Rheumatoid Arthritis

Question 1

What is the 1st line in RA

Answer 1

Methotrexate - gold standard given within 3 months of diagnosis

Question 2

what is the mode of action for methotrexate

Answer 2

• prodrug
• anti-inflammatory
• inhibits purine metabolism
• inhibits cytokine production and activation of immune cells like macrophages, T-cells and neutrophils
• inhibits DHFR

Question 3

why does Methotrexate have a higher affinity to DHFR compared to dihydrofolate?

Answer 3

it has an additional hydrogen bond or iconic bonds which prevents the binding of FH2 and its conversion to N5, N10 methylene FH4

Question 4

what drugs can you give in RA?

Answer 4

• Corticosteroids
• DMARDs - Methotrexate, Sulfasalazine, Hydroquinone, Leflunomide
• NSAIDs
• Paracetamols
• TCAs
• Biologics

Question 5

what are Biologics?

Answer 5

comes from living organisms or living cells
- have large complex molecular structures
- expensive
- examples include Adalizumab, Certolizumab, etanecept, infliximab,

Question 6

what biologic can be given instead of Methotrexate?

Answer 6

Adalizumab
Certolizumab
Etanecept
tocilizumab

Question 7

what treatment do you give for severe active RA

Answer 7

Rituximab in combination with Methotrexate

Question 8

what are the standards for the continuation of Rituximab + Methotrexate?

Answer 8

• there is an adequate response following initiation of therapy
• adequate response is maintained following retreatment with dosing interval of atleast 6 months.
• Adequate response = DAS28 of 1.2 points

Question 9

Adalizumab, Etanecept, infliximab, certolixumab, golimumab, tocilizumab and abatacept, all in combination with methotrexate is allowed as options only if….

Answer 9

disease is severe - DAS28 of 5.1 AND
disease has not responded to intensive therapy AND
the companies that provide these drugs as agreed in their patient access scheme.

Question 10

DMARDs and cDMARDs can be offered in combination?

Answer 10

yes
oral Methotrxate
leflunamide
sulfasalazine
hydroxyquinine

Question 11

how are steroids given?

Answer 11

certain steroids can be given - Prednisolone, Methylprednisolone
- medium length course
oral prednisolone - starting 60mg/day gradually reduced to 7.6mg over 7 weeks.
Methylprednisolone - 120mg IM or on PRN basis

Question 12

what is the mode of action for Hydroxychloroquine?

Answer 12

interferes with antigen presentation and activation of immune cells.

Question 13

what is the mode of action for Sulfasalazine?

Answer 13

prodrug
gets broken down into Sulfapyridine and 5-aminosalysalate
metabolised by intestinal bacteria
has anti-inflammatory, immunosuppressive and Antibiotic action
can be used for RA, UC and CD
interactions - acetaminophen

Question 14

what is the mode of action for Leflunomide

Answer 14

pyridine synthesis inhibitor
DMARDS
slows down structural damage associated with RA

Question 15

what are the non pharmacological intervention for RA?

Answer 15

exercise
diet
psychological/Education
Stress reduction
surgical intervention
physiotherapy

Question 16

what other organs does RA damage?

Answer 16

cardiovascular - inflammation in heart risk of pericarditis
lymphatic system - enlarged lymph nodes and spleen
joint inflammation tendonitis muscular pain
eye inflammation - uveitis
may cause Fever, weight loss
fatigue
rashes - salmon coloured, fleeting
Haematological complications

Question 17

what does DAS show?

Answer 17

DAS28 - 5.1 = active disease
DAS28 <3.2 = low disease activity
DAS28 <2.6 = remission
3.2 - 5.1 = moderate RA activity

Question 18

what tests are needed for diagnosis

Answer 18

serology test - C-reactive protein, ESR, RF, Anti-CCP

urea test - albumin decreased.

Question 19

what are the clinical presentation?

Answer 19

often sets off as Fever, Malaise, arthralgia (pain in joints), Weakness before the progress to joint inflammation.

Question 20

what are the common signs and symptoms?

Answer 20

persistent symmetric polyarthritis (synovitis) of HAND and FEETS
progressive articular deterioration
Difficulty in performing everyday tasks
it also affects the upper extremities - metacarpophalangeal joint, wrists, elbows, shoulders. lower extremities - ankles, feet, knees hips

Question 21

what genes causes or are involved in RA?

Answer 21

HLA-DR1 and HLA-DR4 - increases the severity of and development
Red meat intake
coffee - too much
high salt intake
smoking
hormonal - disproportionate between female and male - prolactin