Pharm Antiviral Chemotherapy And Prophylaxis

Front 1

What is acyclovir used for? What are other drugs in this class? What do you use for herpes zoster?

Back 1

HSV, VZV, and EBV.

HSV induced mucocutaneous and genital lesions as well for encephalitis. Prophylaxis immunocompromised PTs.

For herpes zoster, use famciclovir.

Note: no effect on latent forms of HSV and VZV.

Front 2

What is the MOA of acyclovir? What is the mode of resistance?

Back 2

Acyclovir is phosphorylated by viral thymidine kinase to dGTP that inhibits viral DNA polymerase and leads to chain termination by incorporating into the viral DNA strand.

Resistance from lack of thymidine kinase.

Front 3

Treatment of CMV infections in immunosuppression and organ transplant. Are they used with other drugs?

Back 3

Ganciclovir, valganciclovir (primary drugs). Because of their toxicity (pancytopenia), they are used only with CMV. But they can treat HSV, HZV, and EBV.

Also: cidofovir, foscarnet, fomiversin

Front 4

What is the MOA of Ganciclovir? Mode of resistance?

Back 4

An analogue of guanosine, it is phosphorylated by CMV viral kinase or HSV/VZV thymidine kinase into 5'monophosphate that inhibits DNA polymerase

Resistance by mutated CMV DNA polymerase or lack of viral kinase.

Front 5

What are the SE of Ganciclovir?

Back 5

Pancytopenia, renal toxicity.

More toxic to host enzymes than acyclovir.

Front 6

What is cidofovir MOA and its use? Its SE?

Back 6

Since phosphorylation does not require viral kinase, cidofovir is active against many acyclovir and ganciclovir-resistant strains.

Nephrotoxicity is the major dose-limiting toxicity.

Front 7

What is the second line drug (in acyclovir resistant strains) for CMV, its MOA and what is special about their MOA and its SE? Mode of resistance.

Back 7

Foscarnet. It inhibits DNA polymerase that binds to the pyrophosphate-binding site and does not need thymidine kinase-deficient or viral kinase to become activated.

Foscarnet is also a backup for ganciclovir for CMV retinitis; acyclovir-resistant HSV.

Nephrotoxicity.

Resistance: mutated DNA polymerase.

Front 8

How do you treat HIV?

Back 8

Current approach is to use 3 or more antiretroviral drugs, such as nucleoside reverse transcriptase with inhibitors of HIV protease.

Front 9

What is the MOA of nucleoside reverse transcriptase inhibitors (NRTIs)?

Back 9

They are converted into triphosphates by the host cell kinases, which then inhibits HIV reverse transcriptase and act as chain terminators via their insertion into the growing DNA chain.

Cross-resistance is common, but incomplete.

Front 10

What are some NRTIs?

Back 10

Zidovudine (prototype). Lamivudine is felt to be the backbone of most combination therapy regimens. Also, didanosine, stavudine, emtricitabine, and albacavir, tenofovir.

Zalcitabine, no longer used due to better drugs.

Lamivudine is also used in treatment of chronic HBV.

Front 11

What are the SE of NRTIs?

Zidovudine, abacavir, didanosine, stavudine and zalcitabine.

Back 11

When NRTIs are taken alone or in combination with other antiretroviral agents, may cause lactic acidemia with severe hepatomegaly, fat redistribution (lipodystrophy) and steatosis.

Zidovudine: bone marrow suppression leading to anemia and neutropenia.

Abacavir: hypersensitivity (do NOT reintroduced once discontinued for hypersensitivity--death).

Didanosine: pancreatitis

Stavudine, didanosine and zalcitabine: peripheral neuropathy.

Stavudine increases hepatic transaminases and highest incidence of lipoatrophy, hyperlipidemia, and lactic acidosis of NRTIs.

Tenofovir: renal insufficiency/Fanconi syndrome

Front 12

What is the MOA of nonnucleoside reverse transcriptase inhibitors (NNRTIs)?

