Self care - psoriasis TX part 2

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juliennehanley
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123215
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Self care - psoriasis TX part 2
Updated:
2011-12-13 17:47:47
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self care psoriasis
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moderate to severe treatments of psoriasis
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  1. Which component of light can potentially cause more extensive and deeper damage to cells, but has less erythema and burning?
    UVA
  2. Which light is most therapeutic?
    Broadband UVB, 80-100% clearance of lesions
  3. Which type of light does the Goeckerman regimen use?
    Broadband UVB
  4. What is the MOA of any phototherapy?
    • cross-linking strands of DNA
    • decreases DNA synthesis
    • decreases mitosis
    • decreases epidermal cell turnover
  5. What are Psoralens?
    • photosensitizers - methoxsalen, 8-methoxypsoralen (8-MOP)
    • chromophore
    • anti-mitotic
    • used with UVA
  6. What are the side effects of phototherapy?
    • burning, painful erythema
    • photoaging
    • loss of vision
    • carcinogenic - squamous cell carcinoma esp in male genitalia, malignany melanoma
  7. When is UVB used?
    ideal of thin plaques, large BSA, responsive to sunlight
  8. What are general cahracteristics of UVB therapy?
    • deacreases DNA synthesis
    • does not require a sensitizer
    • sunburn, photoaging, skin cancer
  9. When do most patients achieve a 75% clearance with UVB therapy?
    7-8 weeks
  10. What can UVB therapy be used in combination with?
    • Anthralin (ingram regimen)
    • Coal tar (Goeckerman regimen)
  11. What should you do is using UVB with tazarotene?
    reduce UVB dose by 1/3 b/c tazarotene can cause skin thinning and easier burning
  12. What should you avoid doing if being treated with UVB therapy?
    pre-treating with lubricants
  13. How is UVB therapy dosed?
    • high energy 308 nm laser
    • administered 3 times a week
    • exposure based on skin type
    • maintainence therapy to prolong remissions - ave 6-8 treatments/month
  14. When is UVA therapy used?
    plaque, guttate, pustular psoriasis
  15. What does UVA therapy require? How is this dosed?
    • sensitizer (psoralens -- PUVA)
    • 8-MOP (most common) given 0.6-0.8 mg/kg 75-90 min prior to UVA exposure, based on skin type
    • or soak in bath for 15 min prior to UVA
    • Methoxsalen and trioxsalen can be used but increase nausea
  16. Which type of phototherapy has longer remissions?
    UVA
  17. How is UVA therapy dosed? When do most patients have 80% clearance?
    • 80% clearnace after 10-20 treatments (4-8 weeks)
    • Maintainence dose is twice a month
  18. Which drugs are photosensitizing and should be avoided with concurrent use of UVA phototherapy?
    • fluoroquinolones
    • sulfonamides
    • tetracyclines
    • sulfonyureas
  19. What side effects can UVA therapy have?
    • lethargy
    • nausea
    • headaches
    • hyperpigmentation
    • increased risk of squamous cell carcinoma
  20. What can UVA therapy be used in combination with?
    • calcipotriene - apply after UVA
    • tazarotene - deacrease UVA dose by 1/3
  21. What is acitretin (Soriatane)?
    • oral, aromatic retinoid
    • metabolite of etretinate
  22. Why is etretinate no longer used?
    stayed in system 2-3 years, long half-life
  23. What is the MOA of acitretin?
    • anti-proliferative
    • anit-keratinizing
    • anti-inflammatory
  24. What are the side effects of acitretin?
    • dry skin and mucous membranes
    • alopecia
    • arthralgias
    • decrease night vision (rare)
    • hepatotoxicity
    • pseudotumor cerebri (rare)
    • TERATOGEN!
