Autoimmune part 2 Flashcards
What is Psoriasis
An autoinflammatory skin conditions that causes
- rash with withcy scaley skin patches: commonly on flexor areas, scalp, elbows, etc.
- a hyperkeratoitic state = chornic and non cure
- cycles; through flares and remission events
- can creat an arthrtic component
Process
- overactive immune system = skin cells multiple too quickly kertinocyte hyerproliferationa = creates plaques
Factors which dictate what treament for psoriasis
Goals for treatment
Monitor (how long to check up for topical and oral)
- site of disease involvement: skin v elbows = different potency
- age of ot.
- severity of diseae & % of BSA covered = oral or topical
- concurrent disease states: psA = TNFs, HTn, CAD, etc.
- DDI
- pregnant
Goals
- minimize or emliniate the plaques to be less boterhsome
- alleviate ithcy and need to scratch
- reduce frequency of flares
- avoid ADR from meds
- maintain and improve QOL for pt
Monitoring
- should see effects of topical in 2-4 week
- should see effects of systemic in 8-12 weeks
- see changes in BSA and % covered
- see changes in pt. perferences and symptoms
Monitoting: Meds
- monitor ADR of meds
- labs at baseline and follow up depending on each medications (systemic)
Non-Pharm tratements of psoriasis
- oatmeal baths
- moisturizer and lotions =moist skin
- avoid irritants and soaps, detergents
- skin protection: watch the sun!!!
- reduce stress
CLassification of Psoriasis
mild
moderate
severe
Mild = < 3% of BSA
moderate = 3-10% of BSA
severe = 10%+ of BSA
Treatment algorithm for Mild-Moderate Psoriasis
1st = choose a topical agent and try it
**also continue useing the mositurizers & step down to lowest potency once possible to maintain control no matter the level **
if 1st choice of topical agent isnt working = try alternative topical or a dual topical, adding nother or swapping
if 2nd choice doesnt work = consider try combo of two topicals if you havent already then try a topical + systemic
First Line Options for Topical Psoriasis Treatment
discus combination and rotational thearpy
(these can be combined with others (steroid + vit D, etc.)
combination: combinet wo agents with goal or maintaining or imporving efficacy while decreasing toxicity (using lower doses of each)
rotational: use 1 then swap to other, or 1 at night and 1 in morning
Topical Corticosteroids cornerstore therapy
- limit use of high potency < 4 weeks
- decreases erythema, sacling and itch
Topical Vitamin D analogs: calcipotrience/calcitriol
- inhibits keratinocyte proliferation
Topical Synthetic Retinoid: tazarotene
- modualtes kertinocyte proliteration and decreases inflammatory markers excression
Topical Calcineurin inhibtor = tacrolimus/piecrolimus
- immunomodulators
Targeted phototherapy
First Line Psoriasis Topical Treatment: Topical Corticosteroids
- MOA
- pharmacodynamics
- high v low dose potency pearls
Corticosteroids: Topical
MOA: work to decreased inflammation and decrease the psoriasis and assoicated symptoms
Pharmacodynamics
- takes 1-2 days
- absorbtion depends on integritiy of skin: might take a litte on thick elbow skin v face & it depends on cream, gel, ointment, etc.
DDI: not likely as its topical
Potencies: as the psoirasis gets better, move to lowe potency
- High & super High = only use BID for less than 4 weeks
- Low Potency: for face and skin folds (class 6 and 7)
First Line Psoriasis Topical Treatment: Topical Corticosteroids
how does vehicle of administeration impact
ADR of topicals
counceling points
Vehilce
- oitment: most effective
- foams, shampoo’s, sprays, gels, solutions, oils and gels are good for scalp
- can alternate type depending on day/night
ADR for topical
- skin atrophy
- telangiestasia
- striae
- acne & folliculitis
- purpura
- contact derm. and rosacea
- cortocisteroids systemic effects (less liekly but possible)
- the longer you use the less effective they are
Counceling Points
- dont use high doses more than 2x daily for 4 weeks
- after it improves; decrease potency
- after it improves; can combine weaker steroids with other product
First Line Psoriasis Topical Treatment: Vitaming D2 Analogs: Calcitriol & Calcipotriene
MOA
ADR
Vitamind D3 Analogs: Calcitriol and Calcipotriene
MOA: inhibit keratincyte proliferation and therefore decrease plaques
- take about 2 weeks to work
ADR
local: irratant contact derm, buring, itchy, edema, peeling, dryness and redness
systemic: RARE: hypercalcemia and papathyroid hormone suppression
DDI: unlikely since topical
First Line Psoriasis Topical Treatment: Topical Retinoid (Tazarotene)
MOA
pharmacodynamics
CI
ADR
Tazarotene : topical retinoid
MOA: decrease karatinocyte proliferation and inhanace inflammatory infilteration in the plaque
pharmacodynamics
- takes 1 week; beenfirts can remain for 12 weeks
CI (think of accutane)
- CONTRAINDIACTED IN PREGNANCY:
- should NOT be used in those of Child bearing age; neeg negative preg. test 2 weeks before starting
ADR
- irritation at site of application, burn,itchy and redness
- photosensitivty!
