivudine?

Back 42

usually mild; GI upset, HA, insomnia, fatigue

renal metabolism requires dosage adjustment in renal insufficiency

Front 43

which NRTI penetrates most tissues, including CNS, but causes peripheral neuropathy, esp w/ co-administration of didanosine or zalcitabine?

Back 43

Stavudine

(Zalcitabine also causes peripheral neuropathy)

Front 44

Which NRTI has the greatest incidence of lactic acidosis w/ hepatic steatosis?

Back 44

Stavudine

Front 45

What type of protein is Tenofovir?

MOA?

Back 45

Nucleotide

Acts like NRTIs to competitively inhibit reverse transcriptase and cause chain termination

Front 46

what side effect is mutual to all NRTIs?

Back 46

lactic acidosis and severe hepatomegaly with steatosis

Front 47

What antiviral may inhibit the renal excretion of acyclovir and ganciclovir?

Back 47

Tenofovir

Front 48

names of NRTI's?

Back 48

-ines and -vudines (and Abacavir)

Front 49

Names of PIs?

Back 49

-avirs

Front 50

Toxic effects of Tenofovir?

Back 50

GI upset, asthenia, HA, acute renal flr (rare) and Fanconi's syndrome (rare)

Front 51

benefit of Zalcitabine?

toxic effects?

Back 51

high oral bioavailability

can increase toxicity of nephrotoxic drugs, peripheral neuropathy, pancreatits, esophageal ulcers, stomatitis, arthralgias

Front 52

Which NRTI is distributed to most tissues including CNS and is eliminated via hepatic metabolism and renal excretion (must reduce in pts with cirrhosis and uremic pts)?

Back 52

Zidovudine

Front 53

Primary toxic effect of Zidovudine?

Back 53

bone marrow suppression (additive with other myelosuppressive drugs) --> anemia, neutropenia

Front 54

which drugs increase the plasma levels of Zidovudine?

which drugs increase the clearance?

Back 54

azole antifungals and protease inhibitors

Rifampin

Front 55

MOA of NNRTIs?

Back 55

Block viral nucleic acid synthesis by binding to a site on reverse transcriptase (different than the site of NRTIs) do not require activation by phosphorylation, and do not compete with nucleoside triphospates

Front 56

mechanism of resistance to both NRTIs and NNRTIs?

Back 56

mutations in the pol gene

Front 57

NNRTIs?

Back 57

Delavirdine
Efavirenz
Nevirapine
Tenofovir

Front 58

What drugs decrease the blood levels of Delavirdine?

What drugs increase the blood levels?

Back 58

antacids, ddI, phenytoin, rifampin, nelfinavir

azole antifungals, macrolides

Front 59

Major side effects with Delavirdine?

Back 59

drug interactions because it is metabolized by CYP3A4 and CYP2D6

Skin rash

Front 60

Which NNRTI can be given once daily?

Back 60

Efavirenz

Front 61

major problem with NNRTIs?

Back 61

drug interactions b/c metabolized by CYP enzymes

Front 62

what should you tell a patient to do to increase the bioavailability of Efavirenz?

Back 62

take with fatty foods

Front 63

Toxic effects of Efavirenz?

Back 63

CNS dysfxn
skin rash
elevated plasma cholesterol
teratogenic

Front 64

Which NNRTI has good oral bioavailability, penetrates most tissues (CNS) and has a half-life > 24h?

Back 64

Nevirapine

Front 65

Which NNRTI is effective in preventing HIV vertical transmission?

Back 65

Nevirapine (given as single dose to mothers at onset of labor and to neonate)

Front 66

Toxic effects of Nevirapine?

Back 66

skin rash
Stevens-Johnson syndrome and severe toxic epidermal necrolysis

Front 67

What drugs increase the blood levels of NNRTIs?

What drugs decrease them?

Back 67

cimetidine and macrolide abx

enzyme inducers (e.g. Rifampin)

Front 68

MOA of PIs?

Back 68

Inhibit HIV-1 aspartate protease enzyme that is used to cleave precursor polyproteins to form the final structural proteins of the mature virion core

Front 69

Resistance mechanism against PIs?

