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1. Rheum RC > Medications / Vaccines > Flashcards

Medications / Vaccines Flashcards

1
Q

NSAID MoA

A

-Inhib prostaglandin synthesis via COX inhibition

MAYBE:
-Possibly inhib NFkB, neutrophil aggregation/ adhesion, thus: less superoxide, degradative enzymes, cytokines

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2
Q

COX1 vs COX2 selective drug examples

A

Nonselective: low dose ASA
-1 selective: ibuprofen, naproxen, indomethacin
-2 selective: diclofenac, meloxicam
-2 highly selective: celecoxib

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3
Q

** How do NSAIDs cause asthma**

A

– COX inhibition result in less PGE2 production (bronchodilator)

– COX inhibition → AA precursor shunting down leukotriene pathway (proinflammatory)

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4
Q

** Alternatives in RA if NSAID allergy**

A

-Tylenol

-Allergy Desensitization

-Leukotriene ANT

-COX2 selective inhibitor (Celecoxib)
-Salsalate (NSAID that does not inhib COX; decreases NFkb)

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5
Q

GC antiinflamm MoA

A

Genomic: Binds cytoplasmic GC R’s to enter nucleus increase transcription of antinflammatory proteins (IL10, IkB), and inhib proinflammatory cytokines genes (chemokines, COX2, adhesion molecules)

Nongenomic:
Antiinflamm via
- Binding lymphoctyes/monocyte membrane GC receptors
- Reducing Ca & Na cycling across cell membranes

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6
Q

GC fx on Innate Immune system

A

– Inhib NFkB → suppress Cox2 synthesis

– Inhib PG production (via lipocortin1 production)

– Causes more bradykinin degradation → vasoconstriction (less swelling/pain)

– Interfere w/ phagocytosis and cytokine production by macrophages/neutrophils

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7
Q

GC fx on Adaptive system

A

Inhib T helper, Th1> Th2 & Th17 production (anergy to TB and skin testing)
-Cause dendritic cell apoptosis
-Redistributes T cells and monocytes to tissues (monocytopenia)
-Inhib mast cell degranulation

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8
Q

Steroid conversion

A

Cortisol (hydrocortisone) 20mg =
-Prednisone = prednisolone = 5mg =
-Methylprednisolone = Triamcinolone = 4mg =
-Dexamethasone = 0.75mg

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9
Q

Factors affecting GC dose efficacy

A

– Increase clearance: Age (<12yo), hyperthyroid, nephrotic syndrome, HD,
– Increased metabolism: anticonvusants, rifampin
– Reduce absorption: aluminum/Mg antacid

– Decreased conversion: Liver dz
– Decreased metabolism: erythomycin, ketoconazole,

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10
Q

**GC adverse fx **

A

-Weight gain, increased TG and BG
-HTN
-Growth suppression (less if <0.5mg/kg)
-AVN, Osteoporosis
-Muscle weakness
-Cataract, Glaucoma
-Skin bruising, striae, hirsuttism, delayed wound repair
-PUD

-Infection: PJP, TB, fungal, herpes, CMV,
-Decreased response to vaccines
-Allergy testing affected

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11
Q

When to start PJP PPx

A

Steroid >15-20mg/d for >3-4wks
Age >60

-Disease affects lungs (GPA, DM)

-Additional immunosuppression (CYC, Ritux, TNFi)
-Low CD4
-Lymphopenia

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12
Q

**7 potential side-effects from intra-articular steroid injections

A

Pain
-Bleeding
-Nerve injury
-Post injection flare
-Infection
-Hypopigmentation
-Tendon rupture
-Tissue atrophy
-Vasovagal reaction
-Osteonecrosis

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13
Q

When to suspect adrenal insuff

A

Cushingoid
->20mg pred >3wks
->5mg >1y
-Fasting plasma cortisol <5-10ug/dL

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14
Q

HCQ dosing +
when to decrease dose

A

<5mg/kg daily
-Decrease if liver, renal dz, or tamoxifen use

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15
Q

** HCQ screening interval**

A

-Baseline
-Yearly after year 5
-Yearly after baseline if: higher than recommended dose, coexistent eye dz, >60yo, tamoxifen use, renal/liver dz

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16
Q

**HCQ screening regimen- what optho tests **

A

-Fundus examination
-Visual fields
-Spectral domain optical coherence tomography (SD OCT)

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17
Q

**How to reduce ocular tox in HCQ **

A

Prescribe correct dose
-Regular screening
-Assess for risk factors: higher than recommended dose, coexistent eye dz, >60yo, tamoxifen use, renal/liver dz

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18
Q

** 3 types of ocular tox from HCQ **

A

-Keratopathy (corneal deposits)

-Retinopathy/Bulls eye Maculopathy (binds melanin in retinal pigment epithelium damaging photoreceptors)

-Cycloplegia (Ciliary body dysfunction)

-Decreased visual acuity → blurred vision, photophobia

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19
Q

** HCQ nonocular side fx **

A

GI: N/V, diarrhea, cramps

-Derm: rash, HYPERPIGMENTATION, exacerbate psoriasis

-Cardio: Cardiomyopathy (test trop/BNP after 5-10y), QT prolongation

-CNS: H/A, dizzy, tinnitus

-MSK: Myopathy/neuropathy esp if renal insuff

-Heme: Aplastic anemia, hemolysis (rare unless G6PD def)

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20
Q

** HCQ MoA**

A

-Weak bases accumulate in acidic lysosomes in APCs (DC, macrophage)→ disrupt Ag processing, MHC2 bonding, and presentation to T cell
-Inhib binding of RNA/DNA to TLR → less IL1, IL6, IFN, and PGs

-May also inhib NFKb and COX (block PG action)

