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Pharmacology II

CH 38: Antiviral Drugs IStudy Guide

TREATMENT OF RESPIRATORY VIRUS INFECTIONS

Treatments only exist for Influenza A and B and RSVNeuraminidase inhibitors

Oseltamivir Tamiflu

Zanamivir Relenza

Ribavirin Virazole

General -influenzaorthomyoxovirus; contain neuroamidinase enzymes

-prevents release of new virons and their spread from cell to cell

-effective against Influenza A and B

-Administered PRIOR to exposureprevent infection

-Administered WITHIN 24-48 hrs after onset of infection

reduces intensity and duration of Sx

-synthetic guanosine analog

-tx ofinfants and young children with SEVE

RSV infection

-NOT FOR ADULTS

-effective in chronic hep C when combined

interferon-a-2b

-may reduce mortality and viremia of Lassa

fever

MOA -osteltamivir is a transition state analog of salic acid substrate

and serves as INHIBITORS of enzyme activity

-inhibits viral neuroamidase

-prevents viral mRNA capping and blocking

RNA-dependent RNA polymerase

-INTERFERES w/ protein synthesis

Pharmokinetics OsteltamivirOralprodrugactivated by liver

Zanamivir inhaled orintranasal

-Oral and IV absorption increased w/ fattmeal

-Aerosol used in certain respiratory viral

conditions

Adverse Effects Osteltamivir

-GI discomfort

-Nausea

**TAKE WITH FOOD

Zanamivir

-irritation to respiratory tract

-AVOID in pts with SEVERE REACTIVE

ASTHMA or COPD broncospasm can

occur w/ fatality

-Dose dependent transient anemia w/ IV

-AEROSOL MAY BE SAFERbut respiratory

function can deteriorate quickly after

initiation of aerosol tx

-CONTRAINDICATED in pregnancy

TREATMENT of HEPATIC VIRAL INFECTIONS

Hep B and C are most common causes chronic hep, cirrhosis, hepatocellular carcinoma Only hepatic viral infxns with tx available

Interferon IFN

General -inducible glycoproteins interferes w/ ability of virus to infect

cell

-interferon--2a approved for tx ofhepB and C,

condylomata acuminata, cancers (hairy cell leukemia and

Kaposis sarcoma)

pegylated formulations (Pegasys) bis-

monomethoxy polyethylene glycol covalently

attached to increase size of molecule

-decreases rate of absorption

-decreases renal clearance

-decreased immunogenicity

-LENGTHENS DURATION OF ACTION

MOA -degradation of viral mRNA and tRNA

Pharmokinetics -SubQ-cellular uptake and metabolism by liver and kidneyno active compound in plasma

Adverse Effects -flu-like sx on injection (myalgias, arthralgias, GI

disturbances, fever, chills)

-FATIGUE and DEPRESSION COMMONdecrease with

subsequent injections

-Bone marrow Suppression

*BLACK BOX WARNING*may cause severe

depression and suicidal thoughts

*BLACK BOX WARNING*DISCONTINUE DRUG IF

worsening of:

-autoimmune disorders

-thyroiditis

-TTP

-ITP

-RA

-Interstitial nephritis

-SLE

-Psorias

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Interferon IFN

Drug

Interactions

-interferes w/ hepatic drug metabolism

-toxic accumulations of thiophylline reported

Lamivudine Epivir

General -inhibitor ofHBV DNA polymerase (Hbv Epivir) and HIV reverse transcriptase (Epivir)

-inexpensive

-high rate of drug resistance

-role diminishing due to new drugsMOA -competitively at concentrations that have negligible to host DNA polymerase

-inhibits reverse transcriptase

Pharmokinetics -intracellular half-life much longer than plasma half-lifeINFREQUENT dosing

-absorbed orally

-excreted unchanged in urine

Adverse Effects -WELL TOLERATED

-HA and dizziness

TREATMENT of HERPESVIRUS INFECTIONS

Includes: cold sores, viral encephalitis, genital infxns, Drugs exert actions during acute phaseNO EFFECT during LATENT phase (except for foscarnet) inhibits HBV polyermase

Acyclovir Zovirax

General -prototypic antiherpetic therapeutic agent

-effective againstHSV 1 & 2, VZV, some Esptein-

Barr virus-mediated infxns

-DRUG OF CHOICE for HSV encephalopathy

-commonly used in GENITAL HERPES

MOA -guanisine analong lacks true sugar moiety

-virus-infected cells most susceptible

-causes premature DNA-chain termination

Pharmokinetics -IV, oral, topical

-accumulates in pts w/ renal failure

Adverse Effects -depend on route

-Topicallocal irritation

-Oral HA, diarrhea, N/V

-IV transient renal dysfunction in high doses or in dehydrated pt

Resistance -usually found in HIV pts

-cross-resistance w/ other cyclovirs

Foscarnet

General -NOT purine and pyrimidine analog

-Phosphonoformate (physrophosphate derivative)

-broad in vitro antiviral activity

-approved for CMV retinitis in immunocompromised hosts and acyclovir-resistant HSV and herpes zoster infxns

Pharmokinetics -must be injected IV

-must be given frequently to avoid relapse when plasma levels fall

-excreted through glomerular filtration and tubular secretion into urine

Adverse Effects -Nephrotoxicity

-anemia

-nausea

-fever

Resistance -cross-resistance btwn foscarnet and ganciclovir or acyclovir is UNCOMMON

Ganciclovir Cytovene (or Valganciclovir)

General -analog of acyclovir 8-20x greater activity against CMV (only approved for CMV)

-tx of CMV retinitis in immunocompromised pts and CMV prophylaxsis in transplant pts

MOA -nucleotide competitively inhibits viral DNA polymerase and can be incorporated into the DNA (decreases rate

if chain elongation)

Pharmokinetics -Gangciclovir IV; accumulates in pts w/ renal failure

-Valganciclovir Oral

Adverse Effects -dose dependent neutropenia

-carcinogenic, embryotoxic, teratogenic in experimental animals

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Penciclovir (Denavir) Famiciclovir (Famvir)

General -acyclic guanosine nucleoside derivative active

against HSV-1, HSV-2, VZV

- Cold sores and labialis

-prodrug of penciclovir

-approved for tx ofacute herpes zoster

MOA -inhibits HSV DNA polymerase -metabolized to active penciclovir

Pharmokinetics - topical

-Bone pain and healing shortened approx.

day in duration

-orally

Adverse Effects -HA

-nausea