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Anti-viral agents
Viral replication consists of several steps : (1) attachment of the virus to the host cell;
(2) entry of the virus through the host cell membrane; (3) uncoating of viral nucleic
acid; (4) synthesis of early regulatory proteins, eg, nucleic acid polymerases;
(5) synthesis of RNA or DNA;
(6) synthesis of late, structural proteins;
(7) assembly (maturation) of viral particles; and
(8) release from the cell. Antiviral agents can potentially target any of these steps.
Mode of action:
Acyclovir, a guanosine analog that lacks a true sugar moiety, is
monophosphorylated in the cell by the herpes virus encoded enzyme,
thymidine kinase . Therefore, virus-infected cells are most susceptible.
The monophosphate analog is converted to the di- and triphosphate forms
by the host cells.
a- Acyclovir triphosphate competes with deoxyguanosine triphosphate as
a substrate for viral DNA polymerase.
b-Itself incorporated into the viral DNA, causing premature DNA-chain
Pharmacokinetics: Administration of acyclovir can be by intravenousi,
oral and topical routes . 20% of oral dose is absorbed from the gut.
The drug distributes well throughout the body, including the
cerebrospinal fluid (CSF).
Acyclovir accumulates in patients with renal failure.
Adverse effects: Side effects of acyclovir treatment depend on the route
of administration. For example,
* local irritation may occur from topical application;
* headache, diarrhea, nausea, and vomiting may result after oral
*Transient renal dysfunction may occur at high doses or in a dehydrated
patient receiving the drug intravenously.
Clinical indications:
A-herpes simplex infections:
1-Skin infections(primary and recurrent labial and genital infections).
prolong recurrence period.
2-Ocular keratitis.
3-prophylaxis(prevention of recurrent infection take 6-12months).
4-Encephalitis, disseminated diseases
B-varicella-zoster infections:
1-Chickenpox infection particularly in immunocompromised patients or
immunocompetent with pneumonitis or hepatitis (i.v.).
2-Herpes zoster infections as oral best withen 48 h of appearance of rash
or i.v. in immunocopromised patients.
Q1: Child five years old with chickenpox infections with low fever
and good feeding and normal activity . what is route of acyclovir.
Q2: What is a preferred route in the treatment of viral encephalitis?
And why?
Q3: Patient had recurrent herpes viral infection , consult a doctor
for this a problem, doctor give him acyclovir for 6-12months . what is
a possible side effect encountered in this patient? How prevent it?
2-Penciclovir and famciclovir
Penciclovir is only administered topically .. Famciclovir is another acyclic
analog of 2'-deoxyguanosine, is a prodrug that is metabolized to the active
penciclovir Penciclovir triphosphate has an intracellular half-life 20- to 30fold longer than does acyclovir triphosphate., it is given 8orally for treatment
of herpes simplex and acute herpes zoster infections.
Ganciclovir is an analog of acyclovir that has 8- to 20-times greater activity
against CMV the only viral infection for which it is approved. It is currently
available for treatment of CMV retinitis in immunocompromised patients
and for CMV prophylaxis in transplant patients.
Mode of action: same as acyclovir
Adverse effects: Adverse effects include severe, dose-dependent neutropenia.
2-Foscarnet: It is approved for
1-CMV retinitis in immunocompromised hosts when ganciclovir is
2-acyclovir-resistant HSV and herpes zoster infections.
Cidofovir is approved for treatment of CMV-induced retinitis in patients with
AIDS when other drugs is unsuitable.
Agents used for respiratory viruses:
Neuraminidase inhibitors:
Orthomyxoviruses that cause influenza contain the enzyme neuraminidase,
which is essential to the life cycle of the virus. Viral neuraminidase can be
selectively inhibited by the sialic acid analogs, oseltamivir (tamifluļƒ’) and
zanamivir . These drugs prevent the release of new virions and their spread
from cell to cell. Unlike the amantadine , oseltamivir and zanamivir are
effective against both Type A and Type B influenza viruses.. Administered
prior to exposure, neuraminidase inhibitors prevent infection, and when
administered within the first 24 to 48 hours after the onset of infection, they
have a modest effect on the intensity and duration of symptoms.
Pharmacokinetics: Oseltamivir is an orally active. Zanamivir, on the other
hand, is not active orally and is either inhaled or administered intranasally.
Adverse effects: The most common side effects of oseltamivir are
gastrointestinal discomfort and nausea, which can be alleviated by taking the
drug with food.
Zanamivir is not associated with gastrointestinal disturbance, because it is
administered directly to the airways. Irritation of the respiratory tract does
occur, however. Zanamivir should be avoided in individuals with severe
reactive asthma or chronic obstructive respiratory disease, because
bronchospasm may occur with the risk of fatality.
B-Inhibitors of viral uncoating
The therapeutic spectrum of the adamantine derivatives, amantadine and
rimantadine , is limited to influenza A infections. Both drugs reduce the
duration and severity of systemic symptoms if started within the first 48 hours
after exposure to the virus .
Mode of action: The primary antiviral mechanism of amantadine and
rimantadine is to block the viral membrane matrix protein, M2.
4-Anti-hepatitis agents
A-Hepatitis C
Ribavirin is used in treating infants and young children with severe RSV
infections. [Note: It is not indicated for use in adults.] Ribavirin is also effective
in chronic hepatitis C infections when used in combination with interferonalpha. Ribavirin may
Mode of action: ribavirin exerts its antiviral action by blocking RNAdependent RNA polymerase
Interferons are host cytokines that exert complex antiviral, immunomodulatory,
and antiproliferative activities . Interferon (IFN)-alfa appears to function by
induction of intracellular signals following binding to specific cell membrane
receptors, resulting in inhibition of viral penetration.
Treatment of Hepatitis B Virus Infection
Entecavir is an orally administered guanosine nucleoside analog
competitively inhibits all three functions of HBV DNA polymerase.
Lamivudine inhibits HBV DNA polymerase and HIV reverse transcriptase .
Antiretroviral agents:
Nucleoside & Nucleotide Reverse Transcriptase Inhibitors
The NRTIs act by competitive inhibition of HIV-1 reverse transcriptase and can
also be incorporated into the growing viral DNA chain to cause termination.
Each requires intracytoplasmic activation via phosphorylation by cellular
enzymes to the triphosphate form. Most have activity against HIV-2 as well as
Include: abacavir ,didanosine ,lamivudine ,stavudine, ziduvodine.
Nonnucleoside Reverse Transcriptase Inhibitors
The NNRTIs bind directly to HIV-1 reverse transcriptase , resulting in blockade
of RNA- and DNA-dependent DNA polymerase. Unlike the NRTI agents,
NNRTIs neither compete with nucleoside triphosphates nor require
phosphorylation to be active.
Include dilavirdine, efavirenz, nevirapine.
Protease Inhibitors
Protease is responsible for cleaving these precursor molecules to produce the
final structural proteins of the mature virion core; protease inhibitors (PIs) result
in the production of immature, noninfectious viral particles .
Include: amprenavir, saquinavir, indinavir, ritonavir.