Exam 4: Clinical Pharmacology and Therapeutics of Antivirals Flashcards
What type of virus is Herpes Simplex Virus?
Double stranded DNA
Herpes virus can be in what 2 stages?
Active/lytic (producing new cells)
Latent (dormant)
Can HSV be cured?
No
Where does HSV1 infect?
Oral mucosa
Where does HSV2 infect?
Genital mucosa
What is the most common presentation of HSV1?
Cold sores
What is the most common presentation of HSV2?
Bumps, blisters, or ulcers around the genitals or anus
Which HSV viruses can enter the central nervous system?
Both HSV1 and HSV2
*HSV1 is the more common cause of encephalitis
What are the important facts about acyclovir?
Prodrug, needs to be triphosphorylated
Poor bioavailability, not affected by food
Renal elimination
Dose adjust in obesity
What is the main adverse effect of acyclovir?
Nephrotoxicity
IV form causes this
What is the dosing of acyclovir for Genital HSV?
Primary Infection:
400 mg po TID for 7-10 days
200 mg po q 4 hrs for 7-10 days
Recurrent:
800 mg po TID for 2 days
800 mg po BID for 5 days
Suppression:
400 mg po BID
What is the dosing of acyclovir for Oral HSV?
400 mg po TID for 5-10 days
*same for suppression
What is the dosing of acyclovir for HSV encephalitis?
10 mg/kg IV q8h for 14-21 days
*use adj bw
What are the main facts about Valacyclovir?
Prodrug of acyclovir
Better bioavailability than acyclovir
Not affected by food
What is the dosing of valacyclovir for oral herpes?
2g q12hr for 1 day
What is the dosing of valacyclovir for genital herpes?
Primary: 1g po BID x 7-10 days
Recurrent:
500mg po BID x 3 days
1g po daily x 5 days
Suppression:
500mg-1000mg po daily in immunocompetent patients
500mg po BID in HIV patients
What are the main facts about Famciclovir?
Prodrug of penciclovir, activated through triphosphorylation
Linear kinetics
Food slows absorption*
Famciclovir interacts with what drug?
Probenecid
-decreases renal clearance of famciclovir
What is the main side effect of famciclovir?
Acute renal failure (nephrotoxic)
What is the dosing of Famciclovir in oral herpes?
1.5 g single dose
What is the dosing of famciclovir in genital herpes?
Primary: 250 mg po TID x 7-10 days
Recurrent infection:
125mg po BID x 5 days
1 g po BID x 1 day
500 mg po x 1, then 250 mg po BID x 2 days
Suppression
250mg po BID
What type of virus is Varicella Zoster?
DNA virus
Varicela zoster virus is dormant where in the body after the initial infection?
Sensory nerve ganglia
What is the dosing of acyclovir for Varicella chicken pox?
800 mg po q 4 hrs (5x day) for 5-7 days
What is the dosing of acyclovir for Zoster (shingles)?
800 mg po q 4hrs (5x day) for 7-10 days
What is the dosing of acyclovir for severe disseminated disease or VSV encephalitis?
10mg/kg IV q8hr for 14-21 days
(use adjusted body weight)
What is the preferred drug for Varicella Zoster?
Valacyclovir
(better dosing)
What is the dosing of Valacyclovir for Varicella (chicken pox)?
1 g po q8hr for 5-7 days and until lesions have crusted
start within 24 hours of symptom onset
What is the dosing of Valacyclovir for Zoster (shingles)?
1 g po q8h for 7 days
preferred over PO acyclovir
*Start within 48-72 hr of rash onset
What is the preferred treatment for disseminated zoster?
Start with IV acyclovir (10mg/kg IV) for 10-14 days, then transition to valacyclovir once improved
What can famciclovir treat with regard to VZV?
Zoster (shingles) only
What is the dose of Famcyclovir for Zoster (shingles) treatment?
500 mg po TID for 7 days
begin within 72 hrs of rash onset
Cytomegalovirus is an opportunistic infection, what does this mean?
