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Flashcards in HIV drugs Deck (15):

Fusion Inhibitor

Enfuvirtide/ Fuzeon


Enfuvirtide/ Fuzeon

-Class: fusion inhibitors
-MOA: bind gp41
- Inhibit binding and fusion of virus to host cell
- It’s a protein
-Admin: SC injection 2x/day
-difficult to use -
-not yet recommended for use
-used in patients that are resistant to other meds
-AE: Local injection site reaction
-Increased rate of bacterial pneumonia
-Hypersensitivity reaction


CCR5 antagonist




-Class: CCR5 antagonist
-MOA: blocks co-receptor and thus prevents entry of the virus
→only works against HIV that is CCR5-tropic (there is a test to see if given strain of HIV virus is in this category)
-USE: in cases of resistance to other drugs
→ not part of a standard regiment
-AE: cough, fever, rash, URI, MSK symptoms, abdominal pain, postural dizziness
-chance of hepatotoxicity and CV events
-metabolized by cp450 and so its metabolism may be affected by enzyme inducers and inhibitors


Integrase inhibitor




-Class: Integrase inhibitor
-MOA: targets the viral integrase
-USE: patients who have failed other treatments due to resistance
-beginning to be used in combination with 2 NRTIs in initial treatment
-drug interactions: Rifampin can enhance elimination of raltegravir via enhance glucuronidation
-divalent cations (ie in antacid) may bind raltegravir and inhibit its action
-AE are minor: diarrhea, nausea, headache


Nucleoside analogues (NRTI)

Zidovudine (AZT)
Stavudine (d4T)
Lamivudine (3TC)
Abacavir (ABC)


Zidovudine (AZT)
Stavudine (d4T)
Lamivudine (3TC)
Abacavir (ABC)

-Class: Nucleoside analogues (NRTI)
-MOA: *Inhibit reverse transcription→chain termination
- 2’3’ dideoxyanalogues phosphorylated to triphospates via host cellular kinases
- Reverse Transcriptase is more susceptible to drug than host DNA polymerase
- drug also cause chain termination of DNA as it is being transcribed from RNA
- Pharm: eliminated by kidney → require dosage adjustment in renal insufficiency
- 2 NRTIs would compete with each other so don’t give 2 at the same time → they also can have additive toxicity
-USE: 1st line therapy
-AE: Mitochondrial toxicity and lactic acidosis → low frequency but high risk
-Mitochondrial DNA pol. is sensitive to drug →defective mito DNA→defective ATP produced→abnormal ox-phos→lactate production
• myalgias, proximal muscle wasting
• pancreatitis,
• peripheral neuropathy,
• myopathy,
• cardiomyopathy,
• hepatic stenosis,
• lipid dystrophy, tissue lipoatrophy (fat loss)

Zidovudine: AE → anemia + neutropenia
Abacavir: AE → Hypersensitivity, not related to mit toxicity
-inhibitors of cyp450 can increase level of some drugs in this class, including AZT; inducers of cyp450 such as rifampin can decrease levels


Nucleotide analogue




-Class: Nucleotide analogue
-MOA: *Inhibit reverse transcription
- Same MOA as nucleoside analogue, but does not need to be phosphorylated
-AE: Weakness, Headache, Diarrhea
-AE due to mit toxicity have not been reported!


Non- nucleoside reverse transcriptase inhibitors (NNRTI)




-Class: Non- nucleoside reverse transcriptase inhibitors (NNRTI)
-MOA: inhibit reverse transcriptase but NOT by interacting at active site of enzyme → inhibit by different mechanism so can combine with nucleoside analogue to reduce viral load → NO chain termination
-Mixed inducer-inhibitor of Cyp450 and CYP3A with Efavirenz
-CYP450 3A inducer with Nevirapine
-CYP450 3A inhibitor with Delavirdine
-USE: Efavirenz and Nevirapine are inducers → they may ↓ levels of protease inhibitors
-AE: Efavirenz: CNS—dizziness, vivid dreams, ; ↑ transaminase; teratogen
Rash— can get Steven-Johnson syndrome → more common with Nevirapine
Hepatitis— seen esp. w/ Nevirapine early in treatment (drug is a substrate for cyp450 and an inducer)


Protease inhibitor




-Class: Protease inhibitor
-MOAL Normally: proteases chop up larger proteins used in viral assembly → HIV virus contains an aspartate protease (pol gene encoded) that contain a dipeptide structure not seen in humans → protease inhibitors block this dipeptide region
- they are competitive enzyme inhibitors
- P450 inhibitors→drug interactions
-AE: GI tolerance (Nausea, Vomiting, Diarrhea)
- Hyperglycemia, insulin resistance, decreased glucose tolerance, new onset of DBM, diabetic ketoacidosis → monitor diabetics + be aware of new onset diabetes (polydipsia, polyphagia, polyuria)
- Lipodystrophy: changes in fat distribution
• peripheral fat wasting
• central fat accumulation
• look like Cushings pts
- Hyperlipidemia → esp. Ritonavir (may get cardio problems or pancreatitis)
- Hepatotoxicity— ↑ transaminase levels → may or may not get hepatitis
- Osteonecrosis, osteopenia, osteoporosis


Preferred combinations: the way to go!

-Non-Nucleoside Reverse Transcriptase Inhibitors based regimen: efavirenz + lamivudine/zidovudine + (tenofovir/stavudine)→except for pregnant woman or women w/ pregnancy potential!

-Protease Inhibitor based regimen: lopinavir/ritonavir + (lamivudine/ zidovudine or tenofovir/emtricitabine)

-Integrase-based regimen: Raltegravir + (tenofovir/emtricitabine or zidovudine/lamivudine)

-Truvada: tenofivir/emtricitabine → daily dosing prophylactically can reduce infection rate among those at high risk of contracting the virus by almost 70%