Pharm Flashcards
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
