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Stack #209882
HIV Drugs
| Question | Answer |
|---|---|
| What cells express CD4 receptors and :: are infected with HIV ? | 1) T-Lymphocytes (T-Helper Cells)__2)Monocytes__3)__Dendritic Cells__3)Brain Microganglia |
| How does Acute HIV present? | S/Sx include RASH,fever,sore throat, myalgia, lymphadenopathy |
| HIV Set Point | Virus replicates and reaches a set point takes about a yr to reach constant set point. Higher set Points = rapid progression to AIDs |
| How Does Chronic HIV present? | Usually as opportunistic infections. |
| AIDS = CD4 count of _____ OR a AIDs Defining Illness | <200 cells/uL (takes about 10 yrs) |
| Name 6 Complications of Chronic HIV Infection | 1) Infections (OI, TB, HSV, Thrush)__2)Cancer (Kaposis sarcoma, lymphoma)__3)Neurological(encephalopathy)__4)Hematopoeittic (neutropenia, throbocytopenia, anemia)__5)Renal (neprhopathy)__6)Cardiovascular(cardiomyopathy) |
| Normal Adult CD4 count | 500-1600 cells/uL (40-70% of all lymphocytes) |
| What is the difference between genotypic and phenotypic HIV resistance testing? | Genotypic uses gene amplification to determine if HIV has a predocumented type of mutation. ___Phenotypic resistance is tested by measuring effectiveness of standard drug [ ] on cultured HIV (less preferred) |
| Can ART therapy be stopped? | Interruptions of ART is NOT recommended except for serious toxicities of inability to take oral meds. Usually causes immediate virologic rebound and CD4 decline. |
| 5 Indications for initiating ART | 1) Hx of AIDS defining illness__2)CD4<3250__ 3)Pregnant women__ 4)HIV nephropathy__5)Hep B coinfection when HBV tx is indicated |
| Nucleoside Reverse Transcriptase Inhibitors (NRTI)___ MOA | compete for reverse transcriptase w/ endogenous nucleotides (leads to early DNA termination after integration) |
| NRTI Class Side Affects | Lactic Acidosis, Pancreatitis, Lipoatrophy(due to mitochondrial toxicity) |
| Zidovudine | NRTI____BMS, Myopathies __ Don't use w/ Stavudine |
| Lamivudine | NRTI____Well tolerated (1st Line)__Don't use w/ Emtricitabine |
| Emtricitabine | NRTI___Well tolerated (1st line) skin hypersensitization__Don't use w/ Lamivudine |
| Stavudine | NRTI___Peripheral Neuropathy, Myopathies__don't use with Zidovudine or Didanosine |
| Didanosine | NRTI___Peripheral Neuropathy__N/D |
| Abacavir | NRTI___Hypersensitivity that can be FATAL upon rechallenge *HLA-B*5701 testing*, cardiac disease |
| Tenofovir | NRTI___NVD, Renal dysfunction, well Tolerated |
| Non-Nucleoside Reverse Transcriptaes Inhibitors (NNRTI)___MOA | Binds non-competitively to reverse transcriptase causing conformational change that halts enzyme activity |
| NNRTI Side Effects | Rash (common, All effect CYP450 NZ |
| Efavirenz | NNRTI___1st Line, CNS effects common :: don't use in pysch cases, P450 inducer, |
| Neviripine | NNRTI___Hepatitis(common), AVOID if CD4 >400 men or >250 in women to avoid hepatotoxicity, used peri partum, P450 inducer |
| Delaviridine | NNRTI___Hepatotoxic*, P450 inducer, NOT USED CLINICALLY |
| Etravirine | NNRTI (2nd Gen)___many DI, Avoid w/ ATV, FPV, TPV, unboosted PI, and NNRTIs, *2nd Line Agent* |
| Protease Inhibitors (PI)___ MOA | Inhibit Protease which cleaves the idividual virus components; prevents viral maturation |
| PI Class Effects | GI Intolerance, Lipodystrophy, hyperlipidemia, hyperglycemia, hepatotoxicity, Pancreatitis (less common) |
| Ritonavir | PI___paresthesis, taste changes, very potent P450 inhibitor, Now ONLY for BOOSTING |
| Atavanavir | PI___ Requires ACIDIC environment for absorption, No documented lipid abnormalities w/o ritonavir |
| Lopinavir | PI___Always given w/ ritonavir and can be given once or twice daily. |
| Darunavir | PI___Contains sulfa moiety |
| Fosamprenavir | PI___contains sulfa moeity, prodrug of amprenavir requires less frequent dosing |
| Tipranavir | PI___only approved for ART experianced patients |
