Antivirals

Front 1

Acylovir

mechanism

Back 1

"Zovirax"
anti-herpetic


needs to be first mono-phosphorylated by viral thymidine kinase (TK) & then activated to "Acylovir-triphosphate"

substrate and inhibitor of viral polymerase--gets incorporated into the DNA of virus (purine analog) and terminates chain (because it lacks the ribosyl 3-hydroxyl group)

Front 2

Acylovir

indications

side effects

Back 2

Herpes Simplex (HSV) and varicella-zoster (VZV)
*does not get rid of latent virus

reduces viral shedding in genital herpes, decreases acute neuritis in shingles but no effect in postherpetic neuralgia. reduces symptoms if used early in chickenpox. prophylactic for immunocompromised

SE:
Crystalluria
neurotoxicity (seizures, headache, confusion, agitation)

(not hematotoxic!)

Front 3

Valacyclovir

Back 3

"Valtrex"
Pro-drug
oral bioavailability increased 50%

Prevention of CMV reactivation in immunocompromiced.
HSV, EBV, VZV, mucocutaneous herpes, HSV denritic keratitis

SE:
Crystalluria
neurotoxicity (seizures, headache, confusion, agitation)
prodrug--converted to acyclovir

Front 4

Famciclovir

Back 4

Pro-drug--converted to penciclovir (similar to acyclovir)

used in short term tx of localized herpes zoster

Front 5

Ganciclovir

Back 5

A GANG of CYCLES--HSV, VZV, CMV, EBV

more toxic than Acylovir but broader coverage (CMV!)

SE: Reversible neutropenia & thrombocytopenia (careful if pt is on AZT)

deoxyguanosine analogue

Valganciclovir--ester prodrug--converts to ganciclovir

Front 6

Foscarnet

Back 6

not an antimetabolite but still inhibits viral DNA and RNA polymerase
binds to pyrophosphate binding site reversibly but non-competetively (FOScarnet--pyroFOSphate analogue)
Does not require activation by viral kinase
Use: CMV retinitis & acyclovir resistant HSV infections.
When used w/ ganciclovir--synergism

SE: nephrotoxicity
hypocalcemia--paresthesias, arrhytmias & seizures

Front 7

Amantadine

Back 7

blocks viral penetration/uncoating (M2 protein--membrane ion channel)
(increases DA release-PD)
"A MAN To DINE takes off his coat"

USE: PD--increases dopamine & anticholinergic, prophylaxis and tx of infuenza A, Rubella

SE: Ataxia, dizziness, slurred speech, livedo reticularis--discoloration of skin
renal excretion-adjust if renal defect
Resistance: mutated M2

Rimantadine--does not cross BBB--fever CNS SE. 4-10 X more active

Front 8

Zanamivir
Oseltamivir

Back 8

Influenza A & B tx and prlxs
Inhibit influenza neuramidase--release of progeny virus is decreased via prevention of clumping of virus for better penetration

SE: nausea & vomiting

Zanamivir--wheezing, bronchospasm (not recommended for pt's w/ copd or asthma)

Front 9

Ribavirin

Back 9

Inhibits IMP dehydrogenase leading to inhibition of guanine nucleotides

triphosphate form--inhibits viral RNA polymerase and end capping of viral RNA

USE:
respiratory syncytial virus
Hep C (PO)
Lassa fever (IV)
measles pneumonitis
influenza
SE:
Severe teratogen
Hemolytic anemia

Front 10

Interferons
alpha
beta
gamma

Back 10

INF alpha--Hep B & C,Kaposis, Hairy Cell Leukemia, Actinic Keratosis, Superficial Basal Cell Carcinoma, and External Genital Warts

INF beta--MS(inhibits the production of Th1 cytokines and the activation of monocytes)

INF gamma--NADPH oxidase deficiency (chronic granulomatous disease) and osteopetrosis (marble bone disease-osteoclast/remodeling/ modeling defect

SE: Flu-like symphtoms, Myelosupression, Neurotoxicity, autoimmune-e.g. thyroiditis

interferon leads to upregulation of MHC I and therefore to increased presentation of viral peptides to cytotoxic CD8 T cells
increases p53--apoptosis in virus infected cells

T cells (cytotoxic and Th1) and Natural Killer cells secrete interferon gamma. Its major functions are to activate macrophages (they become angry macs) and to increase the expression of class II MHC on APC.

Front 11

Rifampin

Back 11

Use: TB, leprosy (delays resistance to Dapsone when used w/ Rifampin),meningococcal & inluenza B prophylaxis

Inhibits DNA dependent RNA polymerase--blocks viral packaging and assembly

SE: minor hep tox & drug interactions (revs up P450)

4 R's of Rifampin
Rna polymerase inhibitor
Revs up P450
Red/orange body fluids
Rapid resistance if used alone
4 R's

Front 12

Protease inhibitors

Back 12

HIV therapy--inhibits assembly of new virus by blocking protease in progeny virions

SE: GI intolerance, hyperglycemia, lipodystrophy, thrombocytopenia (indinavir)
"navirs" --"Never (navir) tease a pro (pro-tease)

Saquinavir
Ritonavir
Indinavir
Nelfinavir
Amorenavir
Tipranavir

Front 13

Reverse Transcriptase Inhibitors

Nucleosides

Back 13

Preferentially inhibit reverse transcriptase of HIV

SE: BM suppression, peripheral neuropathy, lactic acidosis, megaloblastic anemia (AZT-- zidovudine)
pancreatitis (ddI)

Zidovudine (AZT)- pyrimidine analogue

Didanosine (ddI)- purine

Stavudine- thymidine

Zalcitabine

Lamivudine (3TC)-cytosine
(also used against Hep B)

Abavir (ABC)-least toxic-rare fatal hypersensitivity rxn

Tenovir- adenosine- 1/day dose
Tenofovir--studied as a "pre-exposure prophylaxis" in high risk populations

Front 14

Reverse Transcriptase Inhibitors

Non-Nucleosides

Back 14

preferentially inhibit HIV reverse transcriptase
--no phosphorylation needed for activity

"NEVer Ever DELiver nuclosides"

NEVirapine (NVP)-rash, SJ
Efavirenz (EFV)-CNS SE (1/day)
DELavirdine(DLV)-GI,rash

SE: Rash, GI upset, CNS, (Steven-Johnsons & toxic epidermal necrolysis--NVP)

metabolized by CYP3A
Nevirpine & Efavirenz rev up P450
Delaviridine inhibits P450

(reduced levels when given w/ rifampin)

Front 15

Fusion Inhibitors

Back 15

Entry Inhibitor (EI)
blocks entry of virus by binding to viral gp41
Enfuvirtide (Fuzeon)
used in combo therapies

SE: injection site rxn--administered subcutaneously 2X/day

Front 16

HAART

Back 16

Highly active antiretroviral therapy
All patients with history of an AIDS-defining illness or severe symptoms of HIV infection regardless of CD4+ T cell count receive ART or if CD4 count is less than 350

a) 1 non-nucloside inhibitor + 2 nucleoside inhibitors

b) 2 nucleoside inhibitors + 1-2 Protease inhibitor

triple class regimens not recommended

EI regimen--investigational

c)three nucleoside inhibitors

Front 17

Antivirals that block nucleic acid synthesis

Back 17

purine & pyrimidine analogs, RTI's

Front 18

Antivirals that block viral release

Back 18

neuraminidase inhibitors (influenza)
e.g. Zanamivir, Oseltamivir