Glucocorticoid:
- MOA
- use
- inhibits which pro-inflammatory mediators?
- effects on leukocytes
MOA:
- bind and block promotor sites of proinflamm genes IL-1 alpha and IL-2 beta.
- decrease production of TNF-alpha
Use: sx relief for pain secondary to inflammation
-inhibits phospholipase A2, cyclooxygenase 2, nitric oxide synthetase, prostaglandins, leukotrienes, thromboxanes
Leukocytes:
-decreased adherence to vascular endothelium, leukocytes cant exit the circulation as readily therefore entry to sites of infection and tissue injury are impaired.
Glucocorticoids:
- effects on inflammatory response
- effects on acquired immunity
Suppression of inflamm response:
-neutrophils increased resulting in increased WBC d/t impaired transport, increased production from BM, and decreased apoptosis.
-decreased eosinophils, monocytes, and lymphocytes.
Acquired immunity:
- decreases APC (Mf and Dendritic Cells)
- decreases T cells and B cells.
Glucocorticoids:
- which vaccines should be avoided by pts on long term therapy?
- What main infections are you concerned about with long term therapy?
Live virus vaccines are CI in those on chronic steroid therapy.
-MMR, Varicella, Small pox
Main infections:
- herpes zoster
- staph
- candida
Glucocorticoids:
- SE are based on what?
- SE
SE are time and dose dependent
SE:
- Red cheeks
- moon face
- buffalo hump
- ecchymoses
- thin skin
- high BP
- red striation
- thin arms and legs
- pendulus abd
- poor wound healing
- osteoporosis
Glucocorticoids:
- action on the bones
- how do we monitor for toxicity?
Bone:
-increase bone absorption and decreases osteoblastic activity. Readily absorbed but not as easily built up
Toxicity:
- BP
- Serum glucose
- lipid profile
- eye exam
- bone density
Rheumatoid arthritis:
- what medications are used for short term sx management?
- what medications are used for long term tx?
Short term sx management: NSAIDS or glucocorticoids
Long term: DMARDs (Dz modifying anti-rheumatic drugs) these are taken as life long therapy.
RA: What are the DMARD medications?
How soon should we achieve remission after starting DMARDS? If you dont then what?
Non-biological:
- methotrexate
- sulfasalazine
- hydroxychloroquine (Plaquenil)
- Leflunomide (Avara)
- D-Penicillamine
- gold salt
- azithroprine (Imuran)
- cyclosporine
Biological: (monoclonal abys)
- Etanercept (Enbrel)
- Adilimumab (Humira)
- infliximab (Remicade)
- Aakinra (kineret)
- Abatacept (Orencia)
Should achieve remission in 3months after starting DMARD therapy, if you dont you change DMARD or go to combo therapy. Maximal effects between 3-6mo
What is the initial DOC for treatment of RA? What is the 2nd line drug for RA?
WHat is used if first and 2nd line fail?
MEthotrexate
Second line: sulfasalazine
3rd line: Leflunomide (Avara)
RA: Methotrexate:
- time to effects
- dosing
- MOA
- all patients require this supplement while taking this?
Time: benefits seen in 2-6wks
Dosing: 7.5mg ONCE weekly, you do this to decrease toxicity..multiple doses actually increases risk of liver toxicity.
MOA:
- has direct effects in the joint and systemically dials back the immune system.
- reduces neutrophil adhesion, suppresses cell mediated immunity, antiproliferative effect on synovial fibroblasts and endothelial cells.
- inhibition of IL-1, IL-6, and IL-8
- inhibits synovial collegenase gene suppression.