| Indinavir | PI___kidney stones, alopecia, dry skin, Hyperbilirubinemia with atazanavir DO NOT USE TOGETHER. (hardly used anymore) |
| Saquinavir | PI___Reformulated but still barely used |
| Amprenavir | PI___use replaced by foramprenavir |
| Enfurvitide | Fusion Inhibitor___SubCut ONLY Bid, inj. site rxn, no known drug interactions, ART EXPERIANCED ONLY |
| Maraviroc | CCR5 Receptor Antagonist___Only used in pt w/ CCR5 tropic virus (must assay pt), hepatotoxicity, allergic rxn, CYP3A4 substrate, ART EXPERIANCED PT ONLY |
| Raltegravir | Integrase Inhibitor (prevents integrase from incoporating viral DNA into host), ND, HA, CK elevations, *NO P450 Metab** ONLY ART EXPERIANCED PT |
| What is the general Initial Treatment Regimen? | 2NRTIs + NNRTI OR PI(fusion inhibtor, CCR5 antagonist, and integrase inhibitor not recommended in initial ART) |
| Considerations in Choosing dosing regimen | comorbidities, adherence potential, dosing convenience, ade, DI, pregnancy potential, drug resistance, gender and CD4 if considering neviripine, HLAB*5701 if considering abacavir |
| Advantages of NNRTI | long half lives, less metabolic toxicity than PI, preserves PI options for future |
| Disadvantages of NNRTI | lower genetic barrier to resistance, cross-resistance amongst most NNRTI, rash, hepatotoxicity, DI (not as bad as PI) |
| Advantages of PI | higher genetic barrier to resistance, NNRTI options preserved for future use |
| Disadvantages of PI | metabolic complications, GI intolerance, DI* |
| Advantages of NRTI | established backbone of combo tx, minimal drug interactions, well tolerated |
| Disadvantages | lactic acidosis, hepatic steatosis(rare), ade of specific agents, mitochodrial disadvantages |
| When do you change regimens? | Virologic Failure, Immunologic failure, Clinical progression, Intolerable side effects |
| Virologic Failure | HIV RNA >400 after 24 wks___>50 after 48 wks___>400 after viral suppresion |
| Immunologic Failure | Failure to achieve and maintain adequate CD4 count despite viral suppression |
| Clinical Progression | Occurence of HIV related events >=3 months on therapy |
| Baseline Monitoring Parameters while on ART | CD4 count, Plasma HIV RNA, Lipids, Chem 7 , LFT, CBC/diff, other infections, resistance testing if HIV RNA >500-1000c/ml, HLA-B*5701 if using abacavir |
| Monitoring at 2 wks | Adherence, ADE, Consider VL and CD4 count (VL dec of 0.5log) |
| Monitoring at 4 wks | Adherence, ADE, VL should see a dec of AT LEAST 1 log |
| Once Stable Monitoring Q 3 months | VL, CD4, Chem-7, LFTs, CBC, ADE, adherence ALWAYS monitor for OI, ADE, ADherence |
| Virologic Failure--> what do you do? | 1) Assess drug resisance__ 2) Goal is max virologic supp of <50c/ml__3) Base ARV selection on med hx, resistance, tolerability, adherence, future tx options__3) AVOID tx interuption may cause viral rebound, immune decompensation, clinical progression |
| How do you change Regimen in Virologic Failure? | 1) Add at least 2 (pref 3) fully active agents to an optimized backround ARV regimen.__Consider potent RTV boosted PI, new MOA (fusion inhib etc)__ One active drug should NOT be added--> add combo |
| What drug should be avoided in women of childbearing age that are not pregnant? | Efavirenz and possibly Tenofovir |
| Pregnant Women ON HAART | continue tx, include zidovudine, avoid efavirenz in 1st trimester |
| Pregnant Women STARTING HAART | Avoid Efavirenz, Initiate Nevirapine (if CD4<250), Initiate zidovudine |
| What should be given to a newborn infant of infected mother? | Zidovudine for 6 weeks after delivery |
| Post-Exposure Prophylaxis -general | If exposure severe (Puncture) give >=3 drugs___ If less severe (splash) give 2 drugs___ exposure to most body fluids does not require prophylaxis |
| Post Exposure Prophylaxis- specific drugs | Less Severe: Tenofovir OR Zidovudine + Emticitabine OR Lamivudine_____More severe: as above Plus Lopinavir/ritonavir___Duration 4 wks or until pt is proven HIV negative |
Created by:
stormesk
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