Antivirals Flashcards
List 3 Neuraminidase Inhibitors?
Oseltamivir
Peramivir
Zanamivir
Pk of neuraminidase inhibitors?
Oral oseltamivir is a prodrug, activated in the gut and liver; it is well absorbed and reaches peak serum concentrations in 1h. More than 99% of active oseltamivir is excreted renally.
Zanamivir is administered intranasally with approx. 4-20% of the inhaled drug being absorbed systemically. The absorbed drug is not metabolized and is excreted unchanged
in the urine, whereas the unabsorbed drug is excreted in the feces.
Peramivir is administered IV and is an option for patients who cannot take a drug orally or via inhalation
AE of oseltamivir?
nausea, vomiting, diarrhea,
abdominal pain, insomnia and vertigo.
Neuropsychiatric adverse effects, including
delirium, abnormal behavior, and hallucinations have been reported.
Neuraminidase inhibitors guidelines for children?
Oseltamivir and peramivir are approved for the treatment of children (>1y) and adults with
influenza A or B infections. Zanamivir is approved for the treatment of children (>7y) and
adults with influenza A or B infections
Treatment should be started within 48h of disease
onset. The neuraminidase inhibitors are effective in reducing the febrile period during infection. Both drugs are also used for postexposure prophylaxis against influenza A and
B. For this indication they should be started within 48h of exposure
Ae of zanamivir?
Inhaled zanamivir is well tolerated. Acute bronchospasm with decline in respiratory function has been reported and its use should be restricted in patients with breathing
difficulties (eg, asthma and COPD).
Other adverse effects include headache and GI
symptoms.
Hypersensitivity reactions and neuropsychiatric adverse effects occur rarely.
Ae of peramivir?
IV peramivir is associated with peeling and severe itching of the skin, cough, GI discomfort, fever and
muscle pain
Discuss Oseltamivir-resistant resistance in influenza?
Oseltamivir-resistant influenza A has been reported. Mutations in the neuraminidase gene
account for the resistance. Oseltamivir resistance among influenza B viruses occurs less frequently. Oseltamivir resistant strains are normally also resistant to zanamivir.
Recommendations neuraminidase inhibitors?
Neuraminidase inhibitors are currently recommended for the treatment or prophylaxis of influenza in pregnant women and women up to 2 weeks postpartum; they are
recommended as an adjunct to vaccination and should not be used as a substitute for vaccination in pregnant women
Name 2 M2 inhibitors?
Amantadine
Rimantadine
MOA of M2 inhibitors?
Amantadine and rimantadine inhibit replication of influenza A virus by impairing the function of the membrane protein M2. Present only in influenza A virus, M2 is an acid activated ion channel required for viral uncoating and nucleocapsid release.
M2 inhibitors PK?
Amantadine is well absorbed after oral administration and is excreted by glomerular
filtration and tubular secretion. Rimantadine is well absorbed orally but undergoes
extensive hepatic metabolism before it is excreted in the urine.
Benefits of amantadine and rimantadine?
Amantadine and rimantadine are effective for treating susceptible influenza A infection,
resulting in a more rapid recovery and reduction of the duration of symptoms by approx.
1 day, if given within 48h of disease onset. They are also effective as prophylaxis for
preventing symptomatic influenza A infection in exposed persons. Seasonal influenza vaccination, however, remains the preferred method for prevention
How has resistance affected M2 inhibitors?
Emergence of resistance has limited their use in the clinical setting. Amantadine
resistance, characterized by amino acid substitution in the M2 protein, emerges within 2-4 days of treatment. M2 mutation confers cross resistance with rimantadine. Because of widespread resistance, both amantadine and rimantadine are no longer recommended
for empiric treatment of influenza.
AE of Amantadine?
Amantadine is generally well tolerated. Among its adverse effects are mild neurologic
symptoms such as anxiety, disorientation, and headache, especially in elderly patients
and those taking neuroaffective drugs.
