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
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
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)
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)
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
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
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
8
Q
Steroid conversion
A
Cortisol (hydrocortisone) 20mg =
-Prednisone = prednisolone = 5mg =
-Methylprednisolone = Triamcinolone = 4mg =
-Dexamethasone = 0.75mg
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,
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
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
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
13
Q
When to suspect adrenal insuff
A
Cushingoid
->20mg pred >3wks
->5mg >1y
-Fasting plasma cortisol <5-10ug/dL
14
Q
HCQ dosing +
when to decrease dose
A
<5mg/kg daily
-Decrease if liver, renal dz, or tamoxifen use
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
16
Q
**HCQ screening regimen- what optho tests **
A
-Fundus examination
-Visual fields
-Spectral domain optical coherence tomography (SD OCT)
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
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
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)
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
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)
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
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
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)
25
** List 3 MTX side effects that won’t be fixed by folic acid **
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
26
**Ways to reduce side fx of MTX **
Split dosing
-Reduce dose
-Folinic acid (day after MTX)
-Folic acid
-SC over PO for GI
-OCP for teratogenicity
27
Dose adjusting MTX for renal fcn
Reduce by 25% for CrCl<80ml/min
-Reduce by 50% for CrCl<50ml/min
-DO NOT use if Cr Cl <30mL/min
28
Alcohol limit in MTX
<3-5/week
29
** MTX MoA**
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
30
** 3 reasons for pre-treatment MTX liver biopsy at baseline**
Prior excessive EtOH consumption
-Persistently abnormal baseline AST values
-Chronic Hep B/C infection
31
**Whatis the rxn between MTX and Septra,
--How does it happen
-- How to treat**
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
32
** How does injectable gold work**
~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
33
LFN Side fx
Nonspec: N/V/D, rash
-**ILD/Pneumonitis**
-**Peripheral Neuropathy**
-**HTN**, DLPD
-Myelosuppression (Cytopenia)
-Hepatotox
-Teratogenecity
34
**LFN MoA**
Inhib dihydroorotate dehydrogenase (DHODH) →
Decreased synthesis of uridine →
Decreased pyrimidine synthesis → stopping lymphocyte cell division (less immune cells)
35
**LFN dose**
20mg PO daily
36
How to reverse LFN
Cholestyramine 8g TID x11d (does not hv to be consecutive)
37
Managing increased LFTs in LFN
>1x but <2x = follow
->2x ULN or persistent minor elevation = reduce dose
->3x ULN = stop LFN and consider cholestyramine
38
** -List vaccine that are given in 40yF pre biologic start **
>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
39
** List nonlive and **live** vaccines **
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
40
**MTX management for NON-LIVE vaccine **
-- Influenza
-- Other non-live attenuated
- Influenza: HOLD MTX for 2 weeks AFTER vaccine (if dz activity allows)
-- Other non-live attenuated: CONTINUE
41
**RTX management for NON-LIVE vaccine **
-- Influenza
-- Other non-live attenuated
- Influenza: CONTINUE
-- Other non-live attenuated: time vaccine for when next ritux due, then HOLD for 2 weeks AFTER (if dz activity allows)
42
**Prednisone management for NON-LIVE vaccine **
-- Influenza
-- Other non-live attenuated
- Influenza: GIVE vaccine at any dose
-- Other non-live attenuated:
-GIVE vaccine unless 20mg or more (should wait until <20mg)
43
** Management of nonMTX/RTX immunosuppression for NON-LIVE vaccines:
-- Influenza
-- Other non-live attenuated**
- Influenza: CONTINUE
-- Other non-live attenuated: CONTINUE
44
** 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
- 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
45
**When to give rotavirus vaccine to infants exposed to immunosuppression in T2/T3**
-- TNFi
-- Ritux
TNFi: GIVE WITHIN 1st 6 months of life
-Ritux: DO NOT give until AFTER 6months of life
46
Recommendations for medication management for live vaccines
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
47
ACR20
20% improvement in TJC, SJC, and 3/5 of:
- Pt pain score,
- HAQ
- Pt global score
- Physician global score
- ESR or CRP
48
AZA side fx
-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)
49
Why TPMT test
TPMT metabolizes thiopurines, if inactivated → excess AZA → fatal myelosuppression (cytopenias, macrocytosis)
50
How to adjust AZA with CBC or other drugs
If cytopenias → reduce by 50% or DC
-If use w/ allopurinol/febuxostat → reduce dose by 75% or do not use combo
51
AZA DDI
AZA inactivated by xanthine oxidase (inhibited by allopurinol and febuxostat) and TPMT (inhib by SFZ)
-Septra , SZS increase leukopenia risk
-AZA decrease warfarin fx
52
AZA MoA
Converted to 6MP then 6TGN which decreases purine synthesis → inhib DNA, RNA, protein synthesis → cytotox and decreased cell proliferation
53
MMF side fx
-Myelosuppression
-GI
-Hepatotox
-**NOT nephrotoxic**
-Infxn (PJP, HZV, CMV)
-Lymphoproliferative malignancy (EBV)
54
MMF dose
500-1500BID
-1000 BID if Cr Cl <30 and in Asians
55
MMF vs Myfortic
500mg MMF = 360mg Myfortic
-Switch to Myfortic if GI side fx w/ MMF
56
MMF MOA
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
57
CYC dosing
PO: 50-200mg (0.7-2mg/kg/d)
-IV: 0.5-1g/m2 BSA or 15mg/kg monthly
-OR 500mg IV q2wks x6
58
Adjusting CYC dosing
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
59
CYC MOA
Alkylates DNA → crosslinks and breaks → apoptosis and decreased DNA synthesis.