Indications for using Systemic Treatment for Psoriasis
Treatment Alogorithm for systemic
2
Indications for Systemic Meds.
- BSA > 10% = severe psoriasis
- moderate psoriasis (3-10) = but a loack of response to topical treament
- mild psoriasis ( < 3) BUT impacting QOL (like the face)
Treatment Algorithm
#1: start here
- start with NON-biological systemic agent + topical treament
- start with biologic ONLY IF they have psoriatic arthritis
- conitnue useing moisturizer and stepdown to less potent if symptoms are maintained
if that doesnt work
- use alterantive traditional systemic agent
or - use biologica agent
- either tranditional or biologic = add on topical too
- use biologic or other combo of systemic + topical
First Line Psoriasis Systemic Treatment
traditional (non-biologic) treaments
biologic treatments
Traditional Treatments : these are older, cheaper but end-organ toxic effects seen with methotrexate and cyclosporine
- methotrexate
- cyclosporines
- acitretin
Biological Treaments: new agents, expensive, injectable, less toxic to bone, liver, kidneys
these can also be considered first line alongside trandtional therapy if no pt. factors limiting and cost isnt an issue
Traditional Systemic Psoriasis Treatment: Methotrexate
MOA
used for what
ADRs
CIs
Methotrexate
- used for cancer, RA and psoriasis
MOA
- folate antimetabolite: decresed folates ability to work and therefore decreased DNA synthesis and cell replication
- able to target the keratinocytes and reduce the epithelial cells
ADR
- Liver Toxicity
- pulmonary toxicity
- pancytopenia
- megaloblastic anemia: lacking floate
- increase lymphoma risk: immunosupp.
- Nasuea
- myleosupression
Contraindications
- pregnant/BF
- alcoholism
- chronic liver disease
- immunodeficiency (HIV,etc.)
- pre-exisiting blood disorder
caution in drug interactions: p glycoprotein substrate
Methotrexate BBW’s
Drug-Drug Interactions
BBW
- serious adverse reations: death and adverse reactionsof GI, kidneys, liver, lungs and skin
- contraindicated in pregnancy: casues fetal death
give folate with all methotrexate pt. on days they’re not getting the methotrexate
Drug-Drug Interactions : these can increase methotrexate blood concentrations by inhibiting clearance of methotrexate
- NSAIDs: due to renal excretion
- Antibioics: (bactrum, penicillin, minocycline, cipro) : due to renal excretion
- others: diuretics, phenytoinin, colchicine: due to PGP interactions
seen in high dose methotrexate
First Line Psoriasis Systemic Treatment: Traditional Systemic: Cyclosporine
MOA
pharmacodynamics
DDI
Cyclosporine
MOA: inhibit IL-II
Pharmacodynamics:
- CYP3A4 excreted: watch inducers and inhibitors
- PGP interations
DDI: LOTS OF INTERACTIONS ask a pharmacsist
- avoid atorvostatin, aldosterone antagonists, live vaccines
BBW
- increased risk of skin malignancy
- can cause systemic hypertension and nephrotoxicity
reserved for use < 12 weeks!!!! so dont really use this
PEARLS
- CANNOT BE USED WITH METHOTREXATE!!! cannot combine the two : too much immunosupprresion (cant be used with any other immunosup.)
CI
- renal dysfunction: cannot use
Systemic Treament: Psoriasis
Traditional Systemic : Acitretin
MOA
pharmacodynamis
Pearls
Acitretin: oral retinoid & vitamin A derivative
MOA: inhibits expression of IL-6
Pharmacodymanics
- administer with food to increase biavalibiltiy
- active metaboliste lingers for a year, as half life is 120 days!!!!
