ANTI VIRAL

CHEMOTHERAPEUTICS AND
PROPHYLAXIS

ARJO S. SURJODIPRODJO
INTERNATIONAL SCHOOL OF
NURSERY
 INTRODUCTION
Virus forms intra cellular obligate parasite that its replication depend
deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein
synthetic process of host cell. Therefore, medicines inhibited viral
replication, inhibited host cell function and prima causa of toxicity
too.
Viral replication reach its maximum when first clinical symptom
appear. Therefore, medicines inhibited viral replication should be
given far of sickness become chemoprophylaxis (ex : amantadin
for influenza A and methisaxon for poxvirus)
Viral replication consist of : (1) adsorption and penetration to
sensitive cell, (2) nonstructural protein synthetic, (3) RNA and DNA
synthetic, (4) slow synthetic of structural protein, (5) Viral particle
maturation and its release from cell.
Antiviral medicine act based at viral replication stages
Adsorption and penetration inhibition of sensitive cell
Intracellular synthetic ibhibition
ADSORPTION AND PENETRATION INHIBITION OF
SENSITIVE CELL
Gamma globulin contain specific anti body as surface antigen to virus
penetration inhibition
Intra muscle administration 0,025 0,25 ml/kg BW as long as incubation time
should cure infection caused measles, hepatitis, rabies, poliomyelitis etc
Protective effect of globulin would last 2 3 weeks after injection. Hence,
medicine could be administered every 3 week since long incubation time
Viral replication usually a part inhibition, that active immunity formation might
be participated by temporary passive immunity of gamma globulin (active-
passive immunization)
Intra venous of gamma globulin could be given when intra muscle pathways is
impossible
Amantadin and rimantadin are tricyclic symmetrical adamantanamin that
inhibited release of certain microviral capsule (influenza A, rubella and several
tumor virus inner sensitive cell)
Usual dose of amantadin or rimantadin is 200 mg daily. These medicines are
effective for 2 3 days before infection and minimize symptom and severity
after 6 7 days after infection of influenza A. Absorption of amantadine is
almost completely from intestine when oral administration is taken.
Patients of kidney insufficiency might be minimize of dose, even so elderly
clients. Its half time is going to 12 hours in healthy renal patient, however 30
hours for rimantadine. Rimantadine as effective as amantadine, but had not
adjustment in dose for kidney insufficiency patients
Other clinical application of amantadine is taken in Parkinson disease
Non clinical effects of amantadine are insomnia, unclear speaking, ataxia, and
other disturbance of CNS, however rimantadine are lighter
INTRACELLULAR SYNTHETIC
INHIBITATION (1)
INHIBITION OF INITIAL PROTEIN SYNTHESE

Guanidin and hydroxybenzimidazole could

inhibit replication of certain enterovirus
RNA, but could not the other. They inhibit
formation of polymerase RNA in the safely
level of host cell in vitro. However, they had
not therapeutical activity in vivo.
 INTRACELLULAR SYNTHETIC
INHIBITATION (2)
NUCLEIC ACID SYNTHETIC INHIBITION
Ribavirin could inhibit either RNA or DNA virus. This substance act by
disturbance of guanisin monofosfat formation, and furthermore nucleic acid
formation
Usual dose of ribavirin 15 mg/kg BW gave a good yield. In aerosol form,
this medicine would be inhibit replication of respiratory cyncicial virus in
infant, and minimize severity, symptom and duration of sickness
Ribavirin is drug of choice for Lassa fever
Pyrimidine and purine analog :
1. Idoxuridine inhibit replication of herpes simplex virus in cornea and assist
to cure herpes cerathitis.
2. Cytharabine inhibit DNA synthetic and disturb replication of DNA virus
( daily dose 0.3 2 mg/kg BW during 5 days). Caution : unuseful for
varicella or herpes diseminata
3. Trifluridine inhibit DNA virus synthetic. Solution 1% might be given to
cornea infected of h simplex or vaxinia. Caution: do not use systemical
 INTRACELLULAR SYNTHETIC INHIBITATION (3)

4. Vidarabine effective purine analog with lowest toxic. In ointment 3%

effective for H cerathitis and vaxionia. Topical administration is ineffective
for h simplex lesion in skin or mucouse membrane. Vidarabine could be
given systemic because of its relatively lower toxicity . Ten days systemic
administration would be given large decrease in death rate of
encephalistis caused herpes, however only 40% of cured patients could
reach normal quality of life. The verry good yielding found if medication is
start before comma happen. Systemic vidarabin (15 mg/kg BW) would
restrict severity herpes simplex neonatal, encephalistis caused herpes,
herpes zoster (in patient had not immunity). However, vidarabin is less
effective than acyclovir
5. Acyclovir would phosphorylation of herpes virus. Acyclovir should given
250 mg/m2 every 8 hours during 18 days intravenous as prophylaxis
before transplantation of spinal cord take place for seropositive patient.
Administration after transplantation of heart to prevent severe herpes
(from happened lesion) is effective to herpes lesion. The same dose is
recommended for initially infection of herpes simplex, especially on
women urethral tract. Oral administration of 200 mg acyclovir 5 times a
day has a same effect as intravenous, included for primary genital
herpes. Topical application of 5% acyclovir could limiting mucocutan
lesion of herpes simplex
 INTRACELLULAR SYNTHETIC INHIBITATION (4)

