Antiviral 1 - Intro and Herpes viruses

Question 1

How big are viruses?

Answer 1

Smallest form of life; 20-300 nm

Question 2

Viruses are classified as ______. This means what? (3 things)

Answer 2

Parasites

They are parasites because they:
Rely on host for replication
Are difficult to target; can lead to collateral damage (bc we have to target our own cells to get them)
Encode for few proteins

Question 3

What proteins do viruses encode?

Answer 3

Nucleocapsid
Polymerase
Receptor proteins

Question 4

What’s the difference between a naked and enveloped virus?

Answer 4

Naked viruses consist of capsomers surrounding nucleic acid (icosahedral)

Enveloped viruses are surrounded by glycoproteins, lipid bilayer, and matrix proteins. Inside the cell there is RNA covered by capsid proteins

Question 5

What problems are there with antiviral therapy?

Answer 5

Infections aren’t detected immediately bc immune system not activated by unique components of the virus

Massive proliferation of virus = need for rapid overwhelming intervention (Ebola infection to death is 5 days)

Virus “hijacks” the host cells, which decreases immune response and it’s also hard to distinguish host from pathogen

Rapid viral evolution: High mutation rate of virus, massive numbers of virus particles, mutations occur through jumping species

They are highly infectious

Question 6

What are the 3 types of viruses?

Answer 6

DNA viruses (double stranded)
RNA viruses (single stranded, + and - types)
Retroviruses (Two copies of RNA)

Question 7

What are the 2 types of herpes simplex virus?

Answer 7

Type 1 - mouth, face, skin, esophagus, or brain

Type 2 - genitals, rectum, hands or meninges

Question 8

What does Varicella-Zoster cause?

Answer 8

Chicken pox

Shingles

Question 9

What does Cytomegalovirus cause?

Answer 9

Retinitis
Esophagitis
Colitis

Question 10

What does Epstein-Barr cause?

Answer 10

Infectious mononucleosis
Burkitt Lymphoma (Jaw malignancy; first cancer linked to virus)

Question 11

What was the first cancer linked to a virus? What virus was it?

Answer 11

Epstein-Barr virus causes Burkitt lymphoma

Question 12

What does Herpes Simplex cause?

Answer 12

6 and 7 - Roseola

8 - found in 90% of Karposi sarcoma patients

Question 13

Does Herpes virus cause acute or latent infections?

Answer 13

Can be acute or latent

Question 14

What is HPV Type 1?

Answer 14

Cold sores

Question 15

What is HPV Type 2?

Answer 15

Genital herpes

Question 16

CMV - acute or latent?

Answer 16

Acute infections show no symptoms in children

Chronic infections can occur in immune-compromised patients

Question 17

How is a latent infection established?

Answer 17

Virus penetrates into the skin where it replicates, then enters the cutaneous neurons and migrates into the ganglion where it remains in a latent state

Virus can subsequently be reactivated and travel through the sensory neurons to the epidermis

Question 18

What are guanine analogs?

Answer 18

A type of antiviral that inhibits DNA synthesis by entering itself into the DNA, and since they lack a sugar, the next base pair can’t be added so elongation is stopped.

Question 19

Name the guanine analogs (6)

Answer 19

Acyclovir
Penciclovir
Ganciclovir sodium
Valacyclovir
Famciclovir
Valganciclovir hydrochloride

Question 20

Why don’t acyclovir/valacyclovir kill us if they inhibit DNA synthesis?

Answer 20

They are selectively phosphorylated by viral thymidine kinase and added to viral DNA

Question 21

What are the indications for Acyclovir, Valacyclovir?

Answer 21

Herpes simplex

Varicella-zoster

Question 22

Why does resistance occur with Acyclovir, Valacyclovir?

Answer 22

Altered thymidine kinase

Question 23

What is the bioavailability of Acyclovir?

Answer 23

22% - HSV

Question 24

What is the bioavailability of Valacyclovir?

