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CPT > Lecture 14 - Immunosupressants > Flashcards

Lecture 14 - Immunosupressants Flashcards

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1
Q

What conditions do rheumatologists managed?

A

Disordered immune systems:
Inflammation arthritis
Rheumatoid arthritis
Systemic Lupus Erythematous
System I vasculitis

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2
Q

What is rheumatoid arthritis?

A

Autoimmune condition

Attacks synovium (covering of the joint)
Inflammation change, proliferation of synovium forming a thickened pannus which leads to cartilage damage

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3
Q

What joint is often damaged in rheumatoid arthritis?

A

Metacarpophalangeal joints

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4
Q

What are some pro-inflammatory mediators?

A

IL-1
Il-6
TNF-a
Metalloproteinases

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5
Q

What are some anti inflammatory mediators?

A

IL-4
TGF-Beta

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6
Q

What is the pathogenesis for rheumatoid arthritis?

A

In balance between anti-inflammatory and pro-inflammatory mediators

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7
Q

How do we diagnose rheumatoid arthritis??

A

Clinical diagnosis:
-Stiffness in the morning improving after an hour
-arthritis of >3 joints
-arthritis of hand joints
-symmetrical arthritis
-rheumatoid nodules (advanced)

X-ray changes
Serum rheumatoid factor

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8
Q

What is the goal of treatment of rheumatoid arthritis?

A

Symptomatic relief
Prevention of joint destruction

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9
Q

What do we call rheumatoid arthritis affect kids?

A

Juvenile Idiopathic arthritis

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10
Q

What increases the risk of you getting rheumatoid arthritis?

A

Family history (genetic0

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11
Q

What is the treatment strategy for rheumatoid arthritis?

A

Early use of disease modifying drugs:
Aim to achieve good disease control
Use correct dosages and combos

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12
Q

Why do we want to avoid the use of long term corticosteroids?

A

Side effects (weight gain, osteoporosis, inc risk of infections)

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13
Q

What is drug assisted remission?

A

Disease goes into remission but have to remain on drugs to do so

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14
Q

What is systemic lupus erythrematous?

A

Autoimmune condition affecting any organ in the body

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15
Q

What are. Some symtoms of lupus?

A

Facial rash
Hair loss
Lung scarring
Kidneys

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16
Q

What is vasculitis?

A

Inflammation of any type of blood vessels

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17
Q

What is the treatment goal for SLE and vasculitis?

A

Systematic relief
Reducing mortality by preventing organ damage

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18
Q

What are some immunosuppressant drugs?

A

Corticosteroids
Methotrexate
Azathioprine
Leflunomide
Cyclophosphamide

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19
Q

How to corticosteroids work as an immunosuppressant?

A

Prevents IL-1 and IL-6 production by Macrophages which inhibts T cells and B cell activation

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20
Q

What is the problem with cortitcosteroids?

A

They aren’t very targeted in the way that they work

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21
Q

What are DMARDs?

A

Disease modifying anti-rheumatic drugs (DMARDs)

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22
Q

What are the 2 categories of DMARDs?

A

Non-biologics

Biologics

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23
Q

What are some examples of non-biologic DMARDs?

A

Methotrexate, sulphasalazine
Leflunomide
Azathioprine

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24
Q

What are some biologic DMARDs?

A

Anti-TNF agents
Rituximab
IL-6 inhibitors
JAK inhibitors

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25
Q

What is Azathioprine used to treat?

A

SLE and vasculitis as maintenance therapy
Inflammatory bowel disease

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26
Q

Why is Azathioprine considered as a steroid sparing agent?

A

Azathioprine given once a patient has first been given steroids for their condition and its improved so Azathioprine is given to help keep disease in remission

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27
Q

What dermatological condition is Azathioprine given for?

A

-Atopic dermatitis
-Bullous skin disease

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28
Q

What is myelosuppression?

A

Suppression of the bone marrow reducing its ability to produce blood cells

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29
Q

What is the method of action of Azathioprine ?

A

Azathioprine broken down to 6-MP
6-MP metabolised by TPMT to active metabolite (TIMP)

This then goes into cells and decreases DNA synthesis and RNA synthesis in INFLAMMATORY CELLS

30
Q

What is the problem with Azathioprine in different individuals?

A

TMPT gene is highly polymorphic so the activity of TPMT is variable

31
Q

What does having low levels of TPMT increase the risk of?

A

Myelosupression

32
Q

What substance do we need to test the levels of before prescribing Azathioprine?

A

TPMT

33
Q

What are the adverse effects of Azathioprine? (Majority of immunosuppressants)

A

Bone marrow suppression
Increased risk of malignancy
Increased risk of infection
Hepatitis

34
Q

What are some calcineurin inhibtors?

A

Cyclosporin
Tacrolimus

35
Q

What dermatological condition can calcineurin inhibitors be used for?

A

Atopic dermatitis
Psoriasis

36
Q

What calcineurin inhibitor is used when a woman want to get pregnant but she has lupus and why?

A

Tacrolimus

Since it cant cross teh placental barrrier

37
Q

Why are calcineurin inhibtors not often used?