All pts require supplemental folic acid 1mg daily
RA: Methotrexate:
- CI
- SE
- Toxicity
- monitoring
CI:
- women contemplating pregnancy
- pregnancy
- liver dz or excessive ETOH
- GFR less than 30ml/min
SE:
- hepatotoxicity
- pulmonary toxicity
- myelosuppression
- nephrotoxicity
- fatigue
- decreased ability to concentrate
- alopecia
- nausea
- stomach upset
- loose stools
- soreness of mouth
- rash on extremities
- HA
- Fever
Toxicity:
- myelosuppression (WORSE if concomitant use of NSAIDS)
- hepatotoxicty
- pulmonary toxicity
Monitor::
- CBC
- LFT
- Albumin
- Creatinine
- PRE-TX XRAY**
RA: Sulfasalazine:
- MOA
- CI
- SE
MOA: inhibition of PMN cell migration, reduced lymphocyte responses, inhibits angiogenesis, decreases inflamm cytokines and IgM RF production
CI:
- sulfa allergy
- pregnancy D
- GI or GU obstruction
- porphyria
- platelet count less than 50K
- LFTs elevated 2x ULN
- Hepatitis
- men wanting to conceive, it lower sperm quantity and quality.
SE: dose dependent
- Nausea, diarrhea
- intestinal or urinary obstruction
- oral ulcers
- orange-yellow pigmentation of skin
- HA
- depression
- Neutropenia*
- thrombocytes*
- agranulcytosis
RA: Sulfasalazine:
- toxicity
- monitoring
Toxicity:
-myelosuppression
Monitoring:
-CBC monthly x3 then CBC q3mo
RA: Leflunomide (Avara)
- use
- MOA
- how long is washout period for women wanting to conceive?
- time to effect
- CI
use: decreases progression of joint erosions and joint space narrowing
MOA:
- antiinflamm and antiproliferative
- decreases production of B and T cells
Wash out period is 2 years; activated charcoal and cholestyramine can be used to reduce the half life to 1 day.
Time to effect: 1-3mo
CI:
- pregnancy
- preexisting liver dz
- alcoholism
RA: Leflunomide:
- SE
- Toxicity
- Monitoring
- interactions
SE:
- MC diarrhea, rash, reversible alopecia, hepatotoxicity*
- weight loss
- htn
- BM suppression
Toxicity:
- hepatotoxicity
- bone marrow suppression
Monitoring:
- monthly x6 then every 2mo:
- -CBC
- -liver enzymes
- -creatinine
Interactions:
- increase warfarin levels
- rifampin increases leflunomide
- bile acid sequesterants decrease effectiveness of leflunomide
RA: Hydroxychloroquine (plaquenil)
- drug class
- use in RA
- MC use
- MOA
- toxicity
- Monitoring
Drug class: antimalarial
Use in RA: does not limit progression of RA, used as single agent only with mild RA and no evidence of joint destruction and no inflamm markers… otherwise used as add on to methotrexate.
MC use is lupus.
MOA:
-interferes with normal Ag processing, inhibits lysosomal enzymes and IL-1 release, inhibits PMN and lymphocyte responses
Toxicity:
-Macular damage
Monitor:
-fundoscopic and visual field exams every 6-12mo
RA: Hydroxychloroquine (Plaquenil)
- SE
- drug interactions
SE:
- nausea
- diarrhea
- abd discomfort
- photosensitivity
- skin pigmentation changes
- rash
- macular damage
Drug interactions:
- decreased metabolism of beta blockers except for atenolol and nadolol (they would require lower dose of beta blocker)
- may increase cyclosporine and digoxin
Tx of severe RA
Use combo of DMARD therapy
Switch to another TNF inhibitor with a different MOA
May need ongoing glucocorticoid therapy
May need ongoing NSAIDS
RA BIOLOGICS: TNF inhibitors
- what are the medications?
- MOA
- time to effect
- SE
- what to do if pt gets injection rxn
Meds:
- Etanercept (Enbrel)
- Infliximab (Remicade)
- Adalimumab (Humira)
MOA:
-bind to TNF-alpha making it inactive. decreases production of IL-6 and CRP ultimately decreasing joint damage!
Time to effect: 2-3doses
SE:
- injection site infections
- infusion reaction to infliximab (Remicade)
- serious infections leading to sepsis
If pt gets injection rxn: STOP medication until infection clears.
