RA Flashcards
PHARMACOLOGIC TREATMENT
(5)
- NSAIDs
- corticosteroids
- DMARDs
- Biologic: anti-TNF
- Biologic: non-TNF
NSAIDs
- Effective in reducing pain, swelling, and stiffness
- Do NOT alter disease ___
- Dose at anti-inflammatory doses
- Use in combination with ___
- progression
- DMARDs
CORTICOSTEROIDS
- Used for anti-inflammatory & ___ properties
- Not used as ___
- Use in combination with DMARD
- Use in ___ flares
- Use in patients with extra-articular manifestations
- immunosuppressive
- monotherapy
- cute
CORTICOSTEROIDS: DOSING
- ___ and ___ have steroid sparing effects
■ Low dose: < 10mg/day of prednisone
■ High dose: > 10mg/day up to 60mg daily
■ Short-term: < ___ months of therapy
Intraarticular injections
o Do NOT use > every __ - __ months
o Use 10 – 25 mg/injection of HC per joint
- NSAIDs, DMARDs
- 3
- 2-3
CORTICOSTEROID ADVERSE EFFECTS
Short Term
- ___ glycemia
- gastritis
- ___ changes
- elevated ___
Long Term
- ___ necrosis
- cataracts
- ___
- growth failure
- ___
- hyperglycemia
- mood
- BP
- aseptic
- obesity
- osteoporosis
DMARDs
Disease Modifying Anti-Rheumatic Drugs
- Potential to decrease/ ___ joint damage & ___ joint integrity
- ___ of initiation is critical
- Onset of action is ___
- prevent, preserve
- timing
- delayed
Conventional Synthetic DMARDs
(4)
- Methotrexate (MTX)
- Sulfasalazine (SSZ)
- Hydroxychloroquine (HCQ)
- Leflunomide
METHOTREXATE
- Most predictable benefit
- DMARD of ___
- DMARD with best ___ outcome
- MOA: inhibit ___ acid reductase (inhibits neutrophil adhesion and chemotaxis)
- choice
- long-term
- dihydrofolic
METHOTREXATE
Dosing Regimen
■ 2.5 mg tablets
■ Dose: ___ mg per ___ by mouth or intramuscularly (up to 15-20 mg – weekly dose can be taken in one day)
■ Onset: __ - __ months
Pharmacokinetics
■ 35- 50% bound to ___
■ Hepatic metabolism with some renal excretion
- 7.5, week
- 1-2
- albumin
MTX: ADVERSE EFFECTS
Hematologic
- Bone ___ suppression
Gastrointestinal
- N/V/D*
- Stomatitis/mucositis
Hepatic
- Cirrhosis
- Hepatitis
- Fibrosis
* = prescribe 1mg/day of ___ acid to reduce symptoms
Pulmonary
- Pneumonitis
- Fibrosis
Dermatologic
- Rash
- Urticaria
- Alopecia
Teratogenic
– Wait one cycle on BCP
– Wait __ months before considering conception
- marrow
- folic
- 3
MTX: CONTRAINDICATIONS
- pregnancy
- chronic ___ disease ( ___ abuse)
- immunodeficienncy
- Pre-existing blood dyscrasias
- Pleural/peritoneal effusions
- Leukopenia/ ___
- CrCL < ___ ml/min
- liver, EtOH
- thrombocytopenia
- 40
MTX: MONITORING
baseline:
- ___
- CBC
- ___
- ___
- albumin
maintenance: CBC, SCr, LFT
- < 3 months: 2-4 weeks
- 3-6 months: 8-12 weeks
- > 6 months: 12 weeks
- CXR
- SCr
- LFTs
LEFLUNOMIDE (Arava®)
Prodrug
■ MOA:
– inhibit de novo biosynthesis of ___
– Interferes with ___ kinase activity
– Inhibit cell cycle progression
- pyrimidines
- tyrosine
LEFLUNOMIDE (Arava®)
Dosage Regimen
■ 10 mg and 20 mg tablets
■ Dose: ___ mg by mouth x 3 days; then 20 mg daily
■ Onset: 1 month
