Flashcards
Antiviral Drugs and AIDS
Cards in this deck (27)
- 1HIV Life Cycle1) Attachment of virus at the CD4 receptor
2) Viral fusion and uncoating
3) Reserve transcriptase makes a single DNA copy of the viral RNA and then makes another to form a double stranded viral DNA and migrates to nucleus
4) Transcription and RNA processing
5) Protease enzyme cleaves polypeptides into functional HIV proteins
6) Virion budding and maturation - 2Classes of Drugs in Clinical Use1) Nucleoside and nucleotide Reverse Transcriptase (NRTIs) Inhibitors
2) Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
3)Protease Inhibitors
4) Entry Inhibitors
5) Integrase Inhibitors
6) Investigational Agents - 32 Drug Regimen Post Exposure Prophylaxis (PEP)Retrovir (zidovudine) + Epivir (lamivudine) twice daily
This combination preparation is recommended in pregnancy - 43 Drug Regimens Post Exposure Prophylaxis (PEP)Retrovir (Zidovudine) + Epivir (Lamivudine) twice daily + Kaletra (Lopinavir + Ritonavir) twice daily.
- 5Nucleoside and nucleotide reverse transcriptase (NRTIs) inhibitors Drug ExamplesZidovudine
Lamivudine - 6Nucleoside and nucleotide reverse transcriptase (NRTIs) inhibitors Zidovudine, Lamivudine InformationActs as chain terminators or inhibitors at the substrate binding site of Reverse
Transcriptase
Imitate Adenosine, Guanine, Thymidine, Cytosine
Incorporate into the growing DNA and inhibit chain formation
All NRTIs have mitochondrial toxicity
Epivir (Lamivudine), Abacavir, Didanosine - 7Nucleoside and nucleotide reverse transcriptase (NRTIs) inhibitors Adverse Drug ReactionsLactic acidosis, Dyslipidemia, and Insulin Resistance may occur.
- 8First anti-HIV drug approvedNRTI known as ASZT or Zidovudine (1987)
- 9Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) ExamplesNevirapine
Efavirenz - 10Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) MOAReverse Transcriptase inhibitors (NNRTIs) inhibit viral DNA replication by binding to reverse transcriptase, and inhibit DNA polymerase
- 11Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) Adverse ReactionsGI disturbances, skin rashes, SJS
- 12Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) MetabolismMetabolized by CYP450 enzyme system and may be inducers or inhibitors, thus the drug interactions
- 13Protease Inhibitors (PIs) ExamplesRitonavir
Indinavir - 14Protease Inhibitors (PIs) MOADuring the reproduction cycle of HIV a specific protease is needed to form mature HIV components
If protease is missing, noninfectious HIV bud are produced
HIV protease inhibitors are specific to HIV protease because it differs significantly from human protease - 15Protease Inhibitors (PIs) Adverse Effects"Cushing" like Syndrome
- 16Entry Inhibitors ExampleEnfuvirtide
- 17Entry Inhibitors MOAEnfuvirtide is a synthetic peptide which block entry of the virus into cell, by preventing conformational change
Binding of the HIV virus to the CD4 lymphocyte receptor is the first step to viral replication
This binding causes a conformational change to the site and allows the viral envelope to fuse w/ cell membrane - 18Entry Inhibitor DeliveryMust be given by subcutaneous injection and is not subject to hepatic enzyme degradation
- 19Entry Inhibitors Adverse EffectsLocal injection site reaction may occur
Eosinophilia and hypersensitivity reaction may occur - 20Integrase Inhibitors ExampleRaltegravir
- 21Integrase Inhibitors MOAIntegrase is a viral enzyme essential for HIV replication
Promotes the integration of viral DNA strands into the host DNA
Raltegravir is a pyrimidine analog that binds integrase and prevents the action
Used in adults patients resistant to other agents - 22Investigational Agents Bevirimat, TNX-355New agents claim better activity, lesser side effects and convenient dosing. Virus maturation inhibitors [Bevirimat], CD4 Receptor Inhibitor (TNX-355)
- 23Antiretroviral Therapy GuidelinesShould be initiated in all patients with a hx of an AIDS-defining illness or with CD4 count <200 cells/mm3
- 24Conditions during which Antiretroviral Therapy should always be initiated regardless of CD4 countPregnancy, HIV-associated nephropathy, HBV co-infection
- 25Highly Active Anti-Retroviral Therapy (HAART) Initial Regimine2 NRTIs w/ an NNTI or a Ritronavir-boosted PI or an Integrase inhibitor
- 26Highly Active Anti-Retroviral Therapy (HAART) Treatment GoalsIn antiretroviral therapy failure, the goal of subsequent tx is suppression of HIV-1 RNA to below detection levels
- 27Highly Active Anti-Retroviral Therapy (HAART) Suggested Combos and RestrictionsTenofovir/Emtricitrabine (a combination of two NRTIs) and Efavirenz (NNRTI)
Efavirenz should not be given to a pregnant women
Tenofovir/emtricitabine and Raltegavir (an Integrase inhibitor)
Tenovir/emtricitabine, Ritonavir and Darunavir (Protease inhibitors)