Arthritis & Gout MT2 Flashcards by Jessyka Yard

what is rheumatoid arthritis

autoimmune disease that causes chronic inflammation of the joints
affects joints first, then surrounding tissues may become affected
usually occurs between 40 and 60 years of age
2 to 3 times more common in women
genetic basis

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what type of disease is RA directly linked to?

cardiovascular disesae
- increase in MI, stroke, heart failure and hypertension than non-RA patients

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what are some symptoms of RA

joint inflammation (swelling, redness, pain and stiffness)
chronic inflammation can lead to damage and deformity of joints

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what are some tests that may be done to diagnosis someone with rheumatoid arthritis

rheumatoid factor test
anti-CCP antibody test
complete blood count
CRP (C-reactive protein)
ESR (eryhtocyte sedimentation rate)
ultrasound/MRI/X-ray
synovial fluid analysis

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what are some causes of RA

infectious agents that deposit into the joints and cause inflammation
genetic link/genetic inheritance
environmental factors (smoking)

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what is the difference between the 1980 pyramid approach of treatment of RA and how RA is treated now

1980 pyramid approach was that topical NSAIDs and aspirin were on the bottom of the pyramid. 2nd line therapy was initiated after a patient had proven radiographic damage. RA was considered a nuisance disease and the treatment of the disease was worse than its natural course, therefore symptomatic treatment only.

currently, pharmacological intervention is necessary early in order to prevent structural damage. multi drug therapy is not only well tolerated but is necessary. the goal is to put disease into remission

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what are some non-pharmacological treatment options for RA

patient education on nature of RA, coping mechanisms
physical and occupational therapy for joint-strengthening and joint protection
prevention of osteoporosis is RA and antiresorptive therapy for those who receive chronic corticosteroids

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what are the “first line” drugs used to reduce inflammation in RA

NSAIDS and corticosteroids

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what are the “second line” drugs used to promote remission of the disease and prevent progressive joint damage in RA

DMARDs and biologics or biologic response modifiers

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corticosteroids are any of the steroidal hormones made by the _______ of the adrenal gland (e.g. cortisol)

cortex (outer layer)

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true or false: steroids inhibit the synthesis of almost all known cytokines

true

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what is the MOA of corticosteroids

they stimulate the synthesis of IF-kappa beta alpha, which is a protein that traps and therefore inactivates nuclear factor kappa B (NF-kB)

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this is an activator of cytokine genes and mediator of the pro-inflammatory action of tumour necrosis factor and IL-1

nuclear factor kappa beta (NF-kB)

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what are some possible side effects of corticosteroids

increased appetite and weight gain
deposits of fat in chest, face, upper back and stomach
swelling and edema due to water and salt retention
high blood pressure, diabetes
slower healing of wounds
black and blue marks
osteoporosis
increased susceptibility to infections
cataracts
muscle weakness
thinning of the skin
stomach ulcers
increased sweating
mood swings

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what is the route of administration for corticosteroids

oral
topical (for eczema, allergic conjunctivitis, or rhinitis)
parenteral/injection
aerosol (for asthma)

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do corticosteroids bind to proteins?

yes, bind to corticosteroid binding globulin (CBG) and albumin in the blood and then enter cells by diffusion

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what is the half life of hydrocortisone

90 min. main effect lasts for 2-8 hrs

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cortisone and prednisone are inactive until converted in vivo to ______________

hydrocortisone

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what organ metabolizes corticosteroids

liver

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what are some examples of medications that should be taken with NSAIDs to offset side effects

-antacids (Sucralfate)
- PPIs (lansoprazole, etc)
- PG analogues (misoprostol)

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examples include methotrexate, chloroquine, hydroxychloroquine, sulfasalazine, leflunomide, biologics, gold salts, penicillamine, cyclosporin and cyclophosphamide

DMARDs - disease modifying anti-rheumatic drugs

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this specific DMARD is classified as an anti-metabolite, but in RA the MOA seems more anti-inflammatory than anti-metabolite. it is an inhibitor of folate (vit. b6) metabolism

methotrexate (Rheumatrex, Trexall)

