Misc. Autoimmune (RA / Gout) Flashcards
(157 cards)
1
Q
What is the underlying cause of Rheumatoid Arthritis?
A
AB development (triggered by some preceding event) within the Synovial Space, leading to joint & connective tissue inflammation / destruction.
2
Q
What is “pannus”?
A
Non-functional scar tissue that develops within the joint space (due to chronic inflammation from RA disease state).
3
Q
Is bone damage in RA reversible? Cartilage damage?
A
Bone: Slightly.
Cartilage: Nope (permanent).
4
Q
What is the most well-defined trigger event for Rheumatoid Arthritis?
A
Smoking
5
Q
What happens to ligaments in RA? Tendons?
A
Ligament: Laxity (overstretching leading to loss of supportive function & increased fall risk).
Tendon: Shorten & become non-pliable / tighter (causes joint to twist into locked positions).
6
Q
Ligament Laxity most commonly affects what areas of the body? Tendon Contractures?
A
Ligament Laxity: Knees & Ankles.
Tendon Contractures: Hands & Wrists.
7
Q
What gender is most commonly affected by RA? Most common age of onset?
A
Females (3:1); 30s - 50s.
8
Q
When is Rheumatoid Arthritis worst throughout the day? Osteoarthritis?
A
RA: 1st thing AM worst, gets better as movement occurs.
Osteo: Best 1st thing AM, gets worse throughout the day.
9
Q
Over what length of time (in wks) must symmetrical joint pain & stiffness be present for a Rheumatoid Arthritis diagnosis to be warranted?
A
6wks
10
Q
What systemic symptoms accompany an RA flare-up?
A
-Muscle Pain
-Fatigue
-Weakness
-Low Grade Fever
-Reduced Appetite
11
Q
What are the most important differences in clinical presentation between RA & Osteoarthritis?
A
RA: Symmetrical Distribution, Morning Stiffness, Presence of Systemic Symptoms (especially during flares).
Osteo: Typically Unilateral Distribution, Progressive Stiffness throughout the day, No Systemic Symptoms.
12
Q
Is swelling of the joint more common in RA or Osteoarthritis?
A
RA; Little swelling with Osteoarthritis.
13
Q
Does the intraarticular space & cartilage shrink in Early Stage RA? Late Stage RA?
A
Early Stage: No.
Late Stage: Yes (more closely resembles Osteoarthritis in this respect).
14
Q
What percentage of RA patients demonstrate bone erosion at the time of their diagnosis?
A
30%
15
Q
Extraarticular consequences of RA in blood vessels, lungs, & eyes?
A
Blood Vessels: Rheumatoid Vasculitis (commonly affects vessels supplying skin, can affect Kidney & Heart supplying vessels).
Lungs: Pleuritis / Pleural Effusion, Fibrosis, Nodule Formation.
Eyes: Iritis / Uveitis (permanent vision loss), Scleritis (just redness).
16
Q
Extraarticular consequences of RA in the heart, muscles, & bones?
A
Heart: Pericarditis, Myocarditis (increases risk of CAD, HF, A. Fib).
Muscles: Weakness & Myalgias.
Bones: Osteopenia (leads to bone loss around affected joints).
17
Q
Extraarticular consequences of RA at the level of the skin & hematologically?
A
Skin: Nodules & Ulcers.
Hematologic: Anemia (due to Chronic Disease).
18
Q
What lab tests (coupled with signs & symptoms of RA) would suggest RA presence?
A
-Elevated Erythrocyte Sedimentation Rate (ESR) & Cross-Reactive Protein (CRP).
-Presence of Rheumatoid Factor (60-70% of patients).
-Anti-CCP as well.
19
Q
A “Patient Assessment of Global Disease Activity” (PtGA) score of </= ___ is suggestive of RA disease remission or low disease activity.
A
2
20
Q
Early recognition & diagnosis of RA is key, as significant damage occurs within the first ____ years of disease onset.
A
two
21
Q
The “start low & go slow” approach to using DMARDs in RA is only appropriate to what patient demographic?
A
Very mild & early RA presentation… Otherwise, treat aggressively!
