ANTI-VIRAL AGENTS

Dr. R. Deepak Anand

INTRODUCTION
 CLASSIFICATION
ANTI-INFLUENZA
ANTI-HERPES
ANTI-HEPATITIS
ANTI-RETROVIRAL
 ANTI-INFLUENZA
ZANAMIVIR
OSELTAMIVIR

AMANTIDINE
RIMANTIDINE
 ZANAMIVIR & OSELTAMIVIR
MOA
 SIALIC ACID ANALOGUES
 COMPETITIVE & REVERSIBLE INHIBITORS OF NEURAMINIDASE OF BOTH
INFLUENZA A & B
 SO BLOCK THE ‘RELEASE’

RESISTANCE
 LESS FREQUENT
 CHANGE IN NEURAMINIDASE / HEMAGGLUTININ

BENEFIT
 DEC. DURATION BY 1 – 1.5 DAYS
 MAY REDUCE COMPLICATIONS

USES
 TREATMENT: BD for 5 days
 PROPHYLAXIS: OD throughout the epidemic
 ANTI-INFLUENZA
OSELTAMIVIR ZANAMIVIR
 ORALLY AVAILABLE  ORALLY INHALED
 ETHYL ESTER PRODRUG
 6O % BIOAVAILABLE  15% BIOAVAILABLE
 7-9 HRS IN PLASMA  MINIMAL PLASMA CONC.
 EXCRETED UNCHANGED IN
URINE
 DOSAGE:  DOSAGE:
 75 mg with food BD/OD  10 mg inhaled BD/OD
 ADR  ADR
 GI disturbances  Cough
 neuropsychiatric  bronchospasm
AMANTADINE & RIMANTADINE
In use for 4 decades
Resistance became rampant in 2005 epidemic of H3N2
MOA
 INHIBITION OF ION CHANNEL FUNCTION OF M2 MATRIX PROTEIN
 THUS BLOCK ‘UNCOATING’

RESISTANCE
 DEVELOPS RAPIDLY IN OVER 50% CASES

BENEFIT
 DEC DURATION BY 50% IF GIVEN WITHIN 24 – 72 HRS ONSET
 ????? PREV. COMPLICATIONS

USES
 NO LONGER RECOMMENDED
 ANTI-INFLUENZA
AMANTADINE RIMANTADINE
 T ½ = 12 – 17 hrs T ½ = 30 hrs
 EXCETION: EXCRETION:
 UNCHANGED IN URINE  HYDROXYLATED IN LIVER
 PLASMA LEVEL: PLASMA LEVEL:
 higher  lower
 ADR ADR
 DIZZINESS, ANXIETY  BETTER TOLERATED
 DIFFICULTY IN
CONCENTRATION
 INSOMNIA, SEIZURES
 WORSENING OF CCF
 ANTI-HERPES
ACYCLOVIR TRIFLURIDINE
VAL-ACYCLOVIR IDOXURIDINE
VIDARABINE
GANCICLOVIR CIDOFOVIR
VAL-GANCICLOVIR
DOCOSAMOL
PENCICLOVIR
FAMCICLOVIR FOSCARNET

FOMIVIRSEN
 HUMAN HERPES VIRUSES
1. HSV 1
2. HSV 2
3. VZV
4. EBV
5. CMV
6. HHV 6
7. HHV 7
8. KSV
 ACYCLOVIR & VAL-ACYCLOVIR
ACTIVE AGAINST:
 HSV 1, HSV 2, VZV, EBV, not CMV.

MOA:
ACYCLOVIR
VIRUS CODED THYMIDINE KINASE

ACYCLOVIR MONOPHOPHATE
HOST KINASES

ACYCLOVIR TRIPHOSPHATE
INHIBITS VIRAL DNA POLYMERASE
INCORPORATES AND CAUSE EARLY CHAIN TERMINATION
 ACYCLOVIR & VAL-ACYCLOVIR
PREPARATIONS
 i. v. , oral, topical

BENEFITS
 Decreases Duration, shedding & complications

DOSAGE
 Acyclovir : 800 mg p. i. d.
 Valacyclovir : 1000 mg t. i. d.

DRAWBACK
 DOES NOT ELIMINATE LATENT INFECTION
 ACYCLOVIR & VAL-ACYCLOVIR
USES
 GENITAL & OROLABIAL HERPES
 HERPES ZOSTER
 HERPES SIMPLEX ENCEPHALITIS

ADR:
 CRYSTALLURIA  RENAL FAILURE (both)
 TTP / HEMOLYTIC UREMIC SYNDROME (Val acyclovir)
 GANCICLOVIR & VAL-GANCICLOVIR
ACTIVE AGAINST:
 HSV 1, HSV 2, VZV, EBV, & CMV.

