Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Few specific antiviral agents exist. Acyclovir (for varicella and herpes simplex pneumonia) is efficacious. Ganciclovir and immunoglobulin are used in immunocompromised patients with CMV pneumonia.
Antiviral agents
Class Summary
Acute lower respiratory tract infection from viral etiologies can be treated with antiviral agents. These agents inhibit DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase.
Agents used include amantadine, rimantadine, zanamivir, oseltamivir, ribavirin, acyclovir, ganciclovir, and foscarnet are used. The influenza drugs may be used as either prophylactic or therapeutic agents. Hyperimmune globulin is used primarily for passive immunization in some viral illnesses.
Amantadine (Symmetrel)
Amantadine prevents penetration of the virus into the host by inhibiting uncoating of influenza A. Amantadine hydrochloride is approved for the prevention and treatment of influenza A virus infection. It is not active against influenza B virus infection.
Rimantadine (Flumadine)
Rimantadine inhibits viral replication of Influenza A virus H1N1, H2N2, and H3N2. It prevents penetration of the virus into the host by inhibiting uncoating of influenza A. Resistance to this agent emerged in the 2005-2006 influenza season and has remained high in the predominant strain of influenza (H3N2). Therefore, the CDC has not recommended its use in the past several influenza seasons.
Zanamivir (Relenza)
Zanamivir inhibits neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, the release of viruses from infected cells and viral spread are decreased. Zanamivir is effective against influenza types A and B. The drug is inhaled through the Diskhaler oral inhalation device. Circular foil discs containing 5-mg blisters of the drug are inserted into the supplied inhalation device.
Oseltamivir (Tamiflu)
Oseltamivir inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, it decreases the release of viruses from infected cells and thus viral spread. Oseltamivir is effective for treatment of influenza A or B infection, although resistant strains of seasonal influenza and H1N1 have been reported. Start within 40 hours of symptom onset.
Ribavirin (Virazole)
Ribavirin inhibits viral replication by inhibiting DNA and RNA synthesis. It has shown in vitro antiviral properties against RSV, parainfluenza, hantavirus, measles, and many other.
Acyclovir (Zovirax)
Acyclovir inhibits activity of both HSV-1 and HSV-2. It has affinity for viral thymidine kinase and, once phosphorylated, causes DNA chain termination when acted on by DNA polymerase. Patients experience less pain and faster resolution of HSV or VZV lesions when used within 24-48 hours of rash onset. Early initiation of therapy is imperative.
Ganciclovir (Cytovene, Vitrasert)
Ganciclovir is a synthetic guanine derivative that is active against CMV, HSV, HHV-6, and HHV-8. It is an acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpesviruses both in vitro and in vivo. levels of ganciclovir-triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation of ganciclovir in virus-infected cells. An oral prodrug, valganciclovir, is now available.
Foscarnet (Foscavir)
Foscarnet is an organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. It inhibits viral replication at pyrophosphate-binding sites on virus-specific DNA polymerases. Poor clinical response or persistent viral excretion during therapy may result from viral resistance. Patients who can tolerate foscarnet well may benefit from initiation of maintenance treatment at 120 mg/kg/d early in treatment. Individualize dosing based on renal function status.
Cidofovir (Vistide)
Cidofovir has demonstrated good in vitro activity against adenoviruses, including serotype 14. Cidofovir has shown some efficacy in treating adenovirus infection in immunocompromised patients, especially HSCT recipients.
Monoclonal Antibodies
Class Summary
Humanized monoclonal antibodies such as palivizumab are useful in the prevention of lower respiratory tract disease caused by RSV in pediatric patients.
Palivizumab (Synagis)
Palivizumab is a humanized monoclonal antibody directed against the F (fusion) protein of RSV. Given monthly through the RSV season, it has been demonstrated to decrease the chances of RSV hospitalization in premature babies who are at increased risk for severe RSV-related illness.
Immune Globulins
Class Summary
High-dose intravenous immunoglobulin has been used successfully in conjunction with ganciclovir for the treatment of CMV pneumonia.
