IBD Flashcards
What are the two types of IBD and when is it most commonly diagnosed
ulcerative colitis and crohn’s disease
Known as “disease of young people”
as the peak age of diagnosis is age 10-25
What is crohns disease
Inflammation of the gastric mucosa
Relapsing and remitting
Crohn’s disease
Can affect anywhere in the whole of GI tract from mouth to anus
Transmural (all layers of intestinal wall) ulceration
Patchy
What is ulcerative colitis
Inflammation of the gastric mucosa
Relapsing and remitting
Ulcerative colitis
Affects the mucosa of colon and rectum
Diffuse, confluent mucosal inflammation and ulceration (doesnt affect all layers of the wall)
Mucosal and submucosal layers involved
What causes IBD
Precise mechanism unknown. Likely combination of factors.
Genetic (first degree relative with IBD – 10 times more likely to develop IBD) Environmental Immunological factors Gut microbes Smoking (but has protective effect in UC!) ?Infection Diet Medication
What are the Signs and Symptoms of IBD (intra intestinal)
Abdominal pain Diarrhoea (watery, bloody, mucus) Tiredness and fatigue Urgency Weight loss Anaemia Fever Nausea and vomiting Abdominal bloating and distension
What are the differences between the symptoms of ibd and uc
Symptoms of CD and UC similar but not identical
UC – more bleeding due to extensive erosion of blood vessels supplying lining of colon
CD – Symptoms of obstruction of bowel more common as entire bowel wall inflamed
What are the extra-Intestinal symptoms
Swollen joints – arthritis
Eye problems – episcleritis, iritis, uveitis
Erythema nodosum – swollen fat under skin causing redness, bumps and lumps
Pyoderma gangrenosum – skin ulceration
Primary sclerosing cholangitis
Define stricutres and fistulas as seen in crohns disease
Strictures
Narrowed segments of bowel
Lead to blockages, acute dilatation, perforation
Fistulas
Abnormal channels lined with granulation tissue
From between intestine and skin/other parts of intestine/organs e.g. bladder
Which body fluid/matter investigations do we use to diagnose ibd
Full history and detailed clinical examination
Blood tests including: full blood count (FBC) inflammatory markers urea and electrolytes thyroid function tests liver function tests bone profile
Stool culture - rule out other infective bacterial causes such as Clostridium difficile
Coeliac screen
What physical investigations can we carry out to diagnose ibd
Faecal calprotectin
Released into intestines in excess when inflammation present
Distinguish between IBD and non-inflammatory causes e.g. irritable bowel syndrome (IBS)
Abdominal imaging
Endoscopy including capsule endoscopy
Colonoscopy
Biopsies taken during above – differentiate between CD and UC
Which index is used to determine the severity of UC
Truelove and Witt’s Severity Index (Adults)
Which index isused to determine the severity of CD and which variables are assessed
Crohn’s Disease Activity Index
Number of variable are assessed to calculate Crohn’s Disease Activity Index (CDAI) including:
Number of liquid or soft stools Severity of abdominal pain General well-being Presence of complications Fever Use of loperamide Presence anaemia Body weight Abdominal mass absent or present
Score calculated which is used to classify disease activity
Number of online calculators available
Give the criteria used to categorise severe active crohns disease
Very poor general health and one or more symptoms including:
Weight loss
Fever
Severe abdominal pain
Frequent diarrhoeal stools daily (≥3 to 4)
May develop new fistulae or have extra-intestinal manifestations
Normally (but not exclusively) corresponds to a CDAI score of ≥300 or a Harvey-Bradshaw score of ≥8 to 9
Summary: which monitoring parameters are used to detect an acute relapse/flare (and to monitor treatment)
Faecal calprotectin
Stool frequency
Presence of blood and/or mucous in the stool
Temperature
C reactive protein (CRP)
U & Es
Heart rate (tachycardia) and blood pressure (hypotension)
What does the strategy for the management of ibd depend on
Treatment of IBD depends on:
Type of IBD (CD or UC)
Location and extent of disease
Severity
Treatment can involve: Medicines Nutritional “supplements” Surgery New and novel approaches e.g. faecal transplant
What are the primary and secondary aims of IBD
Primary aims:
Achieving remission
Maintaining remission
Improving quality of life
Secondary aims:
Avoiding surgery
Reducing long-term steroid use
Reducing risk of development of colorectal cancer
Reducing risk of development other complications
Why do we use different formulations when treating ibd
They will act in different areas
How do corticosteroids work (mechanism of action and rationale) in the treatment of ibd
Mechanism of action:
Reduce inflammation and modulates immune system
Prednisolone - binds to cellular glucocorticoid receptors, inhibiting inflammatory cells and suppressing expression of inflammatory mediators
Used in mild, moderate and severe disease
Choice of agent, route and dose depend on severity of disease
Rationale
Induce disease remission - “flares” usually treated with corticosteroids
Do not prevent progression of disease or development of complications
Which corticosteroids are used for the treatment of IBD
Prednisolone, Methylprednisolone, Hydrocortisone, Budesonide
Which steroid regimen do we use to treat mild-moderate flares
Prednisolone tablets 40mg daily commonly prescribed to treat mild-moderate flare. Dose then reduced by 5mg/week
Which steroid regimen do we use to treat acute-severe flares
Acute-severe disease – hospital admission and IV (as oral route may not be effective) Hydrocortisone 100mg four times a day
What are the side effects of corticosteroids
Number of side-effects including: GI side-effects Fluid and electrolyte imbalance Increased appetite Hypertension Effect on blood sugar Mood and behaviour changes
Infection risk - dampening down immune system
Risk development of osteoporosis (long term use)
Must not be stopped abruptly
(can lead to adrenal suppression)
Steroid Emergency Card
How do aminosalicylateswork (rationale) in the treatment of ibd
Rationale
Induction and maintenance of remission – mild-moderate UC
Less frequently used in mild-moderate CD. Can be used post-surgery
Which formulas are aminosalicylates available in
Variety of topical (rectal) and oral preparations available
Suppositories
Foams - often used for treatment acute attack (flare)
Enemas - “
Tablets – often used for maintenance of remission
Granules
Can give topical and oral together if required e.g. if acute flare
What is the mechanism of action of aminosalicylates
Mechanism of action
MOA not fully understood and thought to be quite diverse
Anti-inflammatory action – reduces inflammation in GI tract through variety of anti-inflammatory processes
Decreases prostaglandin production in the colon and inhibits production of pro-inflammatory cytokines
What was the first aminosalicylate widely used for IBD
Sulfasalazine was the first aminosalicylate to be widely used for IBD
There were some problematic side-effects such as headache, nausea, rashesso it is less commonly used now.