  25. What does acitretin interact with? What happens?
    alcohol - will transform acitretin to etretinate
  26. What types of psoriasis is acitretin used for?
    • plaque
    • guttate
    • erythrodermic
    • pustular
    • PPP
  27. What can acitretin cause?
    • hypervitaminosis A syndrome - dry skin, chapped lips, dry nasal mucosa
    • high triglycerides, liever enzyme alteration, hepatitis
    • tertogenic
  28. How is acitretin dosed? What is its effectiveness?
    • 25-50 mg/day PO (available in 10 or 25 mg capsules)
    • minimally effective alone
    • RePUVA - combination with PUVA (half dose) works better
    • ReUVB - 55% clearing rate with acitretin 30-35 mg + UVB
  29. What should you monitor for toxicity with acitretin?
    • liver function tests (LFT) - ALT, AST, months 0-6 then Q3mos
    • fasting lipids - LDL, HDL, triglycerides, Months 0-4, then Q2-3mos
  30. What is methotrexate?
    • immunosuppressant
    • folic acid analog
    • dihydrofolate reductase inhibitor/antimetabolite
  31. What is the MOA of methotrexate?
    • *MTX suppresses T cell proliferation and activity by:
    • dihydrofolate reductase inhibitor
    • competivite inhibitor of the enzyme substrate - dihydrofolate
    • inhibits DNA synthesis in rapidly dividing cell types
    • anti-mitotic and cytotoxic - perietal and epithelial cells of GI, RBCs and WBCs (including T-cells), cancer cells
  32. What do bacteria utilize as a source of purine bases that humans do not?
    PABA
  33. What are the side effects of MTX due to effects on GI epithelial cells?
    • nausea
    • diarrhea
    • GI bleeding
    • stomatitis (inflammation or ulcers in mouth)
  34. What are the side effects of MTX due to suppression of bone marrow?
    • myelosuppression - anemia, neutropenia, thrombocytopenia
    • interstitial pneumonitis
  35. What are the other side effects of MTX?
    • hepatic fibrosis and cirrhosis
    • teratogenic
  36. What types of psoriasis is MTX used for?
    plaque, pustular, erythrodermic, arthritis
  37. When do patients see and initial response with MTX use? When do 80% achieve response?
    • initial response in 4-6 weeks
    • 80% in 2-3 months
  38. How is MTX dosed?
    • 10-25 mg weekly PO, IM, or IV
    • usually 7.5-15 mg/week then titrate by 2.5 mg/week Q2-4 weeks
    • Often a 2.5 mg test dose is given - if labs are normal increase dose
  39. Why do patients experience MTX side effects? What is given in addition to MTX?
    • decrease in folic acid
    • give with 1-5 mg/day folic acid
  40. What drugs interactions does MTX have?
    • retinoids and alcohol - increased liver toxicity
    • salicylates, sulfonamides, penicillins, NSAIDs - decreased renal elimination
    • phenytoin, barbiturates, salicylates - protein displacement
  41. What contraindications does MTX have?
    • decreased renal function
    • abnormal liver function
    • alcoholism
    • pregnancy
    • breastfeeding
    • anemia
  42. What should be monitored for toxicity with MTX?
    • pregnancy test at baseline
    • CBC with differential, AST, ALT, at weeks 0,1,2,4,6,12,18,24, etc.
    • renal function (SCr, BUN, urinalysis) Q3-4mos
    • liver biopsy after every 1-1.5g, PIIINP may reduce need for biopsy
  43. What is cyclosporine?
    an immunosuppressant that inhibits calcineurin (phosphatase enzyme)
  44. What is the MOA of cyclosporine?
    • inhibits calcineurin which activates (dephosphorylates) transcription factor NFAT (nuclear factor of activated T cells), promotes transcription of IL-2 (T-cell growth factor)
    • blocks DNA transcriptions of factors produced in antigen-stimulated T-cells
    • IL-2, IL-3, IFN-g
  45. What are the side effects of cyclosporine?
    • increased susceptibility to infection
    • hypertension
    • nephrotoxicity
    • GI upset
    • hypokalemia
    • hypomagnesemia
    • hyperuricemia
    • hypertriglyceridemia
    • increase risk of cutaneous, solid organ, and lymphoproliferative malignancies which is further increased if pt has received phototherapy with PUVA
