Rheumatoid Athritis Flashcards
Presentation of Rheumatoid arthritis
Chronic
Symmetrical
Systemic
Progressive
What Rheumatoid Arthritis
Immune system unable to differentiate native from non-native tissues attacking mostly synovial and other connective tissues
What is pannus
Inflammation and proliferation of synovial tissue lining the joints
What is the pathophysiology of Rheumatoid Arthritis
Macrophages release cytotoxins activating free oxygen radicals inducing cellular damage and inflammation
True/false: RA can manifest in areas outside the joints
True
Where does RA most commonly occurs
In diseases that are longstanding, and active
Rheumatoid factor positive
Anti-cyclic citrullinated peptide positive
What are the systemic involvement of RA
Rheumatoid nodules
Vascular
Pulmonary
Ocular
Cardiac
Hematologic
How is RA compared to OA
Proximal fingers joints, wrist, toes and elbow
Symmetric
Inflammation of soft connective tissue and accumulation of fluid
Better with activity
Affects 1% of the population
OA compared to RA
Hips, knees, lower back
Asymmetric
Wearing of cartilage
Worse with activity
15% of the population
To Hal one patients major complaint in the clinic for RA (Clinical presentation)
Diffuse pain > 6 weeks
Morning stiffness < 1 hour
Tenderness with warmth and swelling of affected joints
What labs factors are used to diagnose RA
Rheumatoid factor
ACPA positive
ESR elevated and CRP marker
CBC with differential to identify mild/ moderate thrombocytopenia or anemic
Turbid synovial find
What imaging are used to diagnose and track progression of the disease
Radiography
Ultrasonography
MRI
What is the criteria for RA
Synovitis of at least one joint with no other explanation
A score greater than 6 in 2010 ACR/EULAR classification criteria
What are the nonpharmacologic approach to addressing RA
Rest
PT/OT
Exercise
Surgery
Synthetic DMARDS csDMARDs
Hydroxychloroquine
Methotrexate
Leflunomide
Sulfasalazine
Synthetic targeted DMARDs
Tofacitinib
Upadacitinib
Baricitinib
Biologic DMARDS TNFi
Adalimumab and biosimilars
Certolizumab
Etanercept and biosimilars
Golimumab
Infliximab and biosimilars
Biologic DMARDS non-TNFi
Abatacept
Anakinra
Rituximab
Tocilizumab
Sarilumab
Supportive medication
NSAIDs
Steroids
NSAIDs
Work quickly
Systemic or oral
Does not impact disease progression
Steroids
Work quickly
Systemic or intra-articular injections
Long term risks
Methotrexate MOA
Increase AMP to suppress inflammatory actions of neutrophils, macrophages and lymphocytes
Methotrexate dosing
7.5-25 mg/week
Methotrexate PK
Absorption: 60%
1/2 life: 8 hours
Renally excreted
Methotrexate ADR
Mucositis
GI ulcers
Alopecia
Photosensitivity
Hepatotoxicity
Nausea/vomiting/ diarrhea
Myelosuppression
Which vitamin is giving to reduce ADR methotrexate
B9 = folic acid
How often is methotrexate administered
Weekly
What is methotrexate onset
2-3 weeks of onset use corticosteroids in the meantime
What other formulation is methotrexate available in
Injections
What is important to know when using methotrexate
Not for pregnancy = teratogenic
Do not use with alcohol
For whom is methotrexate contraindicted tor
CrCL < 30 ml/min
What should be monitored for methotrexate
Liver transaminases
Serum creatinine
CBC
Leflunomide MOA
Inhibits pyrimidine synthesis in lymphocytes and osteoclasts activity
How is leflunomide closed
100 mg TID followed by 20 mg daily
Leflunomide PK
Absorption: 80%
1/2 life: 14 days
Renal and hepatic elimination
Leflunomide toxicity
Hepatotoxicity
Alopecia
GI upset
NVD
Rash
What should be monitored of leflunomide is giving in combination with methotrexate
Hepatotoxicity
If leflunomide full dose is intolerable what should be done
Reduce dose by 10 mg and loading dose may be omitted
Why leflunomide not giving to pregnant women
Teratogenic
What should be monitored with leflunomide
Liver transaminases
CBC with platelets
Hydroxylchloroquine MOA
Anti-inflammatory and immunomodulatory effects
Hydroxychloroquine dosing
200-300 mg twice daily
Hydroxychloroquine PK
Absorption: 70%
1/2 life: 40 days
Renally excreted
Hydroxychloroquine ADR
NVD
Rash
Weakness
Macular damage
Pigmentation changes
When is hydroxychloroquine used in RA therapy
Less active form of RA
Should hydroxylchloroquine be taken with food
Yes
What is the onset for hydroxychloroquine
Delayed for upto 6 weeks
What should be monitored with hydroxychloroquire
CBC
Vision
Liver transaminases
Sulfasalazine MOA
Modulate local chemical mediators of inflammatory response
Sulfasalazine MOA
0.5-1 g daily
Sulfasalazine MOA
Absorption:10%
1/2 life: 14 hours
