IHOP Exam 3 Outline.docx

Multiple Sclerosis (Type IV/Cell-Mediated hypersensitivity) First-line: Interferon beta Avonex, Rebif, Betaseron, Extavia, Plegridy; Glatiramer acetate (Copaxone) Second-line: Ocrelizumab, Alemtuzumab, Natalizumab Oral: Fingolimod (Gilenya), Pnesimod (Ponvory), Ozanimod (Zeposia), Teriflunomide (Aub...

Multiple Sclerosis (Type IV/Cell-Mediated hypersensitivity) First-line: Interferon beta Avonex, Rebif, Betaseron, Extavia, Plegridy; Glatiramer acetate (Copaxone) Second-line: Ocrelizumab, Alemtuzumab, Natalizumab Oral: Fingolimod (Gilenya), Pnesimod (Ponvory), Ozanimod (Zeposia), Teriflunomide (Aubagio), Dimethyl Fumerate (Tecfidera) Tx for Dx-related symptoms Primary directly related to disease process Spasticity/Gait issues Baclofen (PO or IT), Tizanidine (PO), Gabapentin/Pregabalin, Dalfampridine (Ampyra) bowel/bladder dysfunction Hyper-reflexic bladder Tx anticholinergics (AE is urinary retention), TCAs Hypo-reflexic bladder Tx int. self-cath, cholinergic agents (bethanechol) Constipation Tx fiber, laxatives, enemas, etc. Cognitive decline Tx stimulants, acetylcholinesterase inhibitors (ex. donepezil) Fatigue Tx: amantadine, methylphenidate, dextroamphetamine, modafinil, armodafinil Secondary stemming from primary problems Depression (more common w/ IFN and natalizumab) 1stline: SSRI (NOT paxil), SNRI UTIs ex. If e. coli: Bactrim x5-7 days, Fosfomycin x2-3 doses Tertiary Pseudobulbar Palsy Tx dextromethorphan/quinidine (Nuedexta) Acute Exacerbations: focal neurologic disturbance lasting >24 hours Corticosteroids Methylprednisolone (SoluMedrol) 500mg – 1g PO/IV x3-10 days SHOULD NOT be discharged on this! AE: HTN, hyperglycemia (may have to start sliding scale while on therapy), GI upset/stomach ulcers, insomnia (don’t give QPM), psychosis First-Generation Injectables (older, well-known, less AE, more frequent inj.) relapsing forms of MS Interferon-beta SQ or IM: Avonex, Rebif, Betaseron, Extavia, Plegridy Glatiramer acetate (Copaxone) SQ Second-Generation Injectables (newer, less well-known, more side effects, less frequent injections, potent) more severe/progressive disease Ocrelizumab (Ocrevus) IV Primary Progressive MS and RRMS Pre-medications: Methylprednisolone 100mg IV 30 mins prior to infusion + Antihistamine 30-60mins prior to infusion +/- APAP Natalizumab (Tysabri) IV Monotherapy for RRMS (in pts unresponsive to other therapies) Monitoring: JC virus (negative required) prior to and every 6 mo during therapy, Alemtuzumab (Lemtrada) Relapsing forms of MS once failed >/=2 DMTs Monitoring: REMS ADR: bone marrow suppression, malignancy, stroke; HA, rash, pyrexia, nausea, fatigue, URTI, thyroid disorders, herpes infection, fungal infections To treat infusion-associated reactions corticosteroids, antipyretics/antihistamines Mitoxantrone (Novantrone) SMPS, PRMS, and worsening RRMS Oral Agents RRMS Fingolimod (Gilenya), Pnesimod (Ponvory), Ozanimod (Zeposia) -MOD MOA: Sphingosine 1 phosphate receptor modulator; ADR: increased LFTs, infection, CV (HTN, edema, hypotension; anything cardiac related RED FLAG!! Teriflunomide (Aubagio) Dimethyl Fumerate (Tecfidera) Rheumatoid Arthritis Oral Agents/Non-Biologic preferred initial agents for mild disease Hydroxychloroquine (Plaquenil) 1st line nonbiologic for MILD disease Monitoring: CBC, Eye exam every 9-12 months Onset: up to 6 weeks Treatment failure: no response after 6 MONTHS Methotrexate (PO preferred) 1st line non-biologic line for