Back 12

They inhibitor HIV reverse transcriptase with no phosphorylation required.

There are no cross-resistance with NRTIs but there are with NNRTIs (resistance to one drug confers resistance with other drugs in NNRTI category).

Front 13

What are some drugs that belong to NNRTIs and their SE?

Back 13

Delavirdine (prototype) and nevirapine: elevated liver function enzymes.

Nevirapine: Steven-Johnson syndrome; induction of CYP

Efavirenz (DOC in this class): teratogenicity, CNS disturbances (delusions, nightmares, insomnia).

They are all inducers of CYP450.

Front 14

What is the MOA of protease inhibitors?

Back 14

HIV virions are dependent on an aspartate protease encoded by the pol gene to cleave the precursor polyproteins to form the final structural proteins of the mature virion core.

Protease inhibitors inhibit protease enzyme; therefore, the virus cannot replicate.

Front 15

What are some drugs that belong to protease inhibitors and their SE?

Back 15

They all end in -navir

Inhibition of lipid-regulating proteins: hyperglycemia, insulin resistance or hyperlipidemia with altered body fat distribution. Buffalo hump, gynecomastia, and truncal obesity. They can all inhibit CYP450, but ritonavir is the most severe (which can be taken advantage of in "boosting" the effects of other protease inhibitors.

Indinavir (prototype): hyperbilirubinemia and nephrolithiasis--drink lots of water!!

Atazanavir, fosamprenavir, lopinavir, nelfinavir, saquinavir: GI distress and diarreha.

Atazanavir: peripheral neuropathy

Amprenavir: rash

Darunavir, tipranavir

Ritonavir: SE is turn positive is inhibition of CYP; therefore, this drug is used to "boost other PIs.

Front 16

What are two entry inhibitors and their MOA?

Back 16

Maraviroc: blocks the receptor CCR5 to prevent viral attachment.

Enfuvirtide: binds to gp41 of the viral envelop to prevent conformational changes required for the fusion of the viral and cellular membranes.

Front 17

What are the SE of enfuvirtide and maraviroc?

Back 17

Enfuvirtide: hypersensitivity reactions at injection site, increase risk of bacterial pneumonia.

Marviroc: muscle/joint pain, liver enzymes are increased

Front 18

What can be used for prophylactic against influenza A (but not B) and to reduce the duration of symptoms?

Back 18

Amantadine and Rimantadine.

Front 19

What is the MOA of amantadine and rimantadine? Their SE?

Back 19

They prevent uncoating of influenza A by binding to M2 protein.

SE: CNS symptoms (ataxia, slurred speech, confusion), and teratogenic; rimantadine has less CNS SE.

Note: also causes release of dopamine from intact nerves; therefore, can also treat Parkinson's disease.

Front 20

What can be used for influenza A and B, and active against both H3N2 and H1N1?

Back 20

Oseltamivir and Zanamivir

Front 21

What is the MOA for oseltamivir and zanamivir?

Back 21

They inhibit neuraminidases produced by both influenza A and B. These viral enzymes cleave sialic acid residues from viral proteins and surface proteins of infected cells.

Front 22

SE of oseltamivir and zanamivir?

Back 22

Oseltamivir: GI symptoms

Zanamivir: bronchospasm in asthmatics.

Front 23

What are some drugs used to treat hepatitis?

Back 23

Interferon-alpha, adefovir-dipivoxil, entecavir, lamivudine, ribavirin

Front 24

What is the MOA of interferon-alpha?

Back 24

To increase the formation of antiviral proteins. They do so by activation of host cell ribonuclease that degrades viral mRNA. IFN-alpha also promotes formation of NK cells to destroy infected liver cells.

Front 25

What is interferon-alpha used for?

Back 25

Used for chronic HBV.

Used with ribavirin for HCV

Also, Kaposi's sarcoma, papillomatosis, genital warts and help to prevent spread of herpes zoster in cancer PTs and reduce CMV shedding after renal transplantation.

Front 26

SE of interferon alpha?