Renally excreted
Sulfasalazine ADR
Myelosuppression
Rash
Headache
NVD
Anorexia
Skin and urine pigmentation
When is the effects of Sulfasalazine seen
2 months
What can decrease absorption of Sulfasalazine
Antibiotic that destroy colonic bacteria
Who should avoid Sulfasalazine
Patient with sulfa allergy
Should Sulfasalazine be taking with full glass of water and food
Yes
What vitamin can be supplemented with Sulfasalazine 1 mg daily
Folic acid
What should be monitored in Sulfasalazine
CBC
Liver transaminases
What is Tofacitinib , Baricitinib, Upadacitinib MOA
Janus kinase inhibitors preventing cytokine/ growth factor signaling
Tofacitinib dosing
5 mg BID
Tofacitinib PK
Absorption; 70%
1/2 life: 3 hours
Renally excreted
Tofacitinib ADR
Myelosuppression
Infection
Diarrhea
Headache
GI perforations
Increased lipids
What should patient that use tofacitinib avoid
biologic or potent immunosuppressant
Strong CYP450 inducers
What changes to dose of tofacitinib should be made when taking with 3A4 and 2C19 inhibitors
Reduce to 5 mg daily
Baricitinib dosing
2 mg daily
Baricitinib and upadacitinib PK
Absorption: 80%
Half life:.12 hours
Elimination: Kidney and feces
Baricitinib ADR
URTI
Hepatic dysfunction
Infections and increased lipids
Upadacitinib dosing
15 mg daily
Upadacitinib MOA
URTI
Nausea
Cough
Pyrexia
What should not be used in patients taking: Tofacitinib, Baricitinib, upadacitinib
Biologics or potent immunosuppressants
What should patient taking; tofacitibinib, Baricitinib or upadacitinib be instructed to monitor
Infection
Shortness of breath
Signs of bleeding
What should be monitored in patients taking: Tofacitinib, Baricitinib, upadacitinib
CBC
Liver transaminases
Lipids
Hemoglobin
BBW: thrombosis and tuberculosis
Upacitinib and Baricitinib
Avoid use with strong CYP3A4 inducers/inhibitors
Baricitinib and upadacitinib
What are the dual of therapy MTX
Leflanomide
HCQ
Sulfasalazine
Tofacitinib
Dual therapy for Sulfasalazine
HCQ
Triple therapy
Sulfasalazine + MTX + HCQ
TNF alpha inhibitors MOA
Suppress inflammatory actions of TNF
TNF alpha inhibitors ADR
Immunosuppression
Heart failure
Hepatotoxicity
Abdominal pain
Infection site reactions
Rash
For whom is TNF alpha inhibitor contradicted
Congestive heart failure relative
What should patient who require TNF alpha inhibitor be tested and treated for?
TB
What type of vaccines should not be used in patients on TNF alpha inhibitors
Live vaccines
TNF alpha inhibitors can increase the risk of?
Serious bacterial and fungal infections
True/false: more than one biologic can be used concomitantly
False
All TNF alpha inhibitor require refrigeration except
Etanercept
What should be monitored in patients on TNF alpha inhibitors
TST
Hepatitis screening
Sx of infections
Which TNF-alpha inhibitors is IV
Infliximab
Which TNF alpha inhibitors are subcut
Adalimumab
Etanercept
Certolizumab
Golimumab
Which TNF-alpha inhibitors is used in combination with metothrexate
Infliximab
Adalimumab
Golimumab
Rituximab
Which TNF-alpha inhibitor requires premedication
Infliximab
For patients with congestive heart failure for whom infliximab recommended what is the dose needed
Not greater than 5 mg/kg
Which has high rate of injection site reaction
Infliximab
Inhibit t-cell activation
Abatacept
Abatacept PK
1/2 life: 13 days
renally excreted
Abatacept ADR
Infection
Infusion reaction
False hyperglycemia
Can use csDMARDs
Abatacept
Tocilizumab
Sarilumab
Rituximab (MTX)
Can worsen COPD
Abatacept
Monitor for TST and signs of infections
Abatacept
Rituximab
Chimeric monoclonal CD-20 antibody
Targets b-cells
Rituximab
Rituximab PK
1/2 life: 18 days
Rituximab ADR
Arthralgias
Myelosuppression
Hyperphosphatemia
Hypertension
Infusion requires premedication
Rituximab
IL-6 receptor antagonist
Tocilizumab
Sarilumab
Tolicizumab PK
1/2 half: 6 days
Tocilizumab MOA
Hypersensitivity reactions
Immunosuppression
GI perforation
Dyslipidermia
Infections
Tocilizumab monitoring parameters
Liver transaminases
CBC
Lipids
Sx of infection
IL-1 receptor antagonist
Anakinra
Anakinra Dosing
100 mg subcut daily
Anakinra PK
1/2 half:4-6 hours
Anakinra ADR
Neutropenia
Diarrhea
Influenza like reaction
Injection site reaction
Which drugs require renal adjustment
Anakinra
Anakmira monitoring parameter
Neutrophil count
Symptoms of infection
Sarilumab dosing
200 mg subcut every 2 weeks
Sarilumab PK
1/2 life concentration dependent: 8-10 days
Sarilumab ADR
Injection site reactions
Dyslipidemia
Infection
Neutropenia
Hepatotoxicity
GI perforation
Sarilumab monitoring parameters
TST
Sx of infections
Liver transaminases
Lipids