Therapeutics of UC/CD Flashcards

1
Q

Management of Crohn’s: mild-moderate

A

INDUCING REMISSION
1. Prednisolone (8 weeks. PO)
2. Budenoside/5-ASA
(C/I, cannot tolerate, distal ileal/ileacecal disease)

ADD-ON THERAPY

  1. Azathioprine/mercaptopurine
  2. Methotrexate

MAINTENANCE

  1. Azathioprine/mercaptopurine
  2. Methotrexate
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2
Q

Management of Crohn’s: moderate-severe

A

INDUCING REMISSION

  1. Hydrocortisone (PO/IV)
  2. Biologics (adalimumab/vedolimumab/ustekinumab/infliximab)

ADD-ON THERAPY

  1. Azathioprine/mercaptopurine
  2. Methotrexate

MAINTENANCE

  1. Continuing biologics
  2. Azathioprine/mercaptopurine
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3
Q

Management of Crohn’s: fistulating disease

A

INDUCING REMISSION

  1. Antibiotics/drainage of abscess
  2. Biologics (infliximab/adalimumab)

ADD-ON THERAPY
1. Azathioprine/mercaptopurine

MAINTENANCE

  1. Continuing biologics
  2. Azathioprine / methotrexate
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4
Q

Management of UC: mild

A

INDUCING REMISSION

  1. 5-ASA
  2. Prednisolone/budenoside/beclomethasone

ADD-ON/MAINTENANCE

  1. 5-ASA
  2. (>2 exacerbations) Azathioprine/mercaptopurine
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5
Q

Management of UC: moderate

A

INDUCING REMISSION

  1. 5-ASA
  2. Prednisolone/budenoside/beclomethasone
  3. Tacrolimus

ADD-ON/MAINTENANCE

  1. 5-ASA
  2. Azathioprine/mercaptopurine
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6
Q

Management of UC: severe

A

INDUCING REMISSION

  1. IV Hydrocortisone
  2. IV Ciclosporin
  3. Biologics (Infliximab)
  4. Surgery

ADD-ON/MAINTENANCE

  1. Continue biologics
  2. Azathioprine/mercaptopurine
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7
Q

Benefits of Budenoside

A

Less effective and expensive
Used in disease affecting distal ileum, ileocecal, and ascending colon

Reduced s/e due to extensive first pass metabolism (less adrenal suppression)

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8
Q

5-ASA

A

5- aminoasalicylates (Others- olsalazine)

1) Sulfalazine (5-ASA + sulfapyridine)
- less commonly used now
- useful for patients with cross-overs e.g. suffer from RA/joint issues

2) Mesalazine (Coated 5-ASA designed for delivery in the colon)
- Released at pH 7
- Most commonly used

S/E
- Blood dycrasias (abnormal material found)
> brusising, bleeding, sore throat, malaise 
- Hypersensitivity
- Reduced renal function
- Hepatitis
- Headaches
- Dry Skin
- Male infertility (reversible)
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9
Q

What immunosuppressant is suitable in pregnancy?

A

Azathioprine

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10
Q

When are immunosuppressants considered?

A

> 2 exacerbations within 2 months (meaning 2+ courses of steroids)
Steroid-dependent or resistant patients

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11
Q

What are the benefits of immunosuppressants?

A
Reduce need for steroids
Mucosal healing (reduce T cell signalling)
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12
Q

Which immunosuppressants cannot be used in Crohn’s?