-Inhib PLT aggregation/adhesion → prevent clots
-Increase lipoprot R → lower lipid lvl
-Decrease insulin degradation → prevent DM

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21
Q

** SSZ side fx**

A

N/V, Rash
-H/A, dizziness
-Hepatotox
-AZOOSPERMIA (reversible w/i 3 mo of DC)
- Leukopenia (neutropenia, agranulocytosis)
-HYPERSENSITIVITY rxn (transaminase, fever, adenopathy, rash)
-Eosinophilic pneumonitis

-HEMOLYSIS (if G6PD def)

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22
Q

**SSZ MoA **

A

SSZ → sulfapyridine via colonic bacteria → 5ASA (stays in bowel) = local antiinflamm via:

-1. Inhib COX: less PG and leukotriene
-2. Inhib NFkB: less TNFa, IL1, osteoclast formation
-3. Upregulates adenosine → antiinflamm
-4. Inhib B cell fcn

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23
Q

MTX mech of administration diff

A

-PO = SC at doses <15mg
-SC > PO at doses >15mg
-PO split dosing better than single dosing >15mg

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24
Q

MTX Side fx

A

SERIOUS:
-Pneumonitis (must not retry MTX)
-Myelosuppression
-Teratogenicity
-Oral ulcers
-Photosensitivity
-Hepatic tox
-Flu like sx
-Nodulosis
-LCV
-Lymphoma (eg in EBV lymphoma pt on MTX, tx lymphoma by DC MTX)

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25
Q

** List 3 MTX side effects that won’t be fixed by folic acid **

A

Related to folate antagonism:
-Anemia,
-Neutropenia,
-Stomatitis, oral ulcers

-Unrelated to folate antagonism (thought to be secondary to adenosine pathway):
-Nodulosis,
-Hepatic fibrosis,
-Pneumonitis,
-Fatigue
-Nephrotoxicity

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26
Q

**Ways to reduce side fx of MTX **

A

Split dosing
-Reduce dose
-Folinic acid (day after MTX)
-Folic acid
-SC over PO for GI
-OCP for teratogenicity

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27
Q

Dose adjusting MTX for renal fcn

A

Reduce by 25% for CrCl<80ml/min
-Reduce by 50% for CrCl<50ml/min
-DO NOT use if Cr Cl <30mL/min

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28
Q

Alcohol limit in MTX

A

<3-5/week

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29
Q

** MTX MoA**

A

Structural analogue of folic acid and enters cells to inhib purine/pyrimidine synthesis → less T cell proliferation via:

-1. Inhib AICAR transformylase (ATIC) → increases levels of adenosine (regulates neutrophils, suppresses IL6, TNF, IL8, enhances IL1/1RA)

-2. Inhib thymidylate synthetase (TYMS) → decreases pyrimidine synthesis

-3. Inhib dihydrofolate reductase (DHFR) → inhib transmethylation → disrupts cellular function, and decreases purine synthesis for DNA/RNA/prot synthesis

-Inhibit COX & LOX → ↓PG & LT
-Inhibit MMPs → ↓cartilage damage

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30
Q

** 3 reasons for pre-treatment MTX liver biopsy at baseline**

A

Prior excessive EtOH consumption
-Persistently abnormal baseline AST values
-Chronic Hep B/C infection

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31
Q

Whatis the rxn between MTX and Septra,
–How does it happen
– How to treat

A

BOTH are anti-folate
-Septra competes for tubular secretion and displacement of albumin binding sites increasing MTX lvls (decreased excretion)

-Tx: hold MTX, stop septra, give folinic rescue
-MTX is dialyzable

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32
Q

** How does injectable gold work**

A

~to HCQ: taken up into macrophages to inhib Ag processing and presentation

-Inhib NFkB → less TNF, IL1, IL6
-Blocks PG production
-Anti-angiogenic and anti-inflamm properties

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33
Q

LFN Side fx

A

Nonspec: N/V/D, rash

-ILD/Pneumonitis
-Peripheral Neuropathy
-HTN, DLPD
-Myelosuppression (Cytopenia)
-Hepatotox
-Teratogenecity

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34
Q

LFN MoA

A

Inhib dihydroorotate dehydrogenase (DHODH) →
Decreased synthesis of uridine →
Decreased pyrimidine synthesis → stopping lymphocyte cell division (less immune cells)

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35
Q

LFN dose

A

20mg PO daily

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36
Q

How to reverse LFN

A

Cholestyramine 8g TID x11d (does not hv to be consecutive)

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37
Q

Managing increased LFTs in LFN

A

> 1x but <2x = follow
->2x ULN or persistent minor elevation = reduce dose
->3x ULN = stop LFN and consider cholestyramine

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38
Q

** -List vaccine that are given in 40yF pre biologic start **

A

> 18yo and taking immunosuppressive
-Shingrix (herpes Zoster)
-Flu (high dose)
-Pneumovax (and under 65)
-+ COVID +/- hep B/C

->26yo and <45yo taking immunosuppressive and not previous vaccinated
-HPV

->65 with rheumatic disease
-Flu (high dose

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39
Q

** List nonlive and live vaccines **

A

Inactivated:
– High dose adjuvanted Influenza yearly
– Pneumococcal @ start of DMARD therapy, 5y later, and at age 65
– HPV
– Hep B
– Age appropriate: tetanus, meningococcal, H Flu, Shingrix

-Other inactivated vaccines as appropriate: polio, rabies, Hep A/B, typhoid

-Live: MMR, zostavax, nasal flu vaccine, VZV, yellow fever, oral typhoid, rotavirus, smallpox

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40
Q

**MTX management for NON-LIVE vaccine **
– Influenza
– Other non-live attenuated

A
  • Influenza: HOLD MTX for 2 weeks AFTER vaccine (if dz activity allows)