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what is the MOA of methotrexate for RA

it inhibits leukotriene synthesis and dihydrofolate reductase
decreases TNF concentrations

net effect: a decrease in T and B cell proliferation and a decrease in rapidly dividing synoviocytes. there is promotion of apoptosis of activated peripheral T cells

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how much methotrexate is absorbed orally

70% but variable depending on dose

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in terms of distribution, how much methotrexate is bound to proteins

50% bound to plasma proteins

how and how fast is methotrexate excreted

primarily by urine within 48 hrs (clearance may be diminished in elderly and those with decreased renal fxn)

what are some side effects of methotrexate

**contraindicated in pregnancy** - generally well tolerated, but may see some of the following SE's with high doses - mouth sores - headaches - dizziness - hair loss - stomtitis - drowsiness - itching, rash - low WBCs - folate deficiency - accelerated rheumatoid nodulosis - can also have severe liver and bone marrow toxicity, therefore patients need to be monitored

this is an isoxazole derivative

Leflunomide (Avara)

what the MOA of leflunomide

it completely inhibits dihydroorotate dehydrogenase which is required for de novo synthesis of pyrimidines. this blocks the proliferative lymphocyte response in inflammation

true or false: lefluonomide is a prodrug that is converted to active metabolite A77 1726

true

this is highly protein bound and has a half life of 15-18 days. it undergoes extensive enterohepatic recirculation. persisting drug levels seen 1-2 years after discontinuation. not recommended in patients with advanced renal disease

leflunomides active metabolite (A77 1726)

what are some adverse effects and side effects of leflunomide

adverse effects: hepatotoxicity. contraindicated in preganancy - d/c 2 years before attempts at pregnancy side effects: diarrhea, hair loss, reduction in WBC and RBC, hypertension, peripheral neuropathy, itching, rash

this is generally used in the treatment of inflammatory bowel diseases such as UC and chrons, and used as an antimicrobial agent. it is converted by bacteria in the colon into 5-aminosalicylic acid (5-ASA) and sulfapyridine.

sulfasalazine (Azulfadine)

what is the MOA of sulfasalazine

- does not appear to inhibit COX even if 5-ASA is the therapeutic agent appears to inhibit TNF-alpha, IL-1 and NF-kB. also scavenges free radical and oxygen species

what are some side effects of sulfasalazine

GI (N/V), dizziness, change in color of skin or urine, can cause reduction of WBCs and RBCs

what is the MOA of chloroquine/hydroxychloroquine (Plaquenil)

suggested MOAs - inhibits sulfhydryl-disulfide interchange (which is important for proliferation of immune cells) - inhibits enzyme reactions (decreased phospholipase action) - binds to DNA and interferes with replication in immune cells - decreases chemotaxis, phagocytosis, fibroblast growth, and WBC proliferation

this has a very favourable safety profile - rapidly absorbed - plasma levels plateau in 8-14 days - long plasma half-life (3-10 days depending on dosing regimen) - slow urinary excretion - tissue levels are higher than plasma levels - concentrates in pigmented ocular tissue

cloroquine/hydroxychlorquine (Plaquenil)

what are some side effects of chloroquine/hydroxychloroquine (Plaquenil)

relatively safe - GI - skin and hair lesions - muscle weakenss - ocular defects (including retinopathy)

true or false: combination of methotrexate and other compounds (such as leflunomide, sulfasalazine and hydroxychloroquine) is common

true

this is a class of biologic response modifiers Etanercept (Enbrel), Infliximab (Remicade), Adalimumab (Humira), Certolizumab pegol (Cimizia), Golimumab (Simponi)

TNF inhibitors

this is a class of biologic response modifiers Abatacept (Orencia)

CTLA4 fusion to IgG1 (CD4 antagonist)

this is a class of biologic response modifiers Rituximab (Rituxan)

chimeric, anti CD20 monoclonal antibodies

this is a class of biologic response modifiers anakinra (Kineret)

IL-1 receptor inhibitors

this is a class of biologic response modifiers Tocilizumab and Sarilumab

IL-6 receptor inhibitors

_________ are a class of drugs that work by blocking the action of janus kinase enzymes which are involved in the inflammation that causes the symptoms of RA