A

Tacrolimus or Ciclosporin

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13
Q

Overview: Thiopurines

A

Prodrug: Azathioprine
Metabolite: Mercaptopurine
- Inhibit ribonucleotide synthesis and induce T cell apoptosis
- Onset takes 2-3 months to occur

AZ 80% metabolised into MP
Extensively metabolised to active thioguanine nucleotides (checked 4-6 weeks after initiation)

TPMT (thiopurine methyl transferase) levels monitored prior to initiation (dose dependent- intermediate/deficient in enzymes require dose changes)

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14
Q

Side effects of immunosuppressants and monitoring

A
  • Flu-Like symptoms (after 2-3 weeks; self limiting)
  • Nausea
  • Vomiting
  • Idiosyncratic Pancreatitis
  • Liver toxicity
  • Bone marrow suppression

FBC, CRP, LFT, Thioguanine nucleotides

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15
Q

Overview: Methotrexate

A

25mg OW 16/52
Then 15mg OW 40/52

Measure methotrexate polyglutamate levels for first 8 weeks until steady state metabolism

S/E

  • nausea and vomiting
  • lung and liver disease
  • bone marrow suppression
  • mouth ulcers
  • teratogenic
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16
Q

Overview: Ciclosporin

A

IV

  • Steroid-resistant patients
  • Duration 3-6 months
  • Alternative: Tacrolimus
17
Q

At what point must cover against infection be considered?

A

When on 3 immunosuppressants e.g. ciclosporin, azathioprine and steroid

Use co-trimoxazole

Risk of PCP (pneumocystis pneumonia)

18
Q

Overview: Available biological therapies

A

ALL ANTI-TNFa
Patients progressively loose response overtime due to development of antibodies (immunosuppressants used when possible)

1) Infliximab
- genetically engineered murine-human monoclonal antibody antibody
- IV infusion 0, 2, 6, 8 weekly
- Must screen for latent infections such as TB, psoriasis, dermatitis, neuropathy

2) Adalimumab
- fully humanised monoclonal antibody
- better s/e compared to infliximab
- can be administered at home weekly

3) Golimumab
- S/C injection
- 4 weekly
- weight dependent

4) Vedolizumab
- 8 weekly infusion
- Preferred in geriatrics: gut-specific
- Binds to ‘gut homing’ lymphocytes and blocks recruitment of inflammatory cells
- Reduced s/e

19
Q

Contraindications against biological therapies

A

Active infection
Moderate/severe heart failure
Hypersensitivity

20
Q

Pre-screening before biological therapies

A
HIV
Shingles
Hepatitis B and C
Chickenpox 
Tuberculosis
Active malignancy

FBC
LFTs
CRP
Renal function

21
Q

Different antibiotics that can be used

A
  1. Metronidazole
    - 6 months after surgery
    - 3 months after anastomosis surgery
    - Active fistulating disease
    - Bacterial overgrowth
  2. Ciprofloxacin +/- Rifampicin
    - Anti-MAP therapy
    - treating bacterial overgrowth
    - long course, low dose
22
Q

Adjunctive treatments (holistic)

A

Smoking cessation
Diet (i.e. FODMAP diet)
Antimotility and antispasmodic drugs (codeine, loperamide)
Cholestyramine (diarrhoea due to bile acid malabsorption, especially after ileal resection)
Iron and vitamins
Stress management

23
Q

Indications for surgery in UC

Types

A

Unresponsive to medical therapy
UC: toxic megacolon
Colorectal Cancer

  1. Colectomy (partial/full removal)
    - maintain full anal function and consistency
  2. Ileostomy
    - permanent stoma fitted
    - can cause malabsorption problems
24
Q

Indications for surgery in CD

A
  • Unresponsive to medical therapy
  • Disease is treatable by surgery
  • Severe perianal infection, cancer, obstruction, fistulae, abscess, strictures, perforations
  • Short bowel syndrome
  • Stoma
25
Limitations and risks of surgery
- Pouchitis - Faecal incontinence - Prolapse - Anastomatic stricture/leak
26
Aims of treatment
Aggressive treatment during flare Inducing remission Maintaining and symptomatic treatment in remission
27
Choice of therapy depends on...
Severity of disease Disease extent and location Patient preference Response to treatment
28
Generally, what do corticosteroids do?
Inhibit phospholipase A2 activity and AA-PG cascade