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PM3B: Autumn > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

How is inflammatory arthritis characterised

A

Joint Pain

Stiffness- after rest and in the morning (lasts several hours)

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2
Q

When does rheumatoid arthritis normally occur in which patient groups

A

Pre-Menopausal women (3 times more like than men)

30 to 50 years of age

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3
Q

Normochromic and normocytic anaemia is normally associated with rheumatoid arthritis, what does it mean

A

Reduced number of normal sized erythrocytes with normal haemoglobin content associated with chronic disease

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4
Q

What is rheumatoid arthritis

A

Non specific inflammatory response:

Localised tissue damage and release of neo-autoantigens

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5
Q

What is the mechanism of action of rheumatoid arthritis

A
  1. Local tissue damage leads to activation of synovial T cells
  2. B cells activated and produce autoantibodies and rheumatoid factors which form immune complexes
  3. Bind to complement and stimulate neutrophils- produces pro inflammatory cytokines (IL-1 and TNF-alpha) and chemokine
  4. Chronic inflammation- maintained by rheumatoid factors and continuous stimulation of macrophages by pro-inflammatory cytokines and chemokines
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6
Q

How is the chronic inflammation of rheumatoid arthritis maintained

A

Rheumatoid factors and continuous stimulation of macrophages by pro-inflammatory cytokines and chemokines

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7
Q

Describe the pathology of rheumatoid arthritis

A

Chronic Synovitis characterisation

Inflammation of synovial lining of joints, tendons sheaths or bursae

New synovial blood vessels made are induced by angiogenic cytokines and endothelial cell activation- expedites leucocyte extravasion

Synovium proliferates and grows out over cartilage surface- forms pannus

Pannus destroys articular cartilage and subchondral bone- bony erosions

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8
Q

What are the symptoms and features of Rheumatoid arthritis

A

Insidious onset of pain

Early- morning stiffness that lasts more than 30 minutes

Swelling in small joints of hands and feet (symmetrical)

Joint capsules weakened- instability and deformity

Multiple joints involved: wrists, elbows, shoulders, cervical spine, knees, ankles, feet

Affects one side then the other

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9
Q

What can rheumatoid arthritis increase the risk of

A

Atherosclerosis

Infection

Osteoporosis

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10
Q

What is Sjorgens syndrome

A

Dry eyes and mouth due to destruction of epithelial endocrine glands- auto immune disease

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11
Q

How do you diagnose rheumatoid arthritis

A

Blood count: anaemia- nromochromic and normocytic

Thrombocytosis- over production of platelets

Raised ESR and CRP

Presence of serum autoantibodies: Rheumatoid factor, anti-nuclear factor

Presence of Anti-citrulline containing peptide (CCP)

Radiology: presence of soft tissue swelling, joint narrowing, erosion of joint margins

Sterile synovial fluid- high neutrophil count

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12
Q

What is the treatment goals for rheumatoid arthritis

A

Remission of symptoms- return to full function and maintenance of remission

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13
Q

What treatment options are available for Rheumatoid Arthritis

A

NSAIDs- relieving pain and stiffness

Disease Modifying Anti-rheumatic drugs (DMARD):
Penicillamine
Gold Salts
Antimalarials- chloroquine, hydrochloroquine
Sulfasalazine
Methotrexate
Cytokine inhibitors- adalimumab, anakinra, entanercept, infliximab

Corticosteroids: short term

Others: Paracetamol, codeine

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14
Q

What NSAID should be used in rheumatoid arthritis?

A

Ibuprofen:
200 to 400mg THREE times a day

Allows for rapid pain relief (1 week)
Inflammatory effect (3 week)
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15
Q

When should intra-articular injections be used in corticosteroids?

A

Used only if no response to drug therapies

Relieve symptoms in one or two joints- limitation on number of injections into joint (no more than 3 a year)

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16
Q

When can DMARDS be used and how are they used

A

Used only under consultant supervision alongside methotrexate

Can be used individually if combination not tolerated

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17
Q

What is the first choice in DMARD therapy in Rheumatoid Arthritis and its MoA

A

SULFASALAZINE

Immunosuppressant action by scavenging toxic oxygen metabolites produced by neutrophils

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18
Q

What are the common side effects of sulfasalazine

A

First 3-6 months

GI disturbances 
Malaise
Headache
Rashes
Blood disorders
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19
Q

What are the testing required for sulfasalazine and the drug that must be used alongside it

