DMARDs Flashcards
Is RA symmetrical or asymmetrical
Symmetrical
Do DMARDs affect RA disease progression
Yes
What are DMARDs combined with to treat newly diagnosed RA
Methotrexate
Short term glucocorticoid
Another DMARD
When is DMARD mono therapy used in RA
Pregnancy
Co morbidities
How should DMARD therapy be changed in recent onset RA where control is satisfactory
Decr dose
How do DMARDs effect radiographic progression, number of swollen joints, and fatigue severity
Improve radiographic progression and number of swollen joints
No effect on fatigue
What is the anchor drug for RA
Methotrexate
What is given to women before staring methotrexate
Pregnancy test
How is methotrexate administered for RA
Oral
SC or IM can be used if oral ineffective
How does methotrexate dose change over RA treatment
Start on high dose and decrease
Which enzymes do methotrexate inhibit to prevent DNA and RNA production
Dihydrofolate reductase
Thymidylate synthetase
What assessments do patients on methotrexate need every 1-3 months
Full blood count
Liver function tests
Methotrexate MOA
inhibiting dihydrofolate reductase + thymidylate synthetase -> decr RNA + DNA synthesis
JNK activation -> incr ROS -> Induce apoptosis and cell cycle arrest
Inhibit IL1 and NF-kB production
Salfasalazine
Sulphur based antibiotic combining sulfapyridine and 5-amino salicylic acid
Does sulfasalazine act locally or systematically
Sulfapyridine absorbed systematically
5-ASA has local anti inflam action
Sulfasalazine MOA
Not well understood
Concentrates in CT and serous fluid
Suppresses superoxide radical and cytokine production
What other condition is sulfasalazine mainly used for
Ulcerative colitis
Hydroxychloroquine main use
Antimalarial
Hydroxychloroquine MOA in RA
Increases pH in lysozymes decreasing protein modifications
Blocks TLR 9 decreasing dendritic cell activation
Leflunomide MOA
Inhibits pyramiding biosynthesis by inhibiting dihydroorotate dehydrogenase
D penecillin MOA in RA
copper chelator
Decr immune response and IL1 generation
Prevents fibrosis
D pencillamine main side effect
Kidney damage
Why are gold salts not often used for RA treat,ent
Side effects
Traditional DMARDs
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
D pencillamine
Gold salts
Cells/molecules inhibited by Biological DMARDs
TNFa
IL1, 6, 17, 23
B cells
T cells
IL6
JAK
TNFa blocker MOA
Remove TNFa from system before it reaches TNFa receptor
Etanercept
TNFa blocker
Fusion protein of human TNF receptor 2 and human IgG1
Infliximab
TNFa blocker
Monoclonal antibody against TNFa
Adalimumab
Human monoclonal antibody for TNFa
Which molecule is targeted by anakinra canakinumab and rilonacept
IL1
Anakinra - IL1 receptor antagonist
Canakinumab - IL1 monoclonal antibody
Riloncept - binds to IL1
Rituximab
Monoclonal antibody against CD20 on B cells
How does rituximab destroy normal and malignant B cells
Complement dependent cytotoxicity
Antibody dependent cellular cytotoxicity
Recognition by macrophages
Activates apoptosis
What cells do abatacept and balatacept target and what process do they effect
T cells
Disrupt cell signalling through CD28
Which drug is rituximab, and tocilizumab given in combination with
Methotrexate
Tocilizumab
Humanised monoclonal antibody against membrane and soluble IL6 receptor
What drug type are tofacitinib, baricitinib, and upadacitinib
JAK inhibitor
What is JAK
Janus kinase
How are biological DMARDs generated
Genetic engineering
What IL does secukinumab and ustekinumab target
Secukinumab - IL17
Ustekinumab - IL23
Which condition are IL17 and IL23 mainly used for
Psoriasis
Difference between neutralising and non neutralising anti drug antibodies
Neutralising directly interferes with biological drugs ability to work
Non neutralising forms immune complexes around injection site reducing drug conc and pharmacokinetics
What molecule made by the body decreases the effectiveness of biological DMARDs
Anti drug antibodies
