Inflammatory Bowel Disease Flashcards
What 2 distinct conditions does inflammatory bowel disease (IBD) refer to?
Crohn's disease (CD) Ulcerative colitis (UC)
Are CD and UC acute or chronic conditions?
Chronic
What is the peak age of diagnosis for CD and UC?
10-25 years
What is the most common symptom of CD and UC?
Diarrhoea
What is IBD?
Inflammation of the gastric mucosa
Which areas of the GIT are affected in CD vs. UC?
Whole GIT from mouth to anus can be affected vs. mucosa of the colon and rectum
How can the inflammation and ulceration present be described in CD vs. UC?
Patchy vs. diffuse, confluent mucosal inflammation and ulceration
Which layers of the intestinal wall are involved in CD vs. UC?
Transmural (all layers) ulceration vs. mucosal and submucosal (superficial effect)
What are the causes of IBD?
Precise mechanism is unknown and it is likely a combination of the following factors, Genetic Environmental Immunological Gut microbes Smoking (but has a protective effect in UC) Infection Diet (processed food) Medication
What are some of the signs and symptoms of IBD?
Abdominal pain Diarrhoea (watery, bloody, mucous) Tiredness and fatigue Urgency Weight loss Anaemia Fever (more prone to infection) N&V Abdominal bloating and distension
How does IBD cause anaemia?
Blood loss in diarrhoea
What are some of the extra-intestinal manifestations of IBD?
Involve inflammatory processes across the whole body
Swollen joints - arthritis
Eye problems - episcleritis, iritis, uveitis
Erythema nodosum - swollen fat under the skin causing redness and lumps
Pyoderma gangrenosum - skin ulceration
Primarily sclerosing cholangitis (inflammation and scarring of bile ducts in the liver)
What are strictures?
Narrowed segments of bowel
Lead to blockages, dilatation and perforation
What are fistulas?
Abnormal channels lined with granulation tissue
Form between intestine and skin or other parts of the intestine or organs e.g. bladder
Can have implications for absorption of food, nutrients and drugs
When are strictures and fistulas seen?
In Crohn’s disease
What do patients with IBD have an increased risk of?
Colon cancer due to increased cell changes
How is IBD investigated in patients with a suspected diagnosis?
Full history and detailed clinical examination
Blood tests including FBC, inflammatory markers, U&E’s, thyroid function tests, LFT’s, bone profile
Stool culture to rule out other infective bacterial causes such as C. difficile
Coeliac screen
Faecal calprotectin
Abdominal imaging
Endoscopy including capsule endoscopy
Colonoscopy
Biopsies taken during endoscopy/colonoscopy to differentiate between CD and UC
What is faecal calprotectin?
A biochemical measurement of the protein calprotectin in the stool, released into the intestines when excess inflammation is present, used to distinguish between IBD and non-inflammatory causes e.g. IBS
What is a capsule endoscopy?
Allows you to visualise the middle section of the GIT which cannot be done with an endoscopy/colonoscopy, particularly useful in CD
How is UC severity assessed?
In adults, using the Truelove and Witt’s severity index
Classifies a range of symptoms as mild, moderate and severe
How is CD severity assessed?
Calculate Crohns Disease Activity Index (CDAI) using a number of variables e.g. Number of liquid or soft stools Severity of abdominal pain General wellbeing Presence of complications Fever Use of loperamide Presence of anaemia Body weight Abdominal mass absent or present A score is calculated which is then used to classify disease activity There are a number of online calculators available
What is ‘severe active CD’?
Very poor general health and one or more of the following symptoms,
Weight loss
Fever
Severe abdominal pain
Frequent diarrhoeal stools daily
May also develop new fistulae or have extra-intestinal manifestations
What does severe active CD normally, but not exclusively, correspond to?
CDAI score ≥300
Harvey-Bradshaw score ≥8 to 9
What are the monitoring parameters for an acute relapse or flare up?
Faecal calprotectin Stool frequency Presence of blood and/or mucous in stool Temperature CRP (generalised marker of inflammation and infection) U&E's HR (tachycardia) BP (hypotension)
What does treatment of IBD depend on?
Type of IBD (CD or UC)
Location and extent of disease
Severity
What can treatment of IBD involve?
Medicines
Nutritional supplements (e.g. TPN, enteral nutrition)
Surgery
New and novel approaches (e.g. faecal transplant)
What are the primary aims of IBD management?
Achieving remission
Maintaining remission
Improving QoL
What are the secondary aims of IBD management?
Avoiding surgery
Reducing long term steroid use (due to associated complications)
Reducing risk of development of colorectal cancer
Reducing risk of development of other complications
Can the same drugs be used for CD and UC?
There is some overlap, but not all drugs effective in CD would also be effective in UC and vice versa
Can the same drugs be used to include and maintain remission?
Generally, drugs that induce remission do not maintain it
Why do a lot of the pharmacological treatments for IBD have a lot of side effects?
They are potent immunosuppressors
Where do suppositories act and what disease extent are they implicated in?
Rectum
Proctitis (inflammation of inner lining of rectum)
Where do foams act and what disease extent are they implicated in?