– Other non-live attenuated: CONTINUE

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41
Q

**RTX management for NON-LIVE vaccine **
– Influenza
– Other non-live attenuated

A
  • Influenza: CONTINUE

– Other non-live attenuated: time vaccine for when next ritux due, then HOLD for 2 weeks AFTER (if dz activity allows)

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42
Q

**Prednisone management for NON-LIVE vaccine **
– Influenza
– Other non-live attenuated

A
  • Influenza: GIVE vaccine at any dose

– Other non-live attenuated:
-GIVE vaccine unless 20mg or more (should wait until <20mg)

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43
Q

** Management of nonMTX/RTX immunosuppression for NON-LIVE vaccines:
– Influenza
– Other non-live attenuated**

A
  • Influenza: CONTINUE

– Other non-live attenuated: CONTINUE

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44
Q

** Management of immunosuppression for LIVE vaccines: (GUIDELINES)**
-GC, MTX, AZA, LFN, MMF, CNI, PO CYC
-JAKi
-TNF, IL17, IL12/23, BAFF/BLySi, IL6, IL1i, Abatacept, Anifrolimab, IV CYC
-Ritux
-IVIG

A
  • GC (continue if high risk flare or adrenal insuff), MTX, AZA, LFN, MMF, CNI, PO CYC: hold 4 weeks BEFORE AND AFTER live vaccine

– JAKi: hold 1 week before and 4 weeks after

– Inhibitors for TNFa, IL1, 6, 17, 12/23, 23, BAFF/BLyS, IV CYC: HOLD 1 dosing interval before and 4 weeks AFTER

– Ritux: hold 6 months before and 4 weeks after

– IVIG: hold 8,10,11months before and 4 weeks after for 300-400mg/kg, 1g/kg, and 2g/kg

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45
Q

When to give rotavirus vaccine to infants exposed to immunosuppression in T2/T3
– TNFi
– Ritux

A

TNFi: GIVE WITHIN 1st 6 months of life
-Ritux: DO NOT give until AFTER 6months of life

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46
Q

Recommendations for medication management for live vaccines

A

Pred<20 and DMARDS can get live vaccines
-If higher doses, lower to <20mg at least 1mo before live vaccine

-Biologic: off for 3 half lives before getting live vaccine, and restart 1 mo after vaccine

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47
Q

ACR20

A

20% improvement in TJC, SJC, and 3/5 of:
- Pt pain score,
- HAQ
- Pt global score
- Physician global score
- ESR or CRP

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48
Q

AZA side fx

A

-Myelosuppression (worse if TPMT deficiency)
-Hepatotox , Nephrotox
-Pancreatitis
-Hypersensitivity syndrome (fever, hepatitis, ARF, rash w/i 1st 2wks)
-N/V, rash
-Malignancy
-Infxn (HZV, CMV)

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49
Q

Why TPMT test

A

TPMT metabolizes thiopurines, if inactivated → excess AZA → fatal myelosuppression (cytopenias, macrocytosis)

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50
Q

How to adjust AZA with CBC or other drugs

A

If cytopenias → reduce by 50% or DC
-If use w/ allopurinol/febuxostat → reduce dose by 75% or do not use combo

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51
Q

AZA DDI

A

AZA inactivated by xanthine oxidase (inhibited by allopurinol and febuxostat) and TPMT (inhib by SFZ)

-Septra , SZS increase leukopenia risk
-AZA decrease warfarin fx

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52
Q

AZA MoA

A

Converted to 6MP then 6TGN which decreases purine synthesis → inhib DNA, RNA, protein synthesis → cytotox and decreased cell proliferation

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53
Q

MMF side fx

A

-Myelosuppression
-GI
-Hepatotox
-NOT nephrotoxic

-Infxn (PJP, HZV, CMV)
-Lymphoproliferative malignancy (EBV)

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54
Q

MMF dose

A

500-1500BID
-1000 BID if Cr Cl <30 and in Asians

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55
Q

MMF vs Myfortic

A

500mg MMF = 360mg Myfortic
-Switch to Myfortic if GI side fx w/ MMF

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56
Q

MMF MOA

A

MMF → hydrolyzed to active MPA → (inhibits inosine 5 monophosphate dehydrogenase) → decreased synthesis of purine, guanosine → inhib lymphocyte prolif

-MPA inhib carbohydrate transfer to glycoproteins → less adhesion molecules → decrease lymphocyte migration

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57
Q

CYC dosing

A

PO: 50-200mg (0.7-2mg/kg/d)
-IV: 0.5-1g/m2 BSA or 15mg/kg monthly
-OR 500mg IV q2wks x6

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58
Q

Adjusting CYC dosing

A

CBC 10-14d after each dose for nadir
-If WBC <3.5 or neuts <1.5 → reduce dose by 25%
-If nadir >4, dose increased if dz not controlled

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59
Q

CYC MOA

A

Alkylates DNA → crosslinks and breaks → apoptosis and decreased DNA synthesis.
Affects rapidly dividing cells (eg B and T cells)

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60
Q

CYC side fx

A

-Myelosuppression (WBC nadir)
-Infection (esp HSV, screen hep B/C, HIV, TB)

-Hemorrhagic cystitis & bladder Ca (less w/ IV, mesna)
-Malignancy

-Infertility (ovarian failure, azoospermia)
-Teratogenicity

-Pneumonitis, pulm fibrosis
-SIADH
-PRES

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61
Q

** Cyclosporine/Tacro/Sirolimus MoA**

A

Inhib calcineurin to prevent transcription and production of IL2 and subsequent T cell proliferation

