PHARM Influenza (Staudinger)

Question 1

What are the 3 neuraminidase inhibitors used as anti-influenza drugs and which can be given orally, via IV, and inhalation?

Answer 1

• Oseltamivir = oral
• Zanamivir = inhaled/inZpired
• Peramivir = IV

Question 2

Which anti-influenza class has activity against both influenza A and B?

Answer 2

Neuraminidase inhibitors

Question 3

What is the MOA of the neuraminidase inhibitors as anti-influenza drugs?

Answer 3

Interfere with the release (and activation) of influenza A and B progeny from infected host cells

Question 4

What specifically is cleaved by neuroaminidase enzymes?

Answer 4

Neuroaminidase noramlly cleaves sialic acid from glycoproteins found on the cell surface of virions to promote continued viral replication.

NAIs impair the sepration of sialic acid, which renders the virions ineffective, resulting in halted viral spread.

Question 5

Oseltamivir can interfere with flu vaccine effectivess. How can this be avoided?

Answer 5

Wait two weeks before

or 48hrs after

However, oseltamivir does NOT interact with CYP or UDPGT

Question 6

What is the indication of oseltamivir?

Answer 6

Uncomplicated acute illness d/2 Influenza A and B

Prophylaxis is best if started within 48hrs of symptom onset

For 1yo +

Question 7

3 common AE’s of olseltamivir; what may be done to decrease them?

Answer 7

• HA, nausea, and vomiting
• Take w/ food to decrease N/V

Question 8

Doses of oseltamivir need to be adjusted in pt’s with what underlying problem?

Answer 8

Renal insufficiency

Question 9

Which anti-influenza class of drugs can be given as once-daily prophylaxis?

Answer 9

Neuraminidase inhibitors (oseltamivir and/or zanamivir)

Question 10

What are the 2 common AE’s of oseltamivir associated with prophylactic use?

Answer 10

Fatigue and diarrhea

Question 11

What is the indication for zanamivir?

Answer 11

Acute uncomplicated Influenza A or B

Prophylaxis if started within 48hrs of sx onset

12yo +

Question 12

After inhalation of zanamivir, where does 80-90% of it deposit?

Answer 12

Concentrated in lungs and oropharynx (aborbed, and excreted in urine)

Bioavailabilty is ~2%

Question 13

Major AE’s associated with zanamivir; should not be administered with what underlying issue?

Answer 13

Cough

Bronchospam (ocassionally severe)*** –> don’t give to pt w/ underlying airway disease!

Reversible ↓ in pulmonary function

Question 14

What are the contraindications of zanamivir?

Answer 14

Lactose intolerance

CNS dysfnx

Mental illness

Seizures (Watch this!)

Vaccine planned in next 2 weeks, or received in past 48hrs

Question 15

What is the matabolism of zanamivir?

Answer 15

100% eliminated by the kidneys without any metabolic biotransformation

Question 16

When should tx with neuraminidase inhibitors be given to be most effective against influenza?

Answer 16

Within 48 hours

Question 17

What pt population peramivir is recommended for?

Answer 17

18yo +

Question 18

What is the main potential AE of peramivir, and which rare AE has been seen?

Answer 18

Main = diarrhea

Hypersensitivity rxns –> Steven-Johnsons syndrome, Erythema multiforme have rarely been seen

↑ risk for delirium, hallucinations, and abnormal behavior

Question 19

What is the MOA of baloxavir?

Answer 19

Polymerase acidic endonuclease inhibitor

Indicated for acute uncomplicated flu for pts 12yo + starting within 48hrs of sx onset

Question 20

What are the 2 adamantanes used as anti-influenza drugs?

Answer 20

• Amantadine
• Rimantadine

Question 21

Indication for amantadine

Answer 21

Prophylaxis and tx of sign and sx of Influenza A

CONTRAINDICATED: hypersensitivy to amantadine

Question 22

What is the MOA of the adamantanes; amantadine and rimantadine used as anti-influenza drugs?

Answer 22

who knows???

Thought to block M2 proton ion channels, and therefore inhibit entry/uncoating of the viral RNA

May also inhbit reassembly WITHIN infected cells, preventing replication

No interaction with flu vaccne

Question 23

Which adamantane is excreted unchanged in the urine and which undergoes extensive metabolism?

Answer 23

amantadine is excreted unchanged ***

rimantadine undergoes extensive metbolism

*** Fx impairment of the kideneys can increase clearance form 10-14 hr half-life to 7-10 day.

Question 24

Why are the adamantanes no longer recommended for prevention or treatment of influenza?

Answer 24

High rates of resistance in both H1N1 and H3N2 viruses

Question 25

Which anti-influenza class are both teratogenic and embryotoxic?

Answer 25

Adamantanes

Question 26

2 most common AE’s of the adamantanes?

Answer 26

GI (nausea and anorexia)

CNS –> nervousness, difficulty in concentrating, insomnia, light-headedness

Question 27

What is a more serious AE associated with the adamantanes; more frequent with which drug in the class?

Answer 27

• Marked behavioral changes + Delirium + Hallucinations
• Agitation + Seizures
• More frequent w/ amantadine