*IBD 3 (lecture 3) Flashcards
What are the 3 therapeutic strategies that can be used to treat IBD?
Lifestyle advice
Drugs
Surgery
Is diet implicated in the pathogenesis of IBD?
No but it can influence symptoms
What is the common theme of all drug therapies?
They have an anti-inflammatory effect (you should tailor the drugs to the patients needs e.g. mild/ moderate/ severe relapse, tropical, oral, IV administration?
What are the drug therapy options for UC? (4)
5ASA (mesalazine)
Steroids
Immunosuppressants
Anti-TNF therapy
What are the drug therapy options for Crohn’s disease? (3)
Steroids
Immunosuppressants
Anti-TNF therapy
(used to use mesalazine but shown to be as effective)
How does mesalazine work?
Effect on risk of colon cancer?
Side effects? (2)
It has a topical effect having anti-inflammatory properties
Reduces risk of colon cancer
Diarrhoea
Idiosyncratic nephritis
What is a prodrug?
a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug.
What does the fact that 5-ASA are pro-drugs mean?
The active components are released in the colon depending on different factors such as pH, etc.
What type of topical preparations of mesalazine do you get?(2)
Suppositories
Enemas
What are some examples of 5-ASA conjugates?
Sulphasalazine Balsalazide Mezavant Asacol (pH release) Pentasa (delayed release)
Where is pentasa released?
From the duodenum to the colon (unlike the other drugs whcih are either released in the ileum or colon)
What is the advantage and disadvantage of using suppositories over enemas?
Suppositories coat
What aids spread of foam and liquid enemas?
Reflex contraction
How much of an enema stays in the rectum?
less than 10%
What type of enemas do patients prefer?
Foam enemas as it doesn’t make them feel like they need to pass stool
What properties do corticosteroids have?
Systemic anti-inflammatory properties
Examples of corticosteroids? (2)
Prednisolone (oral or topical)
Budesonide
What is the purpose of corticosteroids?
What is the risk with corticosteroids?
What should corticosteroids therefore be used as a bridge to?
To induce remission (short course - start a high dose initially and reduce over 6-8 weeks)
Patients can become dependent on them
Maintenance therapy
What are the side effects of steroids?
Musculoskeletal (avascular necrosis, osteoporosis)
GI
Cutaneous (acne, thinning of skin)
Metabolic (weight gain, diabetes, hyerptension)
Neuropsychiatric
Cataracts
Growth failure
If steroids are not effective, what is then used?
Immunosuppression
What is immunosuppression used for in UC?
“steroid-sparing agents”
What is immunosuppression used for in Crohns?
Maintenance therapy
What are 3 examples of immunosuppressive drugs used to treat Crohns and colitis?
Azathioprine
Mercaptopurine
Methotrexate (used rarely)
Azathioprine:
onset of action?
What enzyme contributes to toxicity?
What drug should not be prescribed with this?
What should be regularly monitored in patients on this?
Side effects (4)?
Slow onset (16 weeks) TPMT Avoid co-prescription of allopurinol (XO inhibitor) Regular blood monitoring required Pancreatitis Leucopaenia Hepatits small risk of lymphoma and skin cancer
What is tumour necrosis factor alpha?
A pro-inflammatory cytokine
What are 2 examples of antibodies to TNF?
How is each given?
Infliximab (IV infusion)
Adalimumab (S/C injection)
What does anti-TNF therapy do?
Promote apoptosis of activated T lymphocytes (rapid onset of action)
How long does Infliximab tend to put patients in remission for?
8-12 weeks (re-treatment maintains remission)
What is infliximab approved for treatment of?
Initially Crohns but is now approved for treatment of moderate - severe UC
What are the adverse effects associated with anti-TNF alpha therapy?
Infusion reaction in 13% of patients (HACA +ve)
Infection
Cancer (lymphoma, solid tumours)
When should anti-TNF alpha be used?
As part of a long term strategy including immune supression, surgery and supportive therapy
Refractory/ fistulising disease
(exclude current infection/ TB)
What are the names of the 2 biosimilar Anti-TNFs that have been produced by different companies and are 1/3 of the cost of Infliximab?
Inflectra
Remsima
When is emergency surgery carried out for IBD?
Failure to respond to medical therapy, small bowel obstruction, abscess, fistulae
When is elective IBD surgery carried out?
Failure to respond to medical therapy
Dysplasia of colon mucosa
Why do you want to minimise the amount of bowel resected in Crohns disease?
The surgery is not curative and if the patient requires a lot of resection they can get short gut syndrome and require lifelong total parenteral nutrition = reduced life expectancy
What is a proctocolectomy?
The surgical removal of the rectum and all or some parts of the colon
What is a brooke ileostomy?
ileostomy in which the divided proximal ileum, brought through the abdominal wall, is evaginated and its edge is sutured to the dermis
What surgery can be done to treat a stricture from Crohns disease?
A longitudinal suture can be made over the suture and then stitched in the horizontal direction
What can be used to treat a Crohns fistula?
Seton suture
What are the 2 possible curative surgery options for UC?
Permanent ileosotmy
Restorative proctocoloectomy and pouch
What functions as the “new” rectum in a restorative proctocoloectomy?
J-pouch (pass stool 5-6 times a day as the pouch is smaller)
