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Therapeutics IV > SLE > Flashcards

SLE Flashcards

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1
Q

SLE

A

Systemic Lupus Erythematosus

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2
Q

Lupus latin for

A

wolf

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3
Q

What is SLE?

A

chronic autoimmune disease

remission and flares/exacerbation

severity can range from mild to threatening

no cure

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4
Q

gender dynamics

A

women: men
10: 1

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5
Q

ANA

A

anti-nuclear antibody

non specific for antibodies against self

if positive = might have lupus (thus test Anti-dsDNA and/oe anti-sm antigen)

Reference range…<1:40 = negative

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6
Q

Anti-dsDNA (anti-double stranded DNA)

A

auto antibodies to DNA

more specific for SLE

can show disease activity

will increase in a flare

increased in lupus nephritis

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7
Q

anti-sm antigen

A

auto antibodies to RNA splicing proteins

antibody most specific to SLE

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8
Q

antiphospholipid antibody

A

*very important

increases clotting factors

if positive, may be at higher risk for clots

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9
Q

Lupus nephritis (LN)

A

deadliest aspect of SLE

occurs in 40 - 60% of pts w/ SLE

terrible prognosis in colored people

MOA: damage and inflammation of the glomerulus

S/Sx: hematuria, proteinuria causing foamy urine; increased Scr, HTN, edema

specific txs target pts with LN

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10
Q

Lupus Cerebritis (CNS Lupus)

A

brain being attacked by body

decreased blood flow to the brain

S/Sx: anxiety, depression, psychosis, seizures

monitoring: lumbar puncture, MRI

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11
Q

minocycline

A

can cause DIL (drug induced lupus)

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12
Q

Most common offenders of DIL

A

quinidine

procainamide

hydralazine

(other agents: minocycline, isoniazid, methyldopa, carbamazepine, chlorpromazine)

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13
Q

DIL course of disease

A
  1. no hx of SLE
  2. development of ANA
  3. > /= 1 clinical feature of SLE
  4. Stop offending agent
  5. Symptom improvement
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14
Q

How to diagnose lupus

A

ACR (American college of rheumatology)

SLICC (systemic lupus international collaborating clinics)

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15
Q

ACR criteria

A

“DOPAMINE RASH”

  • must have >/= 4 of these symptoms to be diagnosed with SLE*
  • Discoid rash
  • Oral ulcers
  • Photosensitivity
  • Arthritis
  • Malar rash
  • Immunologic involvement
  • NEurologic involvement
  • Renal involvement
  • Antinuclear antibody positive
  • Serositis
  • Hematologic involvement
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16
Q

SLICC Criteria

A

biopsy-proven lupus nephritis with systemic lupus:

  • positive ANA
  • positive anti-dsDNA

or

> /= 4 total immunologic AND clinical criteria (must have at least 1 from each group!)

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17
Q

SLICC Clinical Criteria

A

acute cutaneous lupus

chronic cutaneous lupus

non-scarring alopecia

oral/nasal ulcers

joint disease

serositis

renal involvement

neurologic involvement

hemolytic anemia

leukopenia

thrombocytopenia

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18
Q

SLICC immunologic criteria

A

elevated ANA

elevated anti-dsDNA

anti-sm antigen

antiphospholipid antibody

low complement

direct coombs test

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19
Q

Goals of Tx

A

induce and maintain remission of disease

reduce inflammation caused by SLE

prevent flares and treat them when they occur

control symptoms like joint pain and fatigue

prevent organ damage

minimize drug toxicity

improve quality of life

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20
Q

Non-pharmacologic

A

sun protection (broad spectrum, UV-A + UV-B, spf >/= 55)

nutrition (pts may require higher caloric intake during flares)

exercise

immunizations (NO live vaccines can be given to SLE patients due to immunosuppression)

smoking cessation (has been shown to reduce frequency of flares)

