Immunosupression Flashcards
what is Rheumatoid arthritis ?
An auto immune multi system disease , initially in synovium inflammatory and proliferation condition leading to dissolution of cartilage and bone
what is the pathology of RA?
what cause erosion to joints ?
Hyperactivity and imbalance between pro (T-cells and macrophages) and anti (Anti-CCP) inflammatory
mettalloprotienases
what is clinical criteria for RA?
Morning stiffness more than 1 hour , longer = more inflammation
Arthritis of more than 3 joints and hand joints
symmetrical arthritis
rheumatoid nodules - late stage
what is non-clinical criteria for RA?
Serum rheumatoid factor / Anti CCP antibodies
X-Ray changes (6 months - 1yr), subluxations
what are treatment goals for RA?
Symptom relief
Prevention of joint destruction
what treatment principles do we use for RA?
Early use of DMARDs
adequate dosage
use combinations
avoid long term corticosteroids
what symptoms of SLE?
Angry , mallor rash
affects all systems so variable
what are features of Vasculitis ?
LFTs
leucokitic infiltrates
fibrinoid necrosis
Thrombosis
spotty rash
Consolidation in lungs
what are treatment principles in SLE and vasculitis ?
symptomatic relief - arthralgia , Raynaud’s , etc
reduction in mortality
prevention of organ damage
reduction in long term morbidity caused by disease and drugs
how do Corticosteroids work ?
prevent IL-1 and IL-6 production by macrophages
inhibit all stages of T Cell activations
what are Non-biological DMARDs?
Hydroxychloroquine
Sulfasalazine
what are biological DMARDs? why arent they used more ?
Rituximab
Infliximab, Adalimumab
what is Azathioprine used for ?
SLE and vasculitis maintenance therapy
Inflammatory bowel disease
Atopic dermatitis
steroid sparing drug
what can heavily affect pharmokinetics of Azathioprine ? what complications can it lead to so what must be done ?
TPMT enzyme polymorphicity (6-MP)
if low can lead to myelosupression(Low blood counts) so TPMT test is done before
What is Azathioprine’s MOA?
Cleaved to 6-MP
this is Anti-Metabolite decreases DNA and RNA synthesis by reducing Purine synthesis and incorporating into DNA.
what are Adverse effects of immunosuppressants ? how do you monitor them ?
Bone marrow - Monitor FBC
Increased risk of malignancy , infection
Hepatitis - LFTs
what is Ciclosporin and tacrolimus used for ? what is major side efffect? what must you be aware of ?
after Transplantation
dermatitis and psoriasis
Renal toxicity, Gums swell
CYP3A4 inhibitors
name some CYP3A4 inducers ?
Carbemazepine
phenytonin
Omeprazole
rifampicin
what do IL 1,2,3,4 do ?
Hot T-Bone Steak 1= H= Fever 2= T= T cell activation 3= B = Bone marrow 4= S = IgE and IgA
How do Ciclosporin and tacrolimus work ?
Calcineurin inhibitors - prevents IL-2 prod= stops T h cells
C= Cyclophilin protein
T= Tacrolimus protein
Drug/Protein complex inhibits Calcinurin
what is Mycophenolate motfetil used for ?
transplantation
induction and maintenance of Lupus with nephritis
Vasculitis Maintence
how does Mycophenolate motfetil work ?
Fungus inhibits inosine monophospahte dehydrogenase required for guanosine synthesis which impairs B and T cell proliferation whilst sparing other rapidly dividing cells
what are Mycophenolate motfetil ADRs?
nausea , vomiting and diarrhoea
myelosuppression
what are indications for Cyclophosphamide ? what is good about this drug?
Lymphoma , Leukaemia
Lupus nepritis
works in about 10 days (quick), only give for 6 months
what is a major side effect of Cyclophosphamide ? Why and what can be given ?
Acrolein is made and us toxic to bladder = Hemorrhagic cystitis
give water and mesna
what other side effects of cyclophosphamide exist ? what must you do therefore? what is a safer option ?
Increased irks of bladder cancer and other cancers
infertility - rises with dose and age
Mycophenolate mofetil- takes longer to work
what is best treatment for RA? what other things is this drug good for ?
Methotrexate
malignancy
psoriasis
Crohn’s
how does methotrexate work in RA route ?
not via anti-folate
stops adenosine production, stops T cell activation
via AICAR transformylase inhibtion
what are the pharmokinetics of Methotrexate ? what Drug interactions are possible ?
Oral bioavilab = 33% IM bioavail = 76% renal excretion long half life = Weekly dose 50% Protein bound so NSAIDs can displace
what are advantages of Methotrexate ?
Well tolerated
can use for long time
can be used for combinations
what are side effects of methotrexate ? what can counter act these ?
Mucositis
marrow surpresssion
Hepaitis ,
highly tetragenic
Folate supplements
what is Sulfasalazine used for ?
relieve pain and stiffness and also fight infection
what are immunological effects of Sulfasalazine ?
T-cell – inhibition of proliferation – possible T-cell apoptosis – inhibition of IL-2 production • Neutrophil – reduced chemotaxis – reduced degranulation
where is main activity of sulfasalazine ?
within intestine - effective in IBD
What are advantages of sulfasalazine ?
Effective and not much toxicity Long term blood monitoring not needed few drug interactions no carcinogenic potential safe in pregnancy
what are the effects of blocking TNF- alpha ?
decrease Inflammation Cytokine cascade Recruitment of leukocytes to joint decrease angiogenesis VEGF decrease MMP development and maintenance of granulomata
what is a risk on Anti-TNF therapy ? why ?
TB reactivation as TNF- Alpha
released by macrophages in response to M TB infection -screen for latent TB
how does Rituximab work ?
binds specifically to a unique cell surface marker = CD20 on B cells but not on stem cells , etc.
B cells apoptosis
what do B cells do ?
Present antigen to T cells
Produce cytokines and antibodies