Most healthy people’s immune systems can keep the virus from causing illness
-attacks people with weak immune systems
What is the moa of Ganciclovir?
HSV/VZV: Prodrug turned into active form by viral thymidine kinase
CMV: Prodrug converted to active form (monophosphorylated) by a CMV-encoded protein kinase (UL97 gene), then to di- and triphosphate forms by cellular kinases
Drug inhibits viral DNA polymerase and/or incorporation into viral DNA which inhibits viral replication
How does resistance occur against Ganciclovir?
UL97 gene mutation
-leads to viral kinase deficiency or altered viral DNA polymerase
What are the important facts about Ganciclovir?
Low oral bioavailability, take with food to help absorption
Adequate concentrations in CSF, brain, and eye
What drugs does ganciclovir interact with?
Other cytotoxic drugs with risk of bone marrow suppression
Probenecid
avoid combination
What is the main adverse effect of ganciclovir?
Bone marrow suppression
At what level of bone marrow suppression should ganciclovir be stopped?
ANC <500/mm^3
or
Platelet <25,000/mm^3
What is the typical treatment duration of ganciclovir for CMV? (retinitis, esophagitis, colitis, pneumonitis, neurologic disease)
14-21 days
What is the duration of ganciclovir therapy in both prevention and treatment of bone marrow or organ transplant recipients?
5 mg/kg for 7-14 days
then
5mg/kg once daily 7 days/week or 6 mg/kg once daily 6 days/week
What are the important facts about valganciclovir?
Prodrug of ganciclovir
*Take with food (AUC can increase 30% when taken with a high fat meal)
Used for CMV retinitis and CMV disease
What is the typical dosing/duration of Valganciclovir therapy?
900 mg
21 days
What is the MOA of letermovir?
Inhibits pUL56 subunit of viral terminase complex in CMV
Prevents DNA cleavage, interfering with viral DNA processing and packaging into procapsids
Result: Inhibits CMV replication and prevents CMV infection
What is the most important thing to remember about letermovir?
Lots of drug interactions
What are the SE of letermovir?
N/V/D
Peripheral edema
Cough
Headache
Fatigue
Abdominal pain
What are the uses of letermovir?
CMV infection prophylaxis CMV positive adults who have received an allogenic hematopoietic stem cell transplant (HSCT)
What are the important facts about foscarnet?
Directly inhibits DNA polymerase
NOT A PRODRUG
Commonly last line
Only IV
What is the major SE of Foscarnet?
Nephrotoxicity
*patients need to be given hydration to prevent this
What are the 4 drugs used for influenza A/B?
Zanamivir
Oseltamivir
Peramivir
Baloxavir Marboxil
What are the important facts about oseltamivir?
Capsules and Powder for oral suspension
Food delays absorption
Who can receive oseltamivir?
Influenza patients >/= 2 weeks old who have been symptomatic for no more than 2 days
What are the important facts about zanamivir for influenza A/B?
Inhaled
*SE: bronchospasm
Who can receive Zanamivir for influenza?
Patients >/= 7 years old who have been symptomatic for no more than 2 days
Who should not receive Zanamivir?
Patients with underlying respiratory disease
What are the important facts to remember about Peramivir for influenza?
*Only IV med
Not approved for severe influenza requiring hospitalization
Who can receive Peramivir?
Acute uncomplicated influenza patients 18 or older who have been symptomatic no more than 2 days
What is important to remember about Peramivir dosing?
Single dose
What is the MOA of baloxavir marboxil?
Inhibits polymerase acidic (PA) endonuclease
(an influenza specific enzyme in the viral DNA polymerase complex that is required for viral gene transcription)
Leads to inhibition of mRNA synthesis and viral replication
what are the important points about Baloxavir marboxil?
Prodrug
Avoid co-administration with dairy products
Do not administer with live attenuated vaccine (this goes for all influenza drugs)
Who can receive Baloxavir Marboxil treatment?
Uncomplicated influenza patients >/= 12 years old who have been symptomatic for no more then 2 days