JAK inhibitors

this is a JAK inhibitor that blocks JAK1 and 2

Baricitinib

this is a JAK inhibitor that blocks JAK1 and 3

tofacitinib

_________ focus is on methods of action in the cytokine cascade. they reduce signs/symptoms of RA and inhibit. structural damage in patients with moderate.severe to severe RA. they are often given i.v. or sc and either along or in combination with methotrexate for better disease control

biologic response modifiers

________ either "sponge the excess TNF (Etanercept), prevent cell surface and soluble TNF binding to its receptor (infliximab), or bind directly to TNF, blocking TNF receptors (Adalimumab)

TNF inhibitors

_______ selectively inhibits T cells (similar to CTLA4)

Abatacept

________ was originally developed and used for B cell non-Hodgkins Lymphoma and is an anti-CD20 monoclonal antibody

Rituximab

this is an immunosuppressant agent that may be used in RA. the exact MOA is not understood. it used used in patients that have not responded to other medications or in combination therapy

azathioprine (Imuran, Azasan)

this is an immunosuppressant agent that may be used in RA. it primarily affects T cell signalling

cyclosporine (Gengraf, Neoral, Sandimmune)

true or false: treatment with single non-biological DMARDs can achieve remission

true

when are combinations of non-biological DMARDs indicated?

for patients with moderate or high disease activity or prolonged disease duration or for those who fail to respond to a single compound

_________ are reserved for patient with persistent moderate ro high disease activity and indicators of poor prognosis

biologic DMARDs

__________ are often used to bing the level of inflammation quickly under control

short term glucocorticoids

why are glucocorticoids not suitable for long term use

due to adrenal suppression and severe side effects

this is characterized biochemically by hyperuricemia and clinically by episodes of severe, acute arthritis. acute attacks occur as a result of an inflammatory reaction to crystals of uric acid that are deposited in the joint

gout

explain uric acid metabolism

xanthine oxidase breaks down hypoxanthine to xanthine to the keto form of uric acid and finally to the enrol form of uric acid

explain the MOA of allopurinol

this is an analog of hypoxanthine, therefore is serves as a substrate for the enzyme xanthine oxidase and further stops the production of uric acid.

is allopurinol used to treat acute gout attacks or used for prophylaxis

prophylaxis

is allopurinol absorbed well?

rapid oral absorption

is allopurinol bound to plasma proteins

where does allopurinol distribute

in total body water (2/3 less in brain)

what are some side effects of allopurinol

GI irration -> diarrhea

this gout agent is an antibiotic: it interferes with mitotic spindles and arrests cells in metaphase. it causes depolymerization and disappearance of fibrillar microtubules in granulocytes and other motile cells. decreases intracellular translocation involved in histamine release therefore less inflammation

colchicine

is colchicine used to treat acute gout or prophylaxis

acute

is colchicine absorbed well?

rapid oral absorption (peak plasma concentration in 30min - 2hrs)

where is colchicine distributed in the body

high concentration in liver, spleen and kidneys; excluded from heart, muscle and brain

how is colchicine excreted

fecal excretion of metabolites

which population is colchicine less tolerated in

elderly

what are some side effects of colchicine

- GI (N/V/D) - acute poisoning (GI hemorrhage, vascular damage, CNS paralysis) - chronic poisoning (bone marrow effects)

this is a uricosuric agent used to treat gout. it blocks the reabsorption of uric acid, therefore it leaves the body instead of building up

Probenecid (Benemid)

this is a uricosuric agent used to treat gout. it inhibits uric acid reabsorption in the proximal tubule of the kidney

Sulfinpyrazone (Anturane)

what is the MOA of uricosuric agents

inhibition of the URAT1 (anion exchanger) in the kidneys and thus blocking reabsorption

this is another agent that may be used for gout. includes indomethacin or naproxen

NSAIDs

this is another agent that may be used for gout. it inhibits xanthine oxidase

Febuxostat

this is another agent that may be used for gout. it is an anti-hyperlipidemic drug that is most commonly used in combination with allopurinol

fenofibrate

this is another agent that may be used for gout. is is an angiotensin II receptor antagonist. it also blocks uric acid reabsorption. usually used to treat gout in patients who have hypertensions

losartan

this is another agent that may be used for gout. 4g of ascorbic acid daily nearly doubles the fractional excretion of uric acid

vitamin C

Arthritis & Gout MT2 Flashcards

(81 cards)