Back 69

multiple point mutations in pol gene

Front 70

Use of PIs in AIDS are most commonly in combinations with what drugs?

Back 70

Reverse transcriptase inhibitors (NNRTIs and NRTIs)

Front 71

which PI has the most pronounced inhibitory effect on CYP3A4?

Back 71

Ritonavir

Front 72

Side effect of all PIs?

Back 72

CHO and lipid metabolism disorders (hyperglycemia, insulin resistance or hyperlipidemia with altered body fat distribution)

lipid-regulating proteins have active sites similar to HIV protease and may be thus inhibited

Front 73

The absorption of which PI is inhibited by fatty foods?

Back 73

Amprenavir/fosamprenavir

Front 74

Toxic effects of amprenavir/fosamprenavir?

Back 74

GI upset, paresthesias, rash (sometimes severe)

Cross-allergenicity with sulfonamides

Front 75

Which PI can be given once daily but must not be taken simultaneously with antacids?

Back 75

Atazanavir

Front 76

Toxic effects of Atazanavir?

Back 76

GI upset, peripheral neuropathy, rash, hyperbilirubinemia, prolonged QT interval (at high dose)

Front 77

Which PI is the only one NOT associated with dyslipidemias, fat redistribution or a metabolic syndrome?

Back 77

Atazanavir

Front 78

Which PI has more common occurrence of insulin resistance?

Back 78

Indinavir

Front 79

Which PI can cause hyperbilirubinemia and kidney stones, in addition to nausea, diarrhea and thrombocytopenia?

Back 79

Indinavir

Front 80

Which PIs are given together because one enhances the pharmacokinetics of the other by inhibiting its CYP3A metabolism?

Back 80

Lopinavir/ritonavir

(ritonavir inhibits CYP3A to enhance lopinavir, can give smaller dose)

Front 81

Which PI is the safest for pregnancy?

Back 81

Nelfinavir

Front 82

Which PI is characterized by increased oral absorption in the presence of food and a short half-life?

Back 82

Nelfinavir

Front 83

Adverse effects of Nelfinavir?

Back 83

Diarrhea

Front 84

Which drugs inhibit CYP3A4?

Back 84

Amiodarone, azoles, cimetidine, erythromycin, clarithromycin, cyclosporine, diltiazem, fluoroquinolones, indinavir, ritonavir, grapefruit juice, PI's, metronidazole, quinine, SSRIs, tacrolimus

Front 85

Which drugs induce or enhance the activity of CYP3A4?

Back 85

Barbiturates, carbamazepine, corticosteroids, efavirenz, phenytoin, rifampin, troglitazone

Front 86

Toxic effects of Ritonavir?

Back 86

bitter taste, GI upset, paresthesias, elevations of liver enzymes, inhibits metabolism of many drugs

Front 87

Toxic effects of Saquinavir?

How can these effects be lessened?

Back 87

nausea, diarrhea, dyspepsia, rhinitis

GI effects reduced by combination with ritonavir, allowing once-daily dosing

Front 88

MOA of Enfuvirtide?

Back 88

binds to gp41 subunit of viral envelope glycoprotein, inhibiting fusion of viral and host cellular membranes

NOT metabolized by CYP450

Front 89

Mechanism of resistance to Enfuvirtide?

Back 89

mutations in env gene

Front 90

Which anti-HIV drug is administered SQ with other anti-HIV drugs in patients with persistent HIV-1 replication despite ongoing therapy?

Back 90

Enfuvirtide

Front 91

What are the anti-influenza agents?

Back 91

Amatadine/Rimantadine and Osetamivir/Zanamivir

Front 92

MOA of Amantidine/Rimantidine?

Back 92

prevent uncoating of Influenza A virus after penetration by binding to and inhibiting protein M2, which acts as a proton pump to acidify and activate viral RNA transcriptase

Front 93

What are Amantidine and Rimantadine effective against?

Back 93

Influenza A (NOT B)

Front 94

Toxic effects of Amatidine/Rimantidine?