A

Blood counts and liver function tests for first 3-6 months

Folic acid supplements

20
Q

What is the common antimalarial drug used in modern rheumatoid arthritis

A

Hydroxychloroquine

21
Q

What are the problems that may occur from using antimalarials

A

Ocular toxicity or progressive loss of vision with long term treatment

22
Q

What is the mechanism of action with Methotrexate

A

Folic acid antagonist that inhibits dihydrofolate reductase

Reduces availability of tetrahydrofolic acid needed for purine production and DNA synthesis

Suppresses cell division in immune cells, suppresses cell mediated immunity

23
Q

What are the monitoring requirements required for methotrexate

A

Full blood count for blood disorders

Liver function tests for liver cirrhosis

24
Q

What is the dose of methotrexate for rheumatoid arthritis

A

Take ONE 7.5mg tablet everyweek

25
Q

What is usually given alongside methotrexate to prevent adverse side effects

A

Folic acid supplement

26
Q

What are the common side effects associated with methotrexate

A 
Stomatitis
GI disturbance
Alopecia
Mild drug induced hepatitis
Pneumonitis 
Blood disorders/Rash
27
Q

What adverse effects must patient report for methotrexate

A

Bone marrow suppression/blood dyscarasias

Pulmonary Toxicity-SOB

Liver toxicity- nausea, vomiting, abdominal discomfort, dark urine

28
Q

What is the gold salt called used in rheumatoid arthritis and its role

A

Aurothiomalate

Believed to suppress cell mediated immune reactions

29
Q

What is the mechanism of action of penicilliamine

A

Altering synthesis and maturation and cross linking of COLLAGEN (anti collagen antibodies)

Altered production of immunoglobulins

Reduction in circulating immune complexes

Decrease generation of IL-1 and suppression of lymphocyte secretion

30
Q

What are the common side effects of peniclliamine

A 
Nausea
Loss of taste
Rashes
Blood disorders- report this
Proteinuria
hair loss
31
Q

What should you monitor in patients taking penicillimine

A

Monthly blood counts

Urine tests and renal function

32
Q

When should you use Cytokine Modulator biologics

A

Used for highly active rheumatoid arthritis if it fails to respond to TWO STANDARD DMARDS

33
Q

What are cytokine modulators normally used alongside with

A

Used with methotrexate

34
Q

What are the common side effects of Cytokine Modulators

A

Infections- TB, hepatitis B reactivation, septicaemia

Nausea

Vomiting

Abdominal pain

Worsening heart failure

Hypersensitivity reactions

Fever

Headache

Depression

Injection site reactions

35
Q

Give examples of first line biologics used and when are they used

A

Etanercept, Adalimumab and Infliximab

When two standard DMARDS fail

36
Q

What is the role of Infliximab, Golimumab and Etanercept

A

Infliximab (adalinumab as well) and Golimumab: Anti-TNF

Etanercept: recombinant fusion protein of TNF receptor fused to FC region of human IgG

37
Q

What is the role of Rituximab and Abatacept

A

Rituximab: Anti-CD20 monoclonal antibody inhibitor that depletes B cells

Abatacept- recombinant fusion protein of IgG and CTLA-4 that inhibits T cell stimulation

38
Q

What is the role of Tocilizumab and Anakinra

A

Tocilizumab- humanised monoclonal antibody to IL-6 receptor

Anakinra- IL-1 receptor antagonist- not recommend for rheumatoid arthritis

39
Q

What activates TNF, IL-1, IL-6 and IL-8

A

TNF- macrophage

IL-1 - monocyte and macrophage

IL-8 synovial fibroblast

IL-6 Synovial fibroblast

40
Q

What is the role of the new drug Leflunomide

A

Potent inhibitor of pyrimidine synthesis that affects T cell proliferation and is immunomodulatory

41
Q

What are the severe adverse side effects associated with Leflunomide

A

Bone marrow toxicity

Hepatotoxicity

Infection

Malignancy

42
Q

What is the role of Azathioprine and mechanism of action

A

Interferes with purine synthesis and is cytotoxic

MoA:
Represses both cell mediated and antibody immune reactions by preventing clonal expansion of T and B cells

43
Q

What are the adverse effects of Azathioprine

A 
Bone marrow toxicity 
Mild Hepatotoxicity
Infections (herpes zoster)
GI disturbances
SKIN RASHES
44
Q

What is cyclosporin licensed for and its mechanism of action

A

Severe rheumatoid arthritis

MoA:
Suppression of T cell mediated immune responses
Helps slow rate of joint erosion

45
Q

What are the side effects associated with ciclosporin

A 
Nephrotoxicity
Hepatotoxicity 
Hypertension
Anorexia 
Lethargy 
Tremor
Gum hypertrophy
GI disturbance

PM3B: Autumn (19 decks)

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