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Chapter: Medical Microbiology: An Introduction to Infectious Diseases: Antibacterial and Antiviral Agents

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Inhibitors of Cell Penetration and Uncoating - Antiviral Agents

Rimantadine differs from amantadine by the substitution of a methyl group for a hydrogen ion.

Inhibitors of Cell Penetration and Uncoating

Rimantadine differs from amantadine by the substitution of a methyl group for a hydrogen ion. These two amines inhibit several early steps in viral replication, including viral uncoating. They are extremely selective, with activity against only influenza A. In addi-tion, they are effective in preventing influenza but are less useful in treatment of this viral infection due in part to the brief period of viral replication.

Pharmacology and Toxicity

Both amantadine and rimantadine are available only as oral preparations. The pharmaco-kinetics of the two agents is quite different. Amantadine is excreted by the kidney without being metabolized and its dose must be decreased in patients with impaired renal func-tion. In contrast, rimantadine is metabolized by the liver and then excreted in the kidney and dosage adjustment for renal failure is not necessary.

Treatment

In healthy adults or children, amantadine and rimantadine show a slight but statistically sig-nificant improvement in symptoms compared to placebos or antipyretics. It has been as- sumed but not proved that these drugs are efficacious for treatment of influenza in elderly or other high-risk patients who may have more severe influenza. Influenza A strains resistant to these agents may appear rapidly in patients treated for clinical illness. Such strains can spread to patients receiving the drug prophylactically and can impair its efficacy as a preventive.

Prophylaxis

The acyclics amantadine and rimantadine are approximately 70% effective in preventing influenza A illness when given daily during influenza outbreaks. Although illness is pre-vented or diminished, patients may still develop evidence of infection (ie, antibody), which is desirable because this antibody may provide some protection against future influenza A infection. These agents may be given alone or with vaccine. In the latter case, they may be given only until vaccine-induced antibody develops (eg, approximately 2 weeks) or they may be continued if a vaccine response is expected to be poor or marginal.

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