Pharmacology of Anti-Virals

Question 1

List the 4 types of DNA viruses

Answer 1

Herpes viruses (glandular fever, chickenpox, shingles, cold sores)
Pox viruses (smallpox)
Adenoviruses (sore throat, conjunctivitis)
Papillomaviruses (warts)

Question 2

How many human herpes viruses are there?

Answer 2

8

Question 3

Which 3 of the herpes viruses are neurotropic?

Answer 3

HHV-1/HSV-1
HHV-2/HSV-2
HHV-3/VZV

Question 4

Which 3 herpes viruses are lymphotropic?

Answer 4

HHV-4/EBV
HHV-5/ CMV
HHV-6/7
HHV-8

Question 5

How many types of seasonal influenza viruses are there?

Answer 5

4 - A, B, C, D

Question 6

Which influenza viruses cause the seasonal epidemics?

Answer 6

A and B

Question 7

What categories is influenza A broken down into?

Answer 7

Classified according to combinations of HA (haemagglutinin) and NA (neuraminidase) proteins on the surface of the virus

Question 8

Which 2 categories are viral DNA polymerase inhibitors broken into?

Answer 8

nucleoside analogues
non-nucleoside analogues

Question 9

give examples of nucleoside analogues (DNA polymerase inhibitors)

Answer 9

acyclovir, ganciclovir, valaciclovir
(prodrugs)

Question 10

give examples of non-nucleoside analogues (DNA polymerase inhibitors)

Answer 10

foscarnet
cidofovir

Question 11

give examples of M2 inhibitors

Answer 11

amantadine
rimantadine

Question 12

give examples of neuraminidase inhibitors

Answer 12

oseltamivir
zanamivir

Question 13

Which amino acid are the viral dna inhibitors nucleotide analogues mimicking?

Answer 13

guanine

Question 14

How does acyclovir work?

Answer 14

Acyclovir is activated by the enzyme viral thymidine kinase to acyclovir monophosphate
Further phosphorylated by cellular enzymes to triphosphate form (ACV-TP)
This fake building block inhibits viral DNA polymerase leading to chain termination
Only actively replicating viruses are inhibited

Question 15

Does viral DNA polymerase or cellular DNA polymerase have a higher affinity for ACV-TP or

Answer 15

viral dna polymerase has a 10-30 fold greater affinity for ACV-TP

Question 16

Which viruses does acyclovir treat mostly?

Answer 16

HHV1, HHV2, VZV
less so for EBV or CMV

Question 17

Indications and side effects of topical application of acyclovir

Answer 17

Limited, non life threatening mucocutaneous HSV infections
SE: local irritation, funny taste in the mouth

Question 18

Indications and side effects of oral acyclovir

Answer 18

Primary genital herpes, HSV suppression
SE: nausea, diarrhea, headache

Question 19

Indications and side effects of IV acyclovir

Answer 19

Severe HSV infection, HSV encephalitis, VZV infection in immunocompromised host
SE: sweating, rash, emesis, fall in BP

large doses can result in crystallisation in the renal tubules - hydration is important with higher doses

Question 20

Does valaciclovir or acyclovir have higher serum levels

Answer 20

Valaciclovir

Question 21

MOA of valaciclovir

Answer 21

l-valine ester of acyclovir
serum esterases hydrolyse it to free acyclovir
available orally only

Question 22

What is ganciclovir used for?

Answer 22

treatment and prevention of CMV in immunocompromised patients
used IV - poor oral bioavailability

Question 23

What is the prodrug of Penciclovir?

Answer 23

Famciclovir - converted to penciclovir in the intestines and liver

Question 24

What is famciclovir most commonly used for?

Answer 24

Herpes zoster - shingles
available orally only

Question 25

SE of famciclovir

Answer 25

stomach upset headache mild fever

Question 26

What is the drug of choice in patients resistant to acyclovir?

Answer 26

Foscarnet only available IV

Question 27

MOA of foscarnet

Answer 27

Non-nucleoside DNA analogue Binds to a site on the herpesvirus DNA polymerase or HIV reverse transcriptase during viral replication Interferes with the exchange of pyrophosphate from deoxynucleoside triphosphate phosphorylation step is not required unlike the nucleoside analogues

Question 28

Which influenza is the M2 channel present on?

Answer 28

Influenza A only

Question 29

MOA of M2 inhibitors

Answer 29

Bind to M2 channel in the influenza A virus only Prevents ion flux necessary to coat the endosome

Question 30

Which genes are resistant to M2 inhibitors

Answer 30

H5N1 (bird flu) H1N1 (swine flu)

Question 31

When would you use an M2 inhibitor?

Answer 31

in patients at high risk for complications

Question 32

SE of amantadine?

Answer 32

dizziness seizures

Question 33

What does neuraminidase do?

Answer 33

an enzyme found on the virus which cleaves sialic acid and allows for the more efficient release of the virus

Question 34

MOA of neuraminidase inhibitors

Answer 34

inhibit neuraminidase cause newly formed virions to adhere to the cell surface and form viral aggregates and thus limit spread

Question 35

Are neuraminidase inhibitors effective against H5N1 and H1N1?

Answer 35

yes

Question 36

What is the roa of oseltamivir (tamiflu)

Answer 36

oral

Question 37

AE of tamiflu

Answer 37

headache

Question 38

When should oseltamivir be taken?

Answer 38

Within 48 hours of symptoms

Question 39

ROA of zanamivir (relenza)

Answer 39

inhalation

Question 40

AE of zanamivir (relenza)

Answer 40

bronchospasm nasal and throat discomfort

Question 41

What are the 3 classes of interferons?

Answer 41

alpha - leukocytes beta - fibroblasts gamma - t-lymphocytes, NK cells

Question 42

What is interferon a used for?

Answer 42

hairy cell leukemia kaposi's sarcoma chronic hepatitis b and c infection

Question 43

roa of interferon a

Answer 43

parenteral

Question 44

what is interferon b used for?

Answer 44

multiple sclerosis

Question 45

What is interferon gamma used for?

Answer 45

chronic granulomatous disease hodgkin's lymphoma

Question 46

adverse effects of ganciclovir?

Answer 46

haematological - granulocytopenia, neutropenia, anaemia, thrombocytopenia fever nausea vomiting carcinogenic teratogenic mutagenic

Question 47

adverse effects of interferon a

Answer 47

flu-like symptoms alopecia depression hypotension teratogenic