Antiviral medications have been in use for more than 50 years, but it was the rapid expansion of new agents coming to market since the 1990s that brought their use to the generalist pediatrician and other providers. In the last two decades, there have been several landmark placebo-controlled clinical studies evaluating antiviral medications specifically for neonatal viral diseases, most notably for neonatal herpes simplex virus (HSV) infection1,2 and symptomatic congenital cytomegalovirus (CMV) infection3 that have dramatically changed the management and outcomes of these conditions.
The objective of this chapter is to provide the general practitioner with an overview of the antiviral medications currently available for clinical use in the pediatric population outside of those used in the treatment of HIV (see Chapter 57). To understand mechanism of action, a brief overview of viral replication will be provided. An overview of general mechanisms of action and principles of viral resistance to medications will be outlined.
PRINCIPLES OF ANTIVIRAL THERAPY
Viruses are the smallest of all self-replicating organisms. These are simple life forms that consist of a nucleic acid core, either single RNA, single DNA, or double-stranded DNA, surrounded by a protein nucleocapsid, with some also having a lipid envelope. Viruses are considered obligate intracellular parasites in that they must use host cellular processes to complete their replication cycle. The basic steps in viral replication are summarized in Table 10-1.
++ Table Graphic Jump Location TABLE 10-1Steps in Viral Replication ||Download (.pdf) TABLE 10-1Steps in Viral Replication
|Virus attaches to target host cell; involves surface proteins and specific receptors |
|Penetration ||Enveloped viruses penetrate cells through fusion of viral envelope with host cell membrane; nonenveloped viruses penetrate by receptor-mediated endocytosis or translocation |
|Uncoating ||Removal of nucleocapsid to allow viral nucleic acid to be available for transcription |
|Transcription and translation ||Require several enzymes including DNA or RNA polymerases, reverse transcriptase, and enzymes involved in phosphorylation of nucleotides and nucleosides |
|Assembly ||Several steps and proteases involved in assembly of virus particles within cell |
|Release ||Involve different mechanisms, including extrusion from host cell or cytolysis of host cell; neuraminadase is an enzyme produced by influenza virus to destroy a receptor to promote viral release |
The four main categories of antiviral agents currently used are agents for the treatment of influenza viruses and respiratory syncytial virus, agents for the treatment of the herpesviruses, agents for the treatment of hepatitis B and hepatitis C virus, and the largest group, agents for the treatment of human immunodeficiency virus (see Chapter 57).
Neuraminidase inhibitors include oseltamivir, zanamivir, and peramivir. These ...