Antivirals

Question 1

How many types of influenza virus ?

Answer 1

3 types :
Influenza A - multiple host species (infects more than just humans )

Influenza B - lower mortality

Influenza C - common cold like

Question 2

Complications in influenza

Answer 2

Bronchitis
Pneumonia
Sinusitis
Exacerbation of underlying disease

Question 3

Structure of influenza A virus

Answer 3

Picture on iPad

Question 4

Different types of influenza drugs and mechanisms ?

Answer 4

Vaccines - contain hemagglutinin- so body produces antibodies against it

M2 ion channel inhibitor - prevent virus uncoating

Neuraminidase inhibitor -

Question 5

Examples of M2 Ion Channel inhibitors ?

Answer 5

Amantadine

Rimantadine

(Initially developed for Parkinson’s)

Question 6

M2 inhibitors..

Mechanism?
Spectrum?
Side effects?

Answer 6

• tricyclics amines block M2 channel = inhibit viral uncoating
• only influenza A
• CNS and Renal side effects

Question 7

Why can influenza still affect people on these drugs

Answer 7

Due to single point mutation in M2 gene

Quite quickly became resistant

Question 8

Why is Neuraminidases inhibitors better

Answer 8

Surface of influenza is highly variable however

The neuraminidase active site is conserved well across subtypes

Question 9

Action of influenza Neuraminidases and it’s inhibitor

Answer 9

It cleaves hemagglutinin binding

So with inhibitor - virus can no longer be released from cell membrane to go off and cause new infection

Question 10

2 examples of neuraminidase inhibitor

Answer 10

Zanamavir

Oseltamivir

Question 11

Oseltamivir mechanism of action

Answer 11

Reversible inhibitors of
viral neuraminidase enzyme
that cleaves sialic-acid receptor-HA bond between host cell and virus

Question 12

Zanamivir 
Bioavailability?
Administration ?
Detectable ?
Excretion?

Answer 12

• Low oral bioavailability
• inhaled as powder - (oral - rapidly degraded by acid )
• Remains detectable insputum 24hrs post dosing
• Excreted renally

Question 13

Oseltamivir

Bioavailability

Answer 13

• pro drug
• 80% bioavailabilty
• active site changes shape

Used in treatment and as seasonal prophylaxis

Question 14

ADRs of Oseltamivir

Answer 14

Nausea
Vomiting
Abdominal pain
Epistaxis

Question 15

Guidelines for use in primary care
Healthy people
At risk (including pregnant)
Severely immunosuppressed

Answer 15

• no prescription unless pt felt to be at risk
• Oseltamivir ASAP
• Oseltamivir or inhaled Zanamivir (esp if H1N1)

Question 16

Guidelines for use of in secondary care

Answer 16

Oseltamivir if confirmed or suspected flu

Question 17

Secondary care - if H1N1 circulating, what to prescribe

Answer 17

H1N1 - increased risk of Oseltamivir resistance

So consider Zanamivir in severely immunosuppressed

Question 18

Human herpes viruses

Answer 18

Large family of 150 species
DNA viruses

Generally mild primary infection
Establish latent infection
Secondary infection / reactivation

Question 19

HSV1 and 2

Primary infection ?
Recurrent infection ?
Complications ?

Answer 19

Primary - orogenital ulceration , paronychia

Secondary - asymptomaric, cold sores, genital herpes, skin eruptions

complications - meningitis, encephalitis, keratitis, eczema herpeticum

Question 20

HSV 1 and 2 latency site

Answer 20

Neurones (trigeminal, sacral)

Question 21

Treatment

Answer 21

• specific antiviral therapy

- supportive treatment - bacterial complications

Question 22

Antiviral treatment in herpes

Answer 22

Nucleoside analogues
Inhibit herpes viral DNA polymerase

• Aciclovir and valaciclovir (HSV, VZV)

– Cidofovir (CMV, resistant HSV)

– Ganciclovir (CMV, EBV)

(Vir)

Question 23

How many herpes viruses infect humans ?

Answer 23

8 types
Inc,using HSV-1, HSV-2 and VZV ( varicella zoster virus).
EBV (Epstein Barr Virus) is also a member which is associated with various malignant and non-malignant lymphomas

Question 24

Structure and invasion of HSV and EBV

Answer 24

Very similar viral structure
Large double-stranded DNA genome
Covered by a capsid and lipid bilayer envelope

Invasion into host occurs via - interference with MHC Class 1 molecules

Question 25

What does VZV cause

Answer 25

- chickenpox (varicella) | - shingles (herpes zoster )

Question 26

When does shingles present

Answer 26

Shingles presents after reactivation of the virus which lies dormant in dorsal root ganglion after primary chickenpox infection Most prevalent in elderly and immunocompromised with most people suffering at least 1 shingles attack

Question 27

Is chickenpox treated with antiviral agents

Answer 27

Rarely, | Although tropical use of aciclovir has shown to reduce severity of skin lesions

Question 28

Treatment of shingles

Answer 28

- oral antiviral drugs : reduce pain and accelerate healing of blisters - Aciclovir & Valaciclovir are often used - use of antivirals reduces risk of post-herpetic nerve damage

Question 29

When should treatment (antivirals) of shingles be initiated

Answer 29

Antivirals must be given while the virus is still replicating And so, treatment should be initiated within 72hrs of blisters being noticed

Question 30

What does type 1 and type 2 of HSV cause ?

Answer 30

HSV-1 : oral or genital ulceration HSV-2: genital ulceration

Question 31

Treatment of oral herpes infection

Answer 31

Topical antiviral treatment | Typically Aciclovir

Question 32

Treatment for genital herpes lesion and for how long

Answer 32

Oral Aciclovir or Valaciclovir 7-10 days It is common for recurrent lesions to occur from reactivation of latent virus in the dorsal root ganglia. Symptoms are usually less severe than the primary episode.

Question 33

Mechanism of Aciclovir and Valaciclovir

Answer 33

Both are nucleoside inhibitors of viral DNA replication. Aciclovir - is a guanosine analogue active against many DNA viruses Initial activity relies on phosphorylation by thymidine kinase limiting their initial human cell toxicity.

Question 34

How can resistance occur

Answer 34

When thymidine kinase is altered or absent in the presenting virus Is particularly prevalent in severely immunocompromised patients

Question 35

Administrations of Aciclovir

Answer 35

Topical Oral IV Depending on severity and local lesions

Question 36

Aciclovir | Distribution, eliminiation, Half life

Answer 36

Well distributed Eliminated mostly by kidneys T1/2 ~ 3hrs

Question 37

Valaciclovir bioavailability and administration

Answer 37

Greater oral bioavailability than Aciclovir Administration - Oral Is an ester pro-drug of Aciclovir

Question 38

Side effects of Aciclovir and Valaciclovir

Answer 38

Nausea Vomiting Photo-sensitivity

Question 39

What is a risk when these are prescribed alongside other drugs including many antibiotics

Answer 39

Risk of nephrotoxicity

Question 40

What is valganciclovir used for

Answer 40

Used in solid organ transplantation patients