Exam 4 lecture 7 Flashcards
Define lupus
Chronic autoimmune disease with diverse clinical presentation.
Immune system attacks healthy tissue and organs throughout the body.
Control of this disease remains a challenge
Predisposing factors to lupus
Genetics- 1st degree relatives; 20 x more likely to develop SLE
Hormonal- Estrogen production may modulate the incidence and severity of SLE
Env’t- CIgarette smoking, meds, UV light, air pollution, ciruses, stress, pesticides
What is Drug induced lupus erythematosus (DILE)? WHen do symptoms occur? When does resolution occur?
Overreaction to certain meds
symptoms occur 3-6 months of drug initiation
Resolution occurs within weeks of drug dx
What us a mnemonic to memorize drugs that cause DILE
My Pretty Malar Marking Probably Has A TransIent Quality
Every capital letter is a drug (including the I in transiet)
Methimazole
Propylthiouracil
Methyldopa
Minocycline
Procainamide
Hydralazine
Anti-TNF agents (infliximab and etanercept)
Terbinafine
Isoniazid
Quinidine
s/s of lupus (SLE)
Fatigue
Depression
Photosensitivity
Joint pain
N/V
Fever
Weight loss
Malar “butterfly” Rash
What are some mucocutaneous s/s of SLE?
Opthalmologic?
Renal?
mucocutaneous- butterfly rash, discoid rash, raynaud phenomenon
Opthalmologic- Lupus retinopathy
Renal- Lupus nephritis
What is Raynaud Phenomenon
Exaggerated vascular response to cold temperature or emotional stress
What are the two diagnostic tools that will be used for lupus
SLICC
EULAR
How does SLICC criteria work
Must meet > 4 total features with 1 from each group
OR
Biopsy proven lupus nephritis WITH systemic lupus
criteria for EULAR
Patients score is > or = 10 AND atleast 1 clinical criterion is fulfilled
What are some key labs for SLE? WHat is a normal range? WHat is its specificity?
- Anti-nuclear antibody (ANA)- reference range (<1:40)= negative. Positive in lupus patients but not specific
- Anti double stranded DNA (Anti-dsDNA)- Negative, High specificity (correlates with disease activity and is an important marker in lupus nephritis)
- anti- smith antibody (Anti-SM)- negative- High specificity for diagnosis
- Antiphospholipid antibody- negative, increases clotting factors
What are 5 drug classes that patients will be on when they have lupus?
Hydroxychloriquin (HCQ)
NSAIDs
Glucocorticoids
Immunosuppressnats (IS)
Biologics
MOA of HCQ? Place in therapy? Benefit of HCQ? Dosing (exam)
MOA- anti malaria-> inhibit overactive immune cells
Place in therapy- Recommended for ALL pts with SLE
Benefits- reduces flares and help manage pain
Dosing- 200-400mg PO daily
Side effects of HCQ
-opthalmic: retinal toxicity (bulls eye maculopathy)
-Hemolytic anemia if you have G6PD deficiency
- CNS (depression, anxiety)
- CV- QT prolongation
- HS rxn
What type of disorder is G6PD deficiency
X-linked disorder that causes RBCs to prematurely break down (happens more in males)
What drug do we not give if patient has G6PD deficiency
HCQ
Monitoring parameters for HCQ
CBC
LFTs
SCr
EKG
Periodic eye exam 3 onths after eye exams and annually there after
MOA of NSAIDs? Benefits? Place in therapy?
MOA- inhibits COX 1 and 2 to decrease the formation of prostaglandin precursor
Benefits- Antipyretic, anti-inflammatory and analgesic
Place in therapy- 1st line for mild symptoms
Dosing of Ibuprofen and naproxen
Ibuprofen- 400-600 mg PO Q 6-8 H
Naproxen- 500 mg PO BID
Side effects of NSAIDs
GI bleeding, gastritis or perforation
CV- increased BP,worsening HF, CV events
Renal- increased Scr, renal toxicity
Hepatic- Hepatotoxicity
Monitoring parameters for NSAIDs
CBC
LFTs
SCr
BP
S/sx of fluid retention and bleeding
Glucocorticoid MOA? Benefits? Place in therapy?
MOA: Inhibits B and T cell responses
Benefits: Anti inflammatory and helpful during flares
Place- adjunct treatment if not responsive to NSAIDs, HCQ
Dosing of oral glucocorticoid (prednisone)
MIld-moderate disease: Prednisone 5-20 mg/day
Severe: 1 mg/kg/day
IV dosing of glucocorticoid
Methylprednisolone: 500-1000 mg IV x 3-6 days then PO prednisone
For topical glucocorticoids, name low potency, moderate potency and high potency glucocorticoids and where they are used
low potency: Flucinolone and hydrocortisone butyrte (face)
Moderate: Triamcinalone and Betamethasone (Trunk and extremities)
High potency: CLobetasol (scalp sores and palms)
PO/IV glucocorticoids side effects
Opthalmic: glaucoma
CV: increased BP
Bone: Increased risk of osteoporosis
GI: GI bleed
CNS: Psychosis/sleep disturbances
Cushings syndrome
weight gain
Topical glucocorticoids side effets
Skin atrophy, rosacea, telengiectasis
Monitoring for glucocorticoids
Baseline: BP, BMP, FLP, BMD
ROutine
BMP q 6 mo
FLP 6 mo
BMD: annually
Immunosuppressants MOA? Place in therapy? Meds?
