JAKs and PD4s Flashcards
upadacitinib - indications?
AAAAs - Arthritis, Rheumatoid Arthritis, Psoriatic Ankylosing spondylitis AD 12 +
upadacitinib MOA and dose? EASI 75 and 90 vs dupi
JAK 1> 2
15 or 30 mg
EASI 75 70 - dupi 40-50
EASI 90 50 dupi 20-30
so dupi 30 -50
upada 50 -70
Skin s/e of JAKS
acne folliculitis herpes zoster herpes simplex cellulitis CANDIDIASIS URTICARIA
s/e of JAK1s :
must use post GRADUATION
GI: diarrhea, N/V Renal impairment - caution acne Diarrhea URTIs, COUGH, DVT/PE ANEMIA TRANSAMINITIS INFECTIONS inlc HSV/ZOSTER, vaccines les seffective ORAL HERPES, OPPORTUNISTIC CANCERS NASOPHARYNGITIS NEURO - H/A
9r skin - AD, acne, folliculitis, cellulitis, HSV, zoster
GI - N/V/D
RESP/CV - URTIs, nasopharyngitis, DVT/PEs
LABS: CPK, neutropenia (CPK MC lab
JAK what are c/i?
hypersensitivity
warning: pregnancy, TB, severe hepatic damage
labs for JAKS?
preggo (would do vitals too, if severely HTN probably not the drug)
ask about cardiac hx, DVTs, PEs, active infections, severe hyperlipidemia, renal or hepatic impairment, MALIGNANCIES
VACCINES - up to date
Hep Bcab, BsAb/Ag, Cab, HIV ab, TB quanti gold
CBC, LFTs, (Renal), fasting lipids BASELINE, 12 weeks
maybe do CPK since frequently elevated?
which jacks are tofa, upada, bari, abro?
sofa 1, 3
upada 1,2
bari 1, 2
abro 1, 2
dosing for tofa (RA) 5 OD BID
bari 1-4 mg
topical jaks?
tofa 2% BID
ruxolitinib 1.5% BID
JAK - black box?
DVTs/PEs, MIs, serious infections, opportunistic malignancies
VACCINATE FOR VZV
how does upada work in AD?
downregulates IL 4, 13, 31 , TSLPthough phosphorylating and downs regulating pathways involved in inflammation
how do PDE4 work?
PDE4 Inhibition -> HIGH levels of CAMP -> anti inflammatory effects
Mechanism of Action
• cAMP (cyclic adenosine monophosphate) is synthesized from adenosine triphosphate (ATP) by adenylate cyclase
o key regulator in the extracellular ligand signals
o PKA (protein kinase A) pathway expression of proinflammatory cytokines (TNF-alpha, IFN-gamma, IL-17) while production of anti-inflammatory mediators such as IL-10
• when PDE4 is inhibited, cAMP cannot be degraded; high levels of cAMP = downstream anti-inflammatory effects via the PKA pathway
Apremilast approval? pregnancy category
PsO, PsA in adults
c/i preggo hypersensitivity
breastfeeding
preggo C
what monitoring is required on otezla?
- weight monitoring recommended
- monitor mood and recommended renal monitoring
- would still do anti infectious screen and Cr before start
Otezla dosing
30 mg BID
Otezla - s/e
Headaches Mood/depression Weight loss diarrhea, n/v infectious higher (caution in chronic infections, do not combine with other immunosuppressive)
renal - 30 mg OD (vs BID)
Adverse Effects
• GI: diarrhea, nausea, emesis; most common side effect; tend to occur in first few weeks; can minimize with titration; risk may be increased in elderly patients on medications that can cause volume loss, hypotension
• Other: URTI, rhinorrhea, sneezing, congestion, abdo pain, tension headache, weight loss (10-12% lose 5-10% of baseline weight)
• Depression/suicide: some studies show mildly increased depression in patients on the drug BUT rates of suicide attempts higher in placebo group; need to weigh risks/benefits in patients with hx of depression
jak start - full station?
HOW WOULD YOU manage conjunctivitis for dupi?
lid hygiene warm compresses artificial tears topical antihistamines steroid eyedrops CsA drops optho referral