22
Q
DMARD use should take place within ____ months of RA diagnosis.
A
three
23
Q
Non-Pharm measures for treating RA?
A
-Balance of rest & exercise, as forced movement in states of 4 to 10 / 10 level pain worsens condition, but no movement at all causes muscular atrophy.
-Diet Mods / Weight Loss, as less weight bearing down on affected joints is a good thing.
-Occupational / Physical Therapy (to maintain QOL & Functionality).
24
Q
What classes of therapeutic options do we have for RA maintenance treatments? For RA flares?
A
Maintenance: tDMARDs, Biologic DMARDs, Synthetic DMARDs.
Flares: Corticosteroids, NSAIDs, Combo of Both.
25
What drugs are considered to be "Traditional DMARDs"?
Methotrexate, Leflunomide, Hydroxychloroquine, Sulfasalazine
26
tDMARDs have a _____ (fast / slow) onset of action.
slow
27
Which tDMARDs are considered to be the safest? Most potent?
Safest: HCQ, SSZ
Potent: MTX, Leflunomide
28
Why are Methotrexate & Leflunomide considered to be much more potent than HCQ & SSZ?
Directly target the immune system itself rather than inflammatory mediators.
29
MOA of HCQ? SSZ?
HCQ: Neutrophil / Chemotaxis Inhibition.
SSZ: Prodrug conversion to 5-ASA & Sulfapyridine; Modulates inflammatory mediators.
30
MOA of MTX? Leflunomide?
MTX: Anti-Folate (thus impairs DNA synthesis / repair / replication / immune response).
Leflunomide: XXX Pyrimidine Synthesis, leading to AI effects!
31
Dosing regimen for MTX in RA treatment?
7.5mg OW (to start), increase by 2.5 - 5mg / wk until 25mg OW target is met!
32
What's an acceptable MTX dose for someone with tolerability concerns? Is going over 25mg dose more efficacious?
15mg acceptable; No additional efficacy & additional adverse effects when exceeding 25mg OW dose.
33
Can MTX be used with somebody who is renally impaired?
Yep! Can even use in dialysis patients (just have to cut target doses & titrations in 1/2).
34
Of the tDMARDs (HCQ, SSZ, Leflunomide, MTX) which one is best tolerated?
HCQ
35
Side effects of HCQ?
-NVD / Stomach Cramps
-Headache / Dizzy
-Skin Rxns (10%)
36
Side effects of SSZ?
-NVD
-Headache
-Photosensitivity
37
Side effects of Leflunomide?
-Rank Nausea & Diarrhea (60% d/c rate due to this)
-Weight Loss (indirectly from Nausea & Diarrhea)
-Rash / HTN
-Alopecia (is reversible)
38
Side effects of MTX?
-NV
-Tired
-Stomatitis
-Photosensitivity
-Alopecia
-Itchy / Burning Skin
39
How can we manage side effects of MTX?
1) Folic Acid 1-5mg OD (or 5-10mg OW)... Helps with NV / Fatigue / Stomatitis.
2) Split Dosing... Reduces fatigue & GI effects.
3) Sc MTX dosage form... Reduces GI effects.
4) PPI for 3d around MTX dose... Reduces GI effects.
40
Serious adverse effects of LT HCQ usage?
Ocular Toxicity... If on it beyond 5yrs duration, yearly eye exams important!
41
Serious adverse effects of MTX?
-Hepatotoxicity (get LFTs q6mth).
-Hematologic Abnormalities (get baseline counts).
-Pulmonary Toxicity (get baseline chest x-rays).
-Infection rate increases (typically URTIs most common, sometimes Pneumonia).
-Reversible Sterility (6mth - 1yr to return upon d/c).
42
Serious adverse effects of Leflunomide?
-Hepatotoxicity
-Wt. Loss
-Infection Increases
43
Outright CIs of the "safest" tDMARDs?
HCQ:
1) Pre-Existing Retinopathy
SSZ:
1) Salicylate / Sulfa Allergy
2) PPT. Asthma Attacks from ASA or NSAIDs
3) Sev. Renal / Hepatic Impairment
4) Existing GI Ulcers
44
Outright CIs of MTX?
