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Pharmacology (MSK + Neuroscience) > Drugs for Arthritic Disorders (RA, OA) > Flashcards

Drugs for Arthritic Disorders (RA, OA) Flashcards

1
Q

What does SYSADOA stand for?

A

Symptomatic slow-acting drug for osteoarthritis

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2
Q

Name an evidence-based SYS ADOA for osteoarthritis

A

Intra-articular hyaluronic acid

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3
Q

Briefly explain the mechanisms of action of intra-articular hyaluronic acid

A

● 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

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4
Q

List TWO supplements commonly used for osteoarthritis for which there is limited medical evidence

A

Chondroitin sulphate and glucosamine

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5
Q

Name the 4 compartments and 3 things of immune cell reponses

A

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

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6
Q

What is the first-line csDMARD?

A

Methotrexate

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7
Q

List FOUR examples of csDMARDs

A

Methotrexate (first-line)
Sulfasalazine Leflunomide Hydroxychloroquine (best tolerated) Ciclosporin

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8
Q

Briefly explain the mechanisms of action of methotrexate

A

● 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

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9
Q

State the 5 adverse effects of methotrexate

A
  1. hair loss
  2. n/v
  3. leukopenia
  4. pneumonitis
  5. hepatic fibrosis
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10
Q

How can methotrexate-induced nausea/vomiting, mouth and GI uclers, and hair-thinning be reduced?

A

Concomitant folic acid (high dose) or folinic acid given 12‐24hr after methotrexate decreases toxicity

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11
Q

State the mechanism of action of sulfasalazine

A

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

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12
Q

State the common adverse effects of sulfalasazine

A
  1. n/v
  2. rash
  3. neutropenia
  4. haemolytic anaemia
  5. headache
  6. irreversible infertility in males
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13
Q

State the mechanism of action of leflunomide

A

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

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14
Q

State the common adverse effects of leflunomide

A
  1. diarrhoea
  2. elevated LFTs
  3. alopecia
  4. weight gain
  5. teratogenic
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15
Q

What must be done if patient is pregnant and has been prescribed leflunomide before?

A

Cholestyramine washout before pregnancy due to long half life of leflunomide

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16
Q

State the mechanism of action of hydroxychloroquine

A
  • decrease mhc class 2 expression and antigen presentation
  • decrease cytokines (il-1, tnf-a)
  • decrease cartilage resorption
  • antioxidant
17
Q

State the common adverse effects of hydroxychloroquine

A
  1. n/v
  2. stomach pain
  3. diarrhoea
  4. alopecia
  5. occular toxicity
18
Q

State the name of the tsDMARD usually administered

A

tofacitinib!

19
Q

State the pathologies treated by tsDMARD

A
  • moderate/severe RA
  • psoriatic arthritis
20
Q

State the mechanism of action of tofacitinib

A

JAK pathway inhibition -> blocks cytokine production by blocking JAK-STAT (janus kinase-signal transducer and activation of transcription) of gene transcription

21
Q

State the common adverse effects of tofacitinib

A
  1. cytopenia
  2. immunosuppression
  3. hyperlipidemia
  4. anaemia (JAK2 needed for EPO)
22
Q

List THREE examples of bDMARDs

A

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)

23
Q

State the common adverse effects of Anti-TNF mAB

A

RIO LEA
1. respiratory infection
2. increased risk of lymphoma
3. optic neuritis
4. exacerbation of multiple sclerosis
5. leukopenia
6. aplastic anaemia

24
Q

State the mechanism of action of IL-1R antagonist

State the adverse effects

A

anakinra!!!

Binds to IL-1R and prevents IL-1’s binding.

Injections - hypersensitivity

25
Q

State the mechanism of action of anti-IL6R mAb

State the adverse effects

A

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

26
Q

Explain why tocilizumab has drug-drug interactions with drugs undergoing hepatic metabolism

A

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

27
Q

State the mechanism of action of Anti-CTLA4Ig

State the adverse effects

A

abatacept!!

Recombinant fusion protein with CTLA-FcIgG1 binds to CD80 and CD86 and prevnets CD28 activation

repspiratory infection in COPD, increase chance of lymphoma

28
Q

State the mechanism of action of anti-cd20

State the adverse effects

A

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

29
Q

Which drugs induce adverse effect of neutropenia

A
  1. cdDMARD - sulfasalazine
  2. bDMARD - tocilizumab
30
Q

Which drugs induce adverse effect of increasing risk of lymphoma?

A

BOTH ARE bDMARDs!!
1.anti-tnf mab (infliximab, golimumab, adalimumab, etanercept)
2. anti-CTLA4Ig - abatacept

Pharmacology (MSK + Neuroscience) (8 decks)

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