A few trials that compared amantadine and rimantadine suggested similar efficacy;
however, neurologic adverse effects are less severe and frequent with rimantadine.
Amantadine and rimantadine are FDA pregnancy category C. They are not recommended for use during pregnancy
IFNalpha pk?
Available only in parenteral formulation, more than 80% of a subcutaneous or intramuscular dose of IFNalpha is absorbed. Pegylation, which is the process of attachment of IFN to a large inert polyethylene glycol, markedly reduces the rate of absorption and excretion of IFN and therefore increases its plasma concentration. Conventional forms of IFNalpha are usually administered daily or 3 times a week. Pegylated forms can be administered once a week. IFNalpha undergoes extensive renal metabolism, and negligible amounts of IFNalpha are excreted in the urine
Actions of IFNalpha?
The selective antiviral action of IFNalpha is primarily due to activation of a host cell
ribonuclease that preferentially degrades viral mRNA. IFNalpha also promotes formation of
natural killer cells that destroy infected liver cells
IFN uses?
used for treating chronic viral hepatitis alone or in combination with other drugs
When used in combination with ribavirin, the progression of acute HCV infection to chronic HCV is reduced. Pegylated IFNalpha together with ribavirin is superior to standard forms of IFNalpha in chronic HCV. IFNalpha is also used in the treatment of HBV in patients >1 year
Ae of IFN?
Among the more serious adverse effects are neuropsychiatric disorders,
neurological disturbances, myelosuppression, cardiovascular disorders, endocrine disorders, and pulmonary disorders
Other adverse effects are altered liver function, renal insufficiency, and GI problems
Assoication and treatment with depression developed during IFN treatment?
Patients at risk for developing depression are those with preexisting mood and anxiety disorders, those with a history of major depression, and those receiving higher doses of IFNalpha or undergoing long-term treatment regimens.
Selective serotonin reuptake inhibitors have been used successfully to treat patients with IFN-associated depression, allowing therapy to be continued, and as a pretreatment to
prevent its occurrence in high-risk patients
Ribavrin MOA?
mechanism of action of ribavirin is known to be diverse but it is not completely
understood. It may be a competitive inhibitor of cellular enzymes because its antiviral
activity is reversed by guanosine. Its triphosphorylated form is a potent competitive
inhibitor of influenza virus RNA polymerase, and mRNA guanylyltransferase. As a result of this competitive inhibition, intracellular guanosine triphosphate pools are markedly reduced, the capping of viral mRNA is prevented and RNA dependent RNA polymerases
are blocked leading to the inhibition of viral nucleic acid and protein synthesis
Ribavirin pk?
Ribavirin is available in oral, aerosolized, and IV formulations. Oral ribavirin is absorbed extensively, but its bioavailability is only 65% because of first-pass metabolism.
Administration of the aerosolized form leads to high concentrations in the respiratory tract,
with some absorbed systemically. Ribavirin is mainly excreted in the urine
Ribavirin clinical uses?
Ribavirin is approved for use, in combination with IFNalpha for the treatment of HCV. It is also approved for the treatment of RSV in children. When used for the treatment of RSV pneumonia, ribavirin is usually given by the inhalation route, which delivers high concentrations to the site of infection. Oral ribavirin has also been used with good outcomes
Ribavirin off label uses?
Ribavirin has been used, off-label, for the treatment of HSV, influenza, severe
acute respiratory syndrome, coronavirus, La Crosse encephalitis, Nipah encephalitis, Lassa fever, hemorrhagic fever with renal syndrome, Crimean-Congo hemorrhagic fever,
Bolivian hemorrhagic fever, and hantavirus pulmonary syndrome.
Ae of ribavirin?
Aerosolized ribavirin can cause sudden deterioration of respiratory function and
cardiovascular effects. Hemolytic anemia occurs commonly. Severe depression, suicidal
ideation, and relapse of drug abuse may occur, and ribavirin is contraindicated in patients with a history of, or existing, psychiatric disorders
