Anti-Viral & Anti-Fungal Pharmacology

Question 1

Virus Overview

Answer 1

• obligate parasites (cannot multiply outside living cells)
• Lack cell wall and cell membranes
• consist of proteins and nucleic acids (either double or single stranded DNA/RNA) encased in capsid
• replicates inside host

Question 2

Virus hosting

Answer 2

• Varicella & Simplex reside in same ganglia
• Varicella deeper
• Simplex more superficial
• therefor Simplex reactivates easily (minor stress) and Zoster reactivates with significant stress (chemo etc)
• immune system well decreased in elderly thus more zoster in elderly
• Zoster vaccine for 50+

Question 3

Viral replication

Answer 3

1. binds to host cell
2. particle penetrates host cell
3. Duplication of DNA/RNA
4. New viral particle released
5. Cell death (apoptosis) or cell survival (latency)

Question 4

Anti-virals pharma

Answer 4

• based on genetics
• mimics building blocks and prevents DNA replication
• prevents the chain from continuing to grow
• involves viral and human enzymes to intervene

Question 5

DNA building blocks

Answer 5

Bases = Purines/Pyrimidines
Sugars = Ribose or Deoxyribose
1. Base + sugar = Nucleoside
2. Nucleoside + Phosphate = Nucleotide
3. Nucleotides make up Nucleic acid
4. Bonded together Nucleic acid froms DNA
* Antivirals mimic Bases

Question 6

Anti-virals - Nucleosides

Answer 6

• Acyclovir, Valacyclovir, Famciclovir
• chem struct similar to purine nucleoside deoxyguanosine
• under action of thymidine kinase produced by virus, nucleosides block DNA polymerase req for replication
• Treats HSV 1 & 2, Varicella-zoster, epstein-barr & CMV

Question 7

Oral Antivirals Uses

Answer 7

• Herpes Zoster
• HSV
• Bell’s Palsy
• ARN
  CAUTION = Renal impaired or those at risk (check BUN + creatine before use)

Question 8

Acyclovir (oral)

Answer 8

• Nucleoside analogue selectively phosphorylated by HSV & HZV thymidine kinase
• inhibits viral replication
• Only partially absorbed by GI tract
• bioavailability at Tx doses is limited to 20% - high doses at higher freq

Question 9

Acyclovir uses

Answer 9

• primary & recurr genital herpes
• Primary varicella
• Herpes Zoster
  Off Label
• HSV Keratitis
• ARN
• HZO
• Bells palsy
  *HSV prophylaxis

Question 10

H Zoster - Acyclovir

Answer 10

• Tx should start within 72hrs of skin lesions

- 800mg 5 x daily for 7 days

Question 11

HSV Keratitis - Acyclovir

Answer 11

• 400mg 5 x per day (7days)

- Prophylactic 400mg BID

Question 12

Bell Palsy - Tx

Answer 12

• oral steroids within 72hrs of symptom onset
• steroid + oral antiviral
• acyclovir 400mg 5x /day for 10 days
• Prednisolone 50mg for 10 days
• Prednisolone 60mg for 5 days with 5 day taper

Question 13

Valacyclovir

Answer 13

• prodruc of acyclovir
• L-valyl ester - metabolized to acyclovir
• higher bio-availability (3-5X)
• higher plasma ACV concentration - almost similar to IV ACV
• thus dose 500mg BID or 250mg QID

Question 14

Famciclovir

Answer 14

• prodrug of Penciclovir
• PCV = nucleoside analoque similar action as ACV
• Selectively inhibits H-DNA
• Rapidly absorbed and converted - bioavail 77%
• longer half life - less freq dose