MODERATE-SEVERE Leflunomide (similar efficacy to MTX) PK: 14-16 day half-life Dosing: Loading and Maintenance dosing Cholestyramine can expedite removal (such as if pt gets pregnant) Sulfasalazine ADR: skin rash, GI upset, hepatotoxicity (rare) Onset 2 months Biologic Agents preferred for severe/progressive disease; AVOID DUAL BIOLOGICS TNF-alpha inhibitors (SQ or IV) 1st line when NBs fail Monitoring: CBC, latent infection screening (TB), LFTs ADR: infections, malignancies (lymphomas), increased LFTs, leukopenia, thrombocytopenia; Avoid live vaccines Infliximab (Remicade) + MTX IV Infusion infusion reactions Golimumab (Simponi) + MTX SQ Injection Etanercept (Enbrel), Certolizumab (Cimzia) SQ injection +/- MTX; AVOID in HF Adalimumab (Humira) SQ injection +/- other DMARDs Interleukin-6 Antagonists (IV): Tocilizumab, Sarilumab TOCSAR Interleukin-1 Antagonists (SQ): Anakinra T-cell Co-Stimulation Blocker (IV): Abatacept Anti-CD20 (IV): Rituximab + MTX Janus Kinas Inhibitor (PO): Tofacitinib, Baricitinib, Upadacitinib -TINIB ADR: infections, malignancies, major CV events, thrombosis, hepatotox Symptomatic relief: NSAIDs for pain/inflammation; Corticosteroids Bridge DMARD onset; Control flares Treatment algorithms (remember to give treatment for 3 months before changing/escalating) mAbs that require MTX: infliximab, golimumab, rituximab (INGORI) AVOID dual biologic therapy (would torch immune system, pt will get infection) DMARD Naïve Early RA (<6 months) aka New Start Patient HQ + short term steroids is 1st line NB DMARD for mild disease MTX + short term steroids is 1st line NB DMARD for moderate-severe disease If escalates to/persists Moderate or High Disease Activity + LDCS (<10mg prednisone) Combo 2 NB DMARDs (MTX would stay as one of the agents; add on HQ, Sulfa, or LEF) TNF-alpha inhibitor +/- MTX (infliximab, entanercept, adalimu-, certolizu-, golimu- mab) Non-TNF-alpha inhibitor +/- MTX (tocili, sarilu, rituxi-mab; abatacept; tofic, upadac, baric -itinib) In summary: HQ MTX MTX + oral nonbiologic (NB) Biologic DMARD Naïve Established RA (>6 months) DUAL FAILURES basically switch around biologics; won’t get tested on this info Establishment of low disease activity (but not remission) Continue treatment Remission achieved Slowly taper non-biologic DMARD; DO NOT D/C all RA therapy Solid Organ Transplant Induction Agents (allows us to delay initiation of maintenance therapy – usually nephrotoxic/other AE) Non-Cell-Depleting therapies (IV): Basalixumab (Simulect) For LOW immunologic risk patients Cell Depleting Therapies (IV): Thymoglobulin, Alemtuzumab (Campath) VERY potent; causes cell lysis and depletion that takes weeks-months of recovery ADR: infections, malignancies, thrombocytopenia (mon CBC), infusion rxns, neutropenia Maintenance Agents Calcineurin Inhibitors (PO, IV): Tacrolimus, Cyclosporine Monitoring: SCr, BG, BP, K, Mag ADRs: HTN, HLD, neurotoxicity, nephrotoxicity, neoplasm, NODAT/PTDM, electrolyte abnormalities (increased potassium, decreased magnesium), infections Tacrolimus (Prograf BID, Astagraf XL (extended release) QD, Envarsus QD (lower peak than Astagraf XL; peaks are related for AE)) PO: 0.05 to 0.15mg/kg/day divided q12; IV: PO conversion 1:4 Therapeutic drug monitoring: 12-hour trough levels 6-12 ng/mL Cyclosporine (DF NOT interchangeable) PO: 4-12 mg/kg/day divided 12h; IV: PO conversion 1:3 Sandimmune: non-modified Erratic absorption (dependent on GI motility, food, bile) Gengraf, Neoral: modified