Back 94

GI upset, dizziness, ataxia, slurred speech

Amantidine requires dosage adjustment in renal failure

Front 95

MOA of Oseltamivir and Zanamivir?

Back 95

Inhibit neuraminidases of influenza A and B, which cleave sialic acid from viral proteins and surface proteins of host cells to release virions, preventing viral spread

Front 96

When are Oseltamivir and Zanamivir most effective?

Back 96

if used within 24h after onset of sxs

Front 97

Toxic effects of Oseltamivir and Zanamivir?

Back 97

Oseltamivir: GI sxs

Zanamivir: cough, sore throat, bronchospasm in asthmatics

Front 98

What agents are used to suppress viral hepatitis?

Back 98

IFN-α
Adefovir dipivoxil
Lamivudine
Entecavir
Ribavirin

Front 99

MOA of IFN-α?

Back 99

cytokine that increases activity of JAK-STAT receptors that increase txn of antiviral proteins, esp. host ribonuclease that degrades viral mRNA

also promotes formation of NK cells

Front 100

When is IFN-α useful against HBV?

When is it useful against HCV?

Back 100

Used individually or in combination with Lamivudine against chronic HBV

Used in combination with Ribavirin to reduce the progression from acute to chronic HCV

Front 101

What is IFN-α used against?

Back 101

HBV, HCV, Kaposi sarcoma, HPV, preventing dissemination of VZV in cancer pts, reduces CMV shedding after renal txp

Front 102

Toxic effects of IFN-α?

Back 102

GI upset, flulike syndrome, neutropenia, profound fatigue and myalgia, alopecia, reversible hearing loss, thyroid dysfxn, mental confusion, severe depression

Front 103

MOA of Adefovir dipivoxil?

Clinical use?

Back 103

activated by phosphorylation, competitively inhibits HBV DNA polymerase and results in chain termination

suppresses HBV replication, improves liver histology and fibrosis, used against lamivudine-resistant strains of HBV

Front 104

Toxic effects of Adefovir dipivoxil?

Back 104

nephrotoxicity, lactic acidosis, severe hepatomegaly w/ steatosis

Front 105

Clinical uses of Lamivudine?

Back 105

nucleoside inhibitor of HIV reverse transcriptase, also active in chronic HBV; longer half-life in HBV-infected cells than in HIV-infected, is nontoxic when used as monotherapy

Front 106

What increases the risk of pancreatitis in an HBV pt being treated with Lamivudine?

Back 106

Co-infection with HIV

Front 107

MOA of Entecavir?

Back 107

guanosine nucleoside, inhibits HBV DNA polymerase (reverse transcriptase)

Front 108

Toxic effects of Entecavir?

Back 108

HA, dizziness, fatigue, nausea

cross-resistance with Lamivudine

Front 109

MOA of Ribavirin?

Back 109

Inhibits guanosine triphosphate (purine nucleotide) formation, prevents capping of viral mRNA, blocks RNA-dependent RNA polymerases

Front 110

Clinical use of Ribavirin?

Back 110

prevents replication of influenza A/B, parainfluenza, RSV, paramyxoviruses, HCV, HIV

Not effective as monotherapy, used with IFN-α in chronic HCV in pts with compensated liver dz

Front 111

Toxic effects of Ribavirin?

Back 111

Hemolytic anemia (systemic use)
Conjunctival and bronchial irritation (aerosolic use)
Teratogenic

Front 112

which of the systemic antiherpes drugs do not require activation by thymidine kinase?

Back 112

Cidofovir, Foscarnet

Front 113

which of the antiherpes drugs inhibit DNA polymerase but do not cause chain termination?

Back 113

Penciclovir, Famciclovir

Front 114

which antivirals are contraindicated in pregnancy?

Back 114

Emtricitabine (propylene glycol)
Amprenavir/Fosamprenavir (propylene glycol)
Vidarabine
Delavirdine
Efavirenz
Ribavirin

Front 115

What side effect do Acyclovir and Indinavir have in common?

Back 115

Kidney problems -
Acyclovir is very insoluble in urine and can crystallize and cause hematuria; Indinavir can cause kidney stones. Adequate hydration necessary for both