1) Severe Hepatic Impairment
2) Existing Hematologic Abnormalities
3) Pregnant / Breastfeeding (BIG ONE!!!)
45
Outright CIs of Leflunomide use?
1) Mod - Sev Renal (anything < 60mL / min GFR) or Hepatic Impairment
2) Existing Hematologic Abnormalities
3) Pregnant / Breastfeeding (BIG ONE!!!)
46
DDIs of HCQ & SSZ?
HCQ: Other QT-Prolonging agents (ie. Anti-Arrythmics, Anti-Microbials, Certain ADs, Quetiapine).
SSZ: Warfarin (affects INR), MTX (increased nausea).
47
DDIs for Leflunomide?
Bile Acid Sequestrants (can be given deliberately to enhance drug elimination in cases of adverse reactions to the drug).
48
IS MTX CONCURRENT DOSING WITH NSAIDS INAPPROPRIATE???
NOOOOOO DUMBASS (CRA Position Statement got mad at us for this).
49
Why is it okay to dose NSAIDs concurrently with MTX in RA treatment?
Interactions were significant at anti-cancer doses of MTX (ie. 500 - 2000mg Weekly Doses)... WAAAAAY lower in RA management!
50
Christina comes in with the following prescription to treat an upper respiratory infection:
Septra DS (Sulfamethoxazole / Trimethoprim) 800 / 160mg
SIG: 1T OD x 10d
Her PIP Profile says she's on the following meds:
Metformin 500mg (TIID)
Atorvastatin 20mg (Dyslipidemia)
Methotrexate 7.5mg (RA Management)
Naproxen 500mg (RA Flares)
Good to fill?
NOOOO!!!!! MTX interacts with Trimethoprim (greatly increases risk of Pancytopenia irrespective of dose). Don't fill it!!!
51
Is Leflunomide or Methotrexate typically better tolerated?
MTX
52
Rank the tDMARDs by relative potencies.
MTX = Leflunomide > SSZ > HCQ
53
Biologic DMARD usage is reversed for what occasion?
tDMARD (ie. MTX) failure!
54
What are the four classes of Biologic DMARDs?
1) TNF-Alpha Inhibitors
2) IL-1 / IL-6 Inhibitors
3) T-Cell Co-Stim Inhibitors
4) B-Cell Depletors
55
Concerns for all Biologic DMARDs?
-ND / Headache / Malaise
-Injection Site Rxns
-Increased Infection Rates
-Neutropenia
-Malignant Disease Development (Skin Cancer & Lymphomas)
-AB Development
56
What can be done to mitigate injection-site reactions of administered Biologic DMARDs?
90min pre-treatment with Ace + Anti-Histamine + Corticosteroid
57
What opportunistic infections must be pre-screened for in those initiating Biologic DMARD therapies?
-Tuberculosis
-Mycobacterium
-Pneumocystis Pneumonia
-Cytomegalovirus
-Zoster Virus
-Hepatitis B & C
-HIV
58
Counseling Point for patients initiating Biologic DMARD therapies?
"Get up to date on your vaccines!!!"
59
Safest Biologic DMARD in high-risk infection patients?
Abatacept (is the least immunosuppressive option available).
60
Which of the Biologic DMARD classes is the only one without concern of AB development?
IL-6 Inhibitors
61
AB development against Biologic DMARDs typically occurs within the first ___ - ___ months of starting therapy.
two to six
62
Which Biologic DMARD(s) demonstrates the highest risk of AB development? Lowest risk?
Highest: Infliximab (50%)
Lowest: Adalimumab, Etanercept (12%)
63
What drugs would be considered TNF-Alpha Inhibitors?
Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab
64
What strategy both increases the efficacy of and reduces AB development against TNF-Alpha Inhibitors?
Combination with MTX... Up from 40% to 60% ACR50 score.
65
Of the TNF-Alpha Inhibitor drugs, which one(s) are indicated for MTX combination?
Golimumab & Infliximab
66
T or F: TNF-Alpha Inhibitor drugs should always be avoided in pregnancy / lactation.
FALSE!!! All are very safe in pregnancy / lactation!
