Save
Busy. Please wait.
Log in with Clever
or
show password
Forgot Password?
Don't have an account?  Sign up 
Sign up using Clever
or
Username is available taken
show password


Make sure to remember your password. If you forget it there is no way for StudyStack to send you a reset link. You would need to create a new account. Your email address is only used to allow you to reset your password. See our Privacy Policy and Terms of Service.

Already a StudyStack user? Log In

Reset Password
Enter the associated with your account, and we'll email you a link to reset your password.
focusNode
Didn't know it?
click below
 
Knew it?
click below
Don't Know
Remaining cards (0)
Know
0:00
edit
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.

  Normal Size     Small Size show me how

ARV Exam 1

HIV Anti-retroviral Drugs KirkPatrick Guest lecture

GenericBrandAnalog/ MOADrug ClassAdverse EffectsClinical PearlsResistance
Abacavir (ABC) Ziagen Guanosine; Compete for incoporation into the growing vDNA chain by HIV RT; Lack a 3'OH group and thus additional nucleotides cannot be bonded to the NRTI, resulting in DNA chain termination after incorporation by HIV RT NRTI Lipoatrophy, HEPATOMEGALY w/ STEATOSIS, lactic acidosis, neuropathy; DI: Do not inhibit or induce CYP450 interactions HLA-B *5701 screening; if +, high risk of hypersensitivity rxn -consider avoiding w/ CVD due to potential increased risk of MI; No renal adjustment Low barrier to resistance
Emtricitabine (FTC)^a (a—> clinical activity against Hepatitis B virus (HBV)) Emtriva Cytosine; Compete for incoporation into the growing vDNA chain by HIV RT; Lack a 3'OH group and thus additional nucleotides cannot be bonded to the NRTI, resulting in DNA chain termination after incorporation by HIV RT NRTI Lipoatrophy, HEPATOMEGALY w/ STEATOSIS, lactic acidosis, neuropathy; DI: Do not inhibit or induce CYP450 interactions Hyperpigmentation of palms and soles of feet; Severe exacerbation of HBV on discontinuation if active HBV Low barrier to resistance
Lamivudine (3TC)^a (a—> clinical activity against Hepatitis B virus (HBV)) Epivir Cytosine; Compete for incoporation into the growing vDNA chain by HIV RT; Lack a 3'OH group and thus additional nucleotides cannot be bonded to the NRTI, resulting in DNA chain termination after incorporation by HIV RT NRTI Lipoatrophy, HEPATOMEGALY w/ STEATOSIS, lactic acidosis, neuropathy; DI: Do not inhibit or induce CYP450 interactions Severe exacerbation of HBV on discontinuation if active HBV Low barrier to resistance
Tenofovir alafenamide (TAF)^a (a—> clinical activity against Hepatitis B virus (HBV)) *TAF only available in combo products for HIV Vemlidy Adenosine; Compete for incoporation into the growing vDNA chain by HIV RT; Lack a 3'OH group and thus additional nucleotides cannot be bonded to the NRTI, resulting in DNA chain termination after incorporation by HIV RT NRTI Lipoatrophy, HEPATOMEGALY w/ STEATOSIS, lactic acidosis, neuropathy; DI: Do not inhibit or induce CYP450 interactions Severe exacerbation of HBV on discontinuation if active HBV; Lipid abnormalities; weight gain when combined with INSTIs; increasing in popularity Low barrier to resistance
Tenofovir disoproxil fumarate (TDF)^a (a—> clinical activity against Hepatitis B virus (HBV)) Viread^b (b—> available for treatment of HBV) Adenosine; Compete for incoporation into the growing vDNA chain by HIV RT; Lack a 3'OH group and thus additional nucleotides cannot be bonded to the NRTI, resulting in DNA chain termination after incorporation by HIV RT NRTI Lipoatrophy, HEPATOMEGALY w/ STEATOSIS, lactic acidosis, neuropathy; DI: Do not inhibit or induce CYP450 interactions Severe exacerbation of HBV on discontinuation if active HBV; renal impairment (AKI, Fanconi syndrome); Bone demineralization; Decreasing in popularity Low barrier to resistance