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62
Q

Cyclosporine/Tacro Side fx

A

-Nephrotox (reversible), HTN, anemia,
-Hyperuricemia (switch to tacro - less hyperuricemia)
-Hepatotox rare
-Bone pain (lower dose or use CCB)
-Malignancy (lymphoma, skin Ca)
-Infxn,
-H/A, tremor, hyperpigmentation

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63
Q

Apremilast indication and dose

A

PsO, PsA, Behcet
-10mg daily → 30mg BID

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64
Q

Apremilast side fx and monitoring

A

Side fx: diarrhea, weight loss, H/A

-Monitoring: NONE

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65
Q

Apremilast MoA

A

Inhib PDE4 → more intracellular cAMP → decreased proinflammatory mediator (TNFa, IL12, IL23, IFNgamma, inducible NO synthase), increased antiinflamm cytokines (IL10)

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66
Q

Name the JAKs

A

Jak 1, 2, 3
-TYK2

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67
Q

** JAK -STAT normal pathway**

A
  • Cytokine/Growth factors bind and causes dimerization and phosphorylation of receptors
  • STAT transcription factors bind phosphorylated R’s
  • JAK associated w/ R phosphorylates STAT that dimerize and translocate to nucleus to start transcription of inflammatory mediators
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68
Q

** JAKi MOA**

A

JAKi bind JAK on R’s to prevent phosphorylation and STAT binding → Less transcription of proinflamm cytokines

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69
Q

Cytokine receptors assoc’d w/ each JAK

A

-JAK 1: Same as JAK 3 (IL2, 4, 7, 9, 15, 21) + IL6, 10, 27, IFNa/b/g
-JAK 2: IL 6, 12, 27, IFNg, EPO, thrombopoeitin, Prl, growth hormone, GCSF
-JAK 3: IL2, 4, 7, 9, 15, 21
-TYK 2: IL6, 10, 12, 23, 27, IFNa/b

70
Q

** List 4 cytokines that are NON-JAK associated cytokines (2016)**

A

-IL1
-IL17
-IL18
-TNF
-TGFb

71
Q

** JAKi and which JAK they inhib**

A

Tofacitinib: Jak 1,3 > Jak 2
-Baracitinib and Ruxolitinib: Jak 1 = 2
-Upadacitinib: Jak 1 highly selective
-Deucravacitinb (TYK2)

-*all JAKi inhib all JAK to some degree

72
Q

Tofa MoA

A

-Jak 1 inhib → less (IL2, 4, 7, 9, 15, 21) as well as less IL6, 10, 27, IFNa/b/g

-Jak 3 inhib → less IL 2, 4, 7, 9, 15, 21 and less T/B cell signaling

73
Q

** JAKi dose **

A

Tofa 5mg BID or 11mg XR daily (5mg if severe liver/renal dz)
-Can be used alone or with MTX (avoid combo w/ AZA, bDMARDs, cyclosporine)

Upadacitinib 15mg daily
Baracitinib 2mg daily

74
Q

Tofa monitoring

A

CBC, liver, Cr, LIPIDS

75
Q

**Tofa Side fx **

A

~IL6i: HYPERLIPIDEMIA (LDL and HDL), GI PERFORATION , Zoster, myelosuppression

-Hepatotox, Cr increase
-Nasopharyngitis, diarrhea, headache
-MACE events, VTE

-Infxn: decreased vaccine response, CMV, TB, cryptococcus, BK virus, toxo, candidiasis
-Malignancy (lymphoma, solid tumor)

76
Q

Tofa dose adjustment

A

5mg if severe renal/liver

Decrease by half if on antifungal (eg ketoconazole, fluconazole)

77
Q

Bara and Upa side fx

A

Same as tofa

-CK elevation WITHOUT weakness or rhabdo

78
Q

IVIG dosage

A

1-2g/kg over 1-5d

79
Q

IVIG side fx

A

-ANAPHYLAXIS if IgA deficiency
-Aseptic meningitis
-Serum sickness: H/A, Flushing, fevers, chills , Nausea, Hypotension
-Chest tightness, back pain, myalgias
-Leukopenia

80
Q

IVIG indications

A

-DM/PM
-AOSD, MAS
-Kawasaki
-CIDP
-ITP
-Offlabel: APLA, AIHA,

81
Q

IVIG MoA

A

– Binds proinflammatory cytokines & decrease complement activation
– Enhance Treg function
– Inhib dendritic cells to decrease number of activated T cells
– Increases degradation of pathogenic IgG
– AB bind B cell surface Ig to prevent binding to autoantigen

82
Q

PLEX MoA

A

Removes immune complexes and autoantibodies

83
Q

PLEX used for

A

-TTP
-CAPS
-SLE w/ DAH, NPSLE
-NMO
-AAV w/ DAH or RPGN
-Hep B PAN
-Hep C Cryo
-PANDAS

84
Q

**Nomenclature for biologics **
– Cept (eg ETN, abatacept, rilonacept)
– Ximab (eg infx, rtx)
– Zumab (eg certolizumab, tocilzumab, ixekizumab, eculizumab)
– Umab (eg adalimumab, golimumab, belimumab, usteikinumab)
– Ra (eg anakinRa)

A

-Cept: R drug mops up ligand, so it can’t bind to real R
-Ximab: CHIMERIC monoclonal AB
-Zumab: HUMANIZED monoclonal AB
-Umab: FULLY HUMAN monoclonal AB
-Ra: R-ANT

85
Q

** Structure of Infliximab vs Etanercept **

A

Infliximab = Chimeric mouse-human monoclonal antibody: constant regions of human IgG1k + variable region of high affinity anti-human TNF antibody

Etanercept = Two soluble p75 TNF-R extracellular domains linked to Fc portion of human IgG binds TNF to prevent it from binding cell bound TNF-R

