Acyclovir is Tx for? Mech? *HSV* Guanosine analogue; Activated by viral thymidine kinase-->INHIBITS DNA synthesis by competing with dGTP

Acyclovir mech of resistance? Resistance develops due to DECREASE in viral thymidine kinase

Acyclovir pros and cons? NO Bone Marrow effect

Very well-tolerated

Will NOT work against CMV

Excreted by Kidney-->Nephrotoxicity with HIGH IV doses

Acyclovir drug interaction & effect of note? Somnolence/lethargy with Zidovudine

Valacyclovir similar to _________? Admin? Acyclovir

ADMIN: Oral

Famciclovir/Penciclovir similar to ________? Acyclovir

Docosanol mech? Use/admin? INHIBITS viral fusion to cell membrane

OTC for

HSV, cold

sores

(topical)

Ganciclovir/Valganciclovir mech? Inhibits Cytomegalovirus (CMV) DNA replication; Activated by viral kinases in cells infected with herpes or CMV

Ganciclovir/Valganciclovir pros and cons? Less selective than Acyclovir- more toxic Bone Marrow Toxicity!

Ganciclovir/Valganciclovir drug interaction/effect? Do NOT combine with other Bone Marrow drugs (Zidovudine)

Cidofovir uses? Resistant CMV and herpes

Cidofovir adverse effects? Prevention of these? Renal toxicity Use probenecid & hydrate

Foscarnet mech? Inhibits DNA & RNA polymerase, reverse transcriptase

Foscarnet admin/uses? Adverse? IV, resistant herpes and CMV Renal toxicity

Name the drugs used for Herpes (only).

Name the CMV/Herpes drugs. Note:anything that treats Herpes can end with -ciclovir

Oseltamivir, Zanamivir mech? Uses? Neuraminidase inhibitors Active against Influenza A and B

Ribavirin mech? Uses/admin? Inhibits viral RNA synthesis Primary uses are RSV (aerosol) and Hep C (w/IFNs)

Ribavirin adverse effects? Very Teratogenic!!!

Name the Influenza drugs.

Name the RSV drugs. *Ribavirin (Virazole®) Palivizumab (SynagisTM) "PAVLOV's dog ate RIBs in his custom RV"

Lamivudine mech? Reverse transcriptase inhibitor used for HIV; Also inhibits HBV polymerase

Lamivudine adverse effects? DOC for? Few side effects, well-tolerated DOC for CHRONIC Hepatitis B

Interferon alpha-2b MAIN use? alpha-2b with ribavirin for HCV

Interferons adverse effects? (3) Flu-like symptoms CNS – depression, suicide Bone marrow depression

Boceprevir, Toleprevir mech? Uses? Protease inhibitor of HCV For HCV genotype I

Boceprevir, Toleprevir adverse effects/drug interactions?Strong CYP3A4 INHIBITION Bone marrow depression

Name the Hep B and C drugs *Interferon-alfa2b (Intron-A®; PegIntron), Interferon alfa2a (Pegasys)* *Boceprevir (Victrelis),Teleprevir (Incivik),Semeprevir (Olysis)* *Sofosbuvir (Sovaldi) *Lamivudine (Epivir®) *Adefovir (Hepsera®), Entacavir (Baraclude) Telbivudine (Tyzeka) "A-DEFening BOSE TELEfone speaker will SEMPRE-PREVent any LAMe HEP B and C INTERFERence"

HIV Reverse Transcriptase Inhibitors mech? Common adverse effect?Mechanism like Acyclovir All will cause Lactic Acidosis

Name the HIV Reverse Transcriptase Inhibitors (NTRI's).*Zidovudine *Lamivudine (also used for Hep B & C) *Emtracitabine *Tenofovir *Didanosine Zalcitabine Stavudine *Abacavir "DID you REVERSE that TENOR's LAME ABC's back to "ZID", or EM-i-TRICkIng myself?"

Zidovudine pros? Maintain CD4 counts DECREASE risk of transmission to newborns

Zidovudine cons? Neutropenia and anemia

When to stop Zidovudine? What drug interactions (why)?Stop if lactic acidosis or hepatotoxicity develop Don’t combine with Ganciclovir (Bone Marrow) or Acyclovir (can get somnolence when in combo)

Tenofovir, Emtractibine combo is DOC for? Adverse FX?Naïve HIV patients GI, flatulence (Tenofovir)

KNOW serious side FX chart...

