Antivirals

Question 1

Acyclovir

Answer 1

I: HSV1, HSV2, VZV

PK:
-IV or oral, t1/2 3hrs, insoluble in urine
- Topical for cold sores (penciclovir)

MOA:
- inhibits DNA synthesis
- acyclovir + viral TK = acyclovir monophosphate
- acyclovir monophosphate –> Acyclovir triphosphate –>blocks replication

AE:
- nephrotoxic, crystalluria
-hydrate well

Question 2

Valacyclovir

Answer 2

I:
-herpes zoster but also HSV1,2, CMV, VZV

PK:
- oral only, active transport by peptide transporters in intestine
- Dose adjust with renal dysfunction only

AE:
- Nephrotoxic
- GI symptoms
- thrombocytopenia in AIDS patients

MOA: inhibits DNA synthesis, viral TK etc.

• Acyclovir+valacyclovir prevents Herpes recurrence and outbreak suppression
• daily use to avoid spreading HSV to partner
• prodrug of acyclovir

Question 3

Ganciclovir

Answer 3

I:
- CMV

PK:
- oral, IV (doesn’t require DNA activation)

MOA:
- Guanosine analog–>Inhibits DNA Synthesis
- competitive inhibitor of viral dGTP
- viral kinase, then host phosphorylation

AE: Myelosuppression

Question 4

Valganciclovir

Answer 4

I:
-CMV, prophylaxis and long term suppression

PK: oral, activated by esterase in liver and intestine

MOA: inhibits DNA synthesis

AE: myelosuppression

-guanosine analog, competitive inhibitor of dGTP

Question 5

Raltegravir

Answer 5

I: HIV
PK: oral
MOA:
- integrase inhibitor, inhibits vDNA insertion
- binds to Mg active site of integrase
DI: avoid with food with CaCo3, Al, or Mg–>metal chelating, rifampin

Question 6

HIV morning after drug

Answer 6

Raltegravir, tenofobir, disoproxil, emtricitabine
- 72 hour window
-28 day regimen

Question 7

Dolutegravir

Answer 7

I: HIV
PK:
-daily oral dose, achieves steady state in 5 days
- metabolized by UGT1A1
-excreted in feces and urine

MOA: integrase inhibitor
AE: rhabdomyolysis, myopathy
DI: CYP interactions, rifampin, metformin, antiepileptics

Question 8

Efavirenz

Answer 8

I: HIV
PK:
- oral, take on empty stomach, t1/2 45 hours
- Hepatic metabolism CYP3A4 and CYP2B6

MOA:
- directly inhibits RT

AE: Rash, hepatotoxicity, vivid dreams, insomnia, lipodystrophy, suicidal ideation, impaired concentration

CI: pregnancy–>depression, psych illness, neural tube defects

Question 9

Abacavir

Answer 9

I: NRTI for HIV combination therapy

PK: prodrug metabolized by live ADH—>increased AE with alcohol

MOA: incorporates into vDNA, blocks elongation, chain termination

AE: hypersensitivity, fever, rash, GI symptoms

CI: HLA B5701+ can cause SJS, life threatening hypersensitivity rxn

Screen before Rxing med
Abacavir HSR-multiorgan

Question 10

Zidovudine

Answer 10

I: HIV treatment and prophylaxis in adult, kids, perinatal, prevents mother to child transmission

PK: oral, metabolized by liver glucuronidation, crosses placenta and BBB

MOA: terminates DNA transcription

AE: anemia, myelosuppresion,

CI: drugs that slow glucuronidation

Question 11

Tenofivir

Answer 11

I: HIV, HepB and co-infection
PK: oral
MOA: RT inhibitor
AE: kidney injury, decreased bone density/formation, increase bone resorption,

TDF: bone and renal toxicity—>add Ca2+ and Vita supplement
TAF: inc LDLs and total cholesterol

CI: renal impairment, osteoporosis

Question 12

PReP

Answer 12

Emitricitabine, tenofobir, disoproxil fumarate

Question 13

Stavudine

Answer 13

I: HIV
PK: oral, BBB
MOA: RT inhibitor, thymidine analog, inhibits human mtDNA synthesis
AE: peripheral neuropathy, fat redistribution, hyperlipidemia

Question 14

Lamivudine

Answer 14

I:HIV
PK:
MOA: RT inhibitor
AE: lactic acidosis, lipid redistribution
CI: dines

cytidine analog
-Didanosine- adenosine analog

Question 15

Atazanavir

Answer 15

I: HIV
PK: daily, limited oral absorption, substrate for Pgp limits BBB
MOA: reversible inhibition of viral aspartyl protease enzyme–>immature noninfectious virus
AE: inc transaminase lever, hyperglycemia, lipodystrophy, profuse diarrhea, pins and needles of hands, nausea, vomiting, Hyper bilirubinemia
DI: H pump inhibitor

Question 16

Ritonavir

Answer 16

I: HIV, pharmacokinetic enhancer
PK: liver metabolism, biliary excretion
MOA: CYP3A4 inhibitor
AE: liver disease, CYP inhibition

Question 17

Cobiscistate

Answer 17

I: kids, adolescents, boosting activity

Question 18

Indinavir

Answer 18

I: HIV
MOA: protease inhibitor
AE: nephrotoxicity, inc bilirubin

DI: metronidazole, disulfiram–>DLR

Question 19

Maraviroc

Answer 19

I: HIV
PK
MOA: binds CCR5 receptor inhibits interaction with gp120, blocks entry

Resistance-gp120 mutations switch CCR5 to CXCR4

AE: hepatotoxicity

Question 20

Enfuvirtide

Answer 20

I: combination with of HIV drugs
MOA: binds viral envelope gp41 prevents HIV entry, inhibits fusion with CD4 cells

Question 21

Foscarnet

Answer 21

I: CMV retinitis
MOA: DNA synthesis inhibition
PK: dose adjust with renal dysfunction
AE:nephrotoxicity, seizures with e-lyte imbalance