Amantadine infection

Amantadine is an antiviral agent that is active against influenza A infection and against some strains of H5NX avian flu. Draw a three-dimensional representation of amantadine showing the chair cyclohexane rings. 

In pharmacology, two adamantane derivatives. Amantadine (1-adamanta-neamine hydrochloride) and Rimantadine (a-methyl-1-adamantane methyla-mine hydrochloride) (see Fig. 24), have been well known because of their antiviral activity [129]. The main application of these drugs is prophylaxis (treatment to prevent the onset of a particular disease) and treatment of influenza-A viral infections. They are also used in the treatment of parkinsonism and inhibition of hepatitis-C virus. Memantine (1-amino-3,5-dimethyladaman-tane) (see Fig. 24) has been reported effective in slowing the progression of Alzheimer s disease [130]. 

Albumin. Albumin is available in highly pure and uniform form, and exhibits low toxicity and good biological stability. It has been used as a carrier for methotrexate and a variety of antiviral drugs [amantadine, fioxuridine (5-fluorodeoxyuridine), and cytar-abine (cytosine arabinoside)] to treat macrophage tumors and infections caused by DNA viruses growing in macrophages. Heavily modified albumins are known... 

The adamantane moiety is of medicinal chemical interest because of its inertness, compactness relative to lipid solubilizing character, and symmetry. Considerable interest, therefore, was engendered by the finding that amantadine (78) was active for the chemoprophylaxis of influenza A in man. There are not many useful chemotherapeutic agents available for the treatment of communicable viral infections, so this finding led to considerable molecular manipulation. The recent abrupt end of the National Influenza Immunization program of 1976 prompted a new look at the nonvaccine means for prophylaxis or treatment of respiratory tract infections due to influenza A, especially in that the well-known antigenic shift or drift of the virus obviates usefulness of the vaccine but not amantadine. 

Influenza A viral infection Amantadine is indicated for the prophylaxis and treatment... 

Antibodies against the virus but also amantadine and derivatives, interfere with host cell penetration. There are nucleoside analogues such as aciclovir and ganciclovir, which interfere with DNA synthesis, especially of herpes viruses. Others like zidovudine and didanosine, inhibit reverse transcriptase of retroviruses. Recently a number of non-nucleoside reverse transcriptase inhibitors was developed for the treatment of HIV infections. Foscarnet, a pyrophosphate analogue, inhibits both reverse transcriptase and DNA synthesis. Protease inhibitors, also developed for the treatment of HIV infections, are active during the fifth step of virus replication. They prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new vi-rons. 

Amantadine (see Chapter 21, Section Ill.b.l) is a tricyclic symmetric adamantanamine. It inhibits the uncoating stage which takes place for binding of the virus to cells, of the influenza-A virus. It is used prophylactically for influenza-A infection, and when given within 24 hours of onset for active influenza-A. It shows good oral absorption and is excreted in the urine with an elimination half-life of about 12 hours. The adverse effects are mainly on the CNS and include insomnia, restlessness, nervousness and depression. 

Viral resistance develops rapidly in approximately 30% of individuals treated with amantadine or rimantadine. Resistant viruses are associated with the failure of drug prophylaxis in close contacts of infected individuals who have been treated with these antiviral agents. Mutation in the transmembrane domain of the M2 protein is the most frequent cause of resistance to amantadine and rimantadine. 

The Centers for Disease Control s (CDC) Immunization Practices Advisory Committee recommends annual vaccination as the method of choice in the prevention of influenza infection. However, when vaccination is contraindicated or early vaccination is not possible, amantadine and rimantadine are effective prophylactic agents that have been shown to protect approximately 70 to 90% of patients from influenza A infection. Since these drugs do not prevent the host immune response to influenza A, they may be used to prevent infection during the 2- to 4-week period required to develop immunity following vaccination. An additional use of amantadine, unrelated to its antiviral activity, is in the therapy of Parkinson s disease (see Chapter 31). 

Amantadine Symadine, Symmetrel Prevention and treatment of influenza A infections (also used as an antiparkinsonism drug see Chapter 10]... 

Amantadine and rimantadine are administered to individuals already infected with influenza A to lessen the extent of the illness associated with the virus. These drugs are also given prophylactically to individuals who may have been exposed to influenza A and to high-risk patients such as the elderly or those with cardiopulmonary and other diseases. Amantadine may also be somewhat effective in treating certain cases of hepatitis C infection.103 These drugs are typically administered orally, either in capsule form or in a syrup preparation. 

