Drugs for Arthritic Disorders (RA, OA) Flashcards
What does SYSADOA stand for?
Symptomatic slow-acting drug for osteoarthritis
Name an evidence-based SYS ADOA for osteoarthritis
Intra-articular hyaluronic acid
Briefly explain the mechanisms of action of intra-articular hyaluronic acid
● Hyaluronic acid (HA) is a large glycosaminglycan (naturally in synovial fluid)
● Shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication, reduces pain & stiffness
● Induces biosynthesis of endogenous HA & extracellular matrix
List TWO supplements commonly used for osteoarthritis for which there is limited medical evidence
Chondroitin sulphate and glucosamine
Name the 4 compartments and 3 things of immune cell reponses
a
Compartments:
Innate immunity:
(1) Complement
(2) Phagocytes
Adaptive immunity:
(3) B cells
(4) T cells
3 things immune cells do when activated:
(1) Proliferate
(2) Cytokine production
(3) Trafficking and adhesion
What is the first-line csDMARD?
Methotrexate
List FOUR examples of csDMARDs
Methotrexate (first-line)
Sulfasalazine Leflunomide Hydroxychloroquine (best tolerated) Ciclosporin
Briefly explain the mechanisms of action of methotrexate
● Major Action: Increased adenosine levels due to AICAR transformylase and ATIC inhibition
● Minor Action: Inhibits dihydrofolate reductase and thymidylate synthetase
● Overall Effects: Increase in extracellular adenosine level and activation of adenosine A2a receptor
● Anti‐proliferative effects on T cells and inhibition of macrophage functions
● Decrease in pro‐inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis
State the 5 adverse effects of methotrexate
- hair loss
- n/v
- leukopenia
- pneumonitis
- hepatic fibrosis
How can methotrexate-induced nausea/vomiting, mouth and GI uclers, and hair-thinning be reduced?
Concomitant folic acid (high dose) or folinic acid given 12‐24hr after methotrexate decreases toxicity
State the mechanism of action of sulfasalazine
MOA not known but…
1. suppression of b and t cells and macrophages
2. decreased cytokines (tnf-a, il-1, il-6)
3. decreased IgA and IgM RF
State the common adverse effects of sulfalasazine
- n/v
- rash
- neutropenia
- haemolytic anaemia
- headache
- irreversible infertility in males
State the mechanism of action of leflunomide
CONVERTED TO TERIFLUNOMIDE (ACTIVE)
- inhibits dihydrooterate dehydrogenase
- inhibits t cell proliferation and b cell autoantibody production
- inhibits Nf-Kb activation pro-inflammaotry pathway
- decreasdd pyrimidine sytnehsis of grwoth arrest @G1 phase
State the common adverse effects of leflunomide
- diarrhoea
- elevated LFTs
- alopecia
- weight gain
- teratogenic
What must be done if patient is pregnant and has been prescribed leflunomide before?
Cholestyramine washout before pregnancy due to long half life of leflunomide
State the mechanism of action of hydroxychloroquine
- decrease mhc class 2 expression and antigen presentation
- decrease cytokines (il-1, tnf-a)
- decrease cartilage resorption
- antioxidant
State the common adverse effects of hydroxychloroquine
- n/v
- stomach pain
- diarrhoea
- alopecia
- occular toxicity
State the name of the tsDMARD usually administered
tofacitinib!
State the pathologies treated by tsDMARD
- moderate/severe RA
- psoriatic arthritis
State the mechanism of action of tofacitinib
JAK pathway inhibition -> blocks cytokine production by blocking JAK-STAT (janus kinase-signal transducer and activation of transcription) of gene transcription
State the common adverse effects of tofacitinib
- cytopenia
- immunosuppression
- hyperlipidemia
- anaemia (JAK2 needed for EPO)
List THREE examples of bDMARDs
Anti‐TNF mAb (e.g., infliximab, adalimumab, etanercept)
IL‐1R antagonist (e.g., anakinra)
Anti-IL‐6 receptor mAb (e.g., tocilizumab)
Anti‐CTLA4Ig (e.g., abatacept)
Anti‐CD20 (e.g., rituximab)
State the common adverse effects of Anti-TNF mAB
RIO LEA
1. respiratory infection
2. increased risk of lymphoma
3. optic neuritis
4. exacerbation of multiple sclerosis
5. leukopenia
6. aplastic anaemia
State the mechanism of action of IL-1R antagonist
State the adverse effects
anakinra!!!
Binds to IL-1R and prevents IL-1’s binding.
Injections - hypersensitivity
State the mechanism of action of anti-IL6R mAb
State the adverse effects
tocilizumab!!!
Binds to IL-6R and prevents binding of IL-6 to IL6Ra and prevents homodimerisation of IL6Rb signalling
infections, skin eruption, stomatitis, fever, neutropenia, elevated AST/ALT, hyperlipidemia, interacts with CYP450, 34A, 1A2, 2C9
Explain why tocilizumab has drug-drug interactions with drugs undergoing hepatic metabolism
Like most mabs, tocilizumab is cleared by proteolytic metabolism.
But interacts with CYP450 34A, 1A2 or 2C9 substrates
IL-6 decreases expression of these CYP450 enzymes, so tocilizumab blocking IL-6 signalling increases expression
State the mechanism of action of Anti-CTLA4Ig
State the adverse effects
abatacept!!
Recombinant fusion protein with CTLA-FcIgG1 binds to CD80 and CD86 and prevnets CD28 activation
repspiratory infection in COPD, increase chance of lymphoma
State the mechanism of action of anti-cd20
State the adverse effects
rituximab!!!!
Chimeric mAb IgG1 directed at cd20 on pre and mature b cells -> deplete b cells
rash n first dose, respiratory infection in copd patients
Which drugs induce adverse effect of neutropenia
- cdDMARD - sulfasalazine
- bDMARD - tocilizumab
Which drugs induce adverse effect of increasing risk of lymphoma?
BOTH ARE bDMARDs!!
1.anti-tnf mab (infliximab, golimumab, adalimumab, etanercept)
2. anti-CTLA4Ig - abatacept