Pearls
- must use effective birth control for duration of treatment AND FOR THREE YEARS AFTER
- cannot dnoate blood during or for THREE YEARS AFTER
- avoid ALCOHOL!!! and for 2 months after
CI
- pregnancy!!! or those wanting to get pregnent in 3 years after
PEARLS
- can be used with methotrexate
Reasons to Hold or D/C treatment with
Methotrexate
Cyclosporine
Acitretin
Methotrexate
- if significant LFT increase 2x ULN = stop
- if reduction in lekucytes or platlets = stop
- pregnant = stop
Cyclosporine
- if SCr elevates > 25% = stop (kidneys issue)
- consistenet BP elvation despite dose reduction
Acitretin
- increase LFTS = stop (liver)
- patient becomes pregnant
Apremilast
use for psoriasis as a systemic treatment
MOA
ADR
DDI
Apremilast (“last on the market”)
MOA
- PDE4 inibitor: decreases inflammation
Pharmacodynamics
- CYP3A4!!! watch DDI
- avoid strong inducers
ADR
- GI effects (N/V)
- weight loss
- neuropsych. HA, depression , modd changes
Traditional Systemic Psoriasis Treament Monitoring
Methotrexate
Cyclosporine
Acitretin
Methotrexate
at baseline
- LFTs
- CBC with platlets
- Pregnancy test
during treatment
- LFTS
- CBC with platlets
- BUN/SCr
- pregnancy tests
Cyclosporine
at Baseline
- BP
- BUN/SCr
- LFTs
- CBC
- Lipids
during treatment
- BUN/SCr & BP = first 3 months every other week then monthly
- lipids
- magnesium, uric acid, potassium
- CBC
- LFTs
- pregnancy test
Acitretin
at baseline
- FTS
- Renal function test
- lipids
- CBC
- pregnancy test
during treatmen t
- LFTS & Lipids
- CBC
- Renal Function
- Pregnancy test
Biologic Systemic Treatment of Psoriasis
TNF Class
Il-23 Class
Il 12 & 23 Class (one)
Il-17 Class
what are thye
Biologics
- monoclonal antibody treatment which are give Sq Q injection or IV infusion
- increase TB risk
- the antibody formation can decrease over time and decrease effectiveness
TNF
- inflixumab
- Adalimumab
- Certolizumab
- Etanercept
Selective Il-23
- Guselkumbab
- Tildrakizsumab
- Risankizumab
Il-12 and Il-23
- usetekinumab
Il-17
- secukinumab
- izekizumab
- brodalumab
TNF-alpha Inhibitors for Psoriasis
BBW
Precautions with use
BBW
- increased risk of develpoing serious infections: because immunosup.
- specifically BBW for TB!!!
- lymphoma risk increased and other cancers (kids)
Precautions
Antibody formation: decreased effectiveness with increase used
Autoimmunde disorders: rare cases of autoimmune disorders (MS) and lupus like ones reported
Hematologic: all the penias, leuko, thrombo, pan, neutro
hepatic: severe hepatisis, acute fialure, jaundice
Heart Failure: infliximab CI in those with moderate/severe HF
- can cause it or make it woese: caution in milde cases
HIV: caution in these pt. if on ART tehrapy and 0:0 can be ok
Hep B reactivation
TNF Inhibitors for Psoriasis
Monitoring
Baseline
- CBC
- liver functions
- TB
- Hep B/C
- HIV
- symptoms of HF
- symptoms of malignancy
- signs/sympotms of infection
During Treatment
- signs of infection
- annual CBC and TB/HBV
- LFTs and signs of hepatitis and liver dysfunction
- signs of malignancy
- autoimmune disorders
- heart failure signs
TNF INhibitros for Psoriasis
ADR (not the considerations)
ADR
Infection site rxn: red/itchy
infuction rxn: severe can be hypotension, dsypnea, edema, rash
infection!!!
hepoattoxicity
worsening HF
cytopenias
demylinating disorder
dont use live vaccines with these
AVOID IN
- those getting live vaccine
- those with active infections
- those with HF worsening
- those with lupus-like sndrome
CAN BE USED WITH METHOTREXATE!!! in combo
Interluekin-Inhibotrs
ADRs
psoriasis treatment
for all in sum
- infection risk
- URI infection specifically in tildrakinzumab and risankizumab
- neutralizing antibody development : work less over time
Ixekizumab and brodalumab = neutropenia risk!
Ixekizumab = thrombocytopenia
Interleukin Inhibtors Treatment: psoriasis
monitoring what for
Ustekinumab
G,T,R and S
Ixekizumab
Brodalumab
Ustekinsumb
- baseline = TB testing, CBC, LFTs & hepatitis proflie
- continued: yearly PPD, CBC, LFTs and antibody formation
C,T,R & S * brodalumab & Izedkizumab
- baseline = TB testing
- monitoring - sigsn of TB
- brodalumab = watch depression & chrons
- izedkiszumb = wathc IBD
