Anti-virals

Question 1

ADME of acyclovir

Answer 1

Administered topically and IV.

*IV can cause nephrotoxicity, hepatotoxicity

Question 2

Clinical use of acyclovir

Answer 2

HSV infections- herpes encephalitis, neonatal HSV, severe HSV/VSV infections (can penetrate CSF).
*Give foscarnet if resistant to acyclovir (would occur from mutation to viral thymidine kinase)

Question 3

Mechanism of action of ganciclovir

Answer 3

An acyclic guanosine analog (requires 3x phosphorylation like acyclovir) and first phosphorylation done by CMV kinase

• tx and prophylaxis post-transplant for CMV
• can cause myelosuppression

Question 4

Mechanism of action of foscarnet

Answer 4

Treats acyclovir-resistant strains via IV only (doesn’t require activation by the virus). Inhibits DNA and RNA polymerase, HIV RT

• renal toxicity
• hyperphosphatemia, hypokalemia/calcemia/magnesemia

Question 5

Mechanism of action of anti-influenza drugs (oseltamivir, zanamivir)

Answer 5

Neuraminidase inhibitors (inhibit release of influenza progeny by competing for enzyme). Must be given within 48 hours of onset of symptoms. Fights influenza A and B. Zanamivir works against oseltamivir-resistant strains.

Question 6

Mechanism of action of ribavirin (anti-hepatitis drug)

Answer 6

Guanosine analog phosphorylated by host cell –> blocks capping of viral mRNA and inhibits viral RNA-dependent polymerase (causes RNA mutations). May be given with interferon
*can cause hemolytic anemia

Question 7

Mechanism of action of interferons (anti-hepatitis)

Answer 7

Exert antiviral, immunomodulatory, and antiproliferative actions. Boost the immune system (increase phagocytic activity, cytotoxic T cells, etc). Induce intracellular signals that inhibit viral development and release.

Question 8

Contraindications and toxicities of interferons

Answer 8

C: pregnancy (abortifacient)
T: flu-like symptoms (very bad)

Question 9

Mechanism of action of Simeprevir (anti-hepatitis)

Answer 9

Protease inhibitor (NS3/4A).
*can lead to drug-drug interactions b/c P450 inhibitor and P-glycoprotein transporter

Question 10

Mechanism of action of sofosbuvir and ledipasvir (anti-hepatitis)

Answer 10

NSB5 RNA polymerase inhibitor that works against all HCV genotypes (1-6) and protease-resistant strains.

Question 11

Sofosbuvir is a component in…

Answer 11

Harvoni (combined with Ledipasvir)

Question 12

Sofosbuvir toxicity

Answer 12

Sofosbuvir is a p-glycoprotein transporter and shouldn’t be used with p-gp inducers like rifampin

Question 13

Name the nucleoside reverse transcriptase inhibitors (NRTIs)

Answer 13

Abacavir, lamivudine/emtricitabine, tenofovir

Question 14

Mechanism of action of NRTIs

Answer 14

Activated by phosphorylation to triphosphate, competitively inhibit reverse transcriptase

Question 15

General toxicities of NRTIs

Answer 15

Can cause lactic acidosis w/ hepatic steatosis from inhibiting mitochondrial fxn and causing buildup of triglycerides

Question 16

Unique toxicities of abacavir

Answer 16

Remember, an NRTI. Can cause MI (caution with CV dz), fatal hypersensitivity rxns (NEVER give to HLAB5701 mutation

Question 17

Lamivudine/Emtricitabine usage

Answer 17

(NRTI) Used for HBV also by inhibiting HBV RT. Always given with tenofovir.

Question 18

Mechanism of action of tenofovir

Answer 18

A nucleotide RT inhibitor (NtRTI) that causes chain termination after incorporation into viral DNA. Given with emtricitabine for first-line therapy.
*Can cause tubular necrosis, renal failure, Fanconi’s syndrome

Question 19

Name the non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Answer 19

Efavirenz

Question 20

Mechanism of action of efavirenz

Answer 20

(NNRTI) Allosteric inhibitor- binds directly to HIV-1 RT inhibiting DNA and RNA-dependent DNA polymerase activity. Denatures the RT once bound.

• Significant P450 inducer
• Can cause psych disturbances/nightmares

Question 21

Mechanism of action of protease inhibitors

Answer 21

Mimics peptide bonds (peptidomimetics) to trick the protease, inhibiting it and preventing release of core proteins for viral maturation

Question 22

Name the protease inhibitors

Answer 22

Ritonavir, atazanavir, darunavir, lopinavir (only w/ ritonavir combo)

Question 23

Unique characteristics of ritonavir

Answer 23

CYP3A4 inhibitor, so it’s given w/ other PIs to increase serum levels (booster)

• increases triglycerides/LDL –> fat pad (lipodystrophy)
• elevated aminotransferases

Question 24

Contraindication of darunavir

Answer 24

Sulfa allergy

Question 25

Name the entry inhibitors in antiretroviral tx

Answer 25

Maraviroc, enfuvirtide

Question 26

Mechanism of action of maraviroc

Answer 26

Binds selectively to CCR5 on our T-cells preventing binding of HIV to that (one of the two receptors necessary for entrance of HIV into CD4+ cells). Used in HIV-1 resistant strains. Being saved in arsenal.

Question 27

Mechanism of action of enfuvirtide

Answer 27

Binds to gp41 (subunit of viral envelope glycoprotein, preventing the conformational changes required for fusion of the viral cellular membranes - no entry pore formed).
*Given via subcutaneous injection only to experienced HIV patients w/ ongoing HIV replication

Question 28

Name the integrase strand transfer inhibitors (INSTIs)

Answer 28

Dolutegravir, raltegravir

Question 29

Mechanism of action of INSTIs

Answer 29

Binds to integrase (integrase is involved in integrating viral genome into host genome aka strand transfer); inhibits its activity in HIV-1 and HIV-2. *Dolutegravir is effective in HIV strains resistant to previous INSTIs.

Question 30

Mechanism of action of acyclovir

Answer 30

Resembles nucleotide & sugar, tricking viral thymidine kinase into initially phosphorylating it (3 phosphorylations activates it) and goes on to block DNA synthesis