Affects rapidly dividing cells (eg B and T cells)
60
CYC side fx
-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
61
** Cyclosporine/Tacro/Sirolimus MoA**
Inhib calcineurin to prevent transcription and production of IL2 and subsequent T cell proliferation
62
Cyclosporine/Tacro Side fx
-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
63
Apremilast indication and dose
PsO, PsA, Behcet
-10mg daily → 30mg BID
64
Apremilast side fx and monitoring
Side fx: diarrhea, weight loss, H/A
-Monitoring: NONE
65
Apremilast MoA
Inhib PDE4 → more intracellular cAMP → decreased proinflammatory mediator (TNFa, IL12, IL23, IFNgamma, inducible NO synthase), increased antiinflamm cytokines (IL10)
66
Name the JAKs
Jak 1, 2, 3
-TYK2
67
** JAK -STAT normal pathway**
- 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
68
** JAKi MOA**
JAKi bind JAK on R's to prevent phosphorylation and STAT binding → Less transcription of proinflamm cytokines
69
Cytokine receptors assoc’d w/ each JAK
-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
** List 4 cytokines that are NON-JAK associated cytokines (2016)**
-IL1
-IL17
-IL18
-TNF
-TGFb
71
** JAKi and which JAK they inhib**
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
**Tofa MoA**
-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
** JAKi dose **
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
Tofa monitoring
CBC, liver, Cr, LIPIDS
75
**Tofa Side fx **
~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
Tofa dose adjustment
5mg if severe renal/liver
Decrease by half if on antifungal (eg ketoconazole, fluconazole)
77
Bara and Upa side fx
Same as tofa
-CK elevation WITHOUT weakness or rhabdo
78
IVIG dosage
1-2g/kg over 1-5d
79
IVIG side fx
-**ANAPHYLAXIS if IgA deficiency**
-Aseptic meningitis
-**Serum sickness**: H/A, Flushing, fevers, chills , Nausea, Hypotension
-Chest tightness, back pain, myalgias
-Leukopenia
80
IVIG indications
-DM/PM
-AOSD, MAS
-Kawasaki
-CIDP
-ITP
-Offlabel: APLA, AIHA,
81
IVIG MoA
-- 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
PLEX MoA
Removes immune complexes and autoantibodies
83
PLEX used for
-TTP
-CAPS
-SLE w/ DAH, NPSLE
-NMO
-AAV w/ DAH or RPGN
-Hep B PAN
-Hep C Cryo
-PANDAS
84
**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)
-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
** Structure of Infliximab vs Etanercept **
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
**10 things to tell your patients about Etanercept**
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
**List actions Infliximab has that etanercept does not on TNF producing cells**
-**What can ETN bind that IFX cannot**
-- 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
Biologic comorbidity screening
-Infxn: HIV, Hep B/C, TB, Fungal exposure
-Demyelinating dz
-Cancer
-Cardiac history, DLPD, VTE history
-Liver dz
-Preg
-Meds
89
** Why inhibit TNFa in rheum**
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
Why is IL1 inhibited
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
Why is IL5 inhibited
-Produced by Th2 cells and mast cells
Binds IL5-R to:
-Stim B cell growth,
-Produce immunoglobulins
-Activate eosoniphils
92
Why is IL6 inhibited
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
Why is IL17 inhibited
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
Why is IL23 inhibited
IL23 produced by macrophages and dendritic cells
-Enhances survival of Th17 cells,
-Activates memory T cells
-Stimulation of antigen presentation by DCs
95
** Biologic dosing **
-- Etanercept
-- Infliximab
-- Adalimumab
-- Golimumab
-- Certolizumab
- 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
Etanercept contraindication
Uveitis (not effective) or IBD
97
** TNFi side fx**
- 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