Back 26

Bone marrow suppression, alopecia

Front 27

What drug can be used for both HIV and HBV?

SE of of this drug?

Back 27

Adefovir Dipivoxil.

It is a nucleotide analog revers transcriptase inhibitor, thereby inhibiting DNA synthesis. Tenofovir has the same MOA and is used for chronic HBV infection.

Adefovir: Lactic acidosis and severe hepatomegaly with steatosis. Nephrotoxicity is dose-limiting.

Front 28

What is the MOA of entecavir?

Back 28

A guanosine nucleoside analogue that inhibits HBV viral polymerase.

Front 29

MOA of lamivudine?

Back 29

Nucleoside reverse transcriptase inhibitor for treatment of chronic HBV.

Front 30

MOA of ribavirin and its use? Its SE?

Back 30

Guanosine analog that inhibits guanine nucleotide synthesis and to inhibit viral RNA polymerase to inhibit viral replication.

HCV and RSV bronchiolitis

SE: hemolytic anemia, and severe teratogenic compound.

Note: ribavirin is used with IFN-alpha for chronic HCV.

Front 31

Question: Accidental needlestick from an AIDS PT occurred. The CD4 count of 20/uL and viral RNA load of greater than 10^7 copies/mL are in the AIDS PT. What is the appropriate action of treatment to give to the person who had the accidental needlestick?

Back 31

Treat with zidovudine plus lamivudine plus a protease inhibitor for 4 weeks (answer in book)

Treatment is given with three antiviral drugs.

Front 32

Question: PT CD4 count of 45/uL is maintained on 3 drug regimen: indinavir, didanosine, and zidovudine. Prophylactic treat is: fluconazole, rifabutin, trimethoprim-sulfamethoxazole, and valganciclovir. The drug most likely to suppress herpetic infections and provide prophylaxis against CMV retinitis in this PT is?

The does of indinavir in this PT may need to be increased above normal, why?

Back 32

Ganciclovir is the most commonly used drug for CMV. Valganciclovir is a prodrug of ganciclovir. Cidofovir is also very effective.

Cidovovir is also effective against HSV strains, including those resistant to acyclovir.

Rifabutin (like rifampin) increases liver drug-metabolizing enzymes; therefore, indinavir can be affected.

Front 33

Question: What drug is most likely to cause additive anemia and neutropenia if administered to an AIDS PT taking zidovudine?

Back 33

Ganciclovir is a myelosuppressant that can result in ganulocytopenia or thrombocytopenia.

Zidovudine also can cause the same problem alone; therefore, when these two drugs are taken together, colony-stimulating factors may be needed.

Front 34

Question: A nursing mother is diagnosed with genital herpes. She has responded in the past positively for a topically drug. What drug to be used orally is most likely to be prescribed?

Back 34

Valacyclovir (which is converted to is converted to acyclovir).

Foscarnet and trifluridine can also be used for HSV; however:

Foscarnet is not used for genital infections (HSV-2); Trifluridine is used only for topical use for herpes keratoconjunctivitis (HSV-1).

Front 35

Question: Oral formulation of this drug should not be used in pregnant AIDS PT because they contain propylene glycol. One of the adverse effects of the drug is hyperpigmentation on the hands and soles of the feet, especially in African-American PTs.

Back 35

Emtricitabine and fosamprenavir both contain propylene glycol--however, the answer is emtricitabine since it can cause hyperpigmentation.

Also, efavirenz can cause abnormalities in pregnant monkeys. Delavirdine is also teratogenic.

Front 36

Question: What drug binds to a CCR5 receptor of CD4 cells blocking the entry of HIV?

Back 36

Maraviroc

Note: Enfuvirtide binds to gp41 to prevent conformational changes for penetration of the virus.

Front 37

Question: Regarding interferon-alpha, what are true statements?

Back 37

Start of the treatment, PTs experience flu-like symptoms.

Used for genital warts, HBV, and HCV.

Lamivudine is used in monotherapy of HBV infection and does not oppose the effects of IFN-alpha with both are used together.