RA BIOLOGICS: TNF inhibitors
- CI
- interactions
- toxicity
- monitoring
CI:
- latent TB infection (b/c of suppression of immune response pts are at risk for conversion to active TB.) BBW*****
- high risk for opportunistic infections
Interactions:
- Remicade not to be used with Abatacept(orencia) or anakinra (Kineret) d/t increase risk of infection
- Remicade CAN be used in conjuction with methotrexate b/c it decrease the development of invliximab abys (infusion rx)
Toxicity:
- injection site rxn
- increased risk of local or systemic infection
Monitoring:
- PPD prior to therapy
- periodic CBC
RA: Biologics: Anakinra (Kineret)
- drug class
- MOA
- which drug class can you not give these with?
- CI
- SE
- monitoring
drug class: immune modulator
MOA: blocks IL-1 receptor to decrease degree of joint destruction and inflammation
DO not give in combo with TNF inhibitors d/t increased risk of infection.
CI:
- e.coli derived proteins
- preexisting infections or high risk for infection
- dont use with TNF inhibitors
SE:
- skin irritation at injection site
- infection
- angioedema and anaphylaxis
- decrease in WBC
Monitoring:
-CBC monthly x3 then q4mo x1year
RA: nonpreferred DMARDS:
-drugs
DrugS
- d-penicillamine
- azithroprine
- cyclosporine A
- gold compounds
RA: nonpreferred DMARD: d-penicillamine
-MOA
IMURAN (Azithroprine)
- MOA
- toxicity
CYCLOSPORINE A
- MOA
- toxicity
- BBW
GOLD
- MOA
- use
D-penicillamine:
-MOA: unknown in RA other than depresses T cell activity.
Imuran:
-MOA: inhibits enzymatic activity required for dna synthesis, decreased prodduction of T and B cells.
-Major toxicity is bone marrow suppression, carcinogenic = lymphoma in post transplant pts and hepatosplenic T cell lymphoma in IBD pts.
Cyclosporine A:
-MOA: blocks activation of T cells and IL-2
- Toxicity: renal failure
- BBW: only physicians experienced in immunosuppressive therapy…
Gold:
-moa: unknown, decreases prostaglandin production
-Use: used as add on therapy.
SLE:
- medications to avoid that may cause exacerbation
- which meds cause drug-induced lupus
- which medication is best for both cutaneous and musculoskeletal involvement? Just MSK sx?
- which medication is used fro significant organ involvement?
- which meds can be used for severe dz and when steroid resistant?
- If anti-phospholipid positive which medication is required?
Meds to avoid:
- sulfa containing abx (sulfadiazine, bactrim)
- minocycline
- oral contraceptives
Meds causing drug-induced lupus:
- procainamide
- hydralazine
- griseofulvin
Antimalarials (Hydroxychloroquine) work best for both cutaneous and MSK involvement.
NSAIDS for MSK pain.
Medication for significant organ involvement: GLUCOCORITCOIDS.
–cardiopulmonary, hepatic, renal, hemolytic anemia, immune thrombocytopenia
severe dz for when steroid resistant;
- -methotrexate
- -cyclophosphamide
- -azathioprine
- -mycophenolate
- rituximab
anti-phospholipid positive = warfarin fo life. INR 2-3
Gout:
- tx of acute attacks
- prevention management
- when to stop tx of gout
- can you initiate urate-lowering therapies in acute gout attack?
Acute attack:
- NSAIDS #1 (Naproxen and indomethacin, celebrex)
- # 2 colchicine
- # 3 Steroids
Prevention:
- avoid meds that increase uric acid
- Decrease serum uric acid:
- -Xanthine oxidasee inhibitors (allopurinol, febuxostat)
- -uricosuric drugs (probenecid)
Stop tx of gout 2-3 days after sx resolution unless on steroids then need a slower taper to prevent a rebound attack.
NOOOOO. you need to wait until the attack is over otherwise you will make their gout worse.