Sigmoid colon
Procto-sigmoiditis (inflammation of inner lining of rectum and sigmoid colon)
Where do enemas act and what disease extent are they implicated in?
Descending colon to splenic flexure/distal parts of transverse colon Left sided (distal) colitis
Why is selection of formulation important?
Need to select a formulation to work on the particular part of the tract that the patient has issues with
Which agents are used in the pharmacological treatment of IBD?
Corticosteroids Aminosalicylates Immunomodulating agents e.g. Thiopurines, Methotrexate, Ciclosporin, Tacrolimus and biologics Antibiotics Novel treatments
Name 4 corticosteroids used in the treatment of IBD.
Methylprednisolone
Prednisolone
Hydrocortisone
Budesonide
How do corticosteroids act in IBD?
Induce remission by reducing inflammation and modulation the immune system
When are corticosteroids used in IBD?
Usually used to treat flare ups
Mild, moderate and severe disease
Do not prevent the profession of disease or the development of complications (more for management of the acute phase)
Which types of preparations are available for corticosteroids and when are they used?
Oral, topical or IV
Prednisolone tablets commonly prescribed to treat mild-moderate flares
Acute-severe disease usually requires hospital admission and IV hydrocortisone
Why must corticosteroids not be stopped abruptly?
Can cause adrenal supression
A small number of patients taking corticosteroids may develop?
Corticosteroid dependency
What are some of the side effects of corticosteroids?
GI effects Fluid and electrolyte imbalance Increased appetite Hypertension Effect on blood sugar Mood and behaviour changes
What can corticosteroids cause long term?
Osteoporosis
What must all patients taking corticosteroids long term carry with them?
Steroid treatment card
How do aminosalicylates act in IBD?
Anti-inflammatory action
When are aminosalicylates used in IBD?
Induction and maintenance of remission in mild-moderate UC
Less frequently used in mild-moderate CD but can be used post-surgery
Lots of patients have a combination of a steroid and an aminosalicylate
Which types of preparations are available for aminosalicylates?
Suppositories Foams Enemas Tablets Granules
Can you give oral and topical aminosalicylates together?
Yes
What was the first aminosalicylate widely used for IBD and why is it no longer used?
Sulfasalazine
No longer used as it had problematic side effects such as headache, nausea and rash
These were mainly associated with the carrier molecule, sulphapyridine, rather than the active, 5-aminosalicylic acid (5-ASA)
Name 3 aminosalicylates used in the treatment of IBD today.
Balsalazide (5-ASA with another inert carrier molecule)
Olsalazine (5-ASA linked to itself)
Mesalazine (5-ASA in a pH sensitive coating, brands not interchangeable)
What are some of the side effects of aminosalicylates?
Arthralgia (joint pain) Abdominal pain Diarrhoea Dizziness Blood dyscrasia
What are blood dyscrasias?
Effects on white cells, red cells and platelets
Makes the patient more prone to infection, bleeding and anaemia
What are some of the counselling points associated with aminosalicylates?
Report any unexplained bleeding, bruising, purpura (blood spots), sore throat, mouth ulcers, fever or malaise (risk of blood dyscrasia)
Administration advice
If brand is switched, advise patient to report any changes in symptoms
What are the monitoring requirements associated with aminosalicylates?
Renal function (baseline, every 3 months and then annually, more frequently if impairment presents) FBC and immediate cessation if suspected blood dyscrasia
How do thiopurines act in IBD?
Immunomodulators
When are thiopurines used in IBD?
1st line immunomodulators
Considered a stronger treatment than aminosalicylates
Induce (add on therapy) and maintain remission
May have to take for 3-6 months for full effects
‘Steroid sparing’ (used in patients where we can’t get their steroid doses down)
Name 2 thiopurines used in IBD treatment.
Azathioprine (prodrug for Mercaptopurine)
Mercaptopurine
Which types of preparations are available for thiopurines?
Oral
How are thiopurines dosed?
By weight
How is Mercaptopurine metabolised?
Can be metabolised by several different routes
One of these being,
Mercaptopurine → Thioguanine nucleotides (TGN) (active metabolite)
Another being,
Mercaptopurine → Methylmercaptopurine (MeMP) (not pharmacologically active but can cause hepatotoxicity)
by enzyme thiopurine methyltransferase (TMPT)
What is the importance of TMPT?
There is variability in levels between patients
Patients must therefore have there TMPT levels measured prior to starting treatment
This should be repeated after one month or if the patient is not responding to treatment
What does a low TMPT level in a patient mean?
Risk of myelosuppression
Reduce dose
What does a high TMPT level in a patient mean?
Risk of hepatoxicity
What are some of the side effects of thiopurines?
Thiopurines are potent immunomodulators so you would expect effects on the immune system and its cells
Hypersensitivity reactions (immediate withdrawal)
Myelosupression (bone marrow suppression)
Neutropenia and thrombocytopenia
N&V, diarrhoea
Liver disorders
What are some of the counselling points associated with thiopurines?
Signs and symptoms of bone marrow suppression e.g. report any unexplained bleeding, bruising, purpura, sore throat, mouth ulcers, fever or malaise
What are the monitoring requirements associated with thiopurines?