Microemulsion Therapeutic drug monitoring: C2 (2 hr post dose) levels: >1000ng/mL 12-hour trough levels: 125-275 ng/mL AE: HTN, HLD, Hirsutism, Gingival hyperplasia Anti-proliferatives (PO, IV): 720mg Myfortic = 1000mg Cellcept; IV Dosing: 1:1 Mycophenolate (CellCept, Myfortic): Inhibits lymphocyte proliferation AE: GI: diarrhea, teratogenic (REMS), decrease WBC and PLT CellCept (mycophenolate mofetil (MMF)) $ Absorbed in stomach Myfortic (mycophenolate sodium (MPA)) $$$ Enteric coated, absorbed in small intestine (Potentially less GI than MMF) Azathioprine (Imuran) not usually used unless can’t tolerate mycophenolate Inhibits cell proliferation AE: bone marrow suppression, GI, malignancy (skin cancer) DI: allopurinol (will increase azathioprine conc via inhibition of xanthine oxidase) mTOR inhibitors (PO): Sirolimus, Everolimus TDM: trough (3-8ng/mL w/ CNI; 6-10 without CNI) MOA: Binds to FKBP-12 to prevent T-cell proliferation Sirolimus (Rapamune) PO: 2-5mg dialy Everolimus (Zortress) PO 0.75-2mg BID Won’t be added immediately after surgery because it impairs healing of surgical site If using with calcineurin inhibitor, reduce CI dose T-Cell Co-Stimulation Blocker (IV): Belatacept MOA: binding to CD80 and CD86 on APC to block interaction between APCs and T-cells Monitor: EBV serostatus; AE: post-transplant lymphoproliferative disorder (PTLD) Kidney transplantation ONLY ONLY for pts who are EBV seropositive Initial phase: 10mg/kg/dose IV x6 doses (D1, D5, end of wks 2,4,8, 12) Maintenance phase: 5mg/kg/dose IV q4weeks Complications of Solid Organ Transplantation List the common complications of solid organ transplantation CVD HTN: Goal <130/80 HLD: Incidence: 50-60% Metabolic Complications Post-transplantation diabetes (PTDM)/New onset diabetes after transplant (NODAT): Sx of DM + Random BG > 200 mg/dL OR Fasting BG >126 mg/dL OR A1c > 6.5% 4-25% of all kidney transplant recipients Causes Steroids: insulin resistance CNIs (T > C): Beta cell toxicity mTOR inhibitors: beta cell toxicity and insulin resistance Malignancy De novo occurrence in recipient Risk = IS intensity Skin cancer: lymphoproliferative disease, non-Hodgkin lymphoma Recurrent malignancy in recipient 2 yr wait time after treatment of malignancy Breast cancer, renal cell carcinoma, sarcoma, bladder, multiple myeloma Transmission of malignancy from donor Describe the appropriate management of the endocrine, metabolic, and cardiovascular complications CVD HTN Non-pharm: weight loss, sodium restriction, exercise CS minimization Drug therapies: DHP CCBs early ACEi/ARB late BB/diuretic if needed HLD Avoid mTOR inhibitor Treat per ACC/AHA Guidelines Caution w/ statins & CYA Metabolic Complications Risk Factors: >45; Family and/or personal history; H/o gestational DM; Impaired glucose tolerance test; Metabolic syndrome Malignancy Appropriate IS selection and dosing Avoid azathioprine Sun protection (skin cancer) Reduction of IS Switch to mTOR inhibitor Chemotherapy When presented with a patient case, design a treatment plan to manage SOT complications Lupus Hydroxychloroquine (Plaquenil) 200-400mg renal toxicity (annual eye exam) Prednisone/Prednisolone; Methylprednisolone IV (Solu-Medrol) Short term AE : hyperglycemia, immunosuppression; WBC elevation, fluid retention/HTN, GI distress/ulcers Long term AE: bone mineral density loss, HPA suppression NSAIDS Afferent (glomerulus) vasoconstriction, GI distress/ulcers Methotrexate 10-25mg PO weekly