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IMMUNE SYSTEM ANG MALIGNANT DISEASE > IMMUNOSUPPRESSION THERAPY > Flashcards

IMMUNOSUPPRESSION THERAPY Flashcards

1
Q

What are
immunosuppressants?

A
  • They are a group of drugs which are used to suppress rejection in organ transplants and are used to treat chronic inflammatory and autoimmune disease
  • They can also be used in conditions such as inflammatory bowel disease
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2
Q

Examples of immunisuppressants

A
  1. Anti-proliferative drugs
    - Azathioprine
    - Mercaptopurine
    - Mycophenolate mofetil
  2. Calcineurin inhibitors
    - Ciclosporin
    - Tacrolimus
  3. Corticosteroids
    - Prednisolone
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3
Q

Azathioprine MOA

A
  • Antimetabolite which breaks down into mercaptopurine
  • inhibits the repairment and making of DNA
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4
Q

Azathioprine - indications

A
  • Prevents organ rejection in transplant patients
  • Autoimmune disorders e.g. IBD, Rheumatoid arthritis, Myasthenia gravis
  • May also be used for severe eczema
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5
Q

Azathioprine - side effects

A
  • Hypersensitivity → malaise, dizziness, D + V, fever, rash, hypotension, myalgia
  • Bone marrow suppression (Neutropenia and thrombocytopenia) → report sore throat, bruising, bleeding
  • Nausea → more common at start of dose but resolves over time
  • Pancreatitis
  • Teratogenic → avoid in pregnancy
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6
Q

Azathioprine - hypersensitivity

A

malaise, dizziness, D + V, fever, rash, hypotension, myalgia

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7
Q

Azathioprine - Neutropenia and thrombocytopenia

A

report sore throat, bruising, bleeding

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8
Q

Azathioprine - nausea

A
  • more common at start of dose but resolves over time
  • divided doses, taken with food ro an antiemetic or reducing dose may help
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9
Q

Azathioprine - monitoring requirements

A
  • Thiopurine Methyltransferase (TPMT)
  • Regular LFT and FBC in severe liver / renal impairment
  • FBC weekly for first 4 weeks, then at least every 3 months
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10
Q

Azathioprine - caution

A
  • Reduced Thiopurine methyltransferase (TPMT)
    activity
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11
Q

Azathioprine - TMPT levels

A
  • Azathioprine broken down by Thiopurine Methyltranaterase (TPMT)
  • Reduced TMPT → risk of bone marrow suppresssion (myelosuppression), due to lack of metabolism
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12
Q

Azathioprine - interactions

A

Allopurinol
ACEi

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13
Q

Azathioprine + Allopurinol →

A
  • increased risk of haematological toxicity
  • Reduce dose of azathioprine to a quarter of the usual dose
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14
Q

Azathioprine + ACE-I →

A

increased risk of anaemia / leucopenia

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15
Q

Azathioprine - pregnancy

A
  • NEVER
  • The need to continue Azathioprine during pregnancy should be discussed with a specialist
  • Pre-mature birth and spontaneous abortion have been reported
  • Present in low levels in breastmilk
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16
Q

Which is both an immunosuppressant and a cytotoxic drug?
Azathioprine or
Mercaptopurine?

A
  • Mercaptopurine
  • Azathioprine is only an immunosuppressant drug, it is not used as an anti-cancer (cytotoxic) drug
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17
Q

Mercaptopurine - indications

A
  • Severe Acute ulcerative colitis and Crohn’s (however use of it is unlicensed)
  • Maintenance of remission of UC and Crohn’s
  • Leukaemia
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18
Q

Ciclosporin - MOA

A

Calcineurin inhibitor inhibiting lymphokines → suppress cell-mediated response

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19
Q

Ciclosporin - indications

A
  1. IBD
  2. Rheumatoid arthritis
  3. Severe atopic dermatitis and psoriasis
  4. Organ transplantation
  5. Bone-marrow transplantation
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20
Q

Ciclosporin - CI

A
  • Uncontrolled hypertension!
  • Malignancy
  • Uncontrolled infections
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21
Q

Ciclosporin - brand

A

Prescribed and dispensed by brand name

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22
Q

Ciclosporin - pregancy + BF

A

Avoid

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23
Q

Ciclosporin - side effects

A

HYPER- glycaemia, lipidaemia, tension, uricemia, kalaemia (HYPO-Mg)
Renal / Liver impairment
Skin reactions
Gingival hyperplasia
Hair changes
Eye inflammation and visual disturbances (in topical use with eyes)

24
Q

Ciclosporin - Interactions

A
  • Grapefruit + Pomelo juice → increases ciclosporin exposure
  • Purple grape juice → decreases ciclosporin exposure
  • Macrolides
  • Carbamazepine
  • Amiodarone/ digoxin
  • Statins
  • Phenytoin
  • Rifampicin
  • Grapefruit juice
  • Antifungals
  • Tacrolimus
25
Q

Grapefruit + Pomelo juice →

Ciclosporin

A

increases ciclosporin exposure

26
Q

Ciclosporin + Purple grape juice →

A

decreases ciclosporin exposure

27
Q

Ciclosporin - pre-screening

A

Pre-screening: exclude malignancies before systemic use

28
Q

Ciclosporin - monitoring

A
  • Monitor: LFT, Magnesium, Potassium, Lipids, CrCl, Blood Pressure, Renal
  • Trough levels need to be monitored (range depends on indication)
29
Q