Immune globulin IV (Gamimune, Gammagard, Sandoglobulin, Gammar-P)
Immune globulin IV neutralizes circulating myelin antibodies through anti-idiotypic antibodies. It down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T cells and B cells; and augments suppressor T cells. The drug also blocks the complement cascade, promotes remyelination, and may increase CSF IgG levels (10%).
Beta-Agonists
Class Summary
Many patients with viral pneumonia have bronchospasm, which is relieved or improved with the use of beta-agonist drugs.
Albuterol (Proventil)
Albuterol is a beta-agonist used to treat bronchospasm. It relaxes bronchial smooth muscle with its action on beta2-receptors. It has little effect on cardiac muscle contractility.
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| Virus | Viral Culture | Cytologic Evaluation | Rapid Antigen Detection | Gene Amplification |
| Influenza virus | HA*, SV† | IF‡, ELISA§ | RT-PCR# | |
| Adenovirus | CE, SV | Intranuclear inclusions | IF, ELISA | RT-PCR |
| Paramyxoviruses | ||||
| Respiratory syncytial virus | CE, SV | Eosinophilic cytoplasmic inclusions | IF, ELISA | RT-PCR |
| Parainfluenza virus | HA, SV | Eosinophilic intranuclear inclusions | IF, ELISA | RT-PCR |
| Measles virus | HA | |||
| Herpes viruses | ||||
| Herpes simplex virus | CE, SV | Cytoplasmic inclusions | IF, ELISA | PCR |
| Varicella-zoster virus | CE | Cytoplasmic inclusions | IF | RT-PCR |
| Cytomegalovirus | CE, SV | "Owl's eye" cells | IF, ELISA | RT-PCR |
| Hantavirus | Antibodies against FCV** | FVC RNA by RT-PCR | ||
| * HA - Hemaglutination † SV - Shell viral culture ‡ IF - Immunofluorescence § ELISA - Enzyme-linked immunosorbent assay CE - Cytopathogenic effects # RT-PCR - Reverse transcriptase polymerase chain reaction ** FCV - Four corners virus | ||||
| Virus | Treatment | Prevention |
| Influenza virus | Amantadine Rimantadine | Influenza vaccine Chemoprophylaxis with: Amantadine Rimantadine Zanamivir Oseltamivir |
| Respiratory syncytial virus | Ribavirin | RSV immunoglobulin Palivizumab |
| Parainfluenza virus | Ribavirin | |
| Herpes simplex virus | Acyclovir | |
| Varicella-zoster virus | Acyclovir | Varicella-zoster immunoglobulin |
| Adenovirus | Ribavirin | |
| Measles virus | Ribavirin | Intravenous immunoglobulin |
| Cytomegalovirus | Ganciclovir Foscarnet | Intravenous immunoglobulin |
| Amantadine (Symmetrel) | Rimantadine (Flumadine) | Zanamivir (Relenza) | Oseltamivir (Tamiflu) | |
| Mechanism of action | M2 ion channel blockade inhibits HA* cleavage beta block RNA encoding, which reduces early viral replication. | Viral NA† inhibition prevents sialic acid cleavage from HA beta virus gets trapped inside cells, and epithelial spread is blocked. | ||
| Spectrum | Influenza A only | Influenza A only | Influenza A and B | Influenza A and B |
| Oral bioavailability | Good | Good | Poor | Good |
| Protein binding, % | 67 | 40 | None | Minimal |
| Half-life, h | 12-18 | 24-36 | 2.5-5 | 1-3 |
| Excretion | Renal (not removed by hemodialysis) | Renal and gastrointestinal | Renal | |
| Drug interaction | Synergistic CNS toxicity with antihistamines, anticholinergics, CNS stimulants | Beta Plasma level: ASA§, acetaminophen | None | None |
| Renal clearance | TMP-SMZ¶, triamterene, hydrochlorothiazide, quinine sulfate, quinidine | Cimetidine | None | None |
| * HA - Hemagglutinin † NA - Neuraminidase § ASA - Acetylsalicylic acid ¶ TMP-SMZ - Trimethoprim and sulfamethoxazole | ||||