Answer 24

Prodrug with higher bioavailability - 70%

HSV
VZV

Question 25

What are the adverse effects of Acyclovir, Valacyclovir?

Answer 25

N/V Rash Need to maintain hydration bc renal function (crystallizes in renal tubule) CNS - seizures, delirium (high conc) Tremor Bone marrow suppression

Question 26

Counseling points for Acyclovir and Valacyclovir?

Answer 26

Stay hydrated bc they crystallize in renal tubule Probenacid reduces renal clearance Give within first 24 hours to shorten acute illness but it doesn't cure the infection (less intense, shorter duration)

Question 27

Describe penciclovir, famciclovir?

Answer 27

Similar mechanism to acyclovir Used in HSV and VZV Actions and toxicity similar to acyclovir

Question 28

Bioavailability of Penciclovir?

Answer 28

5% - use topically for genital HSV

Question 29

Bioavailability of Famciclovir?

Answer 29

Prodrug - 77% - used for Oral HSV, VZV

Question 30

Indications for Ganciclovir, Valganciclovir?

Answer 30

CMV in transplant and immuno-compromised patients

Question 31

Bioavailability of Ganciclovir

Answer 31

6-9% | Given Oral, IV, Intravitreal (in eye)

Question 32

Bioavailability of Valganciclovir

Answer 32

61% | Given orally

Question 33

Adverse effects of Ganciclovir, Valganciclovir?

Answer 33

CNS (5-15%) - confusion, ataxia, seizures, coma Neutropenia (15-40%) Thrombocytopenia (20-50%) N, V, Rash Diarrhea Increases liver enzymes

Question 34

Which guanine analogs have side effects severe enough that some patients have to stop IV treatment?

Answer 34

33% of pts on ganciclovir, valganciclovir have to stop IV treatment because of side effects

Question 35

What is Cidofovir?

Answer 35

Cytidine nucleotide that inhibits viral thymidine kinase

Question 36

Why is Cidofovir special?

Answer 36

It works in resistant viruses | Doesn't require viral kinase to become active

Question 37

What are the indications for Cidofovir?

Answer 37

``` Herpes CMV Papilloma Polyoma Pox Adenovirus ``` CMV retinitis in HIV patients

Question 38

Adverse effects of Cidofovir?

Answer 38

Glomerular filtration Nephrotoxicity Tubular dysfunction Neutropenia

Question 39

Bioavailability of Cidofovir?

Answer 39

IV only!

Question 40

What is Foscarnet?

Answer 40

Pyrophosphate derivative, inhibits viral DNA polymerase

Question 41

Bioavailability for Foscarnet?

Answer 41

IV admin only | Adjust dose for renal function!

Question 42

Adverse effects of Foscarnet?

Answer 42

It's nephrotoxic and chelates cations (Worry about hypocalcemia, hypomagnesemia, and hypokalemia) Headaches, seizure, fatigue, tremor, hallucinations Cough, dyspnea, pneumothorax Fever, rash Anemia, thrombocytopenia, bleeding!

Question 43

Indications for Foscarnet?

Answer 43

CMV retinitis Acyclovir resistant HSV and shingles Ganciclovir resistant CMV

Question 44

What is Vidaridine?

Answer 44

Purine analog that inhibits viral polymerase

Question 45

What is Vidaridine used for?

Answer 45

Ophthalmic solution for HSV and VZV infections VIDaridine sounds like Visine?

Question 46

Adverse effects of Vidaridine?

Answer 46

Irritation Pain Photophobia

Question 47

What are Trifluridine/Idoxuridine?

Answer 47

Thymidine analogs added into viral DNA by polymerase

Question 48

What are Trifluridine/Idoxuridine used for?

Answer 48

Keratoconjunctivities caused by herpes simplex (???) Ophthalmic ointment only

Question 49

Adverse effects of Trifluridine/Idoxuridine?

Answer 49

Burning and itching, mild irritation of the eye