■ Caution: if also taking MTX b/c ___ toxicity
Pharmacokinetics
■ t ½ = 14 – 16 ___
■ ___ clearance
- 100
- liver
- daysLEFLUNOMIDE (LEF):
ADVERSE EFFECTS - Hepatobiliary
LEFLUNOMIDE (LEF): ADVERSE EFFECTS
- Diarrhea
- Rash
- Alopecia
- Increased ___
- ___
- LFTs
- Teratogenicity
LEF: MONITORING
___ , ___ , and ___
Baseline
Maintenance
- < 3 months: 2-4 weeks
- 3-6 months: 8-12 weeks
- >6 months: 12 weeks
CBC, SCr, LFT
SULFASALAZINE
Prodrug: cleaved in colon to ___ and ___
■ MOA: inhibits ___
Dosing Regimen:
– 500 mg tablets
– Dose: 500mg by mouth twice daily
– 1g 2-3 times daily
– Onset: 1-2 months
- sulfpyradine, 5-ASA
- IL-1
SSZ: ADVERSE EFFECTS
Gastrointestinal
- N/V/D, anorexia
Dermatologic
- ___ / Urticaria/ Photosensitivity
Hematologic
- Leukopenia, ___
- Rare: Hemolytic and aplastic anemia
Caution for ___
- Rash
- thrombocytopenia
- allergy
SSZ: MONITORING
___ , ___ , and ___
Baseline
Maintenance
- < 3 months: 2-4 weeks
- 3-6 months: 8-12 weeks
- >6 months: 12 weeks
CBC, SCr, LFT
HYDROXYCHLOROQUINE
MOA: modification of ___ infiltration in joint
Dosing Regimen
– 200 mg tablets
– Dose: 200 mg by mouth twice daily
– Onset: 2-4 months (D/C if not efficacious in ___ months)
Pharmacokinetics
– ___ metabolism
– ___ excretion
- cytokine
- 6
- hepatic
- renal
HCQ: ADVERSE EFFECTS
Advantage
- No ___, hepatic, renal toxicities
Ocular
- ___ toxicity
- > 70 yo, cumulative dose > 800 g, night/peripheral
changes
Gastrointestinal
– N/V/D (take with ___ )
Dermatologic
– Increase skin ___ , rash, alopecia
monitoring: ___ exam every 6-12 months
- myelosuppression
- retinal
- food
- pigment
- vision
TNF NEUTRALIZERS (5)
- Etanercept
- Infliximab
- Adalimumab
- Golimumab
- Certolizumab
TNF NEUTRALIZERS: WARNINGS/PRECAUTIONS
Risk of ___
Do not use in combination with ___ inhibitors or ___ co-stimulation modulators
Black Box warnings
■ Neurologic / ___ disorders
■ Malignancies
■ Congestive heart failure
■ ___ reactivation
■ No concurrent ___ vaccination administration
- infection
- IL-1, t-cell
- demyelinating
- Hepatitis B
- live
TNF NEUTRALIZERS: ADVERSE EFFECTS
- ___ and rash
- Risk of ___ (upper respiratory most common)
- ___ site reaction
- Exacerbations of ___
- Risk of ___
- Risk of evidence of ___ disease
- HA
- infection
- injection
- CHF
- malignancy
- demyelinating
ETANERCEPT (Enbrel®)
Mechanism of Action
– ___ protein with two soluble TNF receptors fused to the IgG1 molecule
– Binds to and inhibits ___
– Binding occurs before the ___ can interact with cell-surface TNF receptors that would produce an
inflammatory response
Dosage Regimen
– 50mg ___ once weekly
- dimeric
- TNF
- cytokine
- SC
INFLIXIMAB (Remicade®)
Mechanism of Action
- ___ antibody
- Immunoglobulin
- Mouse & human portions to reduce ___ potential
Dosage regimen
- 3 mg/kg IV at 0,2,& 6 weeks then every 8 weeks
- Can increase dose to 10mg/kg or as often as every 4 weeks
- Indicated in combination with ___
- chimaric
- antigenic
- MTX