86
Q

10 things to tell your patients about Etanercept

A
  1. Biological protein made in a lab to block a specific inflammatory protein TNFa
    -2. Injxn self administered under the skin once weekly
    -3. Takes 6-8 weeks to see effect
    -4. Increases risk for infections
    -5. Increases risk of reactivating prior infxn (hep B, TB)
    -6. Can cause allergy/site reaction
    -7. Malignancy risk controversial for melanoma
    -8. Should not be used for CHF (Class 3-4)
    -9. Avoid in personal/fam hx of MS or hx of optic neuritis
    -10. Need to have vaccinations up to date, and avoid live vaccines during
    -11. Need to be held before surgeries
    -12. Small risk of paradoxical psoriasis (on palms and soles)
    -13. RIsk of drug induced lupus
87
Q

List actions Infliximab has that etanercept does not on TNF producing cells

-What can ETN bind that IFX cannot

A

– IFX binds BOTH soluble and cell bound TNFa→ ability to induce apoptosis of cells w/ TNFa bound to surface (including T cells)
– IFX can FIX complement and lyse cells w/ TNFa on surface (ETN cannot)
– IFX forms stable complex w/ soluble TNFa (etanercept forms unstable complexes)

-ETN can bind TNF-B (lymphotoxin)

88
Q

Biologic comorbidity screening

A

-Infxn: HIV, Hep B/C, TB, Fungal exposure
-Demyelinating dz
-Cancer
-Cardiac history, DLPD, VTE history
-Liver dz
-Preg
-Meds

89
Q

** Why inhibit TNFa in rheum**

A

TNFa-R on monocyte and macrophage
-TNFa binding →
– PG
– Proinflamm cytokines/chemokines
– Adhesion molecules (recruit neutrophils/ monocytes into synovium),
– Induce chondrocyte to produce MMP and RANKL

90
Q

Why is IL1 inhibited

A

Proinflamm cytokine existing as IL1a (cytosol & membrane bound) & IL1b (secreted into extracellular space after cleavage from proIL1b by caspase1

ILb is predominant form binding IL1-R →
- Same as TNF: Proinflamm response, PG adhesion molecules, Induce chondrocyte/synoviocyte production of MMP and RANKL
-B cell activation, RF production,
- Activate Th17

91
Q

Why is IL5 inhibited

A

-Produced by Th2 cells and mast cells

Binds IL5-R to:
-Stim B cell growth,
-Produce immunoglobulins
-Activate eosoniphils

92
Q

Why is IL6 inhibited

A

Soluble IL6-R binding IL6 proinflammatory

-Stim Th17 development → IL17 production
-Activate B cell, macrophages, and OC
-Recruits neutrophils
-With IL1 and TNF –> acute phase response (CRP, fibrinogen, fever, anorexia)
-Acts w/ other cytokines to form pannus

93
Q

Why is IL17 inhibited

A

Important in inflammation
-IL17A produced by TH17cells from CD4 Tcells stimulated by IL1, 6, 23, TGFb

-IL17 binds R → increasing IL1, 6 for inflammation; MMPs for cartilage damage, and RANKL for bone erosion

94
Q

Why is IL23 inhibited

A

IL23 produced by macrophages and dendritic cells

-Enhances survival of Th17 cells,
-Activates memory T cells
-Stimulation of antigen presentation by DCs

95
Q

** Biologic dosing **
– Etanercept
– Infliximab
– Adalimumab
– Golimumab
– Certolizumab

A
  • Etanercept: 50mg SC once a week

– Infliximab: 3mg/kg (RA) or 5mg/kg (SpA) IV at week 0,2,6, then q8wks; can increase to 10mg/kg q4weeks

– Adalimumab 40mg SC q2weeks (in uveitis, give 80mg initially then as above); can increase to weekly

– Golimumab: 200mg week 0, 100mg week 2, then 50mg SC monthly

– Certolizumab: 400mg SC at weeks 0,2,4, then monthly

96
Q

Etanercept contraindication

A

Uveitis (not effective) or IBD

97
Q

** TNFi side fx**

A
  • Injxn site rxn , Infusion rxn
  • Infxn: bacterial, TB, opportunistic, PJP
  • Malignancy (bc TNF induced apoptosis of tumor cells; lymphoma, melanoma)
  • Demyelinating syndrome (eg MS, optic neuritis, GBS, myelitis, polyradiculopathy)
  • Autoimmune phenomenon (eg drug induced lupus, LCV, Paradoxical psoriasis, Palmoplantar psoriasis)
  • CHF (avoid in class 3/4)
  • Cytopenia (neut, thrombo, pan)
98
Q

** Ways to circumvent limitations of biologics eg infusion or injection rxn, costs **

A

Costs → use biosimilar
-Infusion rxn: treat w/ steroid or antihistamine
-Injection rxn: rotate site, use citrate free formulation, use lyophylized ETN or certolizumab pegol

99
Q

** TB in TNFi**
– Which TNF worse
– Which test to screen
– When to start TNF if positive

A

IFN > SC formulation
-Monoclonal > ETN to reactivate
-Repeat TB test if ongoing exposure
-Tspot.TB more sensitive than Quantiferon if on immunosuppresive
-If latent: Start TNFi after 4 wks of therapy
If active: complete anti-TB therapy before starting TNFi

100
Q

Hep B/C w/ TNF
– When to start TNF

A

Resolved Hep B→ can receive TNF and check hepatic enzymes and viral loads periodically

-Chronic/Inactive Hep B = NO TNFi or must receive concurrent antiviral ppx (lamivudine etc)

-Hep C → can get TNFi w/o antiviral (monitor hepatic enzyme and viral RNA load)