Didanosine admin (combo w/)? Adverse effect? Combined with Zidovudine Peripheral neuropathy, pancreatitis

Zalcitabine adverse FX? Peripheral neuropathy, Oral ulcers

Stavudine adverse effect? Peripheral neuropathy

Abacavir adverse effect? Significance? Hypersensitivity: do NOT use again!!!

Non-Nucleotide RTIs (NNRTIs) admin? What is preferred drug from this group? When is it NOT preferred and what do you use instead?Use ONLY with nucleoside analogues Efavirenz= preferred drug, EXCEPT in pregnancy -- Switch to Nevirapine

Adverse effect of Efavirenz and Delavirdine? Adverse FX of Nevirapine? (2)Efavirenz and Delavirdine teratogenic! Nevirapine- hepatitis, Stevens Johnson

Name the NNRTIs (NON-nucleoside Reverse Transcriptase Inhibitors).

Name the Protease inhbiitors. ALL end with "–navir!" (Atazenavir, Ritonavir)

Protease inhbiitors drug interactions? Specific effects? (9)Most metabolized by CYP3A4 Many drug interactions: (Cushing's-like) Altered body fat distribution “Buffalo hump” Abdominal fat INCREASES BUT- face is thin (diff from corticosteroids) INCREASE cholesterol/TAGs DM, MI, stroke

Atazanavir uses? DOC for HIV!!!

Ritonavir drug interactions? INHIBITS CYP3A4

Ritonavir typically used how? Typical use? Atypical ingredient?Combined with other Protease Inhibitors to INCREASE their bioavailability Booster! Contains alcohol

Indinavir uses? Adverse FX? X-resist with Ritonavir Kidney stones, HYPERbilirubinemia

Amprenavir/Fosamprenavir (combo drug) atypical ingredient and drug interaxn? Adverse FX?Contains propylene glycol- avoid metronidazole! Stevens-Johnson syndrome/rash

Name the HIV fusion inhibitors. Enfuvirtide (Fuzeon™) Maraviroc (SelzentryTM) "MY-RIVA-ROCks an ENFURiating FUSION against HIV"

Enfuviritide mech? Adverse effect? Prevents fusion and entry of HIV into cell Injection sites reactions

Maraviroc mech? Adverse effects? Resistance? CCR5 on HIV Rash most common Resistance!

Raltegravir mech? Blocks integrase (ONLY integrase inhibitor)

Bad HIV combos and why? (3) Atazanavir/Indinavir (bilirubin) Didanosine/Stavudine (neuropathy) Zidovudine/Stavudine (antagonize each other)

*HSV* Guanosine analogue; Activated by viral thymidine kinase-->INHIBITS DNA synthesis by competing with dGTP

Resistance develops due to DECREASE in viral thymidine kinase

Inhibits Cytomegalovirus (CMV) DNA replication; Activated by viral kinases in cells infected with herpes or CMV

Less selective than Acyclovir- more toxic Bone Marrow Toxicity!

Do NOT combine with other Bone Marrow drugs (Zidovudine)

Neuraminidase inhibitors Active against Influenza A and B

Inhibits viral RNA synthesis Primary uses are RSV (aerosol) and Hep C (w/IFNs)

*Ribavirin (Virazole®) Palivizumab (SynagisTM) "PAVLOV's dog ate RIBs in his custom RV"

Reverse transcriptase inhibitor used for HIV; Also inhibits HBV polymerase

Few side effects, well-tolerated DOC for CHRONIC Hepatitis B

Flu-like symptoms CNS – depression, suicide Bone marrow depression

*Interferon-alfa2b (Intron-A®; PegIntron), Interferon alfa2a (Pegasys)* *Boceprevir (Victrelis),Teleprevir (Incivik),Semeprevir (Olysis)* *Sofosbuvir (Sovaldi) *Lamivudine (Epivir®) *Adefovir (Hepsera®), Entacavir (Baraclude) Telbivudine (Tyzeka) "A-DEFening BOSE TELEfone speaker will SEMPRE-PREVent any LAMe HEP B and C INTERFERence"

*Zidovudine *Lamivudine (also used for Hep B & C) *Emtracitabine *Tenofovir *Didanosine Zalcitabine Stavudine *Abacavir "DID you REVERSE that TENOR's LAME ABC's back to "ZID", or EM-i-TRICkIng myself?"

