antiviral therapy Flashcards
Hepatitis C therapy - drugs
- Interferons - α
- ribavirin
- Simeprevir
- Sofosbuvir
Ribavirin - mechanism of action
inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophophate dehydrogenase
Ribavirin inhibits synthesis of …. by
- guanine nucleotides
- competitively inhibiting inosine monophophate dehydrogenase
Ribavirin - clinical use
- Chronic HCV
2. RSV (palivizumab is preferred in children)
Ribavirin - toxicity
- hemolytic anemia
2. severe teratogen
Simeprevir - mechanism of action
HCV protease inhibitor
prevents viral replication
Simeprevir - clinical use
Chronic HCV in combination with ledipasvir (NS5A inhibitor)
DO NOT USE AS MONOTHERPAY
Simeprevir - toxicity
- photosensitivity reaction
2. rash
Sofosbuvir - mechanism of action
inhibitis HCV RNA-dependent RNA polymerase acting as a chain terminator
Sofosbuvir - clinical use
Chronic HCV in combination with ribavirin +/- peginterferon alfa
DO NOT USE AS MONOTHERAPY
Sofosbuvir - side effects
fatique
headache
nausea
HIV therpay regimen
Highly active antiretrovial therapy (HAART)
HIV therpay - groups of drugs
- protease inhibitors
- Nucleoside Reverse Transcriptase Inhibitor (NRTI)
- Non-nucleoside reverse transcriptase inhibitors (NNRTI)
- Integrase inhibitors
- Fusion inhibitors
HAART - when to start
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
HAART regimen consist of
2NRTIs (Nucleoside Reverse Transcriptase Inhibitor) and 1 of the following: NNRT1 (Non-nucleoside reverse transcriptase inhibitors) or protease inhibitor or integrase inhibitor
Protease inhibitors - drugs
-NAVIR
HIV-1 Protease in encoded by
pol gene
HIV-1 Protease - function
assembly of virions depend on HIV-1 protease, which cleaves the polypeptide products of HIV mrna into theri functional parts
HIV Protease inhibitors - mechanism of action
inhibit HIV-protease –> prevents maturation of new viruses
HIV Protease inhibitors - toxicity
- hyperglycemia
- GI tolerance (nausea, vomiting)
- Lipodystrophy (Cushing-like syndrome)
- Nephropathy (indinavir)
- hematuria (indinavir)
- inhibit cytochrome P-450 (ritonavir)
HIV protease inhibitors with antimycobacterial drugs
Rifampin (a potent CYP/UGT inducer) contraindicated with proteae inhibitors because it can decrease protease inhibitor concentration
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - mechansim of action
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (Lack of OH group
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - drugs
- Abacavir (ABC)
- Didanosine (ddl)
- Emtricitabine (FTC)
- Lamivudine (3TC)
- Stavudine (d4T)
- Tenofovir (TDF)
- Zidovudine (ZDV, formerly AZT)
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - structure
Tenofovir –> nucleotide
the others –> nucleosides and need to be phosphorylated to be active
Zidovudine - special clinical use
general prophylaxis and during pregnancy to decrease risk of fetal transmission
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - side effects
- Bone marrow suppression
- peripheral neuropathy
- lactic acidosis (nucleosides)
- anemia (ZDV)
- pancreatitis (didanosine)
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - pancreatitis is caused by
didanosine
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - anemia is caused by
ZDV
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - lactic acidosis is caused by
nucleosides
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - how to prevent side effects
bone marrow suppression –> granulocyte colony stimulating factor (G-CSF) and erytrhopoietin)
Non-nucleoside reverse transcriptase inhibitors (NNRTI) - drugs
- Delavirdine
- Efavirenz
- Nevirapine
Non-nucleoside reverse transcriptase inhibitors (NNRTI) - drugs and mechanism of action
- 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
Non-nucleoside reverse transcriptase inhibitors (NNRTI) - toxicity
- rash
- hepatotoxicity
- vivid dreams (efavirenz)
- CNS sympoms (efavirenz)
- contraindicated in pregnancy (Delavirdine and efavirenz)
Non-nucleoside reverse transcriptase inhibitors (NNRTI) - which drugs are contraindicated in pregnancy
Delavirdine and efavirenz
HIV - integrase inhibitors - drugs?
- raltegravir
- Elvitegravir
- Dolutegravir
integrase inhibitors - mechanism of action
inhibits HIV genone integration into host cell chromosome by REVERSIBLY inhibiting HIV integrase
integrase inhibitors - toxicity
increased creatine kinase
HIV - fusion inhibitors - drugs
- Enfuvirtide
2. Maraviroc
HIV - fusion inhibitors - drugs and mechanism of action
- Enfuvirtide –> Binds gp41, inhibiting viral entry
2. Maraviroc –> Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120
HIV - fusion inhibitors - toxicity
skin reaction on injection sites (Enfuvirtide)
Abacavir - special characteristic of using
contraindicated if patients has HLA-B*5701 mutation