67
Which of the TNF-Alpha drugs are available in IV dosage form?
Golimumab & Infliximab
68
Outright CIs to TNF-Alpha Inhibitors?
-Active Severe Infection
-Mod - Severe HF
69
TNF-Alpha Inhibitor drugs can cause transient liver enzyme elevations... An ALT above __x the upper limit of normal becomes concerning.
5x
70
What other adverse effects can come about from TNF-Alpha Inhibitors?
-Cause / Worsen HF
-Cutaneous Rxns (Cellulitis, AI Skin Dx's, Malignancies)
-Other AI Conditions (Lupus)
-Seizure Risk
71
Which TNF-Alpha Inhibitor drugs have biosimilars?
Infliximab, Etanercept, Adalimumab
72
Name of weak (Carter Berg Bench Press SAAAAD) IL-1 Inhibitor Drug?
Anakinra
73
Two available IL-6 Inhibitor drugs?
Tocilizumab, Sarilumab
74
Peak effects of IL-1 / IL-6 Inhibitors is ___ - ___ mths.
five to six
75
What are the outright CIs of using Anakinra (IL-1i) & Sarilumab (IL-6i)?
NONE! However, would aim to withhold during active infections.
76
Outright CI to using Tocilizumab?
Active Infection... Like other two related drugs but this is an explicitly labeled CI.
77
Below a CrCl of ___ml / min would warrant a dose adjustment for IL-1 / IL-6i drugs.
< 30mL / min
78
Unique adverse effects of the two IL-6 Inhibitor drugs?
-GI Perforation
-Dyslipidemia
-HTN
79
Is AB development against IL-6i drugs linked to reduced effects (as seen with TNF-Alpha drugs)?
NOOO (unique to this class)!
80
Tocilizumab has one unique DDI... It increases the systemic concentrations of this drug (what is it???) by 4-10x.
Simvastatin
81
In addition to other usual lab tests that are ordered for DMARD patients (ie. Baseline CBCs, LFTs, CrCl, Disease Screens), what other lab test should be ordered for somebody initiating IL-6i drugs?
Lipid Panels (remember heightened dyslipidemia risk)!
82
Abatacept is an example of a ___________ (what drug class is it part of).
T-Cell Co-Stimulation Inhibitor
83
What would be an outright CI for T Cell Co-Stimulation Inhibitors?
COPD (exacerbates condition)
84
Do T Cell Co-Stim Inhibitor drugs have impacts on Liver function?
Nope (main potential use case)
85
What else can be considered adverse effects of T Cell Co-Stim Inhibitor drugs?
-HTN
-Blood Glucose Elevations
86
"MAB" drug that is a B Cell Depletor?
Rituximab
87
Onset of action for Rituximab?
6mths
88
Rituximab requires pre-treatment with _________, __________, & __________.
methylprednisolone, acetaminophen, diphenhydramine
89
HTN, GI Perforation & Blood Glucose increases are adverse effects of Rituximab. What other unique adverse effect can occur from its administration?
Mucocutaneous Rxn's (SJS, TEN)
90
Examples of JAKi drugs?
Tofacitinib, Baricitinib, Upadacitinib
91
Adverse effects of JAKi drugs?
-Infection
-HTN
-Hepatotoxic
-Bradycardia
-GI Perforation
92
Do ABs develop against JAKi drugs?
Nope
93
Of the three JAKi for RA (Tofacitinib, Upadacitinib, Baricitinib), which ones are major CYP3A4 substrates?
First two!
94
The main benefit of Corticosteroid usage in an RA flare is what?
Subjective Symptomatic Improvement
95
A Prednisone equivalent dose of ___ - ___mg / day is appropriate for short-term use.
10 - 15mg
96
What is the average Corticosteroid treatment duration for RA flare management?
2mths (includes time needed for tapering)
97
A Prednisone equivalent dose of ___ - ___ mg / day is considered an appropriate dose for chronic usage.
5 - 10mg
98
What would be some examples of good adjunctive therapies for chronic steroid users who have RA?
-Bisphosphonates
-Ca2+
-Vit. D
99
If multiple yearly courses of Corticosteroids are required for RA management, what should we monitor for?