** Ways to circumvent limitations of biologics eg infusion or injection rxn, costs **
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
** TB in TNFi**
-- Which TNF worse
-- Which test to screen
-- When to start TNF if positive
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
Hep B/C w/ TNF
-- When to start TNF
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
TNF Cancer recommendations
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
** list classes of meds that are contraindicated in:
-- Paradoxical psoriasis
-- Recurrent anterior uveitis
-- 70M w/ HTN
-- Optic neuritis**
- 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
IL1 Biologics
-list them and their
- MoA and Dose
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
Mepolizumab MoA and Dose
Human IgG1k monoclonal AB that targets IL5 which affects activation/survival of eosinophils
-300mg SC q4weeks for eGPA
105
** Toci MoA and dose**
-What to monitor
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
Managing Toci dose w/ increased LFT
> 1-3x ULN: reduce dose and/or switch
->3-5x ULN: DC until < 3x then restart lower dose or switch
->5x = DC toci
107
Managing Toci dose w/ cytopenias
ANC >1 = continue
-ANC .5-1 = stop until ANC >1, then restart at lower dose
-ANC<.5 =DC toci
-Thrombocytopenia <50 = DC
108
** Toci side fx **
~to JAKi: Cytopenias, **Lipid elevation**, **GI PERFORATION**, infection (eg zoster, fungal)
-MAS
-Lowers fx of PPI, statin, OCP
109
Sarilumab MoA and Dose
Anti IL6Ra monoclonal B that binds soluble/membrane bound human IL6Ra
-200mg SC q2weeks
110
** Ustekinumab (Stelara) MoA and Dose**
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
Ustekinumab adverse rxn
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
** Sekukinumab (Cosentyx) dose**
150mg SC weekly x4 (loading dose), then 150mg SC q4weeks
113
** Ixekizumab (Taltz) dose & side fx**
160mg SC loading dose, then 80mg q4wks
-Side fx: injxn rxn,
-nasopharyngitis,
-**IBD flare/development**
-Fungal infxn
114
** Guselkumab (Tremfya) MOA and dosing**
IgG1 monoclonal AB binds IL23 to prevent binding to R → less inflammatory cytokines and chemokines
-100mg week 0,4, then q8weeks
115
** Ritux MoA **
- 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
** Ritux dose **
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
** Ritux indications**
SLE, APLA, IIM
Sjogrens, IgG4, Cryo
ITP, AIHA,
Castleman, NMO
-**DOES NOT WORK IN SPA
118
** Ritux side fx**
**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
Complement targeted therapies MoA
Avocopan: Blocks C5a from binding C5a R (prevents neutrophil priming)
-Eculizumab - anti C5 used in HUS
120
Belimumab MoA
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
** Belimumab indication and dose**
**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
Belimumab tox
Infxn
-Infusion rxn
-Malignancy
-**Depression/suicide**
123
** Abatacept (Orencia) MoA and dose**
- 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
Risk factors for biologic nonresponse
-Young, obese, females
-Smoking
-High dz activity
125
Eculizumab MoA, Indications, and side effect
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
Colchicine MoA
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
Colchicine indications
-FMF
-Behcet, Aphthous stomatitis
-Neutrophilic dermatoses eg Sweets
-Cutaneous LCV
-Pericarditis
-Gout Tx and PPX
128
Colchicine Toxicity RF
Elderly
-Renal/hepatic impairment
-Chronic use
-CYP3A4 inhibitors
129
Colchicne tox
-GI (N/V/D)
-Neuromyopathy (CK, prox weakness, periph neuropathy), rhabdo
-Hepatotox, Nephrotox
-Myelosuppression
-Circulatory collapse
130
ULT dosage
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
ULT DDI
Allopurinol and Febuxostat
-Do not use with AZA or 6MP
-Allopurinol: increases CYC, warfarin, cyclosporine lvls. Decreases excretion of thiazide.
