Inflammatory Bowel Disease Flashcards
Mechanism of action of 5-aminosalicylates
API: mesalazine
Inhibition of prostaglandin, leukotriene synthesis, inhibiting production of reactive oxygen species
What is the main treatment for UC and doses
5-aminosalicylates
4-4.8g a day for treatment and then maintenance 2-2.4g /day
How does 5-ASA in sulfasalazine work?
It is poorly absorbed and thus remains in the terminal ileum/coon - induces remission but inhibiting the COX/leukotrienes/cyotkines, TNFa
Counselling for aminosalicylates?
- swallow whole not chew or crush as halving would cause premature 5-asa release
- Contact Dr if get sore throat, easily bruised, ever - could indicate a blood disorder caused by drug
- Maintain the brands due to differences in release profile
What are the components of sulfasalazine and what they do
sulfapyridine - acetylated in liver, no action in UC. Can also cause folate deficiency, hepatotoxicity.
Mesalazine (5-ASA) is the active component which induces remission
Name 3 brands of aminosalicylate
Asacol MR - Enteric coat delayed release pH >7 in terminal ileum and large bowel
Octasa MR - EC delayed release pH >7 in terminal ileum and colon
Ethylcellulose - coated microgranules to allow slow continous release - duodeum to rectum
Sulfasalazine in the colon - cleaved by intestinal bacteria - azoreductase pH >7
Mesavant XL pH>7 in colon
What is the licensing for mesalazine preparations in UC?
All mesalazine preps are licensed for tretment of milt to moderate acute exacerbations. EXCEPT salofalk 1g tablets which are only licensed for maintenance of remission
Asacol and Octasa MR are for maintenance AND remission for chrons ileo-colitis too
What is salofalk for?
1g tablets, only licensed for maintenance of remission in UC
What formulation would be used if a patient has UC that reaches the sigmoid colon?
This is proctosigmoiditis - Use foam 20-30 ml
What formulation is used for UC proctitis?
Suppository -reaches the rectum, 1g, 2g, 4,g
What formulation would be used for left sided distal colitis?
Enema - up to 100ml, reaches the descending colon –> splenic flexure
What is the order of patient preference of formulations?
Suppository > foam > enema
What are corticosteroids used for?
Mainstay treatment of Chrons flare up (sometimes UC flare), no role in maintenance
What is the main treatment for a chrons flare up and dose?
Corticosteroids - but NO ROLE IN MAINTENANCE - just flare up - Prednisolone 40mg OD, reduced slowly 2 weeks
What are long term risks of corticosteroids and when should they be taken
Long term risks of osteoprosis/peptic ulcer disease
Should be taken in the morning as affects natural sleep hormones. Ideally on lowest effective dose, reducing dose
What rectal steroids are available and when are they used?
Only really used for patients who are not responding / intolerent to PR mesalazine
- Hydrocortisone foam
- Prednisolone
- Budesonide foam
If a conventional glucocorticoid is contraindicated - what can be used for a single inflammatory exacerbation of chrons in a 12 month period?
Budesonide
What is budesonide usually restricted to?
Use in UC if 5-ASA are not tolerated/CI
Why is budesonide not as effective?
Less effective
Undergo FPM - low systemic bioavailability,
BUT: effects confined to GIT and low toxicity, less side effects and less adrenal suppression
What do we need to check before putting a patient on thiopurines e.g Azathioprine/mercaptopurine
If patient is at risk of developing severe s/e - assess Thiopurine Methyltransferase (TPMT) activity, do not offer if TPMT activity is deficient (would cause prodution of toxic purine analogues - cause BM toxicity)
- Can consider it if it is below normal but not deficient.
Monitoring in thiopurines
Monitor for neutropenia even if they have normal TPMT activity
MoA of azathioprine?
Immunosuppressant - purine analogues.
- It is a pro drug for mercaptopurine which is active metabolite
- Inhibition of purine synthesis
What is a s/e of azathioprine?
Bone marrow suppression - DO NOT give in conjunction with purine analogues e.g allopurinol
When is methotrexate considered?
In active and relapsing chron’s when other immunosuppressants are not tolerated or CI
MoA of methotrexate and dosing
Anti-metabolite/folate
- 25 mg / week PO, IM, SC - initiate lower and titrate up until remission induced, maintenance 15mg
S/e of methotrexate and monitoring
S/E - need to take folic acid to reduce, but omit on days taking metho
- Monitor FBC, LFTs
When is ciclosporin used
Acute severe UC - with poor improvements in 72hrs of corticosteroids or no improvement at any time.
- 2mg/kg PO or IV - dont use PO if have diarrhoea
Must have baseline BP, FBC, Cholesterol, LFTs, GCR, Mg levels first
When are monoclonal antibodies used?
TNFa inhibitors (Anti-TNFa) - Inflixumab, adalumimab.
Severe active chrons and severe UC.
- not responded to steroids or immunosuppressants
- Use until treatment failure / 12 months - whatever is shortest time.
- Check for TB before starting
Monitoring when taking TNF-a inhibitors? any counselling?
For infection and skin cancer
Counsel on effective contraception during treatment and for at least 5 months after last dose - both partners
MoA of Inflixumab?
TNFa is implicated in many autoimmune diseases . - regulation of inflammation, Inflixumab is a chimeric monoclonal AB that targets and binds to it, inactivtes it and then reduces inflammatory process
General counselling points for IBD patients?
- Flu jabs?
- Codeine can be used as a painkiller and also causes constipation so could stop the diarrhoea?
- Nutrition and dieticians
- Awareness of increased risk of clotting due to inflammation
- Do they need to be on bone protective agents or take Calcium agents?
What medications are not used when someone has IBD?
NSAIDS, anti-diarrhoeals, opioids - can precipitate toxic megacolon or worsen condition (in colitis). Paracetamol is good.
why is it important to maintain brands of mesalazine?
They have differences in release profiles
