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Antiviral drugs for Sexually

Transmitted Infection (STI)


Yosep Ferdinand Rahmat Sugianto
Department of Dermatovenereology
Dr. Kariadi Hospital
Faculty of Medicine Diponegoro University
Semarang

Introduction
Two types of virus:
DNA and RNA virus
Life cycle of DNA virus:

Life cycle of RNA virus:


HIV

Approaches to treat viral diseases


Challenges in designing anti-viral treatments:
Host cell must be immune to treatment! (to
limit off-target toxicity)
Disease symptoms often associated with
latency period
General anti-viral strategies are to inhibit:
Viral attachment to host cell, penetration, and
uncoating
Viral enzymes:
DNA/RNA polymerases, etc
Reverse transcriptases, proteases, etc.
Host expression of viral proteins
Assembly of viral proteins
Release of virus from cell surface membranes

Antiviral drugs for Herpes


Simplex Virus (HSV)
ACYCLOVIR
A guanosine derivative
which selectively inhibits
viral DNA polymerase
enzyme
Recommended within the
1st 72 hours after
outbreak
Administration: topical,
intravenous, oral
Oral bioavailability only
15%-30%

Acyclovir
Mechanism of action:
Step 1: activation

Acyclovir
Mechanism of action
Step 2: incorporation into growing DNA
chain

Acyclovir
Dosing regimen:
- Primary HSV infection: 3 x 400 mg (7-10 days)
- Recurrent genital HSV: 3 x 400 mg (5 days)
Or 3 x 800 mg (2 days)
- Immunocompromised: 5 mg/kgBW q8h IV (7 days)
Or 5 x 400 mg (14-21 days)
- Encephalitis 10 mg/kgBW q8h IV (14-21 days)
- Suppression therapy:
2 x 400 mg OR 1 x 800 mg
Preparations: tablets 200 and 400 mg

Acyclovir
Common side effects:
- Nephropathy / nephritis
- Lethargy
- Tremors
- Confusion
- Seizure
- Rash
- Drug eruption
Acyclovir is generally well-tolerated, and very rarely cause
side effect.

Valacyclovir

L-valine ester of acyclovir a prodrug


Developed to increase oral bioavailability
of the active drug acyclovir
Converted to acyclovir by intestinal and
hepatic esterases
Mechanism of action is identic to acyclovir

Valacyclovir
Dosing regimen:
- Primary HSV infection:
- Recurrent genital HSV:
- Immunocompromised:
- Suppression therapy:

2
2
2
1

x
x
x
x

1000 mg (10 days)


500 mg (3 days)
500 mg (5-10 days)
1000 mg

Preparations: tablets 500 mg and 1 g

Famcyclovir

A guanine analogue; prodrug of


pencyclovir
Developed to increase oral bioavailability
of the active drug pencyclovir
Mechanism of action is identic to acyclovir

Famcyclovir
Dosing regimen:
- Primary HSV infection:
- Recurrent genital HSV:
Or 2 x 1000 mg (1 day)
- Immunocompromised:
- Suppression therapy:

3 x 250 mg (7-10 days)


2 x 125 mg (5 days)
2 x 500 mg (7 days)
2 x 250 mg up to 1 year

Preparations: tablets 125, 250 and 500 mg


Common side effects: (generally well-tolerated)
Headache, nausea, diarrhea, dizziness

Foscarnet

Foscarnet = trisodium phosphonoformate


Noncompetitively inhibits viral DNA polymerase
Does not require phosphorylation active against
acyclovir-famcyclovir resistant virus
Dosing regimen:
40 mg/kgBW q8h
Or 60 mg/kgBW q12h IV 2-3 weeks
Must be administered via infusion pump with dilute
solution
Side effects: nephrotoxicity, electrolyte disturbance,
headache, fatigue, seizure

Anti Human Papilloma Virus


(HPV) agents
Imiquimod 5% cream
- Enhancing cell-mediated cytolitic
activity against HPV
- Applied three times per week before
bed time up to 16 weeks
- Side effects: local skin reaction i.e
erythema, burning, itching, swelling,
flaking, erosion and ulceration