132
Manifestations and Tx of allopurinol hypersensitivity syndrome
Skin rash (SJS, TEN), fever, eosinophilia, hepatic necrosis, leukocytosis, renal failure
-Tx AHS: high dose steroids and HD (removes oxipurinol)
133
Risk factors allopurinol hypersensitivity syndrome
Female
-Hx of rash on allopurinol
-Renal insuff
-Concomittant diuretic therapeutic,
-Elderly
-HLAB5801
-Korean, Han chinese, Thai
134
Probenecid MoA
Competitively inhib URAT1 and GLUT9 → decreased tubular reabsorption of urate → increased uricosuria
135
Probenecid side fx
-**Acute gouty flare**
-**Urate nephropathy/stones**, **Nephrotic syndrome**
-GI: N/V
-Dermatitis
-Cytopenia eg **Hemolytic anemia** from G6PD deficiency
-**Hypersensitivity**, eg SJS
136
Probenecid contraindications
-Elderly and Low CrCl<50
-24h urine collection >800mg uric acid
-Avoid w/ salicylates (increases uric acid excretion)
**-Uric acid stones**
**-G6PD def**
137
How to minimize Urate nephropathy/stones
-2L/d fluid intake
-Urine alkalinzation (usually not needed) w/ Na bicarb or K citrate → urine pH>6
138
Pegloticase MoA and precautions
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
Type of Calcium to use in osteoporosis
Ca Carbonate absorbed less if achloryhydria or PPI
-Ca Citrate less affected by PPI and if hx of stones
140
How much Ca and Vit D in what
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
Reasons for low vit D
-Low intake (malabsorption, bypass, celiac)
-Severe liver dz,
-Antiepileptic drugs,
142
Bone remodeling process
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
Roles of RANK, RANKL, OPG
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
OP meds dosing
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
Bisphosphonate MoA
Pyrophosphate analogs that affect OC acting on bone by blocking farnesyl diphosphosphate synthase (FDPS) affecting protein trafficking needed for “ruffled border” →OC apoptosis
146
BP side fx
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
How to take BPs
1st thing in morning on empty stomach w/ water → upright and NPO x30-60min
148
BP contraindications
**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
Denosumab MoA
Monoclonal AB against RANK-L ie preventing OB from binding RANK to cause OC activity
150
Dental recommendations w/ denosumab
-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
How to bridge when DC prolia
Start PO BP 6mo after last injxn
-Start IV ZA 9mo after last injxn
152
ONJ Risk factors
-Old
-Invasive oral procedure
-Use of GC, prolonged BP use
-Comorbidities: DM, HTN, DLPD, CKD
-EtOH, Smoking
153
BP recommendations to prevent AFF
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
Counsel HRT
Estrogen replacement prevents # but increases risk BCa and CV events
-Give only for up to 3 y for postmenopausal hot flash
155
SERM (Raloxifene) MoA
E2 Ag in some tissue (bone), E2 ANT (breast)
156
SERM side fx
Hot flash, cramps, VTE
157
TRT pros/cons
Increase bone mass
-No # reduction
158
Teriparatide MoA and dose
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
Teriparatide contraindication
-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
Teriparatide side fx
HyperCa (dig, kidney stone)
-Hyperuricemia
-GI upset
-Arthralgia
161
When to end drug holiday / What is definition of drug failure
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
Markers for:
-- Bone formation
-- Bone resorption
Formation: ALP, osteocalcin, P1NP
-Resorption: Urine/serum N- telopeptides, serum C telopeptides
163
Romosozumab MoA & dose
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
Romosozumab side fx
Arthralgia
-Headache
-Injxn site rxn
**-MACE events
-Hypocalcemia
-ONJ
-AFF**
165
**Indications for splinting**
CTS
-DQ tenosynovitis
-1st CMC OA
-Inflammatory arthritis
166
Types of splints for RA or PsA hands
Finger splint for swan neck or bouttoneire
-Resting hand splint
-Wrist support
-CMC splint (more for OA)
-Knee sleeves
167
Etoposide MoA
Topoisomerase II inhibitor → DNA strand breaks and cell arrest
168
**Which part of cannabis induces psychotic symptoms? **
-**Max dose of cannabis per day as per the statement **
THC (ie preferred lower THC and higher CBD)
-3g
169
** 3 populations where you should not use cannabis **
<25 years
-Allergic
-Pregnant/breastfeeding
-Personal Hx of psychotic illness, substance use disorder, suicidal attempts/ideation
170
*Side effects of cannabis in the short term **
Psychomotor,
-Dizziness,
-Appetite,
-Mood changes,
-Disorientation and
-Psychosis,
-Anxiety.
171
** Young guy with RA on MTX, vaping marijuana, comes in with acute dyspnea, cough, fever - name 4 DDx **
RA induced lung injury (Organizing pneumonia/hypersensitivity pneumonitis)
-MTX-induced hypersensitivity pneumonitis
-Pneumonia
-Vaping associated lung injury
172
Prolia side effectss
AFF
HypoCa
ONJ
Infection
GI side effects
Cytopenias
