Pharm Flashcards Preview

Rheumatology > Pharm > Flashcards

Flashcards in Pharm Deck (33)
Loading flashcards...
1

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.

2

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.

3

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

4

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

5

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

6

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.

7

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

8

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)

9

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

10

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**

11

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

12

RA: Sulfasalazine:
-toxicity
-monitoring

Toxicity:
-myelosuppression

Monitoring:
-CBC monthly x3 then CBC q3mo

13

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

14

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

15

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

16

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

17

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


18

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.

19

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

20

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

21

RA: nonpreferred DMARDS:
-drugs

DrugS
-d-penicillamine
-azithroprine
-cyclosporine A
-gold compounds

22

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.

23

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

24

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.

25

NSAIDS:
-MOA
-CI
-BBW naproxen
-

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.

26

Gout: Colchicine
-must begin within how many hours of onset of gout?
-adminstration

Must begin within 72hrs of onset of gout.

Admin:
-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.

27

Gout:Colchicine:
-SE
-when is dose adjustment needed?
-CI
-if no relief of sx what meds do you add on?

SE:
-diarrhea
-nausea
-vomiting
-reversible peripheral neuropathy
-bone marrow suppression
-myopathy

Dose adjustment:
-greater than 70 years old
-CrCl less than 30ml/min
-avoid dialysis pts

CI:
-renal impairment
-hepatic impairment

If no relief:
-add on glucocorticoid or may be used cautiously with NSAID

28

Gout: Glucocorticoidss:
-admin routes

routes:
-intraarticular
-PO: for those who cant take NSAIDS, colchicine, and not candidates for injection. (Prednisone)
-IV or IM

29

Gout: Management between gout attacks?

When are medications to reduce serum uric acid indicated?

Preventative Medications:
-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
-niacin
-aspirin

Meds to reduce serum uric acid are indicated if:
- 2 or more episodes/year
- tophi
- chronic kidney dz, stage 2 or greater

preventive medications:
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.

30

Gout: WHat is the DOC for lowering Urate levels?

What is the goal serum urate level?

DOC for lowering urate levels is allopurinol.

Goal serum urate level is less than 6.