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3- IBD therapy Flashcards

1
Q

what are aims of IBD therapy?

A
  • Control inflammation + heal mucosa
  • Restore normal bowel habit
  • Improve quality of life
  • Balance the effects of disease with side effects of treatment
  • Avoid long-term complications
  • Be a good advocate for the patient
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2
Q

what are 3 therapeutic strategies for IBD? (very general)

A
  • lifestyle
  • drugs
  • surgery
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3
Q

what effect does smoking have on IBD?

A

smoking aggravates crohn’s but actually helps ulcerative colitis

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4
Q

if stricturing or fistuling crohn’s - whats good to follow?

A
  • low residue (low fibre) as less strain for when moving through structures
  • could be elemental diet (shakes with all nutrients in it, good for paediatric and now also adult, modulen)
  • strict gut rest (e.g, parenteral nutrition)
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5
Q

what is therapeutics for maintenance for ulcerative colitis?

A

for maintenance the 1st step is 5-ASA then step up to immunosuppressants then biologics

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6
Q

what is medication for acute flare for both crohn’s and ulcerative colitis?

A

steroids - IV methylprednisolone then oral prednisolone/budesonide

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7
Q

what therapeutics are for maintenance of crohn’s?

A

1st immunosuppressants then biologics

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8
Q

what are the corticosteroids used for flare ups for ulcerative colitis and crohn’s?

A

IV methylprednisolone for 5 days then oral prednisolone/budesonide for 8 weeks (can use topical for anal disease)

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9
Q

why would you give budesonide over prednisolone for oral steroids for IBD flare ups? (after initial IV)

A

budesonide doesn’t give systemic side effects of prednisolone

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10
Q

what are musculoskeletal side effects of steroids?

A
  • avascular necrosis
  • oestoporosis
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11
Q

what are gastrointestinal steroid side effects?

A
  • hyperphagia
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12
Q

what are cutaneous steroid side effects?

A
  • acne/folliculitis
  • thinning of skin
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13
Q

what are metabolic steroid side effects?

A
  • weight gain
  • diabetes
  • hypertension
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14
Q

what are neuropsychiatric steroid side effects?

A
  • drug induced psychosis (rare)
  • depression
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15
Q

what is possible steroid side effect for children?

A

growth failure

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16
Q

what is mechanism of 5-ASA?

A

5 - aminosalicylic acid = can get tablet or topical

  • inhibits COX & lipoxygenase pathways
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17
Q

what is effect of 5-ASA?

A

anti-inflammatory pathways = decreases cyclooxygenase & lipoxygenase pathways so reduces formation of pro-inflammatory prostaglandin & leukotriene molecules

  • reduces risk of colon cancer
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18
Q

what are side effects of 5-ASA?

A
  • diarrhoea
  • idiosyncratic nephritis = type of kidney inflammation so needs renal function monitoring
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19
Q

what are examples of 5-ASA drug brands and when are they released?

A
  • asacol + salofalk = released when reach certain pH
  • pentasa + octasa = delayed release microspheres
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20
Q

what 5-ASA drug brands released only ileum & colon?

A

asacol & salofalk (as released when certain pH)

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21
Q

what 5-ASA drug brands are released in all of small & large intestine (at each area)?

A

pentasa & octasa (delayed release microspheres) = released in duodenum, jejunum, ileum & colon

22
Q

what 5-ASA drugs are only released in duodenum?

A

the old 5-ASA drugs like salazopyrin and balsalazide

23
Q

what is mesalazine?

A

mesalazine is drug example of 5-ASA →different brand names of these are asacol, salofalk, pentasa, octasa

24
Q

what are 2 types of topical therapy of 5-ASA?

A
  1. suppositories = coated does that is inserted into rectum where dissolve and release medication
  2. enema = foam that is delivered into rectum via nozzle or applicator
25
Q

what is positives & negatives of suppositories?

A

+ve = useful for treating when conditions <20cm away from anal verge
+ve = better mucosal adherence than enemas

-ve = limited reach, can’t reach further than 20cm

26
Q

what are positives and negatives of enema?

A

+ve = treat larger area of spread along rectum & sigmoid colon as reflex contraction helps medication reach further

-ve = only <10% enemas remain in the rectum, rest is expelled or absorbed further up colon

27
Q

should you use enema or suppositories topical therapy for rectosigmoid?

A

rectosigmoid = use enema as need it to spread further

28
Q

should you use enema or suppositories topical therapy for proctitis?

A

proctitis (inflammation localised to rectum) = use suppositories

29
Q

what immunomodulator drugs should be used for crohn’s and when?