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21
Q

NSAIDS

A

FIRST LINE THERAPY

MOA: reversibly inhibits COX-1 and COX-2

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22
Q

NSAID examples

A

naproxen 440-550 mg PO BID

ibuprofen 400 - 800 mg PO q6 - 8h

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23
Q

NSAIDS ADRs

A

gastrointestinal

cardiovascular

renal

hepatic

bleeding, gastritis, perforation

increased BP, worsened heart failure, cardiovascular events

increased Scr, renal toxicity

hepatotoxicity

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24
Q

NSAID monitoring

A

baseline: Scr, urinalysis, CBC, LFTs, BP
annual: Scr, CBC, LFTs, BP

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25
antimalarials
FIRST LINE if no relief from NSAIDs
26
antimalarial examples
hydroxychloroquine (plaquenil) 200 - 400 mg PO QD/divided Chloroquine (aralen) 250 - 500 mg PO QD
27
antimalarial MOA
inhibits movement of neutrophils and eosinophils impairs complement-dependent antigen antibody reactions
28
antimalarials ADRs
``` Retinal Toxicity Corneal deposits (“Bulls Eye maculopathy”) ``` Dermatologic Rashes Pigment Changes (hair/skin) CNS Headache, anxiety, insomnia Gastrointestinal Abdominal pain, decreased appetite, nausea, vomiting, diarrhea
29
antimalarial monitoring: baseline
Ophthalmologic Serum Creatinine (SCr) Complete Blood Count (CBC) Liver Function Tests (LFTs)
30
antimalarial monitoring: periodic
Ophthalmologic exam 3 months after therapy initiation Hydroxychloroquine q 12 months Chloroquine q 3 months
31
corticosteroids (TOPICAL)
MOA: anti-inflammatory, suppress immune response
32
corticosteroids (TOPICAL) place in therapy
SECOND LINE Adjunctive treatment to other systemic agents Presence of cutaneous symptoms Helps decrease use of systemic therapies
33
corticosteroids (TOPICAL) High potency used for
Scalp, soles, palms Clobetasol
34
corticosteroids (TOPICAL) Mid potency used for
Trunk and extremities Triamcinolone acetonide Betamethasone Valerate
35
corticosteroids (TOPICAL) low potency used for
Face Fluocinolone acetonide Hydrocortisone butyrate
36
corticosteroids (TOPICAL) pearls: Body
Creams and Ointments
37
corticosteroids (TOPICAL) pearls: Scalp
Foams and Solutions
38
corticosteroids (TOPICAL) ADRs
Skin Atrophy Rosacea Telangiectasis (spider veins) Limit duration to avoid ADRs
39
corticosteroid (SYSTEMIC) facts
MOA: anti-inflammatory (suppress immune response)
40
corticosteroid (SYSTEMIC) place in therapy
SECOND LINE Mild disease: if not responsive to NSAIDs/antimalarials severe disease: nephritis, pneumonitis, myositis, vasculitis, CNS involvement
41
corticosteroid (SYSTEMIC) examples
Prednisone (maintenance therapy) Methylprednisolone/Prednisone (pulse therapy)
42
corticosteroids (SYSTEMIC) ADRs
HTN hyperglycemia hyperlipidemia hypokalemia osteoporosis wt gain mood disturbances/psychosis infection cataracts
43
corticosteroids (SYSTEMIC) monitoring: baseline
BP, bone mineral density, BMP, FLP
44
corticosteroids (SYSTEMIC) monitoring: routine
BMP q 6 months FLP q 6 months bone mineral density q 12 months
45
cytotoxic agents
MOA: suppression of immune fxn
46
cytotoxic agents: place in therapy
SEVERE DISEASE disease that threatens major organ fxn
47
cytotoxic agents used
cyclophosphamide azathioprine mycophenolate mofetil
48
cyclophosphamide for
lupus nephritis, refractory/life threatening disease
49
cyclophosphamide ADRs
myelosuppression opportunistic infections hemorrhagic cystitis bladder cancer infertility
