Farmakologi Obat-Obat

Antivirus
dr. Suhartomi, M. Biomed
 Replikasi Virus
• Virus tidak dapat menggandakan dirinya sendiri.
• Virus harus menempel dan memasuki sel inang.
• Kemudian, virus menggunakan dari energi sel inang
untuk mensintesis protein, DNA, dan RNA.
• Karena alasan ini, virus ini juga dikenal sebagai
obligate intracellular parasite.
• Oleh karena itu, virus sulit dibunuh karena
merupakan parasit intraseluler. Hal ini
menyebabkan target obat tidak spesifik yang juga
dapat membunuh sel inang.
 Tahapan siklus hidup virus yang
menjadi sasaran obat antivirus

Perlekatan dan Replikasi Genom

Uncoated virus
Penetrasi Virus

Virion form (viral Translasi RNA virus Transkispi Gene

particle), dilepas pada ribosom sel Virus
dari sel inang. inang. (RNA synthesis)
 Antiviral
[Not all viruses, only some viruses can be treated]
• Cytomegalovirus (CMV)
• Hepatitis viruses
• Herpes viruses
• Human immunodeficiency virus (HIV)
• Influenze viruses (the “flu”)
• Respiratory Syncytial Virus (RSV)
 Anti-Viral Drugs
• Banyak obat antivirus merupakan analog purin
atau pyrimidine.
• Banyak obat antivirus merupakan prodrugs. Obat
ini harus mengalami fosforilasi oleh enzim pada sle
inang maupun virus untuk mengaktifkan obat
antiviral.
• Obat anti-virus menghambat replikasi aktif
sehingga pertumbuhan virus berlanjut setelah obat
dihilangkan.
 Karakteristik Obat Antivirus
• Mampu memasuki sel yang terinfeksi virus.
• Mengganggu sintesis dan/atau regulasi asam
nukleat virus
• Beberapa obat mengganggu kemampuan virus
untuk berikatan dengan sel.
• Beberapa obat merangsang sistem kekebalan
tubuh.
 The stages of the viral life cycle
targeted by antiviral drugs

1. Fusion inhibitors (enfuvirtide)

2. Inhibit virus uncoating

(ion channel blocker: amantadine,
rimantadine)
3. Inhibit viral genome replication
(polymerase inhibitor: acyclovir;
reverse transcriptase: zidovudine &
efavirenz)
 The stages of the viral life cycle
targeted by antiviral drugs

4. Inhibit viral maturation : protease

inhibitor (anti HIV drugs : saquinavir &
ritonavir)

5. Block the relase of virus particles from

the host cell: neuramidase inhibitors
Antivirals Drugs-Nonretroviral
Amantadine (Symmetrel)
Narrow antiviral spectrum−active only against
influenza A

Used prophylactically when vaccine is not

available or cannot be given

Therapeutic use can reduce recovery time

CNS effects: insomnia, nervousness,

lightheadedness

GI effects: anorexia, nausea, others

Antivirals Drugs-Nonretroviral
Rimantadine (Flumadine)

Same spectrum of activity, mechanism of

action, and indications as amantadine

Fewer CNS adverse effects

Causes GI upset
 Antivirals Drugs-Nonretroviral
Acyclovir (Zovirax)
Synthetic nucleoside analog

Used to suppress replication of:

• HSV-1(oral herpes), HSV-2(genital herpes),

• VZV (Varicella – chickenpox or shingles)

Drug of choice for treatment of initial and recurrent episodes of

these infections

Oral, topical, parenteral forms

Common Dose of Antiviral Drug in
Herpes Zoster Virus Infection
Patient Group
Neonates
Child (2 to < 18 years old)
Adolescent (≥ 40 kg)
or adult, especially
with mil
immunocompromise (eg,
use of inhaled
glucocorticoids)
Regimen
Acyclovir 10 mg/kg or 500 mg/m2 every
8 h for 10 d
Valacyclovir 20 mg/kg every 8 h for 5 d (not to exceed
3 g/d) or
Acyclovir 20 mg/kg orally 4 times a day × 5 d (not to
exceed 3200 mg/d)
Valacyclovir 1 g orally every 8 h for 7 d or
Famciclovir 500 mg orally every 8 h for 7 d or
Acyclovir 800 mg orally 5 times a day for 7 d
Antivirals Drugs-Nonretroviral
Ganciclovir (Cytovene)
Synthetic nucleoside analog

Used to treat infection with cytomegalovirus (CMV)

Oral, parenteral forms

CMV retinitis
• Ophthalmic form surgically implanted
• Ocular injection (fomivirsen)
 Antivirals Drugs-Nonretroviral
Dose-Limiting Toxicities
ganciclovir and zidovudine

foscarnet and cidofovir

Bone Renal
marrow toxicity
toxicity
 Antivirals Drugs-Nonretroviral
Oseltamivir (Tamiflu) and Zanamivir (Relenza)
• Neuraminidase Inhibitors
• Active against influenza types A & B
• Use: Reduce duration of illness
• oseltamivir: causes nausea & vomiting
• zanamivir: causes diarrhea, nausea, sinusitis
• Treatment should begin within 2 days of influenza
symptom onset
 Antivirals Drugs-Nonretroviral
Ribavirin
• Synthetic nucleoside analog
• Given orally, or oral or nasal inhalation
• Inhalation form (Virazole) used for hospitalized
infants with RSV (respiratory syncytialvirus)
infections
Human Immunodeficiency
Virus (HIV)
• ELISA (enzyme-linked
immunosorbent assay)
• Detects HIV exposure
based on presence of
human antibodies to
the virus in the blood
• Retrovirus
• Transmitted
• Sexual activity,
intravenous drug use,
perinatally from mother
to child
 Five Stages of HIV Infection

Stage 1 • asymptomatic infection

Stage 2 • early, general symptoms of disease

Stage 3 • moderate symptoms

Stage 4 • severe symptoms, often leading to

death
 Opportunistic Infections

Protozoal • Toxoplasmosis of the brain, others

• Candidiasis of the lungs, esophagus, trachea

Fungal • Pneumocystis jiroveci pneumonia, others

Viral • CMV disease, HSV infection, others

• Various mycobacterial infections, others

Bacterial • Extrapulmonary TB

Opportunistic • Kaposi’s sarcoma, others

neoplasias
Antiretroviral Drugs
• Combinations of
multiple antiretroviral
HAART - Highly active
antiretroviral therapy
medications are
common
• Adverse effects vary
Includes at least three
medications.
with each drug and
may be severe−monitor
for dose-limiting
These medications work
in different ways to
toxicities
reduce the viral load. • Monitor for signs of
opportunistic diseases
CCR5, C-C chemokine receptor type 5; NRTIs, nucleoside reverse transcriptase inhibitors; NtRTIs, nucleotide reverse
transcriptase inhibitors; NNRTIs, non-nucleoside reverse transcriptase inhibitors; PIs, protease inhibitors; InSTIs, integrase
inhibitors (integrase strand transfer inhibitors).