ADALIMUMAB (Humira®)
Mechanism of Action
- Recombinant ___ IgG1 monoclonal antibody specific for human ___
- Binds to ___ and blocks interaction with the p55 and p75 cell surface TNF receptors
Indications
- Patients who have inadequate response to one or more ___
- Can be used ___ OR in ___
Dosage Regimen
■ 40mg SC every ___ week
■ If not taking ___ can increase to 40mg SC every week for improved response
- human, TNF
- TNF-a
- DMARDs
- alone, combination
- other
- MTX
GOLIMUMAB (Simponi®)
Indications
- Moderate to severe RA
- Used in combination with ___
Mechanism of Action
- ___ monoclonal antibody specific for ___
- Prevents binding of TNF-alpha to receptors
Dosage Regimen
- 50mg SC once ___
Monitoring Parameters:
- CBC with PLT
- ____
- MTX
- human, TNF-a
- monthly
- LFTs
CERTOLIZUMAB (Cimzia®)
Mechanism of Action
- Binds to membrane associate and soluble ___ and neutralizes
Indications
- RA patients with moderate to severe disease
- Can be used ___ or in ___ with non-BRM DMARDs
Dosage Regimen
- 400mg (2 injections of 200mg) SC at 0,2,4 weeks then 200mg every 2 weeks or 400mg every 4 weeks
- TNF-a
- alone, combo
ANAKINRA (Kineret®)
Indication:
- Moderate to severe RA in patients who have failed one or more ___
- Can use ___ or in ___
Mechanism of Action:
- ___ , non- ___ version of the human ___ receptor antagonist
- Selectivity blocks IL-1 by binding to the IL-1 receptor
- DMARDs
- alone, combo
- recombinant, non-glycosylated, IL-1
ANAKINRA (Kineret®)
Dosage Regimen
■ 100mg SC daily
■ If CrCl < ___ mL/min, use 100mg SC every ___ day
■ Do not use in ___ with TNF agents or ___ (due to increased risk of ___ )
Adverse Effects
■ ___ site reactions
■ Headache, N/V, flu-like symptoms
■ ___ to e.coli-derived proteins
■ Increased risk of serious ___
■ Decreased ___
- 30, other
- combo, abatacept, infection
- injection
- hypersensitivity
- infectons
- neutrophils
ANAKINRA: MONITORING
___ count
- Prior to start
- Monthly for 3 months
- ___ for up to one year
- neutrophil
- Quarterly
SELECTIVE T-CELL CO-STIMULATION MODULATOR
___ (Orencia®)
Indication:
- Moderate to severe RA
- If had inadequate response to one or more __
- Monotherapy or in combination with ___ (not with TNF –inhibitors or IL-1 antagonists)
Mechanism of Action:
- Selective ___ modulator
- Inhibits ___ activation
- Abatacept
- DMARDs
- DMARDs
- co-stimulation
- T-cell
ABATACEPT: DOSING
Available in ___ mg vials
- < 60kg: 500mg IV over 30 minutes
- 60-100 kg: 750mg IV over 30 minutes
- >100 kg: 1g IV over 30 minutes
- Dose at 0, 2, and 4 weeks then every ___ weeks thereafter
- 250 mg
- 4
ABATACEPT: WARNINGS
- Do not use with ___ antagonists or ___ antagonists
- Increased risk of ___
- No ___ vaccination administration
- Caution in patients with ___
- TNF-a, IL-1
- infection
- live
- COPD
ABATACEPT: ADVERSE EFFECTS
- Headache
- Nausea
- Upper respiratory ___
- Nasopharingitis
- ___ reactions
- Serious ___
- ___
- infection
- infusion
- infection
- Malignancy