  46. When is an initial response seen with cyclosporine?
    • 2 weeks
    • 90% have clearing in 10 weeks using 5 mg/kg/day
  47. When can relapse occur when d/c cyclosporine?
    2-4 months after d/c
  48. How is cyclosporine dosed? Titrated up? Titrated down?
    • 3-5 mg/kg/day divided into 2 doses
    • start with 3 mg/kg and increase by 1 mg/kg each month
    • to discontinue, titrate down 0.5 mg/kg every 2 weeks
  49. What should be avoided when using cyclosporine?
    • treatment over 1-2 years
    • concurrent phototherapy
  50. What are the contraindications for cyclosporine?
    • renal dysfunction
    • uncontrolled HTN
    • acute infections
  51. What drugs interact with cyclosporine?
    • CYP 3A4 substrate inhibitors - eryhtromycin, azole antifungals, Ca channel blockers, grapefruit, cimetidine
    • inducers - rifampin, phenytoin, phenobarbital
  52. What should be monitored with cyclosporine use?
    • monthly CBC, SCr, BUN
    • Every 2 weeks for first 3 months then monthly for BP, BUN, K, Mg, uric acid, CBC, lipids
    • inital renal function
  53. Why should you reduce the dose of cyclosporine?
    in SCr increases more than 25% baseline
  54. Which immunomodulatory agents are TNF-a inhibitors?
    • Infliximab (Remicade)
    • Etanercept (Enbrel)
    • Adalimumab (Humira)
    • Golimumab (Simponi)
  55. Which immunomodulatory agent binds and prevents CD2/LFA-3 interaction? What are CD2 markers?
    • Alefacept (Amevive) - fully human fusion protein
    • surface proteins found on memory T cells --> antibody can bind very specifically to memory T cells
  56. Which immunomodulatory agent inhibits IL-12 and IL-23?
    Ustekinumab (Stelara)
  57. What is PASI-75?
    a 75% improvement in psoriasis area and severity index score, used to document effectiveness of therapies in trials
  58. What is alefacept's MOA?
    • antibody binds to CD2markers
    • prevents interaction between dendritic and T cells
    • suppresses T cell mediated response
    • mediates destruction of memory T cells via apoptosis induced by natural killer cells
    • inhibits cytokine production
    • inhibits keratinocyte hyperproliferation
    • inhibits inflammation
    • inhibits immune response
  59. What are the first dose reaction side effects of alefacept?
    • flu-like symptoms - headahce, asthenia, nausea, vomiting
    • increase susceptibility to infections
  60. What are other side effects of alefacept?
    • sore throat
    • increase risk for malignancies and cancer
    • lymphopenia
    • myalgias
    • chills
    • pharyngitis
    • cough
    • nausea
  61. what % of patients experience PASI-75 on alefacept?
    21% at week 14
  62. How is alefacept (Amevive) dosed? When is max effectiveness seen? Is it generally well tolerated?
    • 15 mg IM every week for 12 weeks -->max effectiveness may be seen up to 6-8 weeks after last IM shot
    • OR 7.5 mg IV every week for 12 weeks
    • can repeat once after 12 week holiday
    • yes, well tolerated
  63. What are the precautions when using alefacept (Amevive)?
    • CI in HIV
    • monitor CD4 count biweekly
    • pregnancy category: B
  64. What is the MOA of Ustekinumab (Stelara)?
    • blocks activity of IL12 and IL23
    • binds to p40 chain protein common to both cytokines
  65. What % of patients experience PASI-75 on ustekinumab (Stalere)?
    • 67% at 45 mg (<100 kg)
    • 76% at 90 mg (>100 kg)
  66. How is ustekinumab dosed?
    • <100 kg --> 45 mg SC at 0 and 4 weeks, Q12 weeks after
    • >100 kg --> 90 mg SC at 0 and 4 weeks, Q12 weeks after
  67. What are the side effects/risks of taking ustekinumab?
    • nasopharyngitis
    • URI
    • headache
    • fatigue
    • risk of malignancies - non-melanoma skin cancer, breast, colon, head/neck, kidney, prostate, thyroid cancer
    • rare infections
    • rare Reverse Posterior Leukoencephalopathy syndrome (RPLS)
