IBD (Inflammatory Bowel Disease) Flashcards
What are inflammatory bowel diseases?
Inflammatory bowel diseases are:
Diseases characterised by chronic immune mediated inflammation of the gastrointestinal tract.
Are IBDs curable?
No, IBDs are incurable. The goal is for remission.
_______ often have a progressive destructive course
IBDs often have a progressive destructive course.
What is Crohn’s aetiology according to Ha &Khalil 2015?
Crohn’s aetiology:
* Exact aetiology remains unknown
* complex interaction between genetic predisposition,
* environmental risk factors
* immune dysregulation to intestinal microbiota (Ha & Khalil 2015)
What are the two main forms of IBDs?
Two main forms of IBDs:
Ulcerative colitis
Crohn’s disease
What are the overlapping clinical features of UC and CD?
Overlapping features of UC & CD:
* Diarrhoea
* Pain
* Periodic relapses
* Nutrient deficiency (iron, vitamin B12, folate etc)
* Non digestive system organs also affected
* Arthritis or joint inflammation (Crohn’s and colitis foundation)
What are the characteristics of ulcerative colitis?
Ulcerative colitis symptoms:
* Rectum always affected
* Colon may be affected
* Other parts of intestine may be affected
* Continuous involvement of inflammation
* Inflammation at mucosa only
* Bloody diarrhoea
* Colicky left side pain (bowel, sharp, localized gastrointestinal. spasms, waves)
* Tenesmus (inadequate bowel emptying)
* Arthritis/joint inflammation
What is the prevalence of IBDs in the UK?
Research conducted by Crohn’s & Colitis UK in 2022 suggests 1 in every 123 people in the UK have either Crohn’s disease or ulcerative colitis.
Which habit is shown to reduce ulcerative colitis?
Studies suggest that smoking (nicotine) can protect against ulcerative colitis
What might ulcerative colitis cause?
Ulcerative colitis might cause:
* Leaky colon
* Toxic megacolon
What are the symptoms of Crohn’s disease?
Crohn’s disease symptoms
* Transmural inflammation (muscle layer and mucosal layer affected)
* Skip lesions (some areas aren’t inflamed, makes treatment difficult)
* Strictures and fistulas (can cause blockage and prevent food travelling)
* Any part of GI tract may be affected
* Lower right abdominal pain usually (distal ileum proximal intestine)
* Diarrhoea
* Insiduous onset
* Cobblestone looking inflammation
Can ulcerative colitis usually have acute or insidious onset?
Ulcerative colitis usually has acute onset.
Does Crohn’s disease have acute or insidious onset?
Crohn’s disease usually has insidious onset.
What does transmural inflammation in Crohn’s disease lead to?
Transmural inflammation in Crohn’s disease can lead to scar tissue development which can cause intestinal narrowing.
Why do people with Crohn’s disease tend to have lower right quadrant abdominal pain?
People with Crohn’s disease tend to have lower right quadrant pain as the distal ileum proximal part of the intestine is usually affected.
What percentage of Crohn’s disease sufferers have their distal ileum proximal part of the intestine affected?
45% of Crohn’s disease sufferers are affected in their distal ileum proximal part of the intestine.
Which other parts of the body may be affected in people with IBDs?
Extra intestinal symptoms of IBDs:
Issues with:
* Bones & joints
* Eyes
* Skin
* Pancreas liver biliary system
* Kidney
* Circulation
What is the aetiology of IBDs ?
IBD aetiology:
* largely unknown but important factors are:
* Genetics : immune cell pathogen recognition
* Bacteria: might be changes in the gut microbiome
* Environmental triggers
What is being investigated to help UC?
Faecal transplants are being investigated to treat ulcerative colitis.
What habit might excaberate Crohn’s disease?
Smoking might exaceberate Crohn’s disease.
Genetic concordance has been shown in _________ __________
Genetic concordance has been shown in **Crohn’s disease **but not ulcerative colitis.