Maintain CD4 counts DECREASE risk of transmission to newborns

Stop if lactic acidosis or hepatotoxicity develop Don’t combine with Ganciclovir (Bone Marrow) or Acyclovir (can get somnolence when in combo)

Combined with Zidovudine Peripheral neuropathy, pancreatitis

Use ONLY with nucleoside analogues Efavirenz= preferred drug, EXCEPT in pregnancy -- Switch to Nevirapine

Efavirenz and Delavirdine teratogenic! Nevirapine- hepatitis, Stevens Johnson

Most metabolized by CYP3A4 Many drug interactions: (Cushing's-like) Altered body fat distribution “Buffalo hump” Abdominal fat INCREASES BUT- face is thin (diff from corticosteroids) INCREASE cholesterol/TAGs DM, MI, stroke

Combined with other Protease Inhibitors to INCREASE their bioavailability Booster! Contains alcohol

Contains propylene glycol- avoid metronidazole! Stevens-Johnson syndrome/rash

Enfuvirtide (Fuzeon™) Maraviroc (SelzentryTM) "MY-RIVA-ROCks an ENFURiating FUSION against HIV"

Prevents fusion and entry of HIV into cell Injection sites reactions

Atazanavir/Indinavir (bilirubin) Didanosine/Stavudine (neuropathy) Zidovudine/Stavudine (antagonize each other)

*Interferon-alfa2b (Intron-A®; PegIntron), Interferon alfa2a (Pegasys)* *Boceprevir (Victrelis),Teleprevir (Incivik),Semeprevir (Olysis)* *Sofosbuvir (Sovaldi) *Lamivudine (Epivir®) *Adefovir (Hepsera®), Entacavir (Baraclude) Telbivudine (Tyzeka) "A-DEFening BOSE TELEfone speaker will SEMPRE-PREVent any LAMe HEP B and C INTERFERence"

*Zidovudine *Lamivudine (also used for Hep B & C) *Emtracitabine *Tenofovir *Didanosine Zalcitabine Stavudine *Abacavir "DID you REVERSE that TENOR's LAME ABC's back to "ZID", or EM-i-TRICkIng myself?"

Most metabolized by CYP3A4 Many drug interactions: (Cushing's-like) Altered body fat distribution “Buffalo hump” Abdominal fat INCREASES BUT- face is thin (diff from corticosteroids) INCREASE cholesterol/TAGs DM, MI, stroke

*Interferon-alfa2b (Intron-A®; PegIntron), Interferon alfa2a (Pegasys)* *Boceprevir (Victrelis),Teleprevir (Incivik),Semeprevir (Olysis)* *Sofosbuvir (Sovaldi) *Lamivudine (Epivir®) *Adefovir (Hepsera®), Entacavir (Baraclude) Telbivudine (Tyzeka) "A-DEFening BOSE TELEfone speaker will SEMPRE-PREVent any LAMe HEP B and C INTERFERence"

Acyclovir/Valacyclovir

Acyclovir/Valacyclovir

Acyclovir/Valacyclovir

Famcyclovir

Famcyclovir

Pencyclovir

Trifluridine

Docosanol

Docosanol

Docosanol

Ganciclovir/Valganciclovir

Ganciclovir/Valganciclovir

Ganciclovir/Valganciclovir

Cidofovir

Cidofovir

Cidofovir

Foscarnet

Foscarnet

Foscarnet

Oseltamivir (Tamiflu) and Zanamivir (Relenza)

Oseltamivir SE?

Zanamivir

Amantadine and Rimantidine

Amantadine and Rimantidine

Amantadine SE?

Rimantidine SE?

