Antiviral_part3_Flashcards
What type of virus is Hepatitis C Virus (HCV)?
RNA virus.
How many polyproteins does HCV encode, and how are they classified?
HCV encodes 10 polyproteins: 3 structural proteins and 7 nonstructural (NS) proteins, classified into 7 genotypes and several subtypes.
Which HCV genotypes are most prevalent globally and in Egypt/Middle East?
Genotype 1 is most prevalent worldwide, and Genotype 4 is predominant in Egypt and the Middle East.
What are the clinical findings and primary goal of treatment in HCV infection?
Clinical findings: Hepatitis, cirrhosis, and hepatocellular carcinoma. Primary goal: Viral eradication.
Name the three categories of antiviral drugs used for HCV.
- Direct-acting antiviral drugs (DAA). 2. Pegylated interferon (PEG-IFN) alpha. 3. Ribavirin.
What is the mechanism of action of Direct-Acting Antiviral Drugs (DAAs)?
DAAs act as inhibitors of non-structural proteins (NS), achieving high virological cure rates (>90%).
What factors determine drug selection in HCV treatment?
- Presence of cirrhosis. 2. Viral genotype. 3. Previous failure of therapy.
What is the duration of DAA therapy for HCV?
Treatment duration can range from 8, 12, 16, or 24 weeks (2 to 6 months).
What are the four current classes of DAAs, and what do they target?
Defined by their mechanism of action (MOA) and specific target.
Name one class of DAAs and its key drugs.
NS3/4A protease inhibitors: Asunaprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Voxilaprevir (e.g., Previr suffix).
What type of virus is Hepatitis B Virus (HBV), and what are its clinical findings?
Type: DNA virus. Clinical findings: Hepatitis, cirrhosis, and hepatocellular carcinoma.
What are the main drugs used to treat HBV infection?
- Interferons (Interferon-alfa, Pegylated interferon-alfa). 2. Nucleoside/Nucleotide analogs.
Name some examples of nucleoside and nucleotide analogs for HBV treatment.
Nucleoside analogs: Lamivudine, Entecavir, Telbivudine. Nucleotide analogs: Adefovir dipivoxil, Tenofovir disoproxil, Tenofovir alafenamide.
What is the mechanism of action of nucleoside/nucleotide analogs?
Require intracellular phosphorylation to be active. They inhibit HBV DNA polymerase, causing DNA chain termination.
What type of virus is HIV, and to which family does it belong?
Type: RNA virus. Family: Retroviruses.
What are the structural components of HIV?
Enveloped virus with a capsid containing two copies of RNA strands and associated protein (e.g., reverse transcriptase).
How does HIV replicate?
HIV converts RNA to DNA (via reverse transcriptase), integrates into the host genome, and then produces new viral RNA.
How many classes of antiretroviral drugs are used to treat HIV, and what is their primary goal?
Six classes, each targeting a specific step in the viral life cycle.
What is the primary toxicity of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)?
Mitochondrial toxicity due to inhibition of mitochondrial DNA polymerase gamma, potentially causing lactic acidosis with hepatic steatosis.
Name the NRTIs and their key side effects (S/E).
- Emtricitabine: Minimal side effects. 2. Lamivudine: Minimal side effects. 3. Tenofovir: Renal insufficiency and osteoporosis. 4. Abacavir: Hypersensitivity reaction (associated with HLA B*5701 allele). 5. Zidovudine: Macrocytic anemia and neutropenia. 6. Stavudine: Peripheral neuropathy, pancreatitis, lipoatrophy. 7. Didanosine: Peripheral neuropathy, pancreatitis, lipoatrophy.
What is a key metabolic feature of NRTIs?
NRTIs are not metabolized by cytochrome P450 enzymes, leading to minimal drug interactions.
What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors (NNRTIs)?
NNRTIs bind to and inhibit the reverse transcriptase enzyme, preventing viral RNA replication.
Name common NNRTIs and their key side effects.
- Nevirapine: Rash and hepatotoxicity. 2. Efavirenz: CNS symptoms (dizziness, impaired concentration, nightmares, insomnia, psychosis episodes). 3. Etravirine, Rilpivirine, Delavirdine: Generally milder side effects.
How are NNRTIs metabolized, and what are their interactions with CYP450?
Metabolized by CYP450. Nevirapine acts as an inducer. Delavirdine acts as an inhibitor. Efavirenz and Etravirine are mixed inducers and inhibitors.
What is a major limitation of NNRTIs regarding resistance?
NNRTIs have a low genetic barrier to resistance, meaning resistance may arise from a single mutation.
What are the mnemonic abbreviations for NRTIs?
Sta/Di/Zido/Aba/Te/La/Emtri (Stavudine, Didanosine, Zidovudine, Abacavir, Tenofovir, Lamivudine, Emtricitabine).
What is the role of pharmacological enhancers or boosters in antiretroviral therapy?
They: 1. Combine with certain antiretroviral drugs. 2. Act as inhibitors of CYP450. 3. Increase plasma concentrations of antiretroviral drugs. 4. Enhance drug exposure and decrease dosing frequency.
What is Cobicistat, and what is its primary function?
Cobicistat has no direct antiretroviral activity but is used as a pharmacological enhancer. Example: Elvitegravir-cobicistat.
What is Ritonavir, and how is it used in therapy?
Ritonavir is a protease inhibitor used at low doses to maintain therapeutic levels of other protease inhibitors in combination therapy.