TMPT levels - pre-treatment and on therapy
FBC - weekly for first 4 weeks and then at least every 3 months
When is methotrexate used in IBD?
Maintenance in CD
Alternative to azathioprine
How is methotrexate dosed?
Once weekly
Co-prescription of folic acid
When is tacrolimus used in IBD?
Induce remission in mild-moderate UC if not responsive to other treatments
How is tacrolimus administered?
Orally
When is ciclosporin used in IBD?
Induce remission in severe acute UC refractory to steroids
How is ciclosporin administered?
IV
What are biologics?
Monoclonal antibodies
How do biologics act in IBD?
Bind to inflammatory cytokines (e.g. TNF-α) and reduce their effects
Inhibit inflammatory effects in the gut
When are biologics used in IBD?
Moderate-severe active IBD which is unresponsive/intolerant to other anti-inflammatory and immunomodulating therapies
What are the options if the patient does not respond to the biologic?
Increase dose
Decrease time interval between administration
Is it possible to switch between biologics?
Yes, but requires careful consideration
Name 2 biologics used in IBD treatment.
Infliximab
Adalimumab
What is infliximab?
First TNF blocker approved for IBD
Made from murine (mice) and human AA sequences
How is infliximab given?
IV infusion (usually at an outpatient clinic every few weeks)
What type of reaction can a patient have to infliximab?
Infused related reaction
Flu-like symptoms
Can give pre-medication to prevent this
What must be done before starting treatment with infliximab?
Pre-treatment screening
Includes TB, Hep B, Hep C and HIV
Why must pre-treatment screening be done?
Biologics have a massive impact on the patients immune system
If they had one of these conditions, the biologic could cause a flare up
What is there a risk of with infliximab treatment?
Lymphoma and cancer
What is a ‘biosimilar’?
A non-branded version, essentially a ‘generic’
How should infliximab be prescribed?
By brand
Biosimilars available
What is adalimumab?
Fully humanised TNF blocker
How is adalimumab given?
By SC injection (done by the patients themselves)
Is pre-treatment screening necessary with adalimumab?
Yes
Risk of reactivation of infections and malignancy as with Infliximab
Are infusion related reactions a concern with adalimumab?
No, given SC
Is there a biosimilar available for adalimumab?
Yes
What if a patient becomes refractory (e.g. lost response to intolerant) to TNF-α treatment?
Other monoclonal antibodies can be used that work on different inflammatory components such as ustekinumab and vedolizumab
What is ustekinumab?
Anti-interleukin
Blocks IL-12 and IL-23 and so inhibits inflammatory effects in the gut
How is ustekinumab given?
Initially by IV infusion and then SC injection
What is there a risk of with ustekinumab?
Reactivation of infections and malignancy
What is vedolizumab?
Leukocyte adhesion inhibitor
Inhibits leukocyte migration to parenchymal tissue in the gut and so reduces inflammation
How is vedolizumab given?
IV infusion
What is there a risk of with vedolizumab?
Reactivation of infections and malignancy
What are some therapies we may see in the treatment of IBD in the future?
Faecal Microbiota Transplant (FMT)
Probiotics
New biologics
Small molecule inhibitors of RNA and intracellular cytokine pathways
What is a faecal microbiota transplant (FMT)?
Transfer of gut microorganism from a healthy donor into the intestinal tract of a recipient
How would a FMT treat IBD?
Thought the composition of gut microbes in IBD is different and possibly abnormal
How is a FMT performed?
Routes range from colonoscopy to enteric coated capsules
Can surgery be used to cure UC and CD?
In some UC cases, radical surgery can cure UC (as it only affects a certain part of the GIT)
In CD, surgery can help treat certain areas of disease, manage symptoms and complications but is not curative
What are some IBD complications which require immediate surgery?
Intestinal blockage Bleeding Perforation Fistula Abscess Toxic megacolon (abnormal dilation of the colon which can lead to rupture)
What are some elective surgeries for IBD?
Bowel resection (removal of any part of the bowel, most common for CD patients)
Strictureplasty (alleviates bowel narrowing)
Colectomy (removal of all or part of the colon)
Proctocolectomy with ileostomy (removes the entire colon, rectum and anus)
Fistula treatment
Abscess drainage
What does surgery for IBD have implications for?
Drug absorption and dosing
What is the pharmacists role in IBD?
Recommendations on choice of therapy and treatment options
Ensuring appropriate formulations used
Practice administration advice to patients and other HCP’s
Safe and appropriate use of biologics
Plan on how to stop medicines for those in remission
‘Rescue strategies’ for relapse
Support adherence and health literacy
Therapeutic drug monitoring
Input into IBD standards, NICE guidelines etc.
Use of biosimilars
What is the pharmacists role in IBD, specifically when treating patients on corticosteroids?
Ensure appropriate dose and reduction regimen
Co-prescription of calcium and vitamin D to prevent osteoporosis
Adverse effect monitoring
What is the pharmacists role in IBD, specifically when treating patients on aminosalicylates?
Adjustment of dose during flares/remission
Side effect counselling, specifically in relation to blood dyscrasias