Toxicity includes bone marrow suppression.

Front 38

Question: More than 90% of this drug is excreted in the urine in intact form. Because its urinary solubility is low, PTs should be well hydrated to prevent nephrotoxicity. What drug is being described?

Back 38

Acyclovir.

Nephrotoxic effects: hematuria, crystalluria are enhanced when PTs are dehydrated or with preexisting renal dysfunction. It can cause nephrolithiasis.

Front 39

Used in the prophylaxis and treatment of infection caused by influenza viruses including H1N1 strains, this drug facilitates clumping of mature virions and their adhesion to infected cells.

Back 39

Oseltamivir and zanamivir--they inhibit neuraminidase produced by influenza A and B. They prevent trimming of sialic acid residues from viral protein, which interferes with their clumping and adhesion to host that are already infected.

Front 40

Question: What antiretroviral drugs are safe to use in pregnancy?

Back 40

Lamivudine, lopinavir/ritonavir, nevirapine, and zidovudine.

Front 41

Question: HIV PT with CD4 of 250 and viral load of 15,000. his treatment is 3 drugs of zidovudine, didanosine, and ritonavir; acyclovir for herpes and ketoconazole for oral candidiasis. Because of his weight loss, dronabinol and verapamil for angina. He has anorexia, vomiting, and epigastric pain. He is preliminary diagnosed with acute pancreatitis (elevated amylase).

What drug can cause pancreatitis? What drug should replace it?

Back 41

Didanosine (acute pancreatitis has been reported with several reverse transcriptase inhibitors), but didanosine is the most likely cause.

Lamivudine.

A second protease inhibitor (e.g., atazanavir) with a single reverse transcriptase inhibitor could be affected; however, there is an increase in drug interaction.

Atazanavir is associated with PR interval prolongation and would exacerbate the SE of verapamil.

Front 42

MOA of antiviral drugs:

Cidofovir, ganciclovir, foscarnet, fosamprenavir.

Back 42

Cidofovir: activated by host cell kinases.

Ganciclovir: like acyclovir, inhibits viral DNA polymerase and causes chain termination.

Foscarnet: inhibits viral DNA polymerase without bioactivation.

Fosamprenavir: prodrug of amprenavir, an inhibitor of HIV protease and no effect on reverse transcriptase.

Front 43

Interferons prevent dissemination of?

SE vidarabine?

SE of ganciclovir?

Back 43

Herpes zoster.

Potentially teratogenic.

Similar to radiation therapy (bone marrow suppression) , hepatic and neurologic dysfunction)

Front 44

Drug used for HSV, VZV?

Back 44

Acyclovir (primary drug).

Also: cidofovir, foscarnet, and vidarabine.

Front 45

Drug used for HBV?

Back 45

IFN-alpha, lamivudine (primary drug).

Also: adefovir dipivoxil, entacavir, lamivudine, telbivudine.

Front 46

Drug for HCV?

Back 46

IFN-alpha (primary)

Also: ribavirin.

Front 47

Drug for influenza A?

Drug for influenza B?

Back 47

A: oseltamivir (primary). Also: amantadine, rimantadine, zanamivir.

B: Oseltamivir (primary). Also: zanamivir.

Front 48

What is the key difference between acyclovir and ganciclovir?

Back 48

To become active, acyclovir must first be phosphorylated by virus specific thymidine kinase, while ganciclovir does not.

CMV of the herpesviridae, lacks thymidine kinase, so acyclovir is less active for CMV.

Ganciclovir kills all herpesviridae, including CMV>

Front 49

HAART treatment?

Back 49

Three drugs: two nucleoside reverse transcriptase inhibitors combined with either a protease inhibitor or a non-nucleoside analog.

Regime is tailored to avoid SE.

Front 50

What protease inhibitor has the less impact on lipids compared to others? And what is its SE.

Back 50

Atazanavir. It also causes a rise in indirect bilirubin but rarely clinical jaundice; therefore, this can be used to monitor PTs adherence.