101
Q

TNF Cancer recommendations

A

Do not use in pt w/ melanoma or lymphoma
-Do not start agent until pt cancer free for 5y
May be able to use in pt w/ previously tx solid organ malignancy

102
Q

** list classes of meds that are contraindicated in:
– Paradoxical psoriasis
– Recurrent anterior uveitis
– 70M w/ HTN
– Optic neuritis**

A
  • Paradoxical psoriasis: antiTNFa

– Recurrent anterior uveitis: etanercept (and other TNF), bisphosphonates, moxi, PD1i, immune checkpoint inhibitors

– 70M w/ HTN: LFN (increases BP)

– Optic neuritis: antiTNFa (demyelinating)

103
Q

IL1 Biologics
-list them and their
- MoA and Dose

A

Anakinra: Recombinant IL1R-ANT competitively binds IL1R, so IL1a or IL1b cannot bind
-100mg SC daily (FU CBC like DMARDs)

Canakinumab: IgG1k monoclonal AB that targets IL1B so it can’t bind IL1R for MWS, CAPS, sJIA
-150mg SC q8wks (FU CBC and LFTs)

Rilonacept: soluble decoy receptor for IL1a and ILb for MWS and CAPS
-Loading dose 320mg then 160mg SC weekly (FU CBC and lipids)

104
Q

Mepolizumab MoA and Dose

A

Human IgG1k monoclonal AB that targets IL5 which affects activation/survival of eosinophils

-300mg SC q4weeks for eGPA

105
Q

** Toci MoA and dose**
-What to monitor

A

IgG1k monoclonal AB binds soluble and membrane bound forms of IL6R inhibiting IL6 activity → less Th17 cells (less neutrophil recruitment, OC and B cell activation, and pannus formation)

-162mg SC weekly
-FU CBC, LFT, lipids

106
Q

Managing Toci dose w/ increased LFT

A

> 1-3x ULN: reduce dose and/or switch
->3-5x ULN: DC until < 3x then restart lower dose or switch
->5x = DC toci

107
Q

Managing Toci dose w/ cytopenias

A

ANC >1 = continue
-ANC .5-1 = stop until ANC >1, then restart at lower dose
-ANC<.5 =DC toci
-Thrombocytopenia <50 = DC

108
Q

** Toci side fx **

A

~to JAKi: Cytopenias, Lipid elevation, GI PERFORATION, infection (eg zoster, fungal)

-MAS

-Lowers fx of PPI, statin, OCP

109
Q

Sarilumab MoA and Dose

A

Anti IL6Ra monoclonal B that binds soluble/membrane bound human IL6Ra
-200mg SC q2weeks

110
Q

** Ustekinumab (Stelara) MoA and Dose**

A

Human IgG1k monoclonal AB that binds p40 subunit of BOTH IL12 and IL23 preventing binding to shared cell surface receptor

-Inhib of IL12 → less Th1 response and less TNFa, IFNg, IL2 production
-Inhib 23 → less Th17 response and less IL6, 17, 22, TNFa production

-TH17 and IL23 production by DCs and keratinocytes important in psoriasis

-45mg SC week 0 and 4 then q12wks

111
Q

Ustekinumab adverse rxn

A

Nasopharyngitis
-Nonmelanoma skin cancers
-Serious infxn (IL12/23 important for resistance against mycobacteria/salmonella; IL17 important for resistance against fungal infxn)
-Hypersensitivity rxn

No Nephrotoxicity, hepatotoxicity, cytopenias

112
Q

** Sekukinumab (Cosentyx) dose**

A

150mg SC weekly x4 (loading dose), then 150mg SC q4weeks

113
Q

** Ixekizumab (Taltz) dose & side fx**

A

160mg SC loading dose, then 80mg q4wks

-Side fx: injxn rxn,
-nasopharyngitis,
-IBD flare/development
-Fungal infxn

114
Q

** Guselkumab (Tremfya) MOA and dosing**

A

IgG1 monoclonal AB binds IL23 to prevent binding to R → less inflammatory cytokines and chemokines

-100mg week 0,4, then q8weeks

115
Q

** Ritux MoA **

A
  • IgG1k monoclonal AB against CD20 antigen on B cells
    – B cells eliminated by complement mediated lysis, antibody-dependent cell-mediated cytotox, or apoptosis
    – Less CD4+ T cell activation, plasma cell production

-Igs preserved bc plasma cells dont hv CD20

116
Q

** Ritux dose **

A

RA: 1g IV repeated 2 weeks later

-GPA/MPA:
– 375mg/m2 IV weekly x4 or
– 1g on day 1 and 15; maintenance 500mg IV q6m

117
Q

** Ritux indications**

A

SLE, APLA, IIM
Sjogrens, IgG4, Cryo
ITP, AIHA,
Castleman, NMO

-**DOES NOT WORK IN SPA

118
Q

** Ritux side fx**

A

Infusion rxn, serum sickness

-Increased infxn compared to other biologics
-Viral infxn : Hep B reactivation, hep C, JC virus
-HYPOGAMMAGLOBULINEMIA
-Late onset neutropenia
-Immunizations (give 2-4wks before or 6mo post RTX)
-PML

-**NO CHF, demyelinating, Ca, mycobacterial infxn; ie use Ritux if cant use TNF bc of these

119
Q

Complement targeted therapies MoA

A

Avocopan: Blocks C5a from binding C5a R (prevents neutrophil priming)

-Eculizumab - anti C5 used in HUS

120
Q

Belimumab MoA

A

IgG1k monoclonal AB against B lymphocyte stimulator protein (BLyS)/Bcell activating factor (BAFF) so it cannot promote survival, growth, maturation of autoreactive B cells and allows apoptosis to occur