Zidovudine (AZT) Retrovir Thymine; Compete for incoporation into the growing vDNA chain by HIV RT; Lack a 3'OH group and thus additional nucleotides cannot be bonded to the NRTI, resulting in DNA chain termination after incorporation by HIV RT NRTI Lipoatrophy, HEPATOMEGALY w/ STEATOSIS, lactic acidosis, neuropathy; DI: Do not inhibit or induce CYP450 interactions BBW for hematologist toxicities (neutropenia and anemia); increase MCV sign of adherence; Myopathy; still given IV during labor in pts w/ HIV and VL > 1000 copies/mL to prevent perinatal transmission Low barrier to resistance
Efavirenz (EFV) Sustiva Bind to a hydrophobic pocket on HIV RT near the active polymerase site; binding causes a conformational change in the polymerase domain, reducing its ability to bind to host nucleotides (stopping HIV RT); *NNRTI are not incorporated into vDNA NNRTI Rash (SJS/TEN); Hepatotoxicity (NVP highest risk); Abnormal dreams; Neuropsychiatric; QTc prolongation; Hyperlipidemia; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Psychiatric symptoms (depression, suicide); CNS effects (impaired concentration, abnormal dreams, confusion)- take on empty stomach and at bedtime to avoid CNS effects; increases total cholesterol, triglycerides Lowest barrier to resistance
Rilpivirine (RPV) Edurant Bind to a hydrophobic pocket on HIV RT near the active polymerase site; binding causes a conformational change in the polymerase domain, reducing its ability to bind to host nucleotides (stopping HIV RT); *NNRTI are not incorporated into vDNA NNRTI Rash (SJS/TEN); Hepatotoxicity (NVP highest risk); Abnormal dreams; Neuropsychiatric; QTc prolongation; Hyperlipidemia; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Do not use if HIV viral load > 100,000 copies/ml or CD4 count <200 cells/mm^3 due to increased risk of failure; DEPRESSION; Requires minimum of 500 calories for absorption; Rilpivirine NEEDS an acidic environment for absorption; DI: PPI (contraindicated); Pepcid (take 12h b4 or 4h after rilpivirine; Antacids: (Take 2h b4 or 4h after) Lowest barrier to resistance
Doravirine (DOR) Pifeltro Bind to a hydrophobic pocket on HIV RT near the active polymerase site; binding causes a conformational change in the polymerase domain, reducing its ability to bind to host nucleotides (stopping HIV RT); *NNRTI are not incorporated into vDNA NNRTI Rash (SJS/TEN); Hepatotoxicity (NVP highest risk); Abnormal dreams; Neuropsychiatric; QTc prolongation; Hyperlipidemia; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Lowest barrier to resistance
Etravirine (ETR) Intelence Bind to a hydrophobic pocket on HIV RT near the active polymerase site; binding causes a conformational change in the polymerase domain, reducing its ability to bind to host nucleotides (stopping HIV RT); *NNRTI are not incorporated into vDNA NNRTI Rash (SJS/TEN); Hepatotoxicity (NVP highest risk); Abnormal dreams; Neuropsychiatric; QTc prolongation; Hyperlipidemia; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Lowest barrier to resistance
Nevirapine (NVP) Viramune Bind to a hydrophobic pocket on HIV RT near the active polymerase site; binding causes a conformational change in the polymerase domain, reducing its ability to bind to host nucleotides (stopping HIV RT); *NNRTI are not incorporated into vDNA NNRTI Rash (SJS/TEN); Hepatotoxicity (NVP highest risk); Abnormal dreams; Neuropsychiatric; QTc prolongation; Hyperlipidemia; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers ** highest risk for hepatotoxicity Lowest barrier to resistance
Bictegravir (BIC) Biktarvy catalytic core of the HIV Integrase contains 3 AA that coordinate binding with a divalent metal; INSTIs only bind to the integrase enzyme when it is attached to vDNA; diketo acid group of INSTI binds to cation in active site of HIV integrase, displace 3'OH, interrupting the integration process INSTI Headache, Weight gain, Depression (rare), Insomnia, Diarrhea, Myopathy; DDI: Limited CYP450, Interactions with polyvalent cations— must separate, EVG requires a PK booster Increases SCr without change in GFR; Weight gain; All INSTIs interact w/ polyvalent cations (Al3+, Mg2+, Ca2+, Fe2+, Zn2+; Binding interaction leads to less/no absorption; For all INSTIs: take 2h before or 6h after products containing polyvalent cations like antacids, multi vitamins and other supplements; BIC and DTG can be taken w/ Ca2+ or Fe2+ if done w/ food* High barrier to resistance