6. Gancyclovir is a derivate of acyclovir. It penetrate cythomegalovirus infected

cell and phosphorylated to tryphosphate which especially inhibit polymerase
DNA of cythomegalovirus virus replication inhibited. When it taken
intravenous (5 10 mg/kg BW/day) for 14 days, cythomegalovirus renitis,
pneumonia or gastrointestinalis lesion would be cure. The mainly of side
effects are leucopenia, neutropenia, thrombocytopenia, kidney disturbance,
and spasm.
7. Zidovudin (AZT) and other dideoxynucleoside are potentially medication of
AIDS. AIDS is most dramatic and lethalic dissease caused of HIV (human
immunodeficiency virus). Its retrovirus could prohibit by synthetic
dideoxynucleotides. They act on polymerase DNA of virus DNA synthetic
prohibit decrease of replication of virus. HIV reverse transcryptase is 20
30 times more sensitive than mammalian polymerase cell. Many controlled
clinical test had record that treatment of HIV or ARC (AID related complex)
with AZT could depress HIV production, prolongation age and temporary
decrease of death, and decrease several morbidity opportunistic infection.
Several limphocyt CD4+ would increase during therapy, while mental and
neurologic symptom would be fine. Such was the case, AZT should given
orally 100 200 mg 3 5 times a day. Side effect of AZT is mild. There are
dizziness, agitation, insomnia, diarrhea, skin rash and fever. More severe side
effect is suppression of spinal cord with heavier anemia (need transfusion),
granulocythopenia, and sometimes thrombocytopenia. Other
dideoxynucleosides are didanosin, zalsitabin ans stavudin
 INTRACELLULAR SYNTHETIC INHIBITATION (4)

8. Interferon is a group of endogen glycoprotein that indicate antivirus

activity for non specific virus via cellular metabolic process
participated RNA and protein synthesis. The first interferon is
produced by infected cell of virus (type 1), then produced lymphocyt
(type 2) during immune response. Type 1 interferon acts as inhibitor
of virus replication on cell (by induction host ribosome to form cellular
enzyme prohibit translation of mRNA to virus protein). Interferon
produces of a lot of animal, but it trends to active especially to
species of its origin. Clinical study of human interferon shows iti
activity to viral infection and neoplasm. When it immediately
administered, herpes zoster distribution might prohibit in neoplasm
patient, decreasing of cythomegalovirus release after kidney
transplantation, and inhibit herpes simplex reactivation. In the case of
chronic hepatitis B and C, interferon could depress clinical and
laboratory symptom. When added to pentavalent arsenic, interferon
type 2 increases treatment of viceral leishmaniasis. In several
neoplasm, interferon is useful as accompany medication. Interferon is
agreed to treatment of hairy cell leukemia, Kaposi sarcoma related
AIDS, and condyloma acuminata. Intravenous administration starts
from 106 109 daily. Side effects manifest as fever, weakness, dizzy,
myalgia, anemia, digest tract or cardiac disturbance
 INHIBITION OF PROTEIN SLOW
RELEASE SYNTHESIS

In several poksvirus, vary of thiosemicarbazon

inhibit viral replication by disturbance of slow
structural protein synthesis particle
association of normal cell inhibit.
Methisazon could inhibit replication of variola
when given in 1 2 days after exposure. Dose
of methisazon is 2 4 g/day orally ( 100 mg/kg
BW/day for children) for 3 4 days
 VIRAL PARTICLE RELEASE
Whole association of virus could inhibit by
various of medicines.
Rifampicin inhibits RNA polymerase depended
of DNA on bacteria and mamalian cell.
Rifampicin hampers mature cover particles
association of virus. Inhibition is take place
during cover formation stage and irreversible.
Rifampicin is not used on poksvirus infection, but
its topical application inhibits vacinia lesion.
 PRESENTATION (1)
Acyclovir (Zovirax)
Oral : Capsule of 200 mg, tablet of 800 mg, suspension of 200 mg/5 ml
Parentheral : injection powder of 500, 1000 mg/vial
Amantadine (Symmetrel)
Oral : Capsule of 100 mg, syrup of 50 mg/ml
Human cytomegalovirus immune globulin intra venous (HCIG i.v.)
Parentheral : Injection powder of 2500 mg + 250 mg
Didanosin (Videx)
Oral : Tablet of 25, 50, 100, 150 mg; powder of mouth wash 100, 167,
250, 375 mg
Foskarnet (Foscavir)
Parentheral : 24 mg/ml intra venous
Gancyclovir (Cytovene)
Parentheral : 24 mg/ml intra venous
Hepatitis B immune globulin (HBIG)
Parentheral : vial of 1, 4, 5 ml; Fillable syringe of 0,5 mf
Immune globulin intra venous (IGIV, Gamimune N)
Parentheral : vial of 5% in 10, 50, 100 ml. Iv-powder of 0.5, 1, 2.5, 3, 5,
and 6 g
 PRESENTATION (2)
Interferon alfa-2a (Roferon-A)
Parentheral : Vial of 3, 6, 36 million IU
Interferon alfa-2b (Intron-A)
Parentheral : Vial of 3, 5, 10, 18, 25, and 50 million IU
Interferon alfa-n3 (Alferon N)
Parentheral : 5 million IU/vial
Ribavirin (Virazole)
Aerosol : Powder for preparation of 6g/dl aerosol
Rimantadin (Flumadin)
Oral : Tablet of 100 mg, syrup of 50 mg/5 ml
Human varicela-Zoster Immun Globulin
Parentheral : 125 unit globulin in vial of 2.5 ml
Vidarabin (Vira A)
Parentheral : Suspension for injection 200 mg/ml
Zalsitabin (Hivid)
Oral : tablet of 0.375, 0.75
Zidovudin (azidotimidin, AZT, Retrovir)
Oral : Capsule of 100 mg, syrup of 50 mg/5 ml
Parentheral : 10 mg/ml