Anti Human Papilloma Virus


(HPV) agents
Podofilox 0.5% gel or solution
- Also
known
as
podophyllotoxin,
extracted from podophyllum resin
- Exerts cytotoxic and anti-mitotic effects
- Applied twice daily for three consecutive
days, followed by 4 days free of
treatment, repeated up to 4 cycles
- Side effects: local skin reaction

Anti Human Papilloma Virus


(HPV) agents
Green tea sinecathecins
(polyphenon E ointment)
- Cathecins
are
bioflavonoids,
polyphenols, powerful antioxidants with
antiviral
and
immunostimulatory
properties
- Applied three times daily up to 4 weeks
- Side effects: local skin reaction

Anti Human Papilloma Virus


(HPV) agents
Trichloroacetic Acid (TCA) 50-90%
- Caustic agent, destroys warts through
chemical coagulation of proteins
- Applied only at lesions (very imperative), and
allowed to dry first, used once weekly
- Side effects: irritation and destruction of
surrounding normal tissue scar formation
- To neutralize we can use sodium bicarbonate
(baking soda), or liquid soap preparations

Anti Human Papilloma Virus


(HPV) agents
Cidofovir (still pending FDA approval)
- acyclic nucleoside analogue of deoxycytidine
monophosphate
- acts by selectively inhibiting DNA polymerase
andblocking viral DNA synthesis and
replication,
- Resulting in apoptosis of virally infected cells
- Preparations: Cidofovir 1% cream or gel
- Applied once daily for 5 consecutive days,
every other week (max 6 cycles)
- Side effects: mild-moderate local skin
reaction (pain, pruritus, rash)

Highly Active Antiretroviral Therapy


(HAART)
for Human Immunodeficiency Virus
(HIV)
- HAART is a combination of three
antiretroviral drugs
- Classes of antiretroviral drugs:
Nucleoside reverse transcriptase inhibitor
Non-nuclesoide reverse transcriptase
inhibitor
Nucleotide reverse transcriptase inhibitor
Protease inhibitor
Fusion inhibitor

Highly Active Antiretroviral Therapy


(HAART)
for Human Immunodeficiency Virus
(HIV)

- HAART is a combination of three


antiretroviral drugs, including at least
one protease inhibitor
- Classes of antiretroviral drugs:

Nucleoside reverse transcriptase inhibitor


Non-nuclesoide reverse transcriptase inhibitor
Nucleotide reverse transcriptase inhibitor
Protease inhibitor
Fusion inhibitor

HAART for HIV


Reverse Transcriptase Inhibitors (RTIs):
Nucleoside: Non-nucleoside:
Nucleotide:
Abacavir
Nevirapine
Tenefovir
Didanosine
Delavirdine
Lamivudine
Efavirenz
Stavudine
Loviride
Salcitabine
Zidovudine

HAART for HIV


Protease inhibitors:Fusion inhibitor:
amprenavir enfuvirtide
atazanavir
indinavir
fosemprenavir
nelfinavir
ritonavir
saquinavir

Principles for HIV-AIDS therapy


- Monitor plasma viral load and CD4 count
- Start treatment before immunodeficiency
becomes evident
- Aim to reduce plasma viral concentration
as much as possible for as long as possible
- Use combinations of at least three drugs;
two RTIs and one protease inhibitor
- Change to a new regime if plasma viral
concentration increases

HAART for HIV


National guidance on HIV-AIDS treatment (2011):
First line treatment = 2 NRTI + 1 NNRTI
- Zidovudine + Lamivudine + Nevirapine
- Zidovudine + Lamivudine + Efavirenz
- Tenofovir + (Lamivudine atau Emtricitabine) +
Nevirapine
- Tenofovir + (Lamivudine atau Emtricitabine) +
Efavirenz
Caution: Nevirapine carries risk of inducing adverse
drug reaction, including Stevens-Johnson syndrome

Other cutaneous manifestations of


HAART drugs
Zidovudine:
Hyperpigmentation
Hypertrichosis
Drug hypersensitivity syndrome
Vasculitis

Lamivudine:
Drug eruption
Paronychia

THANK YOU