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Therapeutics IV > SLE > Flashcards

SLE Flashcards

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
Q

antimalarials

A

FIRST LINE if no relief from NSAIDs

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26
Q

antimalarial examples

A

hydroxychloroquine (plaquenil) 200 - 400 mg PO QD/divided

Chloroquine (aralen) 250 - 500 mg PO QD

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27
Q

antimalarial MOA

A

inhibits movement of neutrophils and eosinophils

impairs complement-dependent antigen antibody reactions

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28
Q

antimalarials ADRs

A 
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

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29
Q

antimalarial monitoring: baseline

A

Ophthalmologic

Serum Creatinine (SCr)

Complete Blood Count (CBC)

Liver Function Tests (LFTs)

30
Q

antimalarial monitoring: periodic

A

Ophthalmologic exam 3 months after therapy initiation

Hydroxychloroquine q 12 months

Chloroquine q 3 months

31
Q

corticosteroids (TOPICAL)

A

MOA: anti-inflammatory, suppress immune response

32
Q

corticosteroids (TOPICAL) place in therapy

A

SECOND LINE

Adjunctive treatment to other systemic agents

Presence of cutaneous symptoms

Helps decrease use of systemic therapies

33
Q

corticosteroids (TOPICAL) High potency used for

A

Scalp, soles, palms

Clobetasol

34
Q

corticosteroids (TOPICAL) Mid potency used for

A

Trunk and extremities

Triamcinolone acetonide

Betamethasone Valerate

35
Q

corticosteroids (TOPICAL) low potency used for

A

Face

Fluocinolone acetonide

Hydrocortisone butyrate

36
Q

corticosteroids (TOPICAL) pearls: Body

A

Creams and Ointments

37
Q

corticosteroids (TOPICAL) pearls: Scalp

A

Foams and Solutions

38
Q

corticosteroids (TOPICAL) ADRs

A

Skin Atrophy

Rosacea

Telangiectasis (spider veins)

Limit duration to avoid ADRs

39
Q

corticosteroid (SYSTEMIC) facts

A

MOA: anti-inflammatory (suppress immune response)

40
Q

corticosteroid (SYSTEMIC) place in therapy

A

SECOND LINE

Mild disease: if not responsive to NSAIDs/antimalarials

severe disease: nephritis, pneumonitis, myositis, vasculitis, CNS involvement

41
Q

corticosteroid (SYSTEMIC) examples

A

Prednisone (maintenance therapy)

Methylprednisolone/Prednisone (pulse therapy)

42
Q

corticosteroids (SYSTEMIC) ADRs

A

HTN

hyperglycemia

hyperlipidemia

hypokalemia

osteoporosis

wt gain

mood disturbances/psychosis

infection

cataracts

43
Q

corticosteroids (SYSTEMIC) monitoring: baseline

A

BP, bone mineral density, BMP, FLP

44
Q

corticosteroids (SYSTEMIC) monitoring: routine

A

BMP q 6 months

FLP q 6 months

bone mineral density q 12 months

45
Q

cytotoxic agents

A

MOA: suppression of immune fxn

46
Q

cytotoxic agents: place in therapy

A

SEVERE DISEASE

disease that threatens major organ fxn

47
Q

cytotoxic agents used

A

cyclophosphamide

azathioprine

mycophenolate mofetil

48
Q

cyclophosphamide for

A

lupus nephritis, refractory/life threatening disease

49
Q

cyclophosphamide ADRs

A

myelosuppression

opportunistic infections

hemorrhagic cystitis

bladder cancer

infertility

50
Q

azathioprine for

A

renal flares (long term suppression therapy), to decrease dose of corticosteroid

commonly used as adjunct w/ steroids

51
Q

azathioprine ADRs

A

myelosuppression

opportunistic infections

hepatotoxicity

ovarian failure

thrombocytopenia

52
Q

mycophenolate mofetil for

A

Lupus nephritis

Cutaneous symptoms

Arthritis

Hematologic symptoms

Commonly used as adjunct with corticosteroids

53
Q

mycophenolate mofetil ADRs

A

Myelosuppression

Nausea/vomiting

Diarrhea

BP changes

CNS effects

Metabolic effects

Renal/hepatic concerns

54
Q

Biologic agents for

A

Place in therapy: SEVERE DISEASE…DISEASE THAT THREATENS MAJOR ORGAN FXN

MOA: B-cell reduction

55
Q

Biologic agent examples

A

belimumab (benlysta)

rituximab (rituxan)

56
Q

Biologic agent pearls

A

No live* vaccines 30 days before or during therapy

Don’t use more than ONE biologic agent at a time

57
Q

Examples of live-attenuated vaccines

A

measles, rotavirus, smallpox, tuberculosis, varicella, intranasal influenza vaccines, and yellow fever

58
Q

Belimumab (benlysta) USE

A

Positive autoantibody active SLE

Adjunctive to standard treatment

59
Q

Belimumab (benlysta) MOA

A

Human IgG antibody binds to BLyS

Promotes apoptosis of B cells

60
Q

Rituximab (rituxan) USE

A

Lupus nephritis

Possibly more effective in AA pts or with cyclophosphamide

61
Q

Rituximab (rituxan) MOA

A

Chimeric monoclonal antibody directed at the CD20 antigen on B-cells –> killing of B-cells

62
Q

Additional Therapies

A

methotrexate

TNF-alpha inhibitors

calcineurin inhibitors

63
Q

Voclosporin (Lupkynis®) Info

A

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
Q

Voclosporin (Lupkynis®) AE

A 
Hypertension
Decreased glomerular filtration rate
Diarrhea
Anemia
Headache
Cough
65
Q

Voclosporin (Lupkynis®) Contraindications

A

Concomitant use with CYP3A4 inhibitors

66
Q

Pregnancy should be…

A

…avoided in active disease

67
Q

Active SLE increases the risk for:

A 
Miscarriage
Preeclampsia
Pre-term labor
Fetal growth retardation
Maternal mortality
Increased risk of exacerbation
68
Q

Pregnancy and lupus facts

A

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
Q

Antiphospholipid syndrome (APS)

A

Systemic autoimmune disease characterized by venous or arterial thrombosis and/or pregnancy loss in the presence of persistent expression of antiphospholipid antibodies

70
Q

Antiphospholipid syndrome (APS): Prophylaxis

A

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
Q

Antiphospholipid syndrome (APS): Acute Thrombotic Events/Hx of Thrombosis

A

Therapeutic heparin or LMWH

WARFARIN CONTRAINDICATED IN PREGNANCY

72
Q

SLE Pharmacologic Summary

A

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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