Drugs ribavirin

Although the term nucleoside was once limited to the compounds in Table 28.2 and a few others, cunent use is more permissive. Pyrimidine derivatives of D-arabinose, for exfflnple, occur in the free state in certain sponges and are called spongonticleosides. The powerful antiviral drug ribavirin, used to treat hepatitis C and Lassa fever, is a synthetic nucleoside analog in which the base, rather than being a pyrimidine or purine, is a triazole. 

Fig. 1.2 a Microtiter plate illustrating dose response activity of an extract of the red alga Gigartina skottsbergii (A4) as weU as unrelated and ineffective extract in well F2. b Plaque reduction assay depicting a marked reduction of virus replication in cells treated with extract A4 (50 p-g/mL) compared with No Drug or the unrelated ineffective extract F2. The effect of A4 is similar to that of the control drug ribavirin... 

Fig. 1.4 Hemagglutination assay results from the active fraction of the red alga Gigartina skottsbergii. a Red blood cells (RBCs) hemagglutinate in the presence of influenza virus top row) and with extract A4 -t- virus or extract A4 alone. The bottom two rows present the back titration of the virus used in this experiment, b In contrast to the other anti-influenza drugs (ribavirin, amantadine, rimantadine, and zanamivir) that do not induce hemagglutination of human as well as chicken RBCs, extract A4 does it in a dose-dependent manner...

The alkaloids hirsutine (1) and its 3or-epimer dihydrocorynantheine (2a) belong to the corynanthe group of indole alkaloids. They have been isolated from the plant Uncaria rhynchophylla MIQ, which was used for the preparation of the old Chinese folk medicine kampo . Nowadays, 1 and related compounds attract great attention in medicine because of their growth inhibition of the influenza A subtype H3N2 virus. With an EC50 value of 0.40-0.57 ig/mL 1 has shown itself to be 10-20 times more active than the clinically used drug ribavirine (3).1,2 Furthermore, 1 is known for its antihypertensive and antiarrhythmic activity.3... 

The influenza virus is an RNA-(—)- virus and possesses its own RNA polymerase enzyme. The complete RNA genome codes for eight proteins - two structural (matrix) proteins M, and M2, haemagglutinin, and neuraminidase and four proteins involved in replication, three of which make up the polymerase enzyme. Substrates for this are the usual ribonucleosides and there has been some success with the use of nucleoside analogues as inhibitors of the enzyme. The drug ribavirin has been the most successful, although this has to be administered by aerosol. These days, its major use is for the treatment of infections caused by respiratory syncytial viruses (especially in children), since these can cause long-term morbidity. 

The nucleotide form of ribavirin does not manifest its antiviral activity simply by lowering the GTP levels, but may indeed participate directly in binding to specific G proteins (124). Ribavirin has recently been studied as an inhibitor of vesicular stomatitis virus and La Crosse virus (125). Of the phosphorylated forms of the drug, ribavirin-5 -diphosphate was by far the most potent inhibitor of viral replication for these two viruses. 

The drug ribavirin has been shown to be effective against the viruses in vitro. However, controlled drug investigations have not been performed and the clinical useiulne.ss of these drugs is uncertain. 

The treatment is mainly supportive, and many patients will require intensive care to survive. The antiviral drug ribavirin can be used to treat some of these fevers, but its use will depend on a definite diagnosis of the etiology of the disease. 

PEG-IFN) and the oral drug ribavirin (RBV), and further direct-acting HCV antivirals are progressing through regulatory approval. 

Rl 0AVIRIN. This drug can cause worsening of the respiratory status. Sudden deterioration of respiratory status can occur in infants receiving ribavirin. It is important to monitor respiratory function closely throughout therapy. The nurse should immediately report any worsening of respiratory function to the primary health care provider. 

Ribavirin The patient is told that this drug is given with a small-particle aerosol generator. Any worsening of respiratory function, dizziness, confusion, or... 

A young mother is concerned because her 2-month-old daughter has received a diagnosis ofRSV. The infant is receiving inhalation treatments with ribavirin. The mother questions this treatment. Describe how the nurse could explain treatment with ribavirin to the mother. Discuss what possible effects the drug could have on the infant and on the mother. 

It may be possible to increase the utility of our resources to treat influenza virus infection through combinations of antiviral agents with different modes of action (discussed in Cinatl et al. 2007a De Clercq and Neyts 2007). The sialidase inhibitors, for example, may be able to be used in conjunction with the adamantane-based M2 ion channel inhibitors (Govorkova et al. 2004 Ilyushina et al. 2006), with Ribavirin (Smee et al. 2002) or with non-influenza virus specific therapeutics such as anti-inflammatory drugs (Carter 2007). Combination therapy may also reduce the potential of resistance development (Ilyushina et al. 2006). 

The results of IFN-a-based therapy can theoretically be improved by using better-tolerated drugs that mimic the action of ribavirin and/or by using HCV inhibitors that, when combined, substantially reduce HCV replication. Since the mechanism of action of ribavirin is still unknown, no credible alternative approach is currently available. In contrast, many specific inhibitors of the HCV replication cycle are in preclinical development and several have reached chnical development (Pawlotsky et al. 2007). A number of them are being tested in combination with pegylated IFN-a, with or without ribavirin. 

Resistance is a problem when these drugs are administered alone and will need to be carefully monitored when they are used in combination with IFN-a and ribavirin. 

Drugs such as ribavirin that may directly reduce FIDV replication and specific inhibitors of HBV replication such as lamivudine and adefovir dipivoxU have been tested in combination with IFN-a in patients with chronic hepatitis D. 

Monitor serum creatinine because patients with renal insufficiency (CrCl less than 50 mL/minute) may have reduced ribavirin elimination resulting in increased drug accumulation and toxicity (e.g., hemolytic anemia). 

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