Week 6- Inflammatory Bowel Disease Treatment Flashcards
what are the different types of drugs used to treat IBD?
- Aminosalicylates =NSAID
- Corticosteroids
- Thiopurines
- Methotrexate
- Ciclosporin
- Anti-TNF therapies
- Others like antibiotics…
what are some of the factors that influence the choice of drug and route for IBD?
- Site – Extent & disease severity – Response to current or previous treatment – Patient’s preference – Acceptability & tolerance – Side-effects – Cost – Dosing schedule
what is the first line treatment for IBD?
aminosalicylates they are Non-steroidal anti-inflammatory drugs (NSAID)
what is the active ingredient in aminosalicylates?
5-aminosalicyclic acid (5-ASA)
what are the 4 drugs that are available from the base modifications of 5-aminosalicyclic acid basic structure?
- sulfasalazine
- mesalazine
- olsalazine
- balsalazide
what is the structure of sulfasalazine?
– 5-ASA + Sulfapyridine
– Attached by a diazo bond cleaved by bacteria in colon
what is the structure of mesalazine?
- Modified release 5-ASA
what is the structure of olsalazine?
– Dimer of 5-ASA – cleaves in the lower bowel
what is the structure of balsalazine?
– Pro-drug of 5-ASA, UC only
how do aminosalicylates works?
- sulfasalazine is the sulfapyridine diazotized to 5-ASA.
- the sulfapyridien carries it down to the colon where the diazo bond is cleaved by azoreductase liberating sulfapyridine and 5-ASA, which are absorbed.
- then travel to the liver where they are metabolised and half lives of the drugs are around 5-20hrs.
how does 5-ASA work in the colon?
-Inhibit production of cyclo-oxygenase, thromboxane
synthase, platelet-activating-factor synthetase &
interleukin 1 by macrophages
- Decrease production of immunoglobulin by plasma
cells
– Acts as a scavenger of superoxide radicals released
by neutrophils at inflammatory site
what is aminosalicylates used for ? action
• Primarily used to induce & maintain remission
-can exert a topical action in the colon
- Effectiveness depends on site of inflammation in relation to
dissolution profile
what is the second line therapy for IBD?
CORTICOSTERIODS-
Prednisolone is the preferred choice
When is corticosteriods used to treat IBD and how are they taken?
- used in moderate to serve relapses
- brings symptoms under control promptly
- not suitable for maintenance
- can be taken orally, rectal, parenterally in emergency
- can be used in combination with aminosalicylates or alone
what is the third line of treatment for IBD?
THIOPURINES
What is azathioprine and how does it work?
it is a pro-drug of 6-mercaptopurine which is metabolised by the liver
-used if patient is unresponsive to steroids and aminosalcylates
- its an Immunosuppressant, inhibiting ribonucleotide synthesis
-Effective for both active disease and maintaining
remission in CD and UC
- Possesses steroid-sparing properties
- Can be used with corticosteroids or alone
what is methrotrexate? when used? how it works? dose
- immunosuppresenat ony given in CD
- Inhibits dihydrofolate reductase (cytotoxic effect)
- Anti-inflammatory effect, inhibits cytokines and eicosanoid sythesis
- can induce and prevent relapse in CD
- normally at 25mg once a week
what is ciclosporin?
- Inhibitor of calcineurin= Prevents clonal expansion of T-cell subsets
- rapid onset of action
- Effective in the management of severe acute UC
what are monocolonical antibodies?
- anti-TNF antibodies that are given like infliximab, adulimumab and golimumab
- Anti- α4β7 integrin antibody which is Vedolizumab
what is infliximab?
-its an anti-TNF monocolonal antibody
-has potent anti-inflammatory effects
-and given intravenously
some side effect ca be anaphylactic reaction so only given in environment where resuscitation equipment is present
-inhibits the inflammatory mediators downstream so can lead to immpunosurpressant lead to TB
what is adalimumab?
-A human anti-TNFα monoclonal antibody
- Has potent anti-inflammatory effects
-80mg subcutaneous injection then 40 mg 2 weeks later
OR 40mg x4 over 1-2 days, then 80 mg 2 weeks later
inhibits the inflammatory mediators downstream so can lead to immunosuppersant lead to TB
what is vedolizumab?
is an antibody to the α4β7 integrin expressed on gut homing T helper cells, leads to
reduction in inflammation
-given if patients are not responding to conventional therapy
-IV under specialist supervision
what are other treatments used for IBD?
-metronidazole= for CD patients with perianal involvement
-antidiarrhoeals= codeine and loperamide used with caution as can mask inflammation, infection or obstruction
-cholestyramine =Decrease diarrhoea associated with bile-acid
malabsorption
how does nutrition lay a role in IBD?
-Prone to malnutrition
- Prevalence of protein-energy malnutrition in IBD ranges
from 20-85%
-malnutrition due to, poor nutrient intake, increased metabolism, increased intestinal protein loss(leaky gut), malabsorption
how can nutritional support can help IBD patients?
-mild to moderate attacks= normal diet but avoid coarse fibre may cause obstruction
how does surgical management?
-80% of patients will require an operation
-only if failure of medical therapy, complications, failure to grow in children
-can be life saving curative & eliminates long-term risk of
cancer