What is the peak age of Crohn’s disease?
The peak age of Crohn’s disease is 30-39 years (Ha & Khalil 2015)
Which blood tests are conducted to investigate IBDs?
Blood tests for IBD investigations:
* Inflammatory markers
* Full blood count
* C-Reactive Protein
* Urea and electrolytes
* Liver function tests
* ASCA (Anti-S.cerevisiae antibodies)
* p-ANCA (perinuclear antineutrophil cytoplasmic antibodies)
ASCA is for ________ __________ whereas p-ANCA is for ___________ ________.
ASCA is for Crohn’s disease whereas p-ANCA is for ulcerative colitis.
Which stool test might be conducted for IBDs?
Faecal calprotectin stool test might be conducted for IBDs.
Investigations for IBDS may include which 3 tests?
Investigations for IBDS may include:
* Blood tests
* Stool tests
* Imaging
Upper GI symptoms:?
Lower GI symptoms: ?
Upper GI symptoms: Upper GI endoscopy
Lower GI symptoms: Flexible sigmoidoscopy/EUA
What are the IBD treatment goals?
IBD treatment goals:
*Control inflammation
* Promote and maintain remission
* Relieve symptoms
*Prevent or cure complications
* Control inflammation
* Improve quality of life
* Spare use of steroids
* Avoid surgery
Which types of drugs are used for IBD treatment?
Drugs for IBD treatment:
* Anti-inflammatory drugs
* Immunosuppressants
* Biologics
What do anti-inflammatory drugs do?
Anti-inflammatory drugs reduce inflammation
What do immunosuppressants do?
Immunosuppressants reduce the immune response
What do biologics do?
Biologics target specific components of the inflammatory response.
What are three types of anti-inflammatory drugs?
Three types of anti-inflammatory drugs:
* Sulfasalazine
* Mesalazine (5-ASA)
* Glucocorticoids
Describe the two main actions of glucocorticoids
Two main actions of glucocorticoids:
1. Anti inflammatory & immune suppression by inhibiting the expression of pro inflammatory cytokines (IL-1, IL-2 & TNFa)
2. Inhibiting inflammatory cell action (T-Cells)
* Decreasing T cell function and proliferation
What are the benefits of glucocorticoids?
Glucocorticoid benefits:
* Powerful
* Good for short term use
Why aren’t glucocorticoids used long term?
Glucocorticoids aren’t used long term because of the side effects they may cause.
Which side effects may materialise from long term glucocorticoid use?
Long term glucocorticoid use may cause:
* Cushing’s syndrome
* Osteoporosis
* Hyperglycaemia>T2D
* Negative nitrogen balance
* Increased appetite
* Increased infection susceptibility
* Obesity
________________ reduce pro-inflammatory ___________ production, inhibit a variety of ___________ functions, and interfere with arachidonic acid metabolism
Steroids reduce pro-inflammatory cytokine production, inhibit a variety of leukocyte functions, and interfere with arachidonic acid metabolism
What is Cushing’s syndrome?
Cushing syndrome is:
* a condition caused by having too much of a hormone called cortisol in your body
* may be caused by steroid medication or stress
Name an example of a glucocorticoid
Example of a glucocorticoid:
Prednisolone
Patients may become ____________ dependent.
Patients may become **steroid **dependent.
When are glucocorticoids typically used in IBDs?
Glucocorticoids are typically used for initial IBD treatment then tapered off as other long term treatments are introduced.
What is sulfasalazine?
Sulfasalazine is an anti-inflammatory drug.
What is mesalazine (5-ASA)?
Mesalazine (5-ASA) is an anti-inflammatory drug.
What is a pro drug?
A pro drug is a drug that is inactive upon administration that becomes active once metabolized.
Sulfasalazine is a ____ drug
Sulfasalazine is a **pro **drug
Which gut bacteria is sulfasalazine broken down by?