121
Q

** Belimumab indication and dose**

A

Seropositive SLE (low complements and high dsDNA)
Respond best: Fatigue, Rash, Arthritis
Can be used for LN (NOT SEVERE)
little data for CNS
Heme does not respond

-Dose:
-IV: Loading 10mg/kg at 0,2,4 weeks, then q4weeks for maintenance
-SC: 200mg weekly

122
Q

Belimumab tox

A

Infxn
-Infusion rxn
-Malignancy
-Depression/suicide

123
Q

** Abatacept (Orencia) MoA and dose**

A
  • Human fusion protein made of extracellular portion of CTLA4 fused to Fc fragment of IgG1
  • Binds CD80/CD86 on APCs preventing molecule binding to ligand, CD28, on T cells (ie less T cell activation and less proinflammatory cytokines)

-SC 125mg weekly
-IV weight based

124
Q

Risk factors for biologic nonresponse

A

-Young, obese, females
-Smoking
-High dz activity

125
Q

Eculizumab MoA, Indications, and side effect

A

IgG2/4K monoclonal AB binds C5 and inhib cleavage to C5a and C5b preventing generation of MAC (C5b-9)

-Indication: TMA, atypical HUS, PNH, MG

-Side fx: meningococcemia

126
Q

Colchicine MoA

A

Irrev binds free tubulin dimers to disrupt microtubule formation → inhib neutrophil chemotaxis, phagocytosis, and cytokine secretion

-Inhib phopholipase A2 → less inflammatory PG and leukotrienes

-Modulates pyrin expression

127
Q

Colchicine indications

A

-FMF
-Behcet, Aphthous stomatitis
-Neutrophilic dermatoses eg Sweets
-Cutaneous LCV
-Pericarditis
-Gout Tx and PPX

128
Q

Colchicine Toxicity RF

A

Elderly
-Renal/hepatic impairment
-Chronic use
-CYP3A4 inhibitors

129
Q

Colchicne tox

A

-GI (N/V/D)
-Neuromyopathy (CK, prox weakness, periph neuropathy), rhabdo
-Hepatotox, Nephrotox
-Myelosuppression
-Circulatory collapse

130
Q

ULT dosage

A

Allopurinol 50 or 100mg and increase by similar q2-5wks until <6 or <5 if tophi

-If fail or contraindication: Febuxostat: 40mg and increase to 80mg after 2-5wks

-If contraindication & uricosuric: Pegloticase 8mg over 2hr

-If not uricosuric: Probenecid 250mg BID x1wk then 500mg BID and increase to 500mg q4w if not at goal

131
Q

ULT DDI

A

Allopurinol and Febuxostat
-Do not use with AZA or 6MP

-Allopurinol: increases CYC, warfarin, cyclosporine lvls. Decreases excretion of thiazide.

132
Q

Manifestations and Tx of allopurinol hypersensitivity syndrome

A

Skin rash (SJS, TEN), fever, eosinophilia, hepatic necrosis, leukocytosis, renal failure

-Tx AHS: high dose steroids and HD (removes oxipurinol)

133
Q

Risk factors allopurinol hypersensitivity syndrome

A

Female
-Hx of rash on allopurinol
-Renal insuff
-Concomittant diuretic therapeutic,
-Elderly
-HLAB5801
-Korean, Han chinese, Thai

134
Q

Probenecid MoA

A

Competitively inhib URAT1 and GLUT9 → decreased tubular reabsorption of urate → increased uricosuria

135
Q

Probenecid side fx

A

-Acute gouty flare
-Urate nephropathy/stones, Nephrotic syndrome

-GI: N/V
-Dermatitis
-Cytopenia eg Hemolytic anemia from G6PD deficiency

-Hypersensitivity, eg SJS

136
Q

Probenecid contraindications

A

-Elderly and Low CrCl<50

-24h urine collection >800mg uric acid
-Avoid w/ salicylates (increases uric acid excretion)
-Uric acid stones

-G6PD def

137
Q

How to minimize Urate nephropathy/stones

A

-2L/d fluid intake
-Urine alkalinzation (usually not needed) w/ Na bicarb or K citrate → urine pH>6

138
Q

Pegloticase MoA and precautions

A

Recominant mammalian uricase

-Precaution: G6pd def (hemolytic anemia and methemoglobinemia); can cause gout flare; infusion rxn and anaphylaxis

-Do not use with other ULT

139
Q

Type of Calcium to use in osteoporosis

A

Ca Carbonate absorbed less if achloryhydria or PPI
-Ca Citrate less affected by PPI and if hx of stones

140
Q

How much Ca and Vit D in what

A

Ca (target 1200mg): 300mg in 1 cup milk/yogurg/fruit juice w/ Ca, 1 oz of cheese

-Vit D (target 800 daily): 400IU in 1qt of fortified milk or 3.5oz fatty fish

141
Q

Reasons for low vit D

A

-Low intake (malabsorption, bypass, celiac)
-Severe liver dz,
-Antiepileptic drugs,

142
Q

Bone remodeling process

A

Osteocytes = mechanoR that sense skeletal stress and send signals eg sclerostin to organize bone remodelling

-OC resorbs bone via acid/enzymes over 3-4wks
-OB migrate into resoprtion pits and secrete osteoid → mineralizes w/ CaPO4 crystals (hydroxyapaptite) over 3 mo

143
Q

Roles of RANK, RANKL, OPG

A

RANK = R-activator of NFkB = receptor on OC
-RANKL on OB (or secreted by other cells) binds RANK to stim OC bone resorption

-Osteoprotegerin (OPG) = soluble decoy R produced by OB and BM stromal cells that bind RANKL → prev binding to RANK