50
azathioprine for
renal flares (long term suppression therapy), to decrease dose of corticosteroid commonly used as adjunct w/ steroids
51
azathioprine ADRs
myelosuppression opportunistic infections hepatotoxicity ovarian failure thrombocytopenia
52
mycophenolate mofetil for
Lupus nephritis Cutaneous symptoms Arthritis Hematologic symptoms Commonly used as adjunct with corticosteroids
53
mycophenolate mofetil ADRs
Myelosuppression Nausea/vomiting Diarrhea BP changes CNS effects Metabolic effects Renal/hepatic concerns
54
Biologic agents for
Place in therapy: SEVERE DISEASE...DISEASE THAT THREATENS MAJOR ORGAN FXN MOA: B-cell reduction
55
Biologic agent examples
belimumab (benlysta) rituximab (rituxan)
56
Biologic agent pearls
No live* vaccines 30 days before or during therapy Don’t use more than ONE biologic agent at a time
57
Examples of live-attenuated vaccines
measles, rotavirus, smallpox, tuberculosis, varicella, intranasal influenza vaccines, and yellow fever
58
Belimumab (benlysta) USE
Positive autoantibody active SLE Adjunctive to standard treatment
59
Belimumab (benlysta) MOA
Human IgG antibody binds to BLyS Promotes apoptosis of B cells
60
Rituximab (rituxan) USE
Lupus nephritis Possibly more effective in AA pts or with cyclophosphamide
61
Rituximab (rituxan) MOA
Chimeric monoclonal antibody directed at the CD20 antigen on B-cells --> killing of B-cells
62
Additional Therapies
methotrexate TNF-alpha inhibitors calcineurin inhibitors
63
Voclosporin (Lupkynis®) Info
Approved in 2021 for the treatment of active lupus nephritis. Used in combination with corticosteroids and mycophenolate mofetil MOA: Calcineurin inhibitor, leads to inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens
64
Voclosporin (Lupkynis®) AE
``` Hypertension Decreased glomerular filtration rate Diarrhea Anemia Headache Cough ```
65
Voclosporin (Lupkynis®) Contraindications
Concomitant use with CYP3A4 inhibitors
66
Pregnancy should be...
...avoided in active disease
67
Active SLE increases the risk for:
``` Miscarriage Preeclampsia Pre-term labor Fetal growth retardation Maternal mortality Increased risk of exacerbation ```
68
Pregnancy and lupus facts
Patients should stay exacerbation-free for 6 months prior to pregnancy Estrogen-containing contraceptives should be avoided due to increased risk of clots! Antiphospholipid syndrome can increase the risk of maternal thrombosis or spontaneous fetal death
69
Antiphospholipid syndrome (APS)
Systemic autoimmune disease characterized by venous or arterial thrombosis and/or pregnancy loss in the presence of persistent expression of antiphospholipid antibodies
70
Antiphospholipid syndrome (APS): Prophylaxis
No prior fetal losses: aspirin 81 mg daily Recurrent fetal losses: aspirin 81 mg daily +/- low-dose heparin or low-molecular weight heparin (LMWH)
71
Antiphospholipid syndrome (APS): Acute Thrombotic Events/Hx of Thrombosis
Therapeutic heparin or LMWH WARFARIN CONTRAINDICATED IN PREGNANCY
72
SLE Pharmacologic Summary
Mild SLE: NSAID +/- antimalarial Moderate SLE: NSAID + antimalarial +/- maintenance systemic steroids Severe SLE/Lupus Nephritis/CNS Lupus: NSAID + antimalarial +/- maintenance systemic steroids +/- cytotoxic agent Refractory SLE: NSAID + antimalarial + maintenance systemic steroids +/- cytotoxic agent +/- biologic agent For ALL Severities: topical corticosteroids for cutaneous symptoms; high-dose steroids for flares

Therapeutics IV (19 decks)

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