-Cataracts
-Dyslipidemia
-Hyperglycemia
-Osteoporosis
-Weight Gain
100
If a patient goes in for an IA Corticosteroid injection, what is the limit for number of injections on said joint within 3mths?
1 injection / 3mths on a singular joint
101
How long does symptomatic RA relief last when one undergoes an IA Corticosteroid injection?
4wks
102
Issues with IA Corticosteroid injections?
-Tendon Rupture
-Acute Synovitis
-Local Skin Hypopigmentation
-Septic Arthritis
103
Which NSAID is favored for LTU in RA pain management?
Celecoxib (is gastroprotective)
104
Why do we advise against NSAID / Corticosteroid combinations when managing pain flares in RA patients?
Amplified potential for GI toxicity, ulcer risk, GI bleeds!
105
Do Opioids have utility in RA pain management?
Nope... Avoid.
106
After a timeframe of ___ mths with low disease activity or total remission, DMARD tapers can be initiated.
6mths
107
According to CRA Guidelines, is it appropriate to totally discontinue DMARDs?
NOPE... Reduce dose as much as possible while keeping disease activity low (but not recommended to d/c drugs).
108
When would be a suitable time to step-up DMARD therapies?
Failure to achieve remission or acceptable disease activity after 3 - 6mths at OPTIMAL DOSES!!!
109
How many recurrent RA flares per year would warrant consideration for DMARD step-ups?
1 warrants consideration; 2 flares / yr definitely do it!
110
For how many months prior to impregnation should MTX users have discontinued the drug?
3mths prior to conception (same for Leflunomide once levels < 0.02mg / mL)
111
What is the only Biologic DMARD that does not have a favorable safety profile in pregnancy?
Rituximab
112
Which Biologic DMARD has the most robust data for use in pregnancy?
Certolizumab
113
For those who are breastfeeding, which NSAID is preferred for RA pain management?
Ibuprofen
114
Prednisone doses below ___ mg / day are okay for RA pain management in lactation.
20mg / day
115
In cases of Gout, what is the most common reason for hyperuricemia?
Purine overconsumption in the diet.
116
Hyperuricemia is defined as having serum uric acid levels above ____ umol / L.
420 umol/L
117
Why do Gout flares typically happen within peripheral extremities?
Cold Temps... Extremities have tendency to be colder & solubility of Uric Acid decreases with lowered temps.
118
Aside from Purine Overconsumption, what disease states can cause Uric Acid Overproduction?
Obese
Hypertriglyceridemia
119
How do diuretics cause hyperuricemia?
Fluid leaves joint space, hyperconcentration of Uric Acid within joints.
120
What gender does Gout more commonly affect?
Men
121
Which patients with Asymptomatic Hyperuricemia (ie. > 420 umol / L) should get drug treatments?
Poor Renal Health
> 800 umol / L & no sx
122
Which joints are most commonly affected by gout attacks?
Toes, Instep, Ankle
-Knees, Wrists, Fingers less probable.
123
What are the consequences of Chronic Tophaceous Gout?
-Joint Deformity
-Tissue Damage
-Joint Destruction
-Nerve Compression
-Kidney Stones & Urate Nephropathy
124
Gout Flares typically self-resolve within how many days?
7d
125
Instead of limiting Purine rich foods, what is a more feasible dietary adaptation to prevent Gout Flares?
Caloric Intake Restrictions
126
First NSAID with an official Gout Flare indication?
Indomethacin
127
Why caution Indomethacin use in elderly with Gout Flares?
Crosses BBB (more potential for Drowsiness / Confusion / CNS Effects than other NSAIDs).
128
Naproxen & Ibuprofen dosing regimens for acute gout flares?
Nap: 500mg TID x 2-3d, then cut back to 250-500mg BID.
Ibu: 600-800mg TID x 2-3d, then cut back to 400-600mg TID.
129
Why do we treat with NSAIDs a few days beyond a week even though gout flares self-resolve in one week?
NSAID discontinuation right at 1wk can re-exacerbate gout flares.
130
Prednisone dosing for acute gout flare?
