antiviral therapy

Question 1

Hepatitis C therapy - drugs

Answer 1

1. Interferons - α
2. ribavirin
3. Simeprevir
4. Sofosbuvir

Question 2

Ribavirin - mechanism of action

Answer 2

inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophophate dehydrogenase

Question 3

Ribavirin inhibits synthesis of …. by

Answer 3

• guanine nucleotides

- competitively inhibiting inosine monophophate dehydrogenase

Question 4

Ribavirin - clinical use

Answer 4

1. Chronic HCV

2. RSV (palivizumab is preferred in children)

Question 5

Ribavirin - toxicity

Answer 5

1. hemolytic anemia

2. severe teratogen

Question 6

Simeprevir - mechanism of action

Answer 6

HCV protease inhibitor

prevents viral replication

Question 7

Simeprevir - clinical use

Answer 7

Chronic HCV in combination with ledipasvir (NS5A inhibitor)

DO NOT USE AS MONOTHERPAY

Question 8

Simeprevir - toxicity

Answer 8

1. photosensitivity reaction

2. rash

Question 9

Sofosbuvir - mechanism of action

Answer 9

inhibitis HCV RNA-dependent RNA polymerase acting as a chain terminator

Question 10

Sofosbuvir - clinical use

Answer 10

Chronic HCV in combination with ribavirin +/- peginterferon alfa
DO NOT USE AS MONOTHERAPY

Question 11

Sofosbuvir - side effects

Answer 11

fatique
headache
nausea

Question 12

HIV therpay regimen

Answer 12

Highly active antiretrovial therapy (HAART)

Question 13

HIV therpay - groups of drugs

Answer 13

1. protease inhibitors
2. Nucleoside Reverse Transcriptase Inhibitor (NRTI)
3. Non-nucleoside reverse transcriptase inhibitors (NNRTI)
4. Integrase inhibitors
5. Fusion inhibitors

Question 14

HAART - when to start

Answer 14

often initiated at the time of HIV diagnosis

strongeest indication for patients presenting with AIDS-defining illness, low CD4 (under 5 hundreds), or high viral load

Question 15

HAART regimen consist of

Answer 15

2NRTIs (Nucleoside Reverse Transcriptase Inhibitor) and 1 of the following: NNRT1 (Non-nucleoside reverse transcriptase inhibitors) or protease inhibitor or integrase inhibitor

Question 16

Protease inhibitors - drugs

Answer 16

-NAVIR

Question 17

HIV-1 Protease in encoded by

Answer 17

pol gene

Question 18

HIV-1 Protease - function

Answer 18

assembly of virions depend on HIV-1 protease, which cleaves the polypeptide products of HIV mrna into theri functional parts

Question 19

HIV Protease inhibitors - mechanism of action

Answer 19

inhibit HIV-protease –> prevents maturation of new viruses

Question 20

HIV Protease inhibitors - toxicity

Answer 20

1. hyperglycemia
2. GI tolerance (nausea, vomiting)
3. Lipodystrophy (Cushing-like syndrome)
4. Nephropathy (indinavir)
5. hematuria (indinavir)
6. inhibit cytochrome P-450 (ritonavir)

Question 21

HIV protease inhibitors with antimycobacterial drugs

Answer 21

Rifampin (a potent CYP/UGT inducer) contraindicated with proteae inhibitors because it can decrease protease inhibitor concentration

Question 22

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - mechansim of action

Answer 22

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (Lack of OH group

Question 23

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - drugs

Answer 23

1. Abacavir (ABC)
2. Didanosine (ddl)
3. Emtricitabine (FTC)
4. Lamivudine (3TC)
5. Stavudine (d4T)
6. Tenofovir (TDF)
7. Zidovudine (ZDV, formerly AZT)

Question 24

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - structure

Answer 24

Tenofovir –> nucleotide

the others –> nucleosides and need to be phosphorylated to be active

Question 25

Zidovudine - special clinical use

Answer 25

general prophylaxis and during pregnancy to decrease risk of fetal transmission

Question 26

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - side effects

Answer 26

1. Bone marrow suppression 2. peripheral neuropathy 3. lactic acidosis (nucleosides) 4. anemia (ZDV) 5. pancreatitis (didanosine)

Question 27

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - pancreatitis is caused by

Answer 27

didanosine

Question 28

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - anemia is caused by

Answer 28

ZDV

Question 29

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - lactic acidosis is caused by

Answer 29

nucleosides

Question 30

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - how to prevent side effects

Answer 30

bone marrow suppression --> granulocyte colony stimulating factor (G-CSF) and erytrhopoietin)

Question 31

Non-nucleoside reverse transcriptase inhibitors (NNRTI) - drugs

Answer 31

1. Delavirdine 2. Efavirenz 3. Nevirapine

Question 32

Non-nucleoside reverse transcriptase inhibitors (NNRTI) - drugs and mechanism of action

Answer 32

1. Delavirdine 2. Efavirenz 3. Nevirapine Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotide

Question 33

Non-nucleoside reverse transcriptase inhibitors (NNRTI) - toxicity

Answer 33

1. rash 2. hepatotoxicity 3. vivid dreams (efavirenz) 4. CNS sympoms (efavirenz) 5. contraindicated in pregnancy (Delavirdine and efavirenz)

Question 34

Non-nucleoside reverse transcriptase inhibitors (NNRTI) - which drugs are contraindicated in pregnancy

Answer 34

Delavirdine and efavirenz

Question 35

HIV - integrase inhibitors - drugs?

Answer 35

1. raltegravir 2. Elvitegravir 3. Dolutegravir

Question 36

integrase inhibitors - mechanism of action

Answer 36

inhibits HIV genone integration into host cell chromosome by REVERSIBLY inhibiting HIV integrase

Question 37

integrase inhibitors - toxicity

Answer 37

increased creatine kinase

Question 38

HIV - fusion inhibitors - drugs

Answer 38

1. Enfuvirtide | 2. Maraviroc

Question 39

HIV - fusion inhibitors - drugs and mechanism of action

Answer 39

1. Enfuvirtide --> Binds gp41, inhibiting viral entry | 2. Maraviroc --> Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120

Question 40

HIV - fusion inhibitors - toxicity

Answer 40

skin reaction on injection sites (Enfuvirtide)

Question 41

Abacavir - special characteristic of using

Answer 41

contraindicated if patients has HLA-B*5701 mutation