myelosuppression, hepatotoxicity, DI (NSAIDs, sulfonamides) Azathioprine (Imuran) Rituximab (Rituxan) HBV reactivation Treatments Non specific SLE 1st line: NSAID, hydroxychloroquine, glucocorticoids 2nd line: belimumab, methotrexate, MMF cyclophosphamide Lupus nephritis 1st line: hydroxychloroquine 2nd line: induction (3-6 months) MMF + glucocorticoids, cyclophosphamide maintenance: MMF or azathioprine Neuropyschiatric lupus 1st line: hydroxychloroquine 2nd line: glucocorticoids, cyclophosphamide, azathioprine (anticonvulsants, antidepressants, antipsychotics) Cutaneous lupus 1st line: topicals (corticosteroids, pime/tacrolimus) 2nd line: hydroxychloroquine, MTX, retinoids, MMF, dapsone, thalidomide LAST LINE: rituximab, tacrolimus/cyclosporine, IVIG, plasmapheresis Treatment plan for antiphospholipid antibody syndrome Anticoagulation Primary Prophylaxis: Hydroxychloroquine + ASA 81mg Secondary Prophylaxis (venous): Warfarin INR goal 2-3 Secondary prophylaxis (arterial): Warfarin INR goal 2-3 or 3-4; or Warfarin + antiplatelet NO DOACS SLE medications that are teratogenic: MTX, leflunomide, MMF, cyclophosphamide, thalidomide Hydroxychloroquine is preferred in pregnant patients Prednisone or azathioprine may be added (fetal liver unable to bioactivate to 6MP) Cyclophosphamide INFERTILITY Opportunistic Infections Patients requiring prophylaxis for PJP Prolonged lymphopenia (daily temozolomide, fludarabine) Chronic corticosteroids (20mg prednisone/day x1 month) BTK inhibitors (ibrutinib) + some other risk factor PJP Prophylaxis Bactrim (If sulfa allergy inhaled pentamidine monthly or Dapsone) 1SS daily (400/80) common in HIV, SOT pts 1DS (800/160) MWF common in cancer 1DS BID on Sat/Sun PJP Treatment TMP/SMX (Bactrim) 15-20 mg/kg/day (tmp component) x 21 days Usually IV (limited stability: 2-6 hours) 5mg/kg TMP component q8hrs is a common choice HIGH doses of TMP/SMX likely to increase potassium (HYPERkalemia) Corticosteroids recommended if severe hypoxia (ie PaO2 <70 mmHg) Patients with HIV needing OI prophylaxis CD4+ <200 OR thrush PJP Prophylaxis (see above) CD4+ <150/mm3 Histoplasmosis prophy IF endemic geographic/high exposure Prophy: Itraconazole Treatment: Liposomal amphotericin B, Itraconazole CD4+ <100/mm3 Toxoplasmosis IF IgG+ Prophy: Bactrim DS daily Treatment: Pyrimethamine + leucovorin + sulfadiazine CD4+ <50/mm3 MAC Prophy: Azithromycin 600mg PO twice weekly or Clindamycin 500mg twice daily Treatment: Clarithromycin (Biaxin) 500mg BID + Ethambutol 15 mg/kg/day for 12 months Tx for thrush CMV prophylaxis and treatment toxicities Prophy: Letermovir (DOC) Valganciclovir Myelosuppression, nephrotoxicity Tx: Ganciclovir (or valganciclovir) Myelosuppression, infertility, mutagenic, carcinogenic, teratogenic Foscarnet Nephrotoxicity, seizures or cidofovir in cases of resistance Invasive Fungal Infections Regimen for invasive candidiasis (yeast) consider patient and drug-specific factors Often associated with urinary catheter; most common but most mild Regimen for invasive aspergillosis consider patient and drug-specific factors DOC; Voriconazole Echinocandins most reliable coverage Amphotericin B (lipid formulations) Infusion related reactions premedicate with acetaminophen, diphenhydramine Chills & rigors, N/V Fever, headache, myalgias Nephrotoxicity 1 L normal saline before dose AKI, hypokalemia, hypomagnesemia Lipid formulations are safer than conventional but there is still toxicity Not interchangeable!! Flucytosine AE: