Clinical Pharmacology and Therapeutics of Antivirals (non-antiretrovirals) Flashcards
Where are HSV1 infections typically on the body?
Oral mucosa
Where are HSV2 infections typically on the body?
Genital mucosa
How do you diagnose HSV1?
Swab or PCR testing
How do you diagnose HSV2?
Swab or PCR testing
What types of herpes can cause CNS disorders?
HSV1 and HSV2
How do you diagnose herpes in the CNS?
Lumbar puncture and PCR testing
Mechanism of action of acyclovir
-Prodrug that is converted to active acyclovir triphosphate
-Competitively inhibits viral DNA polymerase to inhibit viral replication
-Can be incorporated into viral DNA causing premature chain termination
How is acyclovir administered
Oral or IV but has poor oral bioavailability
When do you need to dose adjust for acyclovir?
Renally dose adjust and in obesity (use adjusted body weight)
What are the three most common side effects of acyclovir?
-Nephrotoxicity
-Neurotoxicity
-Thrombophlebitis
-Otherwise generally well-tolerated
How can you limit nephrotoxicity in acyclovir?
Administer with maintenance fluids
Acyclovir indications
-Genital HSV (primary and recurrent infection as well as suppression therapy)
-Oral HSV (suppression therapy as well)
-IV for HSV encephalitis (monitor nephrotoxicity)
-Severe disseminated disease or VZV encephalitis (IV)
What is valacyclovir?
A prodrug of acyclovir with the same MOA, adverse effects, and spectrum of activity
What is the difference between valacyclovir and acyclovir?
-Valacyclovir bioavailability is 3-5 times greater
-Better for oral therapy because it requires less frequent dosing
Valacyclovir indications
-Oral and genital herpes (often used in suppression therapy for genital herpes)
-Varicella
-Zoster
-Disseminated zoster after IV acyclovir
When can cytomegalovirus become a problem?
-It is an opportunistic infection so most health immune systems can keep the virus from causing an illness
-Weak immune systems can cause serious infections that commonly affect the eyes or can even cause end organ damage
Ganciclovir MOA
-A prodrug that is converted to an active triphosphate form by cellular kinases
-Active drug inhibits viral DNA polymerase and/or incorporation into viral DNA which inhibits viral replication
What kind of resistances to ganciclovir can occur?
U97 gene mutation leads to viral kinase deficiency or altered viral DNA polymerase
Is ganciclovir oral or IV
Has terrible oral bioavailability so it is only given IV
Ganciclovir drug interactions
-Other cytotoxic drugs with risk of bone marrow suppression
-Probenecid
Main adverse effect of ganciclovir
-Bone marrow suppression
-Stop drug if ANC is less than 500
Ganciclovir indications
-CMV retinitis induction therapy
-CMV esophagitis, colitis, pneumonitis, neurologic disease