Neuraminidase is an essential viral glycoprotein for virus replication and release. The neuraminidase inhibitors zanamivir and oseltamivir have recently been approved for the treatment of acute uncomplicated influenza infection. When a 5-day course of therapy is initiated within 36-48 hours after the onset of symptoms, use of either agent shortens the severity and duration of illness and may decrease the incidence of respiratory complications in children and adults. Unlike amantadine and rimantidine, zanamivir and oseltamivir have activity against both influenza A and influenza B. Zanamivir is administered via oral inhaler. The compound displays poor oral bioavailability, limited plasma protein binding, rapid renal clearance, and absence of significant metabolism. Nasal and throat discomfort may occur—as well as bronchospasm in patients with reactive airway disease. 

In many viral infections the clinical symptoms appear late in the course of the disease at a time when most of the virus particles have replicated. [Note This contrasts with bacterial diseases in which the clinical symptoms are usually coincident with bacterial proliferation.] At this late, symptomatic stage of the viral infection, administration of drugs that block viral replication have limited effectiveness. However, some antiviral agents are useful as prophylactic agents. For example, amantadine [a MAN ta deen] and its congener, rimantadine [rih MAN ta deen] have been shown to be equally effective in preventing influenza A infections. [Note Amantadine is also effective in the treatment of some cases of Parkinson s disease (see p. 87).]... 

Improvement in symptoms of individuals with naturally occurring influenza infection treated with amantadine. 

Correct choice = A. Amantadine is the drug of choice for influenza infections. 

Correct choice = D. Amantadine is effective in the prophylaxis of influenza A infections only if administered before exposure to the virus. If amantadine is started within 48 hr after the onset of the disease, the drug will reduce the duration and severity of systemic symptoms of influenza A infection. 

Therapies for typical human influenza viruses should work in treating avian influenza infection in humans however, influenza viruses can become resistant to drugs such as amantadine and rimantadine, decreasing their effectiveness. Currently no vaccine is available to protect humans against the H5N1 virus that causes... 

Amantadine is effective only against influenza A it acts by interfering with the uncoating and release of viral genome into the host cell. It is well absorbed from the gastrointestinal tract and is eliminated in the mine 3 h). Amantadine may be used orally for the prevention and treatment of infection with influenza A (but not influenza B) virus. Those most likely to benefit include the debilitated, persons with respiratory disability and people living in crowded conditions, especially during an influenza epidemic. 

Amantadine was administered for the first time in 31 patients with OLT due to chronic hepatitis C, who were suffering from severe reinfection of the transplant. Initial therapeutic success was already seen after 3 months a significant fall in transaminases, bilirubin, AP and HCV-RNA litres, with improvement in liver histology (J.A. Goss et al., 1997). In a further study, 22 patients with chronic hepatitis C who had failed to respond to IFN therapy were treated with amantadine (2 x 100 mg). After 6 months of treatment, GPT values showed a reduction in 64% and a normalization in 27% of cases HCV RNA was no longer detectable. This situation was verifiable by PCR even 6 months after therapy in 18% of patients. (238) Amantadine seems to be a well-tolerated and effective virostatic for HCV infection in combination with IFN. (239)... 

Bryson YJ, Monahan C, Pollack M, Shields WD. A prospective double-blind study of side effects associated with the administration of amantadine for influenza A virus prophylaxis. J Infect Dis 1980 141(5) 543-7. 

Rimantadine hydrochloride, an alpha-methyl derivative of amantadine (alpha-methyl-l-adamantane methylamine hydrochloride), is more active than amantadine against influenza A viruses in vitro and in laboratory animals. It is an alternative to amantadine for the prevention and treatment of influenza A virus infections in adults and for the prevention of influenza in children. Adverse effects have been considered to be less common with rimantadine (SEDA-8, 143), and it is generally tolerated better than amantadine, because it causes fewer nervous system adverse effects (1). Unfortunately, rimantadine is more costly, which has led many institutions to develop influenza treatment guidelines. Both drugs work by blocking the M2 ion channel, which is needed to affect a pH change that helps to initiate viral uncoating. 

The drug amantadine and its analogue rimantidine are the only compounds licensed for the prophylaxis and treatment of influenza A infection. These compounds act blocking the ion channel function of the virus protein M2 [14,15], but they may account for the lack of activity against influenza B viruses, which do not possess this protein. 

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