3- IBD therapy

Question 1

what are aims of IBD therapy?

Answer 1

• 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

Question 2

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

Answer 2

• lifestyle
• drugs
• surgery

Question 3

what effect does smoking have on IBD?

Answer 3

smoking aggravates crohn’s but actually helps ulcerative colitis

Question 4

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

Answer 4

• 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)

Question 5

what is therapeutics for maintenance for ulcerative colitis?

Answer 5

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

Question 6

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

Answer 6

steroids - IV methylprednisolone then oral prednisolone/budesonide

Question 7

what therapeutics are for maintenance of crohn’s?

Answer 7

1st immunosuppressants then biologics

Question 8

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

Answer 8

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

Question 9

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

Answer 9

budesonide doesn’t give systemic side effects of prednisolone

Question 10

what are musculoskeletal side effects of steroids?

Answer 10

• avascular necrosis
• oestoporosis

Question 11

what are gastrointestinal steroid side effects?

Answer 11

• hyperphagia

Question 12

what are cutaneous steroid side effects?

Answer 12

• acne/folliculitis
• thinning of skin

Question 13

what are metabolic steroid side effects?

Answer 13

• weight gain
• diabetes
• hypertension

Question 14

what are neuropsychiatric steroid side effects?

Answer 14

• drug induced psychosis (rare)
• depression

Question 15

what is possible steroid side effect for children?

Answer 15

growth failure

Question 16

what is mechanism of 5-ASA?

Answer 16

5 - aminosalicylic acid = can get tablet or topical

• inhibits COX & lipoxygenase pathways

Question 17

what is effect of 5-ASA?

Answer 17

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

• reduces risk of colon cancer

Question 18

what are side effects of 5-ASA?

Answer 18

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

Question 19

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

Answer 19

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

Question 20

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

Answer 20

asacol & salofalk (as released when certain pH)

Question 21

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

Answer 21

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

Question 22

what 5-ASA drugs are only released in duodenum?

Answer 22

the old 5-ASA drugs like salazopyrin and balsalazide

Question 23

what is mesalazine?

Answer 23

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

Question 24

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

Answer 24

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

Question 25

what is positives & negatives of suppositories?

Answer 25

+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

Question 26

what are positives and negatives of enema?

Answer 26

+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

Question 27

should you use enema or suppositories topical therapy for rectosigmoid?

Answer 27

rectosigmoid = use enema as need it to spread further

Question 28

should you use enema or suppositories topical therapy for proctitis?

Answer 28

proctitis (inflammation localised to rectum) = use suppositories

Question 29

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

Answer 29

azathioprine or 6-mercaptopurine = used for maintenance of remission *methotrexate can be used if not tolerant to other 2 but rare

Question 30

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

Answer 30

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

Question 31

what is speed of action azathioprine & 6-mercatopurine?

Answer 31

= slow action

Question 32

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

Answer 32

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

Question 33

what is side effects of azathioprine & 6-mercaptopurine?

Answer 33

- pancreatitis - leukopenia - hepatitis so needs monitoring - small risk of lymphoma, skin cancer (more sensitive to sun)

Question 34

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

Answer 34

biologics

Question 35

what are 2 different mechanisms of biologics?

Answer 35

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

Question 36

why block TNFα?

Answer 36

= 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

Question 37

what are adalimumab and infliximab?

Answer 37

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

Question 38

what is example of chimeric antibody biologic?

Answer 38

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

Question 39

what is an example of humanised antibody biologic?

Answer 39

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

Question 40

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

Answer 40

- 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)

Question 41

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

Answer 41

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

Question 42

what is mechanism of vedolizumab?

Answer 42

= stops immune cells tethering and migrating through gut wall into gut - Gut selective anti-α4β7 integrin therapy - Blocks activity of gut-homing T-cells

Question 43

how is vedolizumab administered?

Answer 43

as an IV or sub-cutaneous injection

Question 44

what is mechanism of ustekinumab? and how administered?

Answer 44

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

Question 45

what are JAK inhibitors?

Answer 45

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

Question 46

what is JAK inhibitor contradicted for/complications?

Answer 46

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

Question 47

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

Answer 47

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

Question 48

what is emergency surgency for IBD?

Answer 48

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

Question 49

what is elective surgery for IBD?

Answer 49

- Failure to respond to medical therapy - high grade Dysplasia or cancer of colon mucosa

Question 50

what type of surgery is for crohn's?

Answer 50

- 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)

Question 51

what is surgery for ulcerative colitis?

Answer 51

= curative option for permanent ileostomy or restorative proctocolectomy and pouch