myelosuppression; caution with hepatic or renal dysfunction Renal elimination allows for treatment of fluconazole-resistant candiduria Fluconazole Can be used in UTIs; Requires renal dose adjustment Safer drug-drug interaction profile (Moderate 3A4, 2C9 inhibitor) Hepatotoxicity Voriconazole TDM Hepatically eliminated IV formulation has renal dose adjustment (toxic excipient in IV formulation which is cleared renally) AE: Visual disturbance’s or hallucinations, hepatotoxicity; dermatologic toxicity (rash; in long term use, could end up as a skin cancer) itraconazole posaconazole TDM Need to take with food Most toxic: Amphotericin B > Azole > Echinocandins HIV Nucleoside/tide reverse transcriptase inhibitors (NRTIs) Class Toxicities Lactic acidosis results from mitochondrial toxicity, elevated lactate, low pH/bicarb, n/v, SOB, can lead to death) Hepatomegaly with steatosis enlarged liver w/ build up of TG and other fats inside liver cells Retrovir (zidovudine/AZT) DST: anemia, neutropenia, headaches, malaise Ziagen (abacavir/ABC) DST: hypersensitivity, increased risk of MI? Epivir (lamivudine/3TC) Emtriva (emtricitabine/FTC) Tenofovir disoproxil/TDF and Tenofovir alafenamide/TAF CI: <30 mL/min DST: renal dysfunction (Fanconi’s syndrome), decreased bone mineral density (TDF>TAF) Videx EC (didanosine/ddl) DST: non-cirrhotic portal hypertension, pancreatitis, CD4 toxicity w/ TDF Zerit (stavudine/d4T) DST: peripheral neuropathy, mitochondrial toxicity, lipoatrophy Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Class Toxicities Hepatotoxicity can result in fulminant failure with NVP Rash CNS effects (especially with efavirenz) Typically resolves w/in first month of therapy Use w/ caution in pts who have existing psychiatric disease Increased suicidality Sustiva (efavirenz/EFV) Increased risk of suicidality Intelence (etravirine/ETR) Edurant (rilpivirine/RPV) Pifeltro (doravirine/DOR) Viramune (nevirapine/NVP) Rescriptor (delavirdine/DLV) Protease Inhibitors (PIs) should be combined with ritonavir or cobicistat Class AE: lipodystrophy is a long term complication metabolic: hyperglycemia and hyperlipidemia morphologic: fat atrophy and fat deposition Reyataz (atazanavir/ATV) AE: hyperbiliruniemia (BANANAvir) Prezista (darunavir/DRV) Integrase Inhibitors (INSTIs) elvitegravir in Genvoya/Stribilid dolutegravir in Tivicay bictegravir in Biktarvy (BIC/FTC/TAF) cabotegravir in Cabenuva (CAB/RPV) Fusion Inhibitors Fuzeon (enfuviritide) Occupational exposures: TDF/FTC or TAF/FTC + RAL or DTG for 4 weeks as prophy PrEP Emtricitabine/tenofovir alafenamide FTC/TAF NOT approved by the FDA for on-demand prep use NOT approved for vaginal exposure (women) FTC/TDF is approved by FDA and recommended by CDC for daily dosing Truvada, Descovy, Apretude PEP Truvada or Descovy + Isentress or Tivicay Brand-Generics: N(tide)RTI, NNRI, PI, Integrase Inhibitors, *preferred regimns Truvada (TDF + emtricitabine) Approved for all populations Descovy (TAF + emtricitabine) Approved for MSM and trans F (M F) Dovato (dolutegravir + lamivudine) Cabenuva (cabotegravir + rilpivirine) Juluca (dolutegravir + rilpivirine) *Triumeq (dolutegravir + abacavir + lamivudine) Abacavir TEST HLA-B*5701 Can be used in pregnancy *Biktarvy (bictegravir + emtricitabine + TAF) Can be used in pregnancy Symtuza (darunavir + cobicistat + emtricitabine + TAF) Genvoya (elvitegravir + cobicistat + emtricitabine + TAF) Stribild (elvitegravir + cobicistat + emtricitabine + TDF)