Antiviral_part3_Flashcards

1
Q

What type of virus is Hepatitis C Virus (HCV)?

A

RNA virus.

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2
Q

How many polyproteins does HCV encode, and how are they classified?

A

HCV encodes 10 polyproteins: 3 structural proteins and 7 nonstructural (NS) proteins, classified into 7 genotypes and several subtypes.

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3
Q

Which HCV genotypes are most prevalent globally and in Egypt/Middle East?

A

Genotype 1 is most prevalent worldwide, and Genotype 4 is predominant in Egypt and the Middle East.

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4
Q

What are the clinical findings and primary goal of treatment in HCV infection?

A

Clinical findings: Hepatitis, cirrhosis, and hepatocellular carcinoma. Primary goal: Viral eradication.

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5
Q

Name the three categories of antiviral drugs used for HCV.

A
  1. Direct-acting antiviral drugs (DAA). 2. Pegylated interferon (PEG-IFN) alpha. 3. Ribavirin.
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6
Q

What is the mechanism of action of Direct-Acting Antiviral Drugs (DAAs)?

A

DAAs act as inhibitors of non-structural proteins (NS), achieving high virological cure rates (>90%).

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7
Q

What factors determine drug selection in HCV treatment?

A
  1. Presence of cirrhosis. 2. Viral genotype. 3. Previous failure of therapy.
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8
Q

What is the duration of DAA therapy for HCV?

A

Treatment duration can range from 8, 12, 16, or 24 weeks (2 to 6 months).

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9
Q

What are the four current classes of DAAs, and what do they target?

A

Defined by their mechanism of action (MOA) and specific target.

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10
Q

Name one class of DAAs and its key drugs.

A

NS3/4A protease inhibitors: Asunaprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Voxilaprevir (e.g., Previr suffix).

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11
Q

What type of virus is Hepatitis B Virus (HBV), and what are its clinical findings?

A

Type: DNA virus. Clinical findings: Hepatitis, cirrhosis, and hepatocellular carcinoma.

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12
Q

What are the main drugs used to treat HBV infection?

A
  1. Interferons (Interferon-alfa, Pegylated interferon-alfa). 2. Nucleoside/Nucleotide analogs.
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13
Q

Name some examples of nucleoside and nucleotide analogs for HBV treatment.

A

Nucleoside analogs: Lamivudine, Entecavir, Telbivudine. Nucleotide analogs: Adefovir dipivoxil, Tenofovir disoproxil, Tenofovir alafenamide.

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14
Q

What is the mechanism of action of nucleoside/nucleotide analogs?

A

Require intracellular phosphorylation to be active. They inhibit HBV DNA polymerase, causing DNA chain termination.

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15
Q

What type of virus is HIV, and to which family does it belong?

A

Type: RNA virus. Family: Retroviruses.

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16
Q

What are the structural components of HIV?

A

Enveloped virus with a capsid containing two copies of RNA strands and associated protein (e.g., reverse transcriptase).

17
Q

How does HIV replicate?

A

HIV converts RNA to DNA (via reverse transcriptase), integrates into the host genome, and then produces new viral RNA.

18
Q

How many classes of antiretroviral drugs are used to treat HIV, and what is their primary goal?

A

Six classes, each targeting a specific step in the viral life cycle.

19
Q

What is the primary toxicity of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)?

A

Mitochondrial toxicity due to inhibition of mitochondrial DNA polymerase gamma, potentially causing lactic acidosis with hepatic steatosis.

20
Q

Name the NRTIs and their key side effects (S/E).

A
  1. 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.
21
Q

What is a key metabolic feature of NRTIs?

A

NRTIs are not metabolized by cytochrome P450 enzymes, leading to minimal drug interactions.

22
Q

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

A

NNRTIs bind to and inhibit the reverse transcriptase enzyme, preventing viral RNA replication.

23
Q

Name common NNRTIs and their key side effects.

A
  1. Nevirapine: Rash and hepatotoxicity. 2. Efavirenz: CNS symptoms (dizziness, impaired concentration, nightmares, insomnia, psychosis episodes). 3. Etravirine, Rilpivirine, Delavirdine: Generally milder side effects.
24
Q

How are NNRTIs metabolized, and what are their interactions with CYP450?

A

Metabolized by CYP450. Nevirapine acts as an inducer. Delavirdine acts as an inhibitor. Efavirenz and Etravirine are mixed inducers and inhibitors.

25
Q

What is a major limitation of NNRTIs regarding resistance?

A

NNRTIs have a low genetic barrier to resistance, meaning resistance may arise from a single mutation.

26
Q

What are the mnemonic abbreviations for NRTIs?

A

Sta/Di/Zido/Aba/Te/La/Emtri (Stavudine, Didanosine, Zidovudine, Abacavir, Tenofovir, Lamivudine, Emtricitabine).

27
Q

What is the role of pharmacological enhancers or boosters in antiretroviral therapy?

A

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.

28
Q

What is Cobicistat, and what is its primary function?

A

Cobicistat has no direct antiretroviral activity but is used as a pharmacological enhancer. Example: Elvitegravir-cobicistat.

29
Q

What is Ritonavir, and how is it used in therapy?

A

Ritonavir is a protease inhibitor used at low doses to maintain therapeutic levels of other protease inhibitors in combination therapy.