Elvitegravir (EVG) Genvoya, Stribild catalytic core of the HIV Integrase contains 3 AA that coordinate binding with a divalent metal; INSTIs only bind to the integrase enzyme when it is attached to vDNA; diketo acid group of INSTI binds to cation in active site of HIV integrase, displace 3'OH, interrupting the integration process INSTI Headache, Weight gain, Depression (rare), Insomnia, Diarrhea, Myopathy; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Only boosted INSTI—> similar DDI issues to the PI’s High barrier to resistance
Dolutegravir (DTG) Tivicay catalytic core of the HIV Integrase contains 3 AA that coordinate binding with a divalent metal; INSTIs only bind to the integrase enzyme when it is attached to vDNA; diketo acid group of INSTI binds to cation in active site of HIV integrase, displace 3'OH, interrupting the integration process INSTI Headache, Weight gain, Depression (rare), Insomnia, Diarrhea, Myopathy; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Increases SCr without change in GFR; Increases CPK, myopathy, and rhabdo, weight gain, Dosed BID for resistance or if DDI w/ CYP3A4 and/or UGT1A1 inducers; preferred ART in pregnancy High barrier to resistance
Raltegravir (RAL) Isentress, Isentress HD catalytic core of the HIV Integrase contains 3 AA that coordinate binding with a divalent metal; INSTIs only bind to the integrase enzyme when it is attached to vDNA; diketo acid group of INSTI binds to cation in active site of HIV integrase, displace 3'OH, interrupting the integration process INSTI Headache, Weight gain, Depression (rare), Insomnia, Diarrhea, Myopathy; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Increases CPK, myopathy, and rhabdo; Hypersensitivity rxn; Dose separation may not work for raltegravir—> avoid polyvalent cations High barrier to resistance
Cabotegravir Vocalbria (oral), Apretude (IM) catalytic core of the HIV Integrase contains 3 AA that coordinate binding with a divalent metal; INSTIs only bind to the integrase enzyme when it is attached to vDNA; diketo acid group of INSTI binds to cation in active site of HIV integrase, displace 3'OH, interrupting the integration process INSTI Headache, Weight gain, Depression (rare), Insomnia, Diarrhea, Myopathy; DDI: All—> major CYP3A4 substrates; EFV and ETR—> moderate CYP3A4 inducers Oral only indicated for lead-in therapy to assess tolerability of cabotegravir (Apretude) and cabotegravir/rilpivirine (Cabenuva) injections; injection site rxn common High barrier to resistance
Atazanavir (ATV) Reyataz Competitive Inhibition; Protease enzyme is made up of 2 identical subunits that exist together in 3 major conformational forms: open, semi-open, or closed; HIV PIs bind to active site, preventing cleavage of viral gag and gag-pol --> resulting in immature, noninfectious viral particles PI Hyperlipidemia, Hyperglycemia/ Insulin resistance; Weight gain; Rash (SJS/TENS); Hepatotoxicity; Hypertension; Lipodystrophy; ECG changes; Diarrhea; Nausea; DDI: Must be taken with a PK booster; CYP3A4, CYP2D6, CYP2C8; CYP2C9, and PgP--> monitor for interactions! Must be taken w/ food ATV (acidic environment for absorption and contraindication with PPIs); -Hyperbilirubinemia (scleral icterus, jaundice)- high bilirubin is a =marker of adherence; -Requires acidic gut for absoprtion Highest barrier to resistance
Darunavir (DRV) Prezista Competitive Inhibition; Protease enzyme is made up of 2 identical subunits that exist together in 3 major conformational forms: open, semi-open, or closed; HIV PIs bind to active site, preventing cleavage of viral gag and gag-pol --> resulting in immature, noninfectious viral particles PI Hyperlipidemia, Hyperglycemia/ Insulin resistance; Weight gain; Rash (SJS/TENS); Hepatotoxicity; Hypertension; Lipodystrophy; ECG changes; Diarrhea; Nausea; DDI: Must be taken with a PK booster; CYP3A4, CYP2D6, CYP2C8; CYP2C9, and PgP--> monitor for interactions! Must be taken w/ food Caution with SULFA allergy (*sulfa moiety but not same as Bactrim Highest barrier to resistance
