Antiviral 1 - Intro and Herpes viruses Flashcards
How big are viruses?
Smallest form of life; 20-300 nm
Viruses are classified as ______. This means what? (3 things)
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
What proteins do viruses encode?
Nucleocapsid
Polymerase
Receptor proteins
What’s the difference between a naked and enveloped virus?
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
What problems are there with antiviral therapy?
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
What are the 3 types of viruses?
DNA viruses (double stranded) RNA viruses (single stranded, + and - types) Retroviruses (Two copies of RNA)
What are the 2 types of herpes simplex virus?
Type 1 - mouth, face, skin, esophagus, or brain
Type 2 - genitals, rectum, hands or meninges
What does Varicella-Zoster cause?
Chicken pox
Shingles
What does Cytomegalovirus cause?
Retinitis
Esophagitis
Colitis
What does Epstein-Barr cause?
Infectious mononucleosis Burkitt Lymphoma (Jaw malignancy; first cancer linked to virus)
What was the first cancer linked to a virus? What virus was it?
Epstein-Barr virus causes Burkitt lymphoma
What does Herpes Simplex cause?
6 and 7 - Roseola
8 - found in 90% of Karposi sarcoma patients
Does Herpes virus cause acute or latent infections?
Can be acute or latent
What is HPV Type 1?
Cold sores
What is HPV Type 2?
Genital herpes
CMV - acute or latent?
Acute infections show no symptoms in children
Chronic infections can occur in immune-compromised patients
How is a latent infection established?
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
What are guanine analogs?
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.
Name the guanine analogs (6)
Acyclovir Penciclovir Ganciclovir sodium Valacyclovir Famciclovir Valganciclovir hydrochloride
Why don’t acyclovir/valacyclovir kill us if they inhibit DNA synthesis?
They are selectively phosphorylated by viral thymidine kinase and added to viral DNA
What are the indications for Acyclovir, Valacyclovir?
Herpes simplex
Varicella-zoster
Why does resistance occur with Acyclovir, Valacyclovir?
Altered thymidine kinase
What is the bioavailability of Acyclovir?
22% - HSV
What is the bioavailability of Valacyclovir?
Prodrug with higher bioavailability - 70%
HSV
VZV
What are the adverse effects of Acyclovir, Valacyclovir?
N/V
Rash
Need to maintain hydration bc renal function (crystallizes in renal tubule)
CNS - seizures, delirium (high conc)
Tremor
Bone marrow suppression
Counseling points for Acyclovir and Valacyclovir?
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)
Describe penciclovir, famciclovir?
Similar mechanism to acyclovir
Used in HSV and VZV
Actions and toxicity similar to acyclovir
Bioavailability of Penciclovir?
5% - use topically for genital HSV
Bioavailability of Famciclovir?
Prodrug - 77% - used for Oral HSV, VZV
Indications for Ganciclovir, Valganciclovir?
CMV in transplant and immuno-compromised patients
Bioavailability of Ganciclovir
6-9%
Given Oral, IV, Intravitreal (in eye)
Bioavailability of Valganciclovir
61%
Given orally
Adverse effects of Ganciclovir, Valganciclovir?
CNS (5-15%) - confusion, ataxia, seizures, coma
Neutropenia (15-40%)
Thrombocytopenia (20-50%)
N, V, Rash
Diarrhea
Increases liver enzymes
Which guanine analogs have side effects severe enough that some patients have to stop IV treatment?
33% of pts on ganciclovir, valganciclovir have to stop IV treatment because of side effects
What is Cidofovir?
Cytidine nucleotide that inhibits viral thymidine kinase
Why is Cidofovir special?
It works in resistant viruses
Doesn’t require viral kinase to become active
What are the indications for Cidofovir?
Herpes CMV Papilloma Polyoma Pox Adenovirus
CMV retinitis in HIV patients
Adverse effects of Cidofovir?
Glomerular filtration
Nephrotoxicity
Tubular dysfunction
Neutropenia
Bioavailability of Cidofovir?
IV only!
What is Foscarnet?
Pyrophosphate derivative, inhibits viral DNA polymerase
Bioavailability for Foscarnet?
IV admin only
Adjust dose for renal function!
Adverse effects of Foscarnet?
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!
Indications for Foscarnet?
CMV retinitis
Acyclovir resistant HSV and shingles
Ganciclovir resistant CMV
What is Vidaridine?
Purine analog that inhibits viral polymerase
What is Vidaridine used for?
Ophthalmic solution for HSV and VZV infections
VIDaridine sounds like Visine?
Adverse effects of Vidaridine?
Irritation
Pain
Photophobia
What are Trifluridine/Idoxuridine?
Thymidine analogs added into viral DNA by polymerase
What are Trifluridine/Idoxuridine used for?
Keratoconjunctivities caused by herpes simplex (???)
Ophthalmic ointment only
Adverse effects of Trifluridine/Idoxuridine?
Burning and itching, mild irritation of the eye
