Antiviral Agents Flashcards
What are the differences between the 3 types of influenza virus?
Type A - multiple host species, capable of antigenic shift and drift, most serious
Type B - only in humans
Type C - common cold like
What type of influenza is bird flu?
Type A (H5N1)
Describe the pathophysiology of the influenza virus
Viral haemaglutinin attaches to sialic acid residues on the host cell and enters by endocytosis
H+ from ATP driven process facilitates fusion between the viral membrane and endosome
H+ from the acidic environment enters the virus via the M2 protein ion channel creating an acidic environment
This breaks down the viral coat of the nucleocaspid releasing the RNA
RNA enters the nucleus for viral replication
New virons bud by reattaching to the sialic acid residues on the membrane and then these binds are broken by the neuramidase protein
Name an M2 ion channel blocker and explain the mechanism of action
Rimantadine, amantadine (amantadine not recommended)
They block the M2 channel by changing the conformation of the pore thus blocking it and inhibiting H+ influx and viral uncoating
Only for influenza type A
What are the main ADRs of M2 ion channel blockers?
Confusion, insomnia, hallucination, nausea, hypotension
Name a neuraminidase inhibitor and describe the mechanism of action
Zanamavir, oseltamivir
Inhibit viral neuramidase meaning new virons can not escape the cell and infect others
Used for influenza type A and B
What are the pharmacological differences between zanamavir and oseltamivir?
Zanamavir - inhaled, low bioavailability, mutations around site does not affect binding
Oseltamivir - prodrug, high bioavailability, can be given as prophylaxis, mutations around site can close it
What are the main ADRs of neuraminidase inhibitors?
Vomiting, abdominal pain, epistaxis
What have clinical trials shown concerning symptom severity and dosing with neuraminidase?
Both active groups reduced symptoms compared to the placebo group but there was no difference in outcome of the active groups (higher does does not reduce symptoms further)
What do clinical trials show concerning initiation of treatment with neuraminidase inhibitors?
The earlier treatment starts after symptom onset the shorter the duration of symptoms. There is significant reduction if administered under 48 hours after onset, there are little benefits after this.
What do clinical trials show concerning mortality and neuraminidase inhibitors?
There is a 70% reduction in mortality risk up to 64 hours after symptom onset.
What do clinical trials show concerning prophylaxis of neuraminidase inhibitor?
RCT showed treatment reduced flu incidence compared to those taking a placebo (over 6 weeks) in healthy adults and those in a residential home.
Which influenza shows resistance to oseltamivir?
H5N1
In H1N1 oseltamivir resistance, what drug would you use instead?
Zanamavir