Ribavirin

Ribavirin

Ribavirin

Palivizumab

Lamivudine

IFN-α2b (Interferon alfa-

2b)

IFN-α2b (Interferon alfa-

2b)

IFN-α2b (Interferon alfa-

2b)

Boceprevir, Telaprevir,

Simeprevir

Boceprevir, Telaprevir,

Simeprevir

Boceprevir, Telaprevir,

Simeprevir

Mech: Taken in cell → phosphorylated by viral thymidine kinase → concentrates in infected

herpes cell (30-300x) → competes w/ dGTP → inhibits viral DNA pol → chain termination

a. Works during the viral synthesis phase

Use: DOC Herpes (wide range of uses), esp. genital

(↓ viral shedding, ↓ pain, formation of new lesions, ↑ speed of healing,)

SE:

a. Non-toxic to normal cells at therapeutic doses = minimal side-effects

b. ↑high IV doses → renal toxicity (only done in severe infx)

c. Prego ok!

Mech: Converted in vitro to Pencyclovir

(just like Acyclovir) Phosphorylated by viral thymidine kinase → competitively inhibits DNA

pol

Kidney excreted

IV form of Famcyclovir

not used (too toxic) → visual haze

Mech: inhibits fusion (plasma membrane + HSV envelope)

Use: Topical tx of cold sores

SE: skin irritation, headache

Mech: Similar to acyclovir (synthetic analog of guanosine)

a. Herpes = phosphorylated by viral thymidine kinase

b. CMV = phosphorylated by kinase phosphotransferase

Use: Broader coverage (hence CMV/Herpes coverage) > more side effects

a. valganciclovir = oral CMV prophylaxis (esp. transplant pts)

b. ocular implant = tx CMV retinitis

SE: Less specific = ↑side-effects

a. Neutropenia (esp. w/ other drugs that cause neutropenia)

(ex. IFN, Boceprevir, telaprevir, simeprevir, zidovudine)

Mech: Cytosine analog (inhibits viral DNA pol)

Use:  kills resistant resistant strains = No enzyme needed for activation  intracellularly

SE : kidney eliminated = renal tubular necrosis → nephrotoxicity & renal insufficiency

Mech: Antisense compound (binds to mRNA in CMV = can’t make protein)

Use : CMV/herpes

SE : Eyes (ocular inflammation, visual impairment)

Mech: Viral neuraminidase inhibitors for influenza A and B → virus can’t get out of the cell

GI (nausea, vomiting)

Respiratory

Mech: Block uncoating of virus (cloaking inhibitors)

Use: Rarely used due to SE → nausea  (tx influenza A only )

Hallutionations (increased dopamine)

Doesn't cross BBB, no CNS Sx

Mech : uncertain (inhibits viral mRNA synthesis)

Use: RSV, hepatitis C (used in almost all protocols), herpes simplex, and influenza

a. Combined w/ IFN to tx of Hep C

SE:

a. TERATOGENIC!!!

b. aerosol = pulmonary issues (eg dyspnea)

c. oral = anemia, depression

d. IFN/Ribavirin combo. = ↑ anemia and depression SE = watch out!

(ABCDE = A, anemia; B, breathing (SOB,); C, chest sore, cardiac; D, depression); E, embryo

dmg)

Monoclonal ab. confers passive immunity to RSV (not commonly used)

Mech:inhibits HBV DNA polymerase and reverse transcriptase

Use: DOC Hep B, also used in HIV (not IFN, old DOC)

Mech: Affects the virus at many different stages →

(synthesis, replication, translation, transcription, processing, penetration,release)

Use:

a. most common for Hep C

b. Chronic Hep B too

c. Combo tx = (IFN-α2b + Ribavirin ) → ↑SE

(+ serine protease inhibitor) if still not effective

SE:

a. Flu-like sx (fever, ,malaise, headache, fatigue, chills → tx w/ acetaminophen)

b. Musculoskeletal (myalgia, arthralgia)

c. Depression → suicide

d. Hematologic (anemia, neutropenia, thrombocytopenia)

e. Tx w/ ribavirin > increased suicidal and anemia effects

Mech: Viral serine protease inhibitors

Use: Combo with interferons and ribavirin

SE: Strong inhibitors of CYP3A4 → ↑ drug interactions

a. anemia, neutropenia, fatigue