Respiratory antivirals

Question 1

MOA of amantadine and rimantadine

Answer 1

block the M2 proton ion channel of the virus particle and inhibit uncoating of the viral RNA within infected host cells, thus preventing its replication.

Question 2

What influenza strains are amantadine and rimantadine good against

Answer 2

historical strains of influenza A only, because only Influenza A has the M2 channel. None of them are active against current Influenza A strains

Question 3

When are amantadine and rimantadine most effective

Answer 3

In the absence of resistance, both amantadine and rimantadine were 70-90% protective in the prevention of clinical illness when initiated before exposure. This is how they were usually used previously, to treat patients at high risk of severe disease when a breakout was occurring, ie when an influenza case was reported in a nursing home.

Question 4

Amantadine and rimantadine adverse affects

Answer 4

The most common adverse effects are gastrointestinal (nausea, anorexia) and central nervous system (nervousness, difficulty in concentrating, insomnia, light-headedness).

More serious side effects of marked behavioral changes, delirium, hallucinations, agitation, and seizures, may be due to alteration of dopamine neurotransmission.

Question 5

Alternate use for rimantadine and amantadine

Answer 5

More serious side effects of marked behavioral changes, delirium, hallucinations, agitation, and seizures, may be due to alteration of dopamine neurotransmission. This side efect of the drug allows it to be given as an adjunct in the treatment of Parkinson’s Disease, which has symptoms due to dopamine depletion.

Question 6

Drug interactions for amantadine and rimantadine

Answer 6

his toxicity is usually looks a lot like anticholinergic toxicity. When given with drugs with anticholinergic side effects like antihistamines, this reaction is also more likely, which is important since many cold/flu remedies contain antihistamines and sympathomimetics. The diuretic drug hydrochlorothiazide and trimethoprim-sulfamethoxazole make this reaction more likely as well.

Question 7

Can amantadine and rimantadine be given in preganancy?

Answer 7

No, teratogenic

Question 8

MOA of OSELTAMIVIR, ZANAMIVIR, PERAMIVIR

Answer 8

The neuraminidase inhibitors oseltamivir and zanamivir are analogs of sialic acid that interfere with release of newly created influenza virus from infected host cells, thus decreasing the spread of infection within the respiratory tract.

Pentamivir is a cyclopentane analog with the same mechanism of action.

-These agents competitively and reversibly interact with the active enzyme site to inhibit viral neuraminidase activity

Question 9

What strains of influenze can oseltamivir, zanamivir, and peramivir be used against

Answer 9

Influenza A and Influenza B

Question 10

When should OSELTAMIVIR, ZANAMIVIR, PERAMIVIR be given

Answer 10

Early administration of these agents is crucial because replication of influenza virus peaks at 24-72 hours after the onset of illness.

Initiation of a 5-day course of therapy within 48 hours after the onset of illness decreases the duration of symptoms, viral shedding and transmission, and the rate of complications such as pneumonia, asthma, hospitalization, and mortality. Once-daily prophylaxis is 70-90% effective in preventing disease after exposure.

Question 11

Oseltamivir bioavailability and side effects and population who can take it

Answer 11

Tamiflu

Oseltamivir is a prodrug that must be taken orally to work, as it is converted to its active metabolite by the gut and liver after absorption.

The major issues with oseltamivir use are the high rate of GI intolerance and vomiting as well as neuropsychiatric symptoms in some children and adults, including hallucinations and night terrors.

Oseltamivir is approved for use to treat influenza in patients age 2 weeks and older, and to prevent flu in patients age 1 year and older.

Question 12

Zanamivir bioavailability, side effects

Answer 12

Zanamivir: (RelenzaTM) this drug is currently licensed to be administered directly to the respiratory tract via inhalation. The concentration of the drug in the respiratory tract is estimated to be more than 1000 times the 50% inhibitory concentration for neuraminidase, and the pulmonary half-life is 2.8 hours.

Potential adverse effects predictably include cough and bronchospasm

Question 13

Who can take zanamivir

Answer 13

approved for treatment of influenza in people age 7 years and older, and for prevention of influenza in age 5 years and older.

Zanamivir administration is not recommended for patients with underlying airway disease, limiting its use in a large group of patients with COPD, asthma, cystic fibrosis, etc that have the highest risk of worse outcomes with influenza

Question 14

Peramivir bioavailabity and side effects

Answer 14

this drug is only available in IV form, limiting its use to hospitalized patients, and has the same toxicities noted as oseltamivi (GI, psychiatric)

Question 15

Resistance to neuraminidase inhibitors

Answer 15

the vast majority of influenza A and all of influenza B are not resistant to the neuraminidase inhibitors. A tiny fraction of H1N1 subtype viruses are resistant to oseltamivir.

Question 16

Benefit of neuraminidase inhibitors

Answer 16

the benefit of these medications is minimal, around the range of 0.5-1 day’s less of symptoms, and likely is not worth the risk of toxicity, including a doubling of the risk of nausea and vomiting in patients who take the medication. In seriously ill patients, there is a benefit of decreased mortality which is worth the potential side effects.

Question 17

Ribvirin (Virazole) MOA

Answer 17

guanosine analog that is phosphorylated by host cell enzymes, and the most accepted mechanism of action is the disruption of purine syntheses by inhibiting inosine monophosphate dehydrogenase. It probably does many other things among them interfering with RNA polymerase

Question 18

Ribvirin side effects and administration

Answer 18

Toxicity includes dose-dependent hemolytic anemia and depression

given as an aerosol that could be inhaled by healthcare workers and is teratogenic, its use in the hospital is rare and handled with extreme precaution.

Question 19

Usefullness of Ribvirin

Answer 19

consistent decrease in need for mechanical ventilation, decrease in length of stay in the pediatric intensive care unit, or reduction in days of hospitalization among ribavirin recipients has not been demonstrated.

The aerosol route of administration, concern about potential toxic effects among exposed health care personnel, conflicting results of efficacy trials, and high cost have led to infrequent use of this drug

Question 20

Palivizumab MOA

Answer 20

Humanized monoclonal antibody IgG directed against an epitope in the A antigen site on the F surface protein of RSV. The F protein is prevented from changing conformation, which prevents fusion of the viral RSV envelope to the plasma membrane of the respiratory epithelial cell. This prevents entry into the cell and replication, thus this prevents RSV infection.

Question 21

When is Palivizumab used

Answer 21

It is only given for prevention, not treatment.

Question 22

Which babies revieve palivizumab

Answer 22

only given to infants at the highest risk of severe RSV disease who also have other conditions, and only given for the 5 months of the peak respiratory season during their first year of life.

Palivizumab provides temporary passive immunity to the RSV virus when given as a monthly intramuscular injection.

Question 23

Eligibility Criteria for Palivizumab Prophylaxis

Answer 23

Infants with CLD of prematurity: I want you to know that prematurity is an indication, but it has to be significant prematurity AND significant evidence of lung damage due to prematurity.

Infants with congenital heart disease (CHD): I want you to know that cyanotic (turning blue) congenital heart disease is not an automatic indication, but some kinds of acyanotic heart disease are an indication, particularly if they cause heart failure.