Rheumatology/ Immunosuppressants Flashcards
What is rheumatoid arthritis?
which age does it occur?
Rheumatoid arthritis (RA)
is an autoimmune disease in which the body’s immune system – which normally protects its health by attacking foreign substances like bacteria and viruses – mistakenly attacks the joints
Usually 30-50 years old, although the disease can occur at any age
what is a prodrug?
A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug
what is this image showing?
RA pathogenesis
balance btw proinflammatory cytokines and antiinflammatory cytokines > is tipped towrds the pro,
Tcells & macrophages r all in OVERDRIVE!
There is persistent synovitis, causing chronic symmetrical polyarthritis with systemic inflammation.
There is over-activation of the inflammatory process. Chemoattractants produced in the joint recruit circulating inflammatory cells
Over-production of tumour necrosis factor (TNF)> activates IL-6 leads to synovitis and joint destruction.
Interaction of macrophages and T and B lymphocytes drives this over-production.
deformities of RA on hand?
what is butonniere deformity? what cuases it?
“or button-hole deformity”
extensor tendon splits, & head of proxiaml phalages pokes through, like a button through a button hole!
Is RA symmetrical or asymmetrical?
Symmetrical!
What is the main auto-antibody found in blood tests?
Autoantibodies to the Fc portion of immunoglobulin G (rheumatoid factor)
What other autoantibodies can occur in RA? Suggest 2
- Anti-cyclic citrullinated peptide (anti-CCP)
- Also referred to as Anti-citrullinated protein antibody (ACPA)
give 4 syndromes in the body that RA can cause
Felty’s syndrome
Caplan’s syndrome
carpal tunnel syndrome
Sjogren’s syndrome
Give 2 other non-articular manifestations of RA
What can occur in the lungs of patients with RA?
Nodules
Other lung diseases including pleural effusion, interstitial lung disease and others.
what investigations should we do?
In history of RA, look for the three S’s
* Stiffness – early morning joint stiffness lasting over 30mins
* Swelling – persistent swelling of one joint or more, especially hand joints
* Squeezing – squeezing the joints is painful (particularly MCP)
How do we diagnose RA?
Symptoms
- Morning stiffness 1 hour
- Arthritis of more than 3 joints
- Arthritis of hand joints
- Symmetrical arthritis
- Rheumatoid nodules>> shouldnt seen it early RA
- Serum rheumatoid factor
- X-ray changes >> happens later on!
Diagnosis chart
RA treatment goals?
- Symptomatic relief
- Prevention of joint destruction
RA treatment strategy?
what about corticosteroids?
• Early use of DMARDS
- o Methotrexate hydroxychloroquine*
- o Sulfasalazine*
- o Leflunomide*
• Aim to achieve good disease control
- Use of adequate dosages
- Use of combinations of drugs
• Avoidance of long-term corticosteroids
Systemic lupus erythematosus (SLE)
- causes, symptoms, diagnosis & pathology
Vasculitis
- causes, symptoms, diagnosis, treatment, pathology
LFT
Lots of consolidation in lung bases
Treatment goals in SLE & vasculitis
- Symptomatic relief e.g arthralgia, Raynaud’s phenomenon (well controlled, make sure their fingers arent dropping off)
- Reduction in mortality
- Prevention of organ damage
- Reduction in long term morbidity caused by disease & by drugs
name the typical Immunosuppressants
MY CCAT
- Corticosteroids
- Azathioprine
- Ciclosporin
- Tacrolimus
- Mycophenolate mofetil
corticosteroids: mechanism of action
Its a bazuka! It just shot down everything, which is why lama
SE STERIODS>> symptoms nafs someone going through old age!
act quickly, releive symptoms, control inflammation
inhibit TRANSCRIPTION FACTORS by binding directly onto DNA>> rapidly inhibit inflammation.
- prevent interleukin (IL)–1 and IL-6 production by macrophages
- inhibit all stages of T-cell activation
Methotrexate
- mechanism of action
- pharmacokinetics
- ADRs
- clinical monitoring
Sulphalazine
- mechanism of action
- pharmacokinetics
- ADRs
- clinical monitoring
Cyclophosphamide
- mechanism of action
- pharmacokinetics
- ADRs
- clinical monitoring
Mycophenolate mofetil
- mechanism of action
- pharmacokinetics
- ADRs
- clinical monitoring
Calcineurin inhibitors (ciclosporin and tacrolimus)
- mechanism of action
- pharmacokinetics
- ADRs
- clinical monitoring
Azathioprine
- mechanism of action
- pharmacokinetics
- ADRs
- clinical monitoring
the newer ‘biologicals’ and their range of indications
which one r commonly used?
derived from proteins already in existence, through the use of recombinent DNA technology, we can transplant the DNA into bacteria & they can produce the drug for us!
& by creating Monoclonal antibodies, we can target ANY SYSTEM in the body!!!
Mechanism
- have very similar structure to proteins or bound to other proteins
- act to block certain pathways
indications
- control inflammation
- IBD
- Asthma
- CONTROL cancer (melanoma)
action of drugs that block TNFα
-what considerations should u take into account?
TB REACTIVATION RISK!
make sure u screen patient for latent TB before anti-TNF treatment! using quantiferon gold test!
bc -TNF is used by the macrophages to help reinforce (strengthen) the Granuloma and keep the bacilius in check and make sure its walled off!
what is this? complication of what drug? how can this be prevented and time taken?
Cyclophosphamide-
Acrolein, metabolite of cyclophosphamide> is toxic to the bladder epithelium and can lead to hemorrhagic cystitis
- aggressive hydration
- Mesna >> orally 2 hrs b4 or IV w/ cyclophosphamide
what is this? what caused it?
Mycophenolate mofetil >> mouth ulcers
catagories of immunosuppressents
If Rheumatoid factor is increased, does that mean she has RA?
What is NOT a rheumatological cause of Joint pain?
Wegners granulamotis
rare multisystem autoimmune disease of unknown etiology. Its hallmark features include necrotizing granulomatous inflammation and pauci-immune vasculitis in small- and medium-sized blood vessels