-Bone resorption driven by RANKL and inhib by OPG

144
Q

OP meds dosing

A

Alendronate 10mg/d or 70mg/wk
-Risedronate 5mg/d or 35mg/wk or 150/mo
-ZA 5mg yearly
-Denosumab 60mg SQq6mo
-Raloxifiene 60mg/d
-Calcitonin 200U/d
-Teriperitide 20mcg SC/d
-Romosozumab 210mg SQ/mo

145
Q

Bisphosphonate MoA

A

Pyrophosphate analogs that affect OC acting on bone by blocking farnesyl diphosphosphate synthase (FDPS) affecting protein trafficking needed for “ruffled border” →OC apoptosis

146
Q

BP side fx

A

PO → GI sx
-IV → acute phase rxn, afib
-**Hypocalcemia, ONJ, AFF ** (as with all OP meds except teriperitide)
-Uveitis, keratitis, optic neuritis, orbital swelling

147
Q

How to take BPs

A

1st thing in morning on empty stomach w/ water → upright and NPO x30-60min

148
Q

BP contraindications

A

Esophageal problems (stricture, achalasia, dysmotility, amalabsorption) → IV>PO
-Hypocalcemia
-Cr Cl<35
-DC as early as possible before pregnancy
-Not sure if affects breastfeeding

149
Q

Denosumab MoA

A

Monoclonal AB against RANK-L ie preventing OB from binding RANK to cause OC activity

150
Q

Dental recommendations w/ denosumab

A

-Do invasive dental work (extraction, implants) before starting Denosumab to decrease ONJ risk
-Schedule procedure 6mo after injxn
-Give next injxn after dental procedure healed

151
Q

How to bridge when DC prolia

A

Start PO BP 6mo after last injxn
-Start IV ZA 9mo after last injxn

152
Q

ONJ Risk factors

A

-Old
-Invasive oral procedure
-Use of GC, prolonged BP use
-Comorbidities: DM, HTN, DLPD, CKD
-EtOH, Smoking

153
Q

BP recommendations to prevent AFF

A

1-2 y D holiday after 5y of BP for osteopenic
-Switch to anabolic or nonBP agent if prev fragility # or v low BMD

-Stop ZA after 3y (no fragility #) or after 6y (hx of fragility #) for 3 years

154
Q

Counsel HRT

A

Estrogen replacement prevents # but increases risk BCa and CV events
-Give only for up to 3 y for postmenopausal hot flash

155
Q

SERM (Raloxifene) MoA

A

E2 Ag in some tissue (bone), E2 ANT (breast)

156
Q

SERM side fx

A

Hot flash, cramps, VTE

157
Q

TRT pros/cons

A

Increase bone mass
-No # reduction

158
Q

Teriparatide MoA and dose

A

34 amino acid fragment of intact PTH activates PTH R on OB and OB precursor prolif, differentiation, and survival → osteoid formation and increased BMD.

-20mcg/d SC x18-24mo

159
Q

Teriparatide contraindication

A

-Other bone diseases: Paget’s disease, HyperPTH, bone mets
-HyperCa, Increased ALP
-Children or young adults w/ open epiphyses

-Pregnancy

-Prior external beam or implant radiation therapy (bc drug can cause osteosarcoma)

160
Q

Teriparatide side fx

A

HyperCa (dig, kidney stone)
-Hyperuricemia
-GI upset
-Arthralgia

161
Q

When to end drug holiday / What is definition of drug failure

A

Fragility fracture occurs
-BMD decreases more than least significant change
-Bone turnover markers increase by >30% or rise to upper 50% of reference range

162
Q

Markers for:
– Bone formation
– Bone resorption

A

Formation: ALP, osteocalcin, P1NP
-Resorption: Urine/serum N- telopeptides, serum C telopeptides

163
Q

Romosozumab MoA & dose

A

Humanized monoclonal AB against sclerostin (protein made by osteocyte that inhibits Wnt; Wnt stimulates OB bone formation)

-Blocking sclerostin = less inhib of Wnt = more bone formation

-210mg SC /mo

164
Q

Romosozumab side fx

A

Arthralgia
-Headache
-Injxn site rxn
-MACE events
-Hypocalcemia
-ONJ
-AFF

165
Q

Indications for splinting

A

CTS
-DQ tenosynovitis
-1st CMC OA
-Inflammatory arthritis

166
Q

Types of splints for RA or PsA hands

A

Finger splint for swan neck or bouttoneire
-Resting hand splint
-Wrist support
-CMC splint (more for OA)
-Knee sleeves

167
Q

Etoposide MoA

A

Topoisomerase II inhibitor → DNA strand breaks and cell arrest

168
Q

Which part of cannabis induces psychotic symptoms? **
-Max dose of cannabis per day as per the statement **

A

THC (ie preferred lower THC and higher CBD)

-3g

169
Q

** 3 populations where you should not use cannabis **

A

<25 years
-Allergic
-Pregnant/breastfeeding
-Personal Hx of psychotic illness, substance use disorder, suicidal attempts/ideation

170
Q

*Side effects of cannabis in the short term **

A

Psychomotor,
-Dizziness,
-Appetite,
-Mood changes,
-Disorientation and
-Psychosis,
-Anxiety.

171
Q

** Young guy with RA on MTX, vaping marijuana, comes in with acute dyspnea, cough, fever - name 4 DDx **

A

RA induced lung injury (Organizing pneumonia/hypersensitivity pneumonitis)
-MTX-induced hypersensitivity pneumonitis
-Pneumonia
-Vaping associated lung injury

172
Q

Prolia side effectss

A

AFF
HypoCa
ONJ
Infection
GI side effects
Cytopenias

1. Rheum RC (23 decks)

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