Flashcards in Pharm Deck (33)
-inhibits which pro-inflammatory mediators?
-effects on leukocytes
-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
-decreased adherence to vascular endothelium, leukocytes cant exit the circulation as readily therefore entry to sites of infection and tissue injury are impaired.
-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.
-decreases APC (Mf and Dendritic Cells)
-decreases T cells and B cells.
-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
-SE are based on what?
SE are time and dose dependent
-thin arms and legs
-poor wound healing
-action on the bones
-how do we monitor for toxicity?
-increase bone absorption and decreases osteoblastic activity. Readily absorbed but not as easily built up
-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?
Biological: (monoclonal abys)
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?
Second line: sulfasalazine
3rd line: Leflunomide (Avara)
-time to effects
-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.
*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
-women contemplating pregnancy
-liver dz or excessive ETOH
-GFR less than 30ml/min
-decreased ability to concentrate
-soreness of mouth
-rash on extremities
-myelosuppression (WORSE if concomitant use of NSAIDS)
MOA: inhibition of PMN cell migration, reduced lymphocyte responses, inhibits angiogenesis, decreases inflamm cytokines and IgM RF production
-GI or GU obstruction
-platelet count less than 50K
-LFTs elevated 2x ULN
-men wanting to conceive, it lower sperm quantity and quality.
SE: dose dependent
-intestinal or urinary obstruction
-orange-yellow pigmentation of skin
-CBC monthly x3 then CBC q3mo
RA: Leflunomide (Avara)
-how long is washout period for women wanting to conceive?
-time to effect
use: decreases progression of joint erosions and joint space narrowing
-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
-preexisting liver dz
-MC diarrhea, rash, reversible alopecia, hepatotoxicity*
-bone marrow suppression
-monthly x6 then every 2mo:
-increase warfarin levels
-rifampin increases leflunomide
-bile acid sequesterants decrease effectiveness of leflunomide
RA: Hydroxychloroquine (plaquenil)
-use in RA
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.
-interferes with normal Ag processing, inhibits lysosomal enzymes and IL-1 release, inhibits PMN and lymphocyte responses
-fundoscopic and visual field exams every 6-12mo
RA: Hydroxychloroquine (Plaquenil)
-skin pigmentation changes
-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?
-time to effect
-what to do if pt gets injection rxn
-bind to TNF-alpha making it inactive. decreases production of IL-6 and CRP ultimately decreasing joint damage!
Time to effect: 2-3doses
-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
-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
-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)
-injection site rxn
-increased risk of local or systemic infection
-PPD prior to therapy
RA: Biologics: Anakinra (Kineret)
-which drug class can you not give these with?
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.
-e.coli derived proteins
-preexisting infections or high risk for infection
-dont use with TNF inhibitors
-skin irritation at injection site
-angioedema and anaphylaxis
-decrease in WBC
-CBC monthly x3 then q4mo x1year
RA: nonpreferred DMARDS:
RA: nonpreferred DMARD: d-penicillamine
-MOA: unknown in RA other than depresses T cell activity.
-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.
-MOA: blocks activation of T cells and IL-2
-Toxicity: renal failure
-BBW: only physicians experienced in immunosuppressive therapy...
-moa: unknown, decreases prostaglandin production
-Use: used as add on therapy.
-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)
Meds causing drug-induced lupus:
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;
anti-phospholipid positive = warfarin fo life. INR 2-3
-tx of acute attacks
-when to stop tx of gout
-can you initiate urate-lowering therapies in acute gout attack?
-NSAIDS #1 (Naproxen and indomethacin, celebrex)
-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.
MOA: inhibit cyclooxygenase and ultimately production of mediators of inflammation (prostaglandins, prostacyclin, thromboxane)
CI: CrCl less than 60ml/min, active of duoden or gastric ulcers, heart failure, uncontrolled htn, allergy, chronic anticoagulation
BBW naproxen: increased risk of stroke, MI, CHF, afib, CV death. At high doses.
-must begin within how many hours of onset of gout?
Must begin within 72hrs of onset of gout.
-requires loading dose 1.2mg followed by dose of 0.6 mg 1 hr later. Then 12hrs later more to dosing for prophylaxis 0.6mg QD or BID
-if already on chronic colchicine and attack develops give loading dose but if loading dose within last 2 weeks you cant give it.
-when is dose adjustment needed?
-if no relief of sx what meds do you add on?
-reversible peripheral neuropathy
-bone marrow suppression
-greater than 70 years old
-CrCl less than 30ml/min
-avoid dialysis pts
If no relief:
-add on glucocorticoid or may be used cautiously with NSAID
-PO: for those who cant take NSAIDS, colchicine, and not candidates for injection. (Prednisone)
-IV or IM
Gout: Management between gout attacks?
When are medications to reduce serum uric acid indicated?
-what are they?
-how long after acute attack can you initiate these?
Can lowering uric acid levels too quickly stimulate gout attack?
avoid meds that increase uric acid or inhibit renal excretion of uric acid such as:
-thiazide and loop diuretics
Meds to reduce serum uric acid are indicated if:
- 2 or more episodes/year
- chronic kidney dz, stage 2 or greater
What: allopurinol, Probenecid
Wait two weeks after an acute attack to initiate prevention therapy.
Yes, lowering uric acid too quickly can stimulate a gout attack.