- anti-malarial drug - Most MILD DMARD

Rheumatologic Pharmacology Flashcards by Jonas Slackman

Goal of therapy in Rhematology treatment

-control inflammatory process -> disease remission

1) pain relief
2) maintain function
3) improve QOL

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5 Markers of treamtmen

1) reduction of number of joints involved
2) pain releif
3) decrease morning stiffness
4) reduce serologic markers
5) improve QOL

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4 groups of drugs

1) anti finflamatories
2) Anti-imflamtory/ imunomodulators (steroids)
3) DMARDS
4) Gout drugs

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3 subgroups of DMARDS

1) immunomodulators
2) immunosupressives
3) biologic agents

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What is the primary frunction of NSAIDS?

reduce inflamation and pain

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Do NSAIDS alter disease progression?

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How long does it take NSAIDs to reduce inflamation?

1-2 weeks

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When does the analgesic effect of NSAIDS begin?

immediately

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Which drug slows the appearance of bone errosions?

Glucocorticosteroids

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At what dose do gluccosteroids supress inflamtion?

-low doses

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What dose to gluccosteroids supress immune system?

high doses >40mg

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How are gluccosteroids often used?

As a bridge therapy between NSAIDs and DMARDS for inflamtions

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What is the first line DMARD?

methotrexate

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What do biologic DMARDS target?

the inhibit TNF alpha and IL

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Do DMARDS slow down the disease or stop it?

slow it down

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How long does it take to see the effects of DMARDs?

3 months

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What are the three principles of Immunomodulating drugs?

1) don’t increase risk of infections
2) not immunosupressive
3) not as powerful as other DMARDS

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What are the two immunomodulating RXs?

Hydroxychloroquine

Sulfalazine

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Hydroxychloroquine

anti-malarial drug

- Most MILD DMARD

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What is the proposed MOA of hydrocychloroquine?

How long does it take it to work?

suppress T-lymphocyte responses to mitogens, inhibit DNA & RNA synthesis, and trap free radicals

-3-6 months

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What skin disorder my hydroxychloroquine cause?

SEVERE PSORIASIS

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What serious ADRS dor hydroxychloroqine have?

torsades
agranulocytosis
aplastic anemia
leukopenia
thrombocytopenia

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What serious opthalmic ADR does hydroxychlorquine have?

Retinopathy

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How often should pts. on hydroxychloquine have an eye exam?

every 2 months

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What two conditions is hydroxychloroquine used in?

RA: slows errosions SLE: fatique, malise, skine

How does sulfalazine compare to hydroxychloroquine?

a little more agressive/effective in treatment

What two conditions is sulfalzine known for treating?

chrons and UC

What does sulfalazine inhibit?

prostaglandins & the release of inflammatory cytokines (IL 2,6,12 thnf alpha)

When does sulfalazine cause hemolytic anemia?

in G6PD pts

What is the serious ADR of Sulfalzine (it is also the drug "known" to cause this)?

SJS

How often should CBC/ hepatic be done for pts. on sufalazine?

-prior to treatment -everory other week - 3 mo - 1/mo - 3 mo 1 every other 3 mo

What conditions is sulfalazine used in?

RA, IBS, Arthritis, psoriatic arthritis

What is the onset for sulfalazine?

1-3 months

What weird thing may sulfalazine cause?

urine and skin turn orange

Why is it important to hydrate while on sulfalazine?

renal stones

How do you take sulfalazine

with food

4 characteristics of Immunosupressing Rheumatic Drugs

1) suplress inflamation and autoimunity 2) take long time to work 3) work better than other DMARDS 4) increase infection risk

Immunosupressive RXs MOA: Methotrexate and Leflunomide

- Antimetabolites: interferes with DNA synthesis, repair, and cellular replication - They inhibit enzymes needed to make amino acids - > decrease immune cell numbers

Meth trexate onset

3-6 weeks

Doseing of Methotrexate

ONCE A WEEK!!!!! -Give 1 mg folate daily extremly toxic if taken daily

Methotrexate contraindications

- pregnancy - blood dyscrasias - renal/hepatic imparitment

What are the 5 BLACK BOX warnings of Methotrexate?

1) fatal hepatotoxicity 2) renal failure 3) pneumonias 4) marrow supression 5) malignant lymphoma

Monitoring of methotrexate

CBC 1/ 4-8 wks

What can patients not consume while on methotrexate?

ETOH

What is the gold standard treatment for RA?

methotrexate

Immunosupressent MOA: Leflunomide

inhibits pyrimidine synthesis, resulting in anti-proliferative and anti-inflammatory effects

half life of Leflunomide

19 days

Dosage of Luflunomide

loading dose

How long does it take to see effect from luflunomide

months

How is luflunomide eliminated?

bile

What drige can you take to increase elimination of lufluminde because it increases bile secretion?