MOA:
GANCICLOVIR
VIRUS CODED PROTEIN KINASE
PHOSPHOTRANSFERASE [ UL 97 ]
GANCICLOVIR MONOPHOPHATE
HOST KINASES

GANCICLOVIR TRIPHOSPHATE
INHIBITS VIRAL DNA POLYMERASE
INCORPORATES AND CAUSE EARLY CHAIN TERMINATION
 GANCICLOVIR & VAL-GANCICLOVIR
PREPARATIONS
 i. v. , oral, intra-vitreal inj., intraocular implant

USE
 Prophylaxis & treatment of CMV diseases in AIDS

DOSAGE
 Ganciclovir : 1000 mg t. i. d.
 Val ganciclovir : 900 mg b. i. d.

ADR:
 PROFOUND MARROW SUPPRESSION
 PENCICLOVIR & FAMCICLOVIR
GUANOSINE ANALOGUES
FAMCICLOVIR  PENCICLOVIR
Only comp. inhibition, no chain termination
ACTIVE AGAINST:
 HSV 1, HSV 2, VZV, EBV, & Hepatitis B.
 OTHERS….
VIDARABINE
TRIFLURIDINE
IDOXURIDINE
 CIDOFOVIR
ACTIVE AGAINST:
 HSV 1, HSV 2, HHV 6, HHV 8, polyoma-, papilloma-, adeno-, pox-,…

CYTOSINE ANALOGUE
MOA:
CIDOFOVIR
HOST CODED THYMIDINE KINASE

CIDOFOVIR MONOPHOPHATE
HOST KINASES

CIDOFOVIR ‘DI’ PHOSPHATE

INHIBITS VIRAL DNA POLYMERASE
INCORPORATES AND CAUSE EARLY CHAIN TERMINATION
 DOCOSANOL
22 CARBON ALIPHATIC ALCOHOL
Inhibits ‘FUSION’
AVAILABLE: 10% cream
Applied 5 times a day, starting within 12 hours…
 FOSCARNET
PHOSPHOFORMICACID
MOA:
 Inh. DNA polymerase at pyrophosphate binding site.

BENEFITS:
 Eff. Against RESISTANT STRAINS also.

DRAWBACK:
 To be given using INFUSION PUMP over 1 – 2 hrs.
 Deposited in bones.

USES:
 RESISTANT HSV, VZV, CMV
 FOSCARNET
ADR:
 RENAL IMPAIRMENT
 Hypo- / hyper- calcemia
 Hypomagnesemia
 Hypokalemia
 Hypo- / hyper- phosphatemia
 FOMIVIRSEN
ANTI-SENSE OLIGONUCLEOTIDE [21 NUCLEOTIDES]
Binds to IE2 region of CMV m-RNA
Also inhibits ADSORPTION.
AVAILABLE:
 Intravitreal inj. 330 mg 2 weeks apart
 ANTI-HEPATITIS
LAMIVUDINE
TELBIVUDINE

ADEFOVIR
TENOFOVIR

ENTECAVIR

INTERFERONS
RIAVIRIN
 LAMIVUDINE
NRTI ANTI RETROVIRAL

TELBIVUDINE
ENANTIOMER OF THYMIDINE
INH. DNA POLYMERASE
 ADEFOVIR &TENOFOVIR
ANALOGUES OF A. M. P.
ACTIVE AGAINST
 HIV
 HBV
 HSV
 CMV

ENTECAVIR
GUANOSINE ANALOGUE
ACTIVE AGAINST
 HIV
 HBV
 INTERFERONS
ANTIVIRAL ; IMMUNOMODULATORY ;
ANTIPROLIFERATIVE PEPTIDES
TYPE 1 : alpha leukocytes
beta fibroblasts & epithelial cells
TYPE 2 : gamma activated T lymphocytes

EFFECTS:
 INCR. ANTIGEN PRESENTATION
 INCR. EXPRESSION OF MHC
 ACTIVATION OF CTL, NK CELL, MACROPHAGE
 INH. PROLIFERATION OF CELLS
 INTERFERONS
ALPHA INTERFERONS are used for hepatitis
RECOMBINANT PRODUCTS
T ½ = 2 – 5 hrs
PEGYLATED PRODUCTS WITH LONGER T ½
ADR:
 FLU-LIKE SYNDROME
 MANY……

D/I:
 THEOPHYLLINE, METHADONE LEVELS INCREASED
 DIDANOSINE  HEPATIC FAILURE
 ZIDOVUDINE  CYTOPENIAS
 RIBAVIRIN
GUANOSINE ANALOGUE
MOA: not clear
 ??? Inh. Synthesis of GTP
 ??? Inh. CAPPING of viral mRNA

ACTIVE AGAINST
 INFL. A & B, PARA-INFL., RSV, HCV, HIV, PARAMYXO.

ADR
 HEMOLYTIC ANEMIA
 PRURITUS, RASH
 DEPRESSION, IRRITABILITY, INSOMNIA.
CONCLUSION
 THANK YOU

HAPPY
WEEKEND