MOA- suppression of immune system from attacking healthy cells
Place in therapy: Adjunct to steroid therapy to lower the dose or insufficient response to HCQ
meds: Methotrexate
Mycophenolate
cyclophosphamide
azathroprine
Methotrexate dosing? side effects?
Mycophenolate dosing? Side effects?
Methotrexate: 5-15 mg once weekly. May cuse BMS, infection
Mycophenolate: 1-1.5 g BID, BMS, infection, malignancy, AIS
Cyclophosphamide dosing and side effects?
Azathioprine Dosing and side effects?
Cyclophosphamide: 1 - 1.5 mg/kg once daily
IV: 0.5 mg/m2 BSA q month c=x 6 months
side effects: BMS, infection, malignancy
Azathioprine: 50 mg daily
BMS, infection, malignancy
Monitor for TPMT deficiency in azathioprine
BMS= bone marrow suppression
Biologics MOA? Place in therapy? Medications?
MOA: Monoclonal antibodies that block B cell mediated immunity
Place in therapy:
- inadequate response to antimalarial and immunosuppressants
- severe disease
Medication
-Belimumab
- rituxiamb
- anifrolumab
Pearls with biologics with lupusq
No live vaccines 30 days before starting therapy OR during therapy
Do not use more than 1 biologic at the same time
Belimumab dosing? Side effects?
10 mg/kg every 2 weeks x 3 doses
HS and infusion rxn
Anifrolumab dosing and side effects
300 mg every 4 wks, HS rxn
Rituximab dosing? Side effects?
1g on days 0 and 15 or 375 mg.m2 once weekly for 4 doses
Side effects- Infusion rxn, Hep B reactivation, ML
premedicate 30 mins prior to administration
What is an additional biologic that can be used in lupus
Calcineurin inhibitors (CNI)
- tacrolimus
- vocolosporin (oral lupus med)
non pharm adjustments for lupus
Balance of rest and exercise
Smoking cessation
Limit sun exposure and use fo sun screen
How common and dangerous is cutaneous lupus? First line treatmemnt? Refractory treatment?
10% of lupus cses, rarely life threatening. Presents with rash and lesions
1st line:
1)TOpica; agents
- GC: clobetasol, betamethasone, hydrocortisone,triamcinalone
CNI: Tacrolimus, pimecrolimus
2)HCQ
3) systemic GC
Refractory
- high dose GC
MTX
MMF (mycophenolate)
how common and dangerous is lupus nephritis? Therapy for class I/II lupus nephritis?
LN is a serious complication of SLE which can affect 6-% of patients within 10 yrs of diagnosis
Therapy
Mild/moderate nephritis
- GC+/- another immunosuppressive AZA, MMF or CNI
Severe nephritis
MMF (preferred) or CYC +/- GC
Triple therapy:
- belimumab + MMF or CYC +/- GC
CNI + MMF +/- GC
Therapy for class III or IV lupus nephritis
-Glucocorticoid
+
-CNI + MPAA
or
-MPAA (Most preferred) (can have induction and maintenance)
or
- cyclophosphamide (2nd line after MPAA)
or
-Belimumab + MPAA or reduced dose cyclophosphamide
Drugs for
FLuid retention
Pain and inflammation?
Diuretic
NSAIDs (recommend tylenol first)
Compare healthy pregnancy vs lupus pregnancy? When is the best prognosis
COntraception?
Lupus pregnancies at more risk for
- miscarriages
- fetal growth retardation etc
Best prognosis is when the patient achieves remission for > 6 months
COntraception
- Avoid estrogen containing contraception
- Screen for antiphosholipif syndrome
Which drugs are safe to use in pregancy? Which should we discontinue
HCQ ( safe throughout pregnancy)
NSAIDs ( discontinue at 20 weeks or later)
GC- safe throughout
MMF, CYC, MTX- contraindicated
AZA- risk vs benefit with proveider
Biologics- do not recommend
What is antiphospholipid syndorme
An auto immune disorder characterized by antiphospholipid syndrome that can cause blood clots and miscarriages
Prophylaxis for antiphospholipid antibody
- no prior fetral loss- apsirin 81 mg
- Recurrent fetal loss- aspirin 81 mg + LMWH
If acute thrombotic event/hx of thrombosis- LMWH
Can we use warfarin in pregnant woman
NEVER