Chloestyramine

How is luflunomide monitored?

CBC monthly for 6 months, then q6-8 wks

Cyclophosphamide

MOST POWERFUL IMMUNOSUPRESSANT

What major complications do pts w/ cyclophosphamide have

bladder CA, myelosupresion, infection

Immunosupressor : Cyclosporine

used for organ trns | -IRREVERSIBLY DECREASES KIDNEY FUNCTION

immunsupressor: Azathioprine

used for chemo and organ trn

Immunosupressor Mycophenolate

used for organ trn

4 Principals of Biologic Agnets

1) made from living organisms or its profucts 2) copies effects a natural substance in imune system 3) engineered 4) decrease inflamation

Biologics include these 3 things

- interlukins - antibodies - vaccines

3 types of Biologics

1) intravenous immunogloculins 2) monoclonoal imunoglobulins 3) JAK inhibitor

Intravenous Immunoglobulin

used in rheumatologic DZ

Monoclonal Antibodies

- against human cell or human profuct | - used in Rheumatologic Dz and chemo

PROS of Biologics against DMARDS

- it's effects on immune system is finer tuned | - fewer side effects

CONS of Biologics

SUPER EXPENSIVE

what do Monoclonal Antibodies primarily work on?

cytokines

Can monoclonal antibodies be given oraly?

NO | -IM, SQ, IV

What is increased with use of monoclonal antibodies?

-infection

Can two different biologics be combined?

can biologics be combined with DMARDs?

Yes

Biologic monoclonalantibody agents that target TNF alpha

Etanercept (Enbrel) infliximab (Remicade), adalimumab (Humira) Golimumab (Simponi), Certolizumab pegol (Cimzia)

Biologic monoclonalantibody agents that target T cell

Abatacept

Biologic monoclonalantibody agents that target 20CD+ Bcell

Rituximab

Biologic monoclonalantibody agents that target IL 1

Anakinra

Biologic monoclonalantibody agents that target IL- 6

Tocilizumab

TNF alpha inhibitory monoclonal antibodies used and onset

- RA, psoriatic arthritis, IBD, Spnydloarathyropathy | - days- 3 months

Serious ADRS of TNF monoclonal antibodies

- opportunistic infections- TB | - aplastic anemia

What needs to be done before starting TNF monoclonal antibodies?

TB testing

JAK Inhibitor MOA: Tofacitinib

- JAK are enzymes that influence immune cell fucntion from cytokine - JAK inhibors reduce cytokine signaling- slow down Dz progession

What 2 DMARDS can JAK NOT BE USED WITH?

AZOTHIOPRINE | CYCLOSPRINE

What RX is used in systemic complaints or skin DZ?

Hydroxychloroquine

What RX is used in mild joint DZ?

- hydroxychloroquine | - sulfalazine

What RX is used in moderate of severe joint DZ?

- METHOTREXATE | - methotrexate + TNF agent

Does gout involve the immune system?

NO just inflammatory aspect

Colchicine MOA

- used for gout | - interrupts urate deposition, WBC can migrate to crystals

Serious ADR of Cholchisine

- myopathy | - myelopsurpression

gout prophylaxis colchicine dose

.6 mg once or twice/ day

prophylatic colchicine MAX

1.2 mg/day

Colchasine dosage in acute attack

1.2 oraly, 6 1 hr later, MAX 1.8/hr, then to prophylaxic dose

NSAIDS used in Gout

- indomethcin - naproxen - sulindac

Probenecid MOA

- uricosuric- increases uric acid in urine - need to drink lots of water - not really used anymore - many drug interactions

Allopurinol MOA and onset

- xanthine oxidase inhibitor- precents uric acid formation | - 2-3 month onset

ADR for Allopurinol

increased gout attack when initiated

Febuxostat MOA

- xanthine oxidase inhibitor | - chornic gout

What is more effective, allopurinol or febuxostat?

Febuxostat

Pegloticase - when do you use it

-use only in refractory gout or when other med have not worked

What meds need to be discontinued when starting a pt. on pegloticase?

any other uric acid lowering meds

What prohylaxic meds need to be given before pegloticase?

antihistmaines | corticosteroids

3 phases of gout treatment

1) acute inflamtion 2) prevent acute inflamation 3) lower uric acid

1st phase acute inflamtion gout trt mild

no RX preference

1st phase acute inflamtion gout trt sever

- cholchisine + NSAID | - steroids + colchasine

2nd phase trt gout- preventing acute inflamation

colchasine low dose + NSAIDS

3rd phase lowering Urich acid levels

- allopurinol | - febuxostat