Ritonavir (RTV) Norvir Competitive Inhibition; Protease enzyme is made up of 2 identical subunits that exist together in 3 major conformational forms: open, semi-open, or closed; HIV PIs bind to active site, preventing cleavage of viral gag and gag-pol --> resulting in immature, noninfectious viral particles PI Hyperlipidemia, Hyperglycemia/ Insulin resistance; Weight gain; Rash (SJS/TENS); Hepatotoxicity; Hypertension; Lipodystrophy; ECG changes; Diarrhea; Nausea; DDI: Must be taken with a PK booster; CYP3A4, CYP2D6, CYP2C8; CYP2C9, and PgP--> monitor for interactions! Must be taken w/ food **Purposeful drug interaction; strong inhibitors of 3A4 and P-gp; increase levels of PIs through inhibition of metabolism; Prolong half-life elimination; -Consequences: Increased serum conc. of other medications Highest barrier to resistance
Lopinavir (LPV) Kaletra Competitive Inhibition; Protease enzyme is made up of 2 identical subunits that exist together in 3 major conformational forms: open, semi-open, or closed; HIV PIs bind to active site, preventing cleavage of viral gag and gag-pol --> resulting in immature, noninfectious viral particles PI Hyperlipidemia, Hyperglycemia/ Insulin resistance; Weight gain; Rash (SJS/TENS); Hepatotoxicity; Hypertension; Lipodystrophy; ECG changes; Diarrhea; Nausea; DDI: Must be taken with a PK booster; CYP3A4, CYP2D6, CYP2C8; CYP2C9, and PgP--> monitor for interactions! Must be taken w/ food Highest barrier to resistance
Maraviroc (oral) CCR5 Antgagonist Entry and attachment Inhibitor Hepatotoxicity (BBW), CV events (MI), orthostatic HOTN in renal impairmen; SJS/TEN; CI: CrCl >/= 30 Requires tropism assay; only effective if HIV strain binds to CCR5 co-receptor; if HIV strain can bind to CXCR4 or mixed (CR5/CR4) maraviroc will not work and HIV will still be able to enter CD4 cell Tropism; Co-receptor Tropism
Fostemsavir (oral) Attachment Inhibitor Entry and attachment inhibitor Do not use with 3A4 inducers; Can increase SCr Used in combination with other ART in heavily treatment experienced patients failing therapy
Ibalizumabuiyk (IV) Post-Attachment Inhibitor Entry and attachment inhibitor Infusion reaction, diarrhea, dizziness, nausea, rash Used in combination with other ART in heavily treatment experienced patients failing therapy
Enfuvirtide Fusion Inhibitor Entry and attachment inhibitor Bacterial pneumonia, hypersensitivity rxn, injection site rxn (pain, erythema), nodules, reported in nearly all patients) Must be reconstituted and used within 24 hours
Lenacapavir (LEN) Sunlenca Capsid inhibitor; Approved for heavily treatment -experienced pts with multi-drug resistant HIV-1 infection -In clinical trials for PrEP Capsid Inhibitor AE: injection site rxn; N/Constipation/D/headache Admin and dosing: Lenacapavir 927 mg (2 x 1.5 mL) SQ injections once every 6 months; initially requires initiation with oral loading doses;
Created by: Xander635
Popular Pharmacology sets

 

 



Voices

Use these flashcards to help memorize information. Look at the large card and try to recall what is on the other side. Then click the card to flip it. If you knew the answer, click the green Know box. Otherwise, click the red Don't know box.

When you've placed seven or more cards in the Don't know box, click "retry" to try those cards again.

If you've accidentally put the card in the wrong box, just click on the card to take it out of the box.

You can also use your keyboard to move the cards as follows:

If you are logged in to your account, this website will remember which cards you know and don't know so that they are in the same box the next time you log in.

When you need a break, try one of the other activities listed below the flashcards like Matching, Snowman, or Hungry Bug. Although it may feel like you're playing a game, your brain is still making more connections with the information to help you out.

To see how well you know the information, try the Quiz or Test activity.

Pass complete!
"Know" box contains:
Time elapsed:
Retries:
restart all cards