A

azathioprine or 6-mercaptopurine
= used for maintenance of remission

*methotrexate can be used if not tolerant to other 2 but rare

30
Q

what immunomodulator drugs should be used for ulcerative colitis and when?

A

azathioprine or 6-mercaptopurine
= can be considered to maintain remission if patients requiring > 2 courses steroids in 12 months due to 2 or more inflammatory exacerbations in 12 months

31
Q

what is speed of action azathioprine & 6-mercatopurine?

A

= slow action

32
Q

what is significance of TPMT activity for immunomodulators drugs azathioprine & 6-mercaptopurine?

A

TPMT activity = enzyme that metabolises these drugs helps to detoxify & eliminate them from body. if people have low TPMT activity (often called low metabolisers) are unable to efficiently metabolize the drugs so can cause toxicity & adverse effects

33
Q

what is side effects of azathioprine & 6-mercaptopurine?

A
  • pancreatitis
  • leukopenia
  • hepatitis so needs monitoring
  • small risk of lymphoma, skin cancer (more sensitive to sun)
34
Q

what is top tier (last resort) of drugs for both ulcerative colitis and crohn’s?

A

biologics

35
Q

what are 2 different mechanisms of biologics?

A
  1. block action of cytokines that drives inflammation e.g. a key cytokine is TNFα
  2. stop immune cells getting into gut wall which is where they contribute to inflammation
36
Q

why block TNFα?

A

= TNFα is pro-inflammatory cytokine so in IBD, excessive production of TNFα contributes to inflammation and tissue damage
- blocking makes rapid improvement of symptoms as decreases inflammation & promotes apoptosis of activated T-lymphocytes

37
Q

what are adalimumab and infliximab?

A

antibodies that target TNFα and bind to prevent it extering inflammatory effect

38
Q

what is example of chimeric antibody biologic?

A

infliximab by IV infusion
chimeric = means composed of both human & non-human components

39
Q

what is an example of humanised antibody biologic?

A

adalimumab by subcutaneous injection
humanised = means derived primarily from human components

40
Q

what are safety problems/side effects of anti-TNFα?

A
  • 13% have infusion reactions
  • some can get infections - reactivation of Tb
  • association with lymphoma and solid tumours
  • very rae but can get demyelination reaction (like multiple sclerosis)
41
Q

what are some examples of biosimilars of infliximab/remicade biologics - what does this mean?

A

= approved subsequent versions of innovator biopharmaceutical products
- Inflectra & Remsima (1/3 of cost of infliximab!)

42
Q

what is mechanism of vedolizumab?

A

= stops immune cells tethering and migrating through gut wall into gut

  • Gut selective anti-α4β7 integrin therapy
  • Blocks activity of gut-homing T-cells
43
Q

how is vedolizumab administered?

A

as an IV or sub-cutaneous injection

44
Q

what is mechanism of ustekinumab? and how administered?

A

it blocks cytokine, IL-12/23
- loading dose given IV, maintenance subcutaneously

45
Q

what are JAK inhibitors?

A

Janus kinase inhibitors = Block phosphorylation & activation of Signal Transducer & Activator of Transcription (STAT) of cytokines

*a biologic tablet

46
Q

what is JAK inhibitor contradicted for/complications?

A
  • CVS risk (lipid profile)
  • Thromboembolic events (DVT/PE)
  • Infections (can be reactivation of Herpes zoster)
  • Teratogenicity
  • Renal / liver / FBC monitoring
47
Q

what are examples of JAK inhibitors - which ones can be used for crohns and which ones ulcerative colitis?

A
  1. Tofacitinib = inhibits JAK 1,2,3
  2. Upacitinic = blocks JAK 1
  3. Filgotinib = targets JAK 1

*all 3 used for UC, only upacitinic for crohn’s

48
Q

what is emergency surgency for IBD?

A

Failure to respond to medical therapy, small bowel obstruction, abscess, fistulae

49
Q

what is elective surgery for IBD?

A
  • Failure to respond to medical therapy
  • high grade Dysplasia or cancer of colon mucosa
50
Q

what type of surgery is for crohn’s?

A
  • surgeons take out infected area and can try deal with fistula and rejoin colon making anastomosis but some patients need colon removed & stoma

= aim to minimise bowel resection since not curative so can get repeated resection and result in short gut syndrome and requirement of lifelong total parenteral nutrition (reduced life expectancy)

51
Q

what is surgery for ulcerative colitis?

A

= curative

option for permanent ileostomy or restorative proctocolectomy and pouch

GI (56 decks)

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