3- IBD therapy Flashcards
what are aims of IBD therapy?
- 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
what are 3 therapeutic strategies for IBD? (very general)
- lifestyle
- drugs
- surgery
what effect does smoking have on IBD?
smoking aggravates crohn’s but actually helps ulcerative colitis
if stricturing or fistuling crohn’s - whats good to follow?
- 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)
what is therapeutics for maintenance for ulcerative colitis?
for maintenance the 1st step is 5-ASA then step up to immunosuppressants then biologics
what is medication for acute flare for both crohn’s and ulcerative colitis?
steroids - IV methylprednisolone then oral prednisolone/budesonide
what therapeutics are for maintenance of crohn’s?
1st immunosuppressants then biologics
what are the corticosteroids used for flare ups for ulcerative colitis and crohn’s?
IV methylprednisolone for 5 days then oral prednisolone/budesonide for 8 weeks (can use topical for anal disease)
why would you give budesonide over prednisolone for oral steroids for IBD flare ups? (after initial IV)
budesonide doesn’t give systemic side effects of prednisolone
what are musculoskeletal side effects of steroids?
- avascular necrosis
- oestoporosis
what are gastrointestinal steroid side effects?
- hyperphagia
what are cutaneous steroid side effects?
- acne/folliculitis
- thinning of skin
what are metabolic steroid side effects?
- weight gain
- diabetes
- hypertension
what are neuropsychiatric steroid side effects?
- drug induced psychosis (rare)
- depression
what is possible steroid side effect for children?
growth failure
what is mechanism of 5-ASA?
5 - aminosalicylic acid = can get tablet or topical
- inhibits COX & lipoxygenase pathways
what is effect of 5-ASA?
anti-inflammatory pathways = decreases cyclooxygenase & lipoxygenase pathways so reduces formation of pro-inflammatory prostaglandin & leukotriene molecules
- reduces risk of colon cancer
what are side effects of 5-ASA?
- diarrhoea
- idiosyncratic nephritis = type of kidney inflammation so needs renal function monitoring
what are examples of 5-ASA drug brands and when are they released?
- asacol + salofalk = released when reach certain pH
- pentasa + octasa = delayed release microspheres
what 5-ASA drug brands released only ileum & colon?
asacol & salofalk (as released when certain pH)
what 5-ASA drug brands are released in all of small & large intestine (at each area)?
pentasa & octasa (delayed release microspheres) = released in duodenum, jejunum, ileum & colon
what 5-ASA drugs are only released in duodenum?
the old 5-ASA drugs like salazopyrin and balsalazide
what is mesalazine?
mesalazine is drug example of 5-ASA →different brand names of these are asacol, salofalk, pentasa, octasa
what are 2 types of topical therapy of 5-ASA?
- suppositories = coated does that is inserted into rectum where dissolve and release medication
- enema = foam that is delivered into rectum via nozzle or applicator
what is positives & negatives of suppositories?
+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
what are positives and negatives of enema?
+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
should you use enema or suppositories topical therapy for rectosigmoid?
rectosigmoid = use enema as need it to spread further
should you use enema or suppositories topical therapy for proctitis?
proctitis (inflammation localised to rectum) = use suppositories
what immunomodulator drugs should be used for crohn’s and when?
azathioprine or 6-mercaptopurine
= used for maintenance of remission
*methotrexate can be used if not tolerant to other 2 but rare
what immunomodulator drugs should be used for ulcerative colitis and when?
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
what is speed of action azathioprine & 6-mercatopurine?
= slow action
what is significance of TPMT activity for immunomodulators drugs azathioprine & 6-mercaptopurine?
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
what is side effects of azathioprine & 6-mercaptopurine?
- pancreatitis
- leukopenia
- hepatitis so needs monitoring
- small risk of lymphoma, skin cancer (more sensitive to sun)
what is top tier (last resort) of drugs for both ulcerative colitis and crohn’s?
biologics
what are 2 different mechanisms of biologics?
- block action of cytokines that drives inflammation e.g. a key cytokine is TNFα
- stop immune cells getting into gut wall which is where they contribute to inflammation
why block TNFα?
= 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
what are adalimumab and infliximab?
antibodies that target TNFα and bind to prevent it extering inflammatory effect
what is example of chimeric antibody biologic?
infliximab by IV infusion
chimeric = means composed of both human & non-human components
what is an example of humanised antibody biologic?
adalimumab by subcutaneous injection
humanised = means derived primarily from human components
what are safety problems/side effects of anti-TNFα?
- 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)
what are some examples of biosimilars of infliximab/remicade biologics - what does this mean?
= approved subsequent versions of innovator biopharmaceutical products
- Inflectra & Remsima (1/3 of cost of infliximab!)
what is mechanism of vedolizumab?
= stops immune cells tethering and migrating through gut wall into gut
- Gut selective anti-α4β7 integrin therapy
- Blocks activity of gut-homing T-cells
how is vedolizumab administered?
as an IV or sub-cutaneous injection
what is mechanism of ustekinumab? and how administered?
it blocks cytokine, IL-12/23
- loading dose given IV, maintenance subcutaneously
what are JAK inhibitors?
Janus kinase inhibitors = Block phosphorylation & activation of Signal Transducer & Activator of Transcription (STAT) of cytokines
*a biologic tablet
what is JAK inhibitor contradicted for/complications?
- CVS risk (lipid profile)
- Thromboembolic events (DVT/PE)
- Infections (can be reactivation of Herpes zoster)
- Teratogenicity
- Renal / liver / FBC monitoring
what are examples of JAK inhibitors - which ones can be used for crohns and which ones ulcerative colitis?
- Tofacitinib = inhibits JAK 1,2,3
- Upacitinic = blocks JAK 1
- Filgotinib = targets JAK 1
*all 3 used for UC, only upacitinic for crohn’s
what is emergency surgency for IBD?
Failure to respond to medical therapy, small bowel obstruction, abscess, fistulae
what is elective surgery for IBD?
- Failure to respond to medical therapy
- high grade Dysplasia or cancer of colon mucosa
what type of surgery is for crohn’s?
- 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)
what is surgery for ulcerative colitis?
= curative
option for permanent ileostomy or restorative proctocolectomy and pouch