  68. Why was efalizumab (Raptiva) pulled from the market in 2009?
    3 cases found progressive multifocal leukoencephalopathy (PML) - damages myelin covering
  69. What classification is infliximab (Remicade)?
    mouse/human chimera
  70. What is the MOA of infliximab?
    • binds to TNF-a
    • prevents TNF-a mediated inflammatory responses
  71. What are the side effects of infliximab?
    • infusion reactions
    • respiratory tract infections
    • reactivation of latent tuberculosis
    • exacerbation of congestive heart failure
    • MS-like syndrome
  72. What is infliximab approved for?
    • psoriasis
    • psoriatic arthritis
    • adult RA
    • ankylosing spondylitis
    • Crohn's
    • UC
    • *better when used continuously
  73. What % of patients experience PASI-75?
    • 80% at week 10
    • 61% PASI-75 at week 50
  74. How is infliximab dosed?
    • 5 mg/kg IV over 2-3 hours weeks 0,2,6, then Q8 weeks
    • can be given with MTX
  75. What are the precautions with infliximab?
    • Monitor CBC, LFT, PPD --can activate latent tuberculosis
    • Pregnancy category B
  76. What is the MOA of etanercept (Enbrel)?
    • binds to TNF-a
    • prevents TNF-a mediated immune and inflammatory responses
  77. What are the side effects of Enbrel?
    • injection site reactions
    • anemia
    • leukopenia
    • thrombocytopenia
    • increased risk of infection
    • exacerbation of CHF and demyelinating disorders
    • headache
    • increase resiratory tract infections
  78. What is etanercept approved for?
    • moderate-severe plaque psoriasis
    • psoriatic arthritis
    • RA
    • ankylosing spondylitis
  79. What age is Enbrel safe to use?
    >4 yoa
  80. What % had PASI-75 using etanercept?
    • 49% at 12 weeks
    • 59% at 24 weeks
  81. How is etanercept dosed?
    • 50 mg SC twice weekly for 12 weeks then 50 mg SC weekly after
    • different dosing for different conditions
  82. What are the precautions with Enbrel?
    • CI in sepsis
    • Monitor CBC, LFT, PPD
    • Pregnancy category B
  83. What is the MOA of adalimumab (Humira)?
    • binds to TNF-a
    • blocks TNF-a binding to TNFRs
    • prevents TNK-a mediated inflammatory responses
  84. What is Humira approved for?
    • psoriasis
    • psoriatic arthritis
    • RA
    • ankylosing spondylitis
    • Crohn's
  85. What % have PASI-75 using adalimumab?
    • 71% at 16 weeks
    • 68% at 60 weeks
  86. How is adalimumab dosed?
    • 40 mg SC every other week
    • Loading 80 mg week 1, 40 mg week 2
  87. What can Humira be used in combination with?
    MTX for psoriatic arthritis
  88. What are the side effects of adalimumab?
    • URI
    • abdominal pain
    • headache
    • rask
    • injection site reactions
    • rarely tuberculosis and opportunistic infections
  89. What are the precautions with Humira?
    • Monitor LFT, CBC, PPD
    • Pregnancy category B
  90. What is golimumab (Simponi) approved for?
    signs and symptoms of active psoriatic arthritis +/- MTX
  91. 51% of patients on golimumab achieved basic control according to what system?
    • American College of Rheumatology (ACR20)
    • nearly half were also on MTX
  92. How is Simponi dosed?
    50 mg SC monthly
  93. What are the side effects of golimumab?
    • URI
    • nasopharyngitis
  94. What should be monitored with Simponi use?
    • LFT
    • infections
    • malignancies
  95. What are the general recommendations when using a TNF-a inhibitor?
    • annual tests for tuberculosis
    • avoid concurrent use with live vaccines
    • avoid in patients with MS or 1st degree relatives
    • Avoid in CHF (class III and IV) and CHF (class I, II) if ejection fraction <50%
    • Screen for hepatitis B

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