Sulfasalazine is broken down by azoreductase to form 5-aminosalicylate (5-ASA) and sulfapyridine.
Sulfasalazine is broken down by azoreductase to form which 2 substances?
Sulfasalazine is broken down by azoreductase to form 5-aminosalicylate (5-ASA) and sulfapyridine.
Where is sulfasalazine activated?
Sulfasalazine is activated in the colon(large intestine).
What is likely to be the cause of the side effects associated with sulfasalazine?
Sulfapyridine is likely to be the cause of the side effects associated with sulfasalazine.
What does 5-ASA do?
5-ASA exhibits an anti-inflammatory effect.
What is the action of sulfasalazine?
The action of sulfasalazine is the inhibition of prostaglandin and leukotriene formation via a negative effect on the cyclooxygenase and lipoxygenase pathways.
And inhibition of pro-inflammatory cytokines (IL-1 and TNFα)
The action of sulfasalazine is the inhibition of _________ and ___________ formation via a negative effect on the cyclooxygenase and lipoxygenase pathways.
The action of sulfasalazine is the inhibition of prostaglandin and leukotriene formation via a negative effect on the cyclooxygenase and** lipoxygenase** pathways.
Where does 5-ASA act?
5-ASA acts in the lumen.
What are prostaglandins?
Prostaglandins:
* group of lipids made at sites of tissue damage or infection
* involved in dealing with injury and illness.
* control processes such as inflammation, blood flow, the formation of blood clots and the induction of labour.
What are leukotrienes?
Leukotrienes:
* group of inflammatory mediators that belong to the eicosanoid family
* lipids
* involved in the inflammation and immune response
Where is 5-ASA poorly absorbed?
5-ASA is poorly absorbed in the gut
Activated receptor-g is a target of ?
Activated receptor g is a target of 5-ASA action
Does sulfasalazine have side effects?
Yes sulfasalazine produces side effects.
What are the side effects of sulfasalazine?
Sulfasalazine side effects:
* GI disturbances
* Headaches
* Lower WBC count (sulfapyridine)
* Steven Johnson syndrome
* Severe cutaneous adverse reactions
* Malaise
What is Steven Johnson syndrome?
Steven Johnson syndrome :
* Rare condition
* Over-reaction’ of the immune system to a trigger (medicine/infection)
* Blistering and peeling of the skin and surfaces of the eyes, mouth and throat
What is malaise?
Malaise:
* a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify
What is cutaneous adverse reaction?
An adverse cutaneous reaction caused by a drug is any undesirable change in the structure or function of the skin, its appendages or mucous membranes and it encompass all adverse events related to drug eruption, regardless of the etiology
What might be used instead of sulfasalazine?
Mesalazine (5-ASA) might be used instead of sulfasalazine. It is a drug that doesn’t contain sulfapyridine, reducing the likelihood of side effects.
What does it mean if a drug is formulated?
Drug formulation is the process of determining the best way to deliver this active ingredient. This could be in a capsule that is time release dependent, pH dependent etc.
Mesalazine can be delivered to _____ part of the gut as it does not need to be activated.
Mesalazine can be delivered to **any **part of the gut as it does not need to be activated.
To target specific regions of the gut, what is done to mesalazine (5-ASA)?
Mesalazine (5-ASA) comes in different formulations to target specific areas of the gut.
What does mesalazine (5-ASA) formulation promote?
Mesalaine (5-ASA) formulation promotes:
* maximal therapeutic efficacy at the lowest possible dose>reduces side effects
Which formulations does mesalazine (5-ASA) come in?
Mesalazine (5-ASA) is available as:
* Enteric coated tablets
* Slow release tablets
* Enemas
* Suppositories
* Foams
Anti-inflammatory drugs are typically used ** term whereas immunosuppressant drugs are used for remission maintenance.
Anti-inflammatory drugs are typically used **short **term whereas immunosuppressant drugs are used for remission maintenance
What do immunosuppressant drugs do?
