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Oseltamivir; Zanamivir - MOA

- neuraminidase inhibitors selective for Influenza A and B
- neuraminidase cleaves a sialic acid residue which is essential for release of the virus from infected cells and subequent spread to other cells; thereby INHIBITING THE RELEASE OF THE VIRUS FROM INFECTED CELLS

Oseltamivir - pharmacokinetics; unique usage

- given orally
- activated in the gut and liver
- excreted by the kidney
- Tx for birdflu
- some strains of influenza A (esp. H1N1) are resistant to oseltamavir

Zanamivir - pharmacokinetics

- given intranasally or by oral inhaler (not orally absorbed)
- Tx initiated 36-48 hrs after symptom onset, and lasts for 5 days

Oseltamivir, Zanamivir - side effects

- Zanamivir may WORSEN RESPIRATORY FUNCTION in pts. with chronic obstructive pulmonary disease or cause BRONCHOSPASMS in asthmatics; also causes throat discomfort
- Oseltamivir may cause NAUSEA and VOMITING which is reduced if taken with food

Amantadine, Rimantadine - MOA

- block uncoating of virus; inhibit release of viral nucleic acids into the cell cytoplasm

Amantadine, Rimantadine - pharmacokinetics

- well absorbed orally
- plasma t1/2 about 20 hrs
90% excreted unchanged by the kidney; 10% is metabolized

Amantadine, Rimantadine - uses

- prevention and Tx of INFLUENZA TYPE A2 (ASIAN FLU) in HIGH RISK PTS.
- PROPHYLACTIC use reduces incidence and severity of symptoms
- treatment may decrease duration of symptoms by 1-2 days

Amantadine, Rimantadine - Side Effects

- NAUSEA, dizziness, occasional vomiting are common
- amantadine is amild dopamine agonist and may cause CNS effects: HALLUCINATIONS, confusion, anxiety, irritability, anorexia
- rimantadine does not cross the BBB and doesn't have CNS effects
- teratogenic in animals
- rarely used since the introduction of oseltamavir

Ribavirin - MOA

- phosphorylated by cellular enzymes to ribavirin-5'-triphosphate
- INHIBITS VIRAL mRNA SYNTHESIS, protein synthesis and viral replication
- may have a greater affinity for inhibition of viral RNA synthesis than host RNA synthesis

Ribavirin - uses

- inhibitory against RSV, herpes simplex and influenza
- combined with interferon for treatment of Hepatitis C
- hospitalized infants and young children wiht severe lower respiratory tract infection caused by RSV

Ribavirin - pharmacokinetics

- AEROSOL ADMINISTRATION 12-20 HRS PER DAY FOR 3-7 DAYS; respiratory tract concentration 100% higher than plasma
- high dose IV therapy may be life saving in LASSA FEVER
- used orally with INTERFERON-ALFA 2b or 2a for treatment of HEPATITIS C, where it improves the liklihood of response to interferon considerably

Ribavirin - toxicity

- PREGNANCY CATEGORY X - teratogenic: both patient and partner must avoid pregnancy
- DYSPNEA, CHEST SORENESS, CARDIAC ARREST, HYPOTENSION
- pulmonary function may decline in pts. with pre-existing pulmonary disease
- HEADACHE, GI problems, insomnia, lethargy, DYSPNEA may occur with oral use
- dose-dependent ANEMIA, DEPRESSION and suicide may occur with oral use
- MAY BE ABSORBED PASSIVELY BY STAFF WORKING WIHT PATIENTS DURING AEROSOL TREATMENT...SHOULD NOT BE ADMINISTERED BY PREGNANT WOMEN!!!

Palivizumab

- monoclonal antibody that confers passive immunity to RSV by fusing with the virus
- used prophylactically once a month in high-risk pediatric patients

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