25-50mg OD x 3-5d
131
What would be some circumstances where acute steroid usage in a gout flare warrants a taper?
-Long course of steroids required (ie. Couple Weeks).
-Multiple Flares / Short Intercritical Period (so bulk intake of steroid is greater in a shorter span of time).
132
Colchicine is a historically old drug (1500BC)... What plant was it derived from?
Autumn Crocus
133
Colchicine should only be initiated within how many hours of a gout flare?
24hrs
134
Optimal Colchicine dosing?
Day 1: 1.2mg (2T) stat, then 0.6mg (1T) 1hr later for a total daily intake of 1.8mg.
Next 7-10d: 0.6mg (1T) OD or BID until resolution of flare.
135
In Renal Impairment, appropriate to use Colchicine?
Probably pick something else... Evidence for how to dose reduce in renal failure not well studied.
136
Outright Colchicine CI?
Concurrent Renal / Hepatic Impairment with co-admin of CYP3A4i drugs!
137
Side effects of Colchicine?
GI Related & Myopathy / Rhabdo potential.
138
Important DDIs with Colchicine?
-Statins (increased myopathy risk).
-Azole Antifungals (ie. Ketoconazole), Clarithromycin (strong CYP Inhibitor).
-Verapamil, Diltiazem, Grapefruit Juice (moderate CYP Inhibitor).
139
Patient has CKD &/or CVD... What drugs do we avoid with acute gout flares?
Colchicine & NSAIDs... Use Corticosteroids with caution.
140
Patient has history of GI problems / Ulcers... Avoid what drugs for acute gout flare treatment?
NSAIDs & CSs... Use Colchicine with caution at its optimized dose range (heightened GI upset potential at weird high dose regimen Dr. Enweani likes to use).
141
Patient is diabetic... Which drugs do we avoid giving for acute gout flares?
CSs (increase blood glucose).
142
Who are candidates for Gout Prophylaxis?
-Hx Complicated Kidney Stones.
- >800umol / L Serum Uric Acid levels.
- >/= 2 Gout Attacks per year.
143
Reasonable serum uric acid targets for gout prophylactic treatment?
< 300 - 360umol / L
144
When bridging prophylactic treatments with NSAIDs or Colchicine, how long do we treat? Why bridge at all?
3-6mths; Prevent flares when lowering Serum Urate levels.
145
Main concerns with Uricosuric Agents (ie. Probenecid, Sulfinpyrazone)?
-Ppt. gout flares & nephrolithiasis
-Bleed risk (Sulfinpyrazone)
146
Outright CIs of Probenecid & Sulfinpyrazone?
CrCl < 60mL / min
ASA Concurrent Use
Hx Kidney Stones
147
XOi drugs?
Allopurinol
Febuxostat
148
Maximal effect of XOi drugs takes place in how many weeks?
2wks
149
Average maintenance dose of Allopurinol is what?
300mg / d
150
How often do we titrate Allopurinol doses?
q4wks
151
Common side effects of Allopurinol?
-Rash & Pruritis (caution presents same as SJS hypersensitivity Rxn!!!)
-Diarrhea
-Ppt. Acute Gout Flare (hence treatment with NSAIDs / Colchicine)
152
Which nationalities of people are more commonly affected by the HLA-B genotype expression (which can predict hypersensitivity syndrome brought upon by Allopurinol use)?
Korean, Thai, Chinese
153
Febuxostat's one outright CI?
Azathioprine / Mercaptopurine use (immunosuppressive nature of these drugs greatly increased with Febuxostat use).
154
Important DDIs of Allopurinol (because both interactions increase Hypersensitivity Syndrome risk)?
ACEi's, All Diuretics
155
Uricase Enzyme drugs (ie. Pegloticase, Rasburicase) convert Uric Acid into what water-soluble metabolite?
Allantoin
156
Main concern with Uricase Enzyme drugs?
AB Development (92%)... Not intended for LTU for this exact reason (require transfer onto Allopurinol or Febuxostat).
157
Best choice for gout prophylaxis in pregnant women?
Allopurinol... Avoid Febuxostat (limited evidence).
