Antivirals + HIV drugs

Question 1

What are the 5 subclasses or anti-retrovirals?

Answer 1

Nucleoside reverse inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, CCR-5 Antagonists, Fusion inhibitors

Question 2

What are the two mechanisms of action for antivirals?

Answer 2

viral DNA chain termination and incorporation into viral DNA polymerase

Question 3

What is the mechanism of Acyclovir?

Answer 3

Acyclovir is activated by viral thymidine kinase to a triphosphate and causes both inhibition of viral DNA polymerase and chain termination

Question 4

What is Acyclovir used to treat?

Answer 4

Treatment for CMV retinitis, Herpes I and II, Varicella Zoster, prophylaxis for immunocompromised

Question 5

What are adverse effects of Acyclovir? Specifically, which patients should avoid?

Answer 5

GI issues, headache, decreased BP, tremors and seizures. Reduces efficacy of anti-seizure drugs.

Question 6

What enzyme is required to activate ganciclovir?

Answer 6

Viral thymidine kinase

Question 7

What is ganciclovir used to treat?

Answer 7

CMV infections prophylaxis and treatment, CMV retinitis

Question 8

What is the mechanism of ganciclovir?

Answer 8

inhibits DNA polymerase and causes chain termination

Question 9

What are the side effects of ganciclovir? Which patients need to be careful with this drug?

Answer 9

blood dyscrasias (reduction in WBC, platelet), seizures, hepatic dysfunction.

Question 10

What is the mechanism of Cidofovir?

Answer 10

does not require viral kinase! Uses host kinases so active against viruses that are Ganciclovir and acyclovir resistant. Activated diphosphate inhibits DNA polymerase.

Question 11

What conditions if Cidofovir used to treat?

Answer 11

CMV retinitis, mucocutaneous HSV infections, genital warts, adenovirus, HPV

Question 12

What are the adverse effects of Cidofovir?

Answer 12

IV drug. Dose dependent nephrotoxicity. Additive nephrotoxicity with amphotericin B and aminoglycoside antibiotics.

Question 13

What is mechanism of Foscarnet?

Answer 13

Does not need to be phosphorylated in body for activation. Inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase.

Question 14

What is Foscarnet used to treat?

Answer 14

alternate in prophylaxis and treatment of CMV.

Question 15

What are the adverse effects of Foscarnet?

Answer 15

FoscarNOT: Nephrotoxicity, NO calcium, Neuro

Question 16

What are the Nucleoside Reverse Transcriptase inhibitors?

Answer 16

Abacavir, didanosine, Emtricitabine, tenofovir, zidovudine

Question 17

What is the mechanism for the NRTIs?

Answer 17

These are prodrugs converted to triphosphate by host kinases. These block reverse transcriptase (RNA-dependent DNA polymerase).

Question 18

What are the side effects of Abacavir?

Answer 18

hypersensitivity reactions

Question 19

What are the side effects of Didanosine?

Answer 19

pancreatitis

Question 20

What are the side effects of emtricitabine?

Answer 20

GI, hyperpigmentation on palms and soles of feet

Question 21

What are the side effects of tenofovir?

Answer 21

GI issues, asthenia (weakness), and headache

Question 22

What is the side effect of Zidovudine?

Answer 22

bone marrow suppression (AZT)

Question 23

What are the non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Answer 23

Delavirdine (prototype), Efavirenz, Etravirine

Question 24

What is the mechanism of non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Answer 24

inhibit reverse transcriptase but are not prodrugs like NRTIs (do not need to be phosphorylated). Bind different sites from nucleotides and nucleosides.

Question 25

What are the adverse effects of non-nucleoside reverse transcriptase inhibitors (NNRTIs)?

Answer 25

Delavirdine - causes skin rash in 20% (teratogenic in animals)
Efavirenz - CNS dysfunction, skin rash
Etravirine - rash, N/D, hepatic dysfunction, increase in levels of cholesterol and transaminases

Question 26

What are the protease inhibitors?

Answer 26

Atanzanavir, Darunavir, Fosamprenavir, Indinavir

Question 27

What is the mechanism of the protease inhibitors?

Answer 27

assembly of HIV virions is dependent on a viral protease to cleave precursor polyproteins. Protease inhibitors block the active site of the HIV-1 protease, preventing formation of structural proteins of the mature virion core.

Question 28

What are adverse effects of protease inhibitors

Answer 28

Think similar effects as Cushings Syndrome: disorders of carbohydrate and lipid regulation, hyperglycemia, insulin resistance, hyperlipidemia, buffalo hump (30-50% incidence), gynecomastia, truncal obesity.

Question 29

What are the Entry Inhibitors?

Answer 29

Maraviroc and Enfuviritide

Question 30

What is the mechanism of the Maraviroc?

Answer 30

Binds CCR-5, transmembrane chemokine receptor, to prevent viral attachment on T cells, macrophages, etc.

Question 31

What are the side effects of Maraviroc?

Answer 31

cough, diarrhea, muscle and joint pain, increased transaminases (AST and ALT)

Question 32

What is the action of Enfuviritide?

Answer 32

binds gp41 subunit on the viral envelope, preventing conformation changes required for fusion of viral and cellular membranes.

Question 33

What are adverse side effects of enfuviritide?

Answer 33

hypersensitivity at injection site

Question 34

What are the integrase inhibitors?

Answer 34

Raltegravir

Question 35

What is the mechanism of Raltegravir?

Answer 35

inhibits final step of strand transfer from viral DNA to host DNA by binding integrase. Prevents HIV DNA inserted into host cell DNA.

Question 36

What are adverse effects of Raltegravir?

Answer 36

GI issues, muscle pain, increase creatine kinase, rhabdomyolysis. Can also cause depression with suicidal ideation (careful!)