Ciclosporin - counselling

A
  • Avoid exposure to UV light / sunlight
  • Topical (eye) use may effect driving / performing skilled tasks
30
Q

Tacrolimus - MOA

A

Calcineurin inhibitor inhibiting lymphokines → suppress cell-mediated response

31
Q

Tacrolimus - brands

A
  1. Increased risk of infections
  2. Neurotoxicity
  3. QT prolongation
32
Q

Tacrolimus - brand

A

Prescribed and dispensed by brand name

33
Q

Tacrolimus - side effects

A

HYPER- glycaemia, uricemia, kalaemia
HYPO/HYPER tension
Renal / Liver impairment
Skin reactions
Visual disturbances
Blood Dyscrasia
Cardiovascular diseases (QT prolongation, cardiomyopathy in children)
Nervous system disorder, peripheral neuropathy

34
Q

Tacrolimus - pregnancy + bf

A

Avoid in pregnancy and breast feeding

35
Q

Tacrolimus - interactions

A

Grapefruit + Pomegranate + Pomelo juice → increases tacrolimus exposure

36
Q

Grapefruit + Pomegranate + Pomelo juice →

A

increases tacrolimus exposure

37
Q

Tacrolimus - contraindications

A

Do not use if patient has hypersensitivity to macrolides

38
Q

Tacrolimus - monitoring

A
  1. Tacrolimus-blood concentration
  2. BP
  3. ECG - for risk of cardiomyopathy
  4. Fasting-blood glucose concentration
  5. Electrolytes
  6. Renal function / Hepatic function
  7. Vision
39
Q

Tacrolimus - counselling

A

Avoid exposure to UV light / sunlight
May effect driving / performing skilled tasks

40
Q

Mycophenolate Mofetil - indication

A
  • Prevents rejection in: renal, cardiac and hepatic transplant
41
Q

Mycophenolate Mofetil - MOA

A
  • Inhibits purine synthesis
  • Metabolised to mycophenolic acid
42
Q

Mycophenolate vs Azathioprine

A
  • Mycophenolic acid has a more selective mode of action that mercaptopurine
  • Therefore it is more specific in preventing acute rejection
  • Risk of blood disorders higher with myco
43
Q

Mycophenolate Mofetil - cautions

A
  • GI disease
  • Children/elderly
  • Increased susceptibility to skin cancer
  • hypogammaglobulin or bronchiestasis
44
Q

Mycophenolate Mofetil - side effects

A

Bone marrow suppression:
Pure red cell aplasia:
Hypogammaglobulinaemia:
Bronchiectasis

45
Q

Mycophenolate Mofetil - Bone marrow suppression

A

report infection or bruising or bleeding

46
Q

Mycophenolate Mofetil - pure red cell aplasia

A

reduce dose or discontinue

47
Q

Mycophenolate Mofetil - Hypogammaglobulinaemia

A

measure immunoglobulin levels in recurrent infections

48
Q

Mycophenolate Mofetil - bronchiectasis

A

Consider if persistent cough and SOB develops

49
Q

Mycophenolate - pregnancy

A
  • PPP
  • congenital malformations
  • spontaneous abortions
50
Q

Mycophenolate Mofetil - MHRA Contraception Advice (teratogenic):

A
  • Women: 1 effective contraception during and 6 weeks after (2 methods preferred)
  • Men: effective contraception during and 90 days after (for partner as well)
51
Q

Mycophenolate - monitoring

A

FBC
- every week for 4 weeks
- twice a month for 2 months
- then every month

52
Q

What are the indications for
Corticosteroids as an immunosuppressant?

A
  • They are used in IBD
  • Corticosteroids are also used in transplant rejection
  • Prednisolone also has an anti-tumour effect, therefore used in oncology
53
Q

Summary

A
  1. Azathioprine
    - Metabolised to Mercaptopurine
    - Do NOT use if TPMT low
    - Bone marrow suppression is the main side effect
  2. Mercaptopurine
    - Do NOT use if TPMT low
    - Immunosuppresant and cytotoxic
    - higher risk of incorrect dosing
  3. Mycopnenolate moreti
    - Bone marrow suppression is the main side effect
    - The key thing to remember is contraception advice is for both MEN and WOMEN
  4. Ciclosporin
    - Should always be prescribed by brand!
    - Monitor: BP, lipids, Electrolytes (K and Mg), Renal and liver
  5. Tacrolimus
    - Should always be prescribed by brand!
    - The same monitoring as Ciclosporin applies, but monitor blood glucose, ECG and Neurotoxicity for Tacrolimus
    - Risk of Neurotoxicity, Hyperglycaemia, and cardiomyopathy are greater with Tacrolimus than with ciclosporin
54
Q

What vaccines would p atients on immunosup pressants require?

A
  1. Measles
    - Advise to avoid anyone with measles
  2. Varicella-Zoster (Chickenpox)
    - Advise to avoid contact with chicken pox
55
Q

Which vaccines should be AVOIDED for patients on
immunosuppressants?

A

LIVE VACCINES
- Patients can get the actual infection from the vaccine

56
Q
A
57
Q
A

IMMUNE SYSTEM ANG MALIGNANT DISEASE (5 decks)

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