Immunosuppressant drugs:
* Suppress the immune system
Name 3 immunosuppressant drugs
Examples of 2 immunosuppressant drugs:
* Methotrexate
* Azathioprine (6-mercaptopurine)
* Cyclosporine
What is Azathioprine (6-mercaptopurine)?
Azathioprine (6-mercaptopurine)
* Immunosuppressant
* Pro drug
* Converted to a false base
What is azathioprine converted to?
Azathioprine is converted to a false base to inhibit DNA synthesis.
What does azathioprine target?
Azathioprine targets rapidly dividing T-cells & cytokines
What is azathioprine shown to do?
Meta-analysis shows that azathioprine is effective at remission maintenance in ulcerative colitis and Crohn’s disease
What do the side effects of azathioprine involve?
Azathioprine side effects:
* Bone marrow suppresion
* Increased infection risk
* Pancreatitis
What are the side effects of azathioprine withdrawal?
Azathioprine withdrawal side effects:
* Hypersensitivity reactions
* Nausea
*
Glucorticoids are anti-inflammatory drugs as well as?
Glucorticoids are anti-inflammatory drugs and immune suppressors.
Enteric-coated mesalazine is for?
Enteric-coated mesalazine is for:
Ileal Crohn’s disease
Slow release mesalazine tablets are for?
Slow release mesalazine tablets for:
Proximal bowel Crohn’s
Mesalazine enemas, suppositories or foams are for?
Mesalazine enemas, suppositories or foams are for:
Distal colonic disease
Foams or suppositories are typically given for ?
Foams or suppositories are typically given for ulcerative colitis
What is methotrexate?
Methotrexate:
* Immunosuppressant
* Folic acid antagonist
Methotrexate is a ___?__ acid antagonist
Methotrexate is a **folic **acid antagonist
What does methotrexate do?
Methotrexate:
* Lowers folic acid levels
* Inhibits dihydrofolate reductase
* Interferes with proinflammatory actions of IL-1
* Promotes release of adenosine which has anti-inflammatory action
Which reductase does methotrexate inhibit?
Methotrexate is an inhibitor of dihydrofolate reductase
Where is methotrexate clinically used?
Methotrexate is used for Crohn’s disease and ulcerative colitis although clinical evidence doesn’t support its use for ulcerative colitis.
What are the side effects associated with methotrexate use?
The side effects associated with methotrexate use are:
* Myelosuppression
* Mucositis
* GI disorders
* Hepatoxicity
* Pneumonitis
* Teratogenic
Supplementation of ? can reduce myelosuppresion and mucositis associated with methotrexate use
Supplementation of ** folic acid **can reduce myelosuppresion and mucositis associated with methotrexate use
What is pneumonitis?
Pneumonitis is inflammation in your lung tissues without an infection.
What is tetratogenic?
Something that can cause foetal abnormalities
What is myelosuppression?
Myelosuppression, also known as bone marrow suppression, is a decrease in bone marrow activity that results in reduced production of blood cells
What are biologics?
Biologics are engineered recombinant antibodies or other proteins
Why are biologics hardly used?
Biologics are very expensive which is why there use is limited
? are a significant breakthrough therapy for treating IBDs
Biologics are a significant breakthrough therapy for treating IBDs
What do biologics do?
Biologics target specific aspects of the IBD disease process
When are biologics typically used?
Biologics are used to induce or maintain remission.
Name a biologic that works for both Crohn’s disease and ulcerative colitis
Biologics that work on Crohn’s disease and ulcerative colitis:
* Infliximab
* Adalimuman
* Vedolizumab
Describe infliximab
Infliximab:
* Biologic
* Chemical antagonist
* Mode of action: Anti-TNFa
* Administrated by: Intravenous/subcutaneous
What are the three ways that biologics may work?
Biologics either:
* Block TNF-a
* Block integrin
* Block interleukins
They block inflammatory response.