A

Causes renal toxicity
Multiple drug interactions (CYP450 interactions)

38
Q

What are some CYP450 inducers?

A

Rifampicin
Phenytoin
Omeprazole
Carbamazepine

39
Q

What are some CYP450 inhibtors?

A

Ciprofloxacin
Many antifungles
Fluoxetine
Paroxetine
HIV antivirals (Indiavir)
Amiodarone

40
Q

What is the mechanism of action of cyclosporin and Tacrolimus? (Calcineurin inhbitors)

A

They inhibit T cells prevention production of IL-2

Cyclosporin binds to cycophilin protein
Tacrolimus bids to Tacrolimus binding protein

41
Q

What is mycophenolate mofetil ((MMF) used for>?

A

Transplantations
Good efficacy as induction and maintenance thepay for lupus nephritis/vacuilits maintenance

42
Q

What is the mechanism of action of mycopphenolate mofetil?

A

Inhibits IMD (inosine monophosphate dehydrogenase) which impairs B and T cell proliferation (spares other rapidly dividing cells)

43
Q

What are the side effects of mycophenolate mofetil?

A

Nausea
Vomiting
Diarrhoea
Myelosupression

44
Q

What is the the mechanism of action of cyclophosphamide?

A

Suppressed T cell and B cell activity by cross linking DNA so it can’t replicates

45
Q

When is cyclophosphamide used?

A

Its very effective:

Lymphoma, leukaemia, solid cancers
Lupus nephritis
Wegeners granulomatosis

46
Q

What enzyme converts the prodrug cyclophosphamide into its active form 4-hydroxycyclophosphamide?

A

CYP450

47
Q

What is an active metabolite of cyclophamside that is very damaging to the body and causes Haemorrhagic cystitis (bladder bleeding)?

A

Acrolein

48
Q

How do we prevent Haemorrhagic cystitis due to acrolein?

A

Give Mesna with hydration to counteract the effects of acrolein

49
Q

What toxic effects can cyclophosphamide cause?

A

Bladder cancer
Lymphoma
Leukaemia
Infertility
Renal damage

50
Q

What drug is better for lupus nephritis instead of cyclophosphamide in a woman who wants to get pregnant?

A

Mycophenolate mofetil

51
Q

What are the uses of methotrexate?

A

Gold standard treatment of rheumatoid arthritis

Malignancy
Psoriasis
Crohn’s disease

Vasculitis
Steroid sparing drug

52
Q

What is the mechanism of actioon of methotrexate in malignancy?

A

Competitive and reversible inhibition of dihdyrofolate reducatse (DHFR)

Stops synthesis of DNA, RNA and proteins since stops Dihdyrofolate REDUCTASE converting dihrydofolate to Tetrahydrofolate which is the key carrier of one-carbon unit is in purine and thymidine synthesis

53
Q

What stage of the cell cycle does methotrexate act in?

A

S-phase

54
Q

What type of cells does methotrexate act the most strongly to?

A

Rapidly dividing cells (replicate DNA more frequently)

55
Q

What supplements do we need to give if giving someone methotrexate?

A

Folic acid

56
Q

How does methotrexate work in rheumatoid arthritis?

A

Not sure

Possibly T cell activation prevented

57
Q

How is methotrexate administer?

A

Oral
Intramuscular (best way for bioavailability)

Methotrexate very lipophilic

58
Q

What are the adverse efffects of methotrexate?

A

Mucositis
Marrow suppression (GIVE FOLIC ACID SUPPLEMNTs)

Hepatitis, cirrhosis
Pneumonia is
Infection risk

TERATOGENIC
ABORTIFACIENT (for ectopic pregnancy)

59
Q

What is sulfasalazine used for?

A

Contain aspirin

Rheumatoid arthritis
Rheumatic polyarthiris
Relieve pain stiffness

60
Q

How does sulfasalazine work?

A

Inhibits T cell proliferation and IL-2 production

Reduced chemotaxis and degranulation of neutrophil l

61
Q

Where does suplphasalazine act?

A

GI issues
Joints

62
Q

What are the adverse effects of sulfasalazine?

A

Myelosupression
Hepatitis
Rash

Nausea
Abdopain vomiting

63
Q

What are the adverse effects of sulfasalazine?

A

Myelosupression
Hepatitis
Rash

Nausea
Abdopain vomiting

64
Q

What are biologics?

A

Extracted from living systems

They are monoclonal antibodies custom to block TNF, IL-6 etc..

65
Q

What are the effects of biological blocking TNF-a?

A

Reduced inflammation
Reduced angiogenesis
Reduced joint destruction
Reduced bone resorption

66
Q

What is the mechanism of action of rituximab?

A

Binds specifically to CD20 which is found on B cells

67
Q

What is the function of B cells?

A

Present antigens to T cells
Produce cytokines
Produce antibodies

68
Q

What does Rituximab do to B cells?

A

B cell apoptosis

69
Q

What condition is rituximab used for?

A

Rheumatoid arthritis
Lupus
Vasculitis

70
Q

What are JAK inhibitors (Janus kinase)?

A

They block loads of receptors

CPT (30 decks)

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