Nucleoside Analogues (HSV)

Question 1

What is Acyclovir’s MOA?

Answer 1

Interferes with DNA polymerase and inhibits viral DNA synthesis

Question 2

ADR’s related to IV Acyclovir:

Answer 2

Renal dysfunction
-acute tubular necrosis
-neurological effects (ataxia, tremor, seizures).

Question 3

ADR’s related to PO Acyclovir:

Answer 3

Headache, skin rash, nausea, vomiting, diarrhea.

Question 4

Major drug interactions for acyclovir:

Answer 4

-Probenecid
-Nephrotoxic drugs (e.g., aminoglycosides, amphotericin B)

Question 5

Absorption for acyclovir:

Answer 5

Poor oral bioavailability (15-20%)

Question 6

Distribution for acyclovir:

Answer 6

Good CSF penetration.
Cross placenta and found in breast milk.

Question 7

What is acyclovir used for?

Answer 7

-Herpes Zoster, HSV & varicella zoster
-genital herpes & varicella

Question 8

How is acyclovir metabolized & excreted?

Answer 8

-Minimal hepatic metabolism
-excreted 90% unchanged in urine

Question 9

What is unique about Valacyclovir’s MOA?

Answer 9

Prodrug which is converted to acyclovir after PO administration

Question 10

ADR’s for valacyclovir:

Answer 10

Same ones as acyclovir but higher incidence;

Question 11

Serious ADR’s for valacyclovir in immunocompromised patients:

Answer 11

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)

Question 12

Drug interactions for Valacyclovir:

Answer 12

-Probenecid
-Nephrotoxic drugs (e.g., aminoglycosides, amphotericin B)

Question 13

Valacyclovir Pharmacokinetics:

Answer 13

Similar to acyclovir after being converted

Question 14

MOA of Famciclovir:

Answer 14

Prodrug converted to penciclovir, which inhibits viral DNA synthesis.

Question 15

ADR’s for Famciclovir:

Answer 15

Headache, dizziness, somnolence, paresthesias.

Question 16

Major Drug interactions for Famciclovir:

Answer 16

Cimetidine: Increases penciclovir levels.
Theophylline: Increases penciclovir area under the curve (AUC).
Digoxin: Minor increase in digoxin levels.

Question 17

How is Famciclovir absorbed & distributed?

Answer 17

rapidly absorbed & metabolized to penciclovir

widely distributed

Question 18

Famciclovir metabolism & Excretion:

Answer 18

Metabolized to penciclovir in the intestine and liver.

Renal excretion.