Name 3 commonly used Aminosalicylates
Balsalazide – 5-ASA with another inert carrier molecule
Olsalazine – 5-ASA linked to itself
Mesalazine – 5-ASA in pH sensitive coating
What is a key consideration that must be taken into account when dispensing mesalazine
Number of different brands and formulations available
Oral mesalazine products are not interchangeable
BNF – “There is no evidence to show that any one oral preparation of mesalazine is more effective than another; however, the delivery characteristics of oral mesalazine preparations may vary”
What are the side effects of aminosalicylates and how do we counsel patients on them
Side Effects Arthralgia, abdominal pain, diarrhoea, dizziness Blood dyscrasias (changes in blood cell counts - low platelets, low wbc count, low haemoglobin)
Counselling
Blood dyscrasias - report unexplained bleeding, bruising, purpura, sore throat, mouth ulcers, fever or malaise
Administration advice e.g. enema, tablets
Ideally maintain same brand - if brand switched then report any changes in symptoms
How do we monitor patients using aminosalicylates
Renal function (baseline, 3 months then annually – more frequent if impairment). Can rarely cause kidney disease and renal impairment Blood dyscrasias – if suspicion – full blood count and immediate cessation
When do we use thiopurines and what is their mechanism of action
Rationale
First-line immunomodulators for IBD used in UC and CD
Induce (add-on therapy) and maintain remission
Can take 3-6 months for full effects
Mechanism of action
Not fully understood – reduces inflammation in the GI tract
Immunomodulator – suppress immune response and inflammation
Metabolites have the capacity to impact on adaptive immune cells, innate immune cells and non-immune cells within the inflamed intestine
“Steroid-sparing”
Azathioprine (pro-drug) metabolised to => Mercaptopurine
(Weight-based dosing
Azathioprine – 2 - 2.5mg/kg/day
Mercaptopurine – 1 - 1.5mg/kg/day)
Give two examples of thiopurines
Azathioprine and Mercaptopurine
How is mercaptopurine metabolised
Mercaptopuruine is metabolised into thioguanine nucleotides (TGN) (the active metabolite).
These are further metabolised by the enzyme thiopurine methlytransferase (TMPT)
What happens if there isnt enough TMPT to break down mercaptopurine
The drug will start accumulating in the body. This can cause side effects - there is a risk of developing myelosurpression.
What happens if theres too much TMPT when administering mercaptopurine
If there is too much TMPT in the body the TGN will not be broken down properly and will instead be converted into mercaptopurine methylmercaptopurine (MeMP)
MeMP is not pharmacologically active and can cause hepatotoxicity
How do we ensure patients have the right balance of TMTP
Patients must have TMPT levels measured prior to starting treatment
low TMPT levels – reduce dose (risk myelosuppression)
high TMPT levels – risk hepatotoxicity
Repeat after one month and also if not responding to treatment
What are the side effects and councelling points of the thiopurines
Side Effects
Hypersensitivity reaction – the drug must be stopped immediately
Myelosuppression (bone marrow suppression)
Neutropenia and thrombocytopenia
GI – nausea, vomiting, diarrhoea
Liver disorders
Counselling
What the signs and symptoms of bone marrow suppression are e.g. report unexplained bleeding, bruising, purpura, sore throat, mouth ulcers, fever or malaise
How do we monitor the use of thiopurines
Monitor
TMPT levels - pre-treatment and on therapy
Full blood count – pre-treatment, weekly for first 4 weeks then at least every 3 months
What are the 3 less common immunomodulators which can be used to treat IBD
Methotrexate
Maintenance in CD (alternative to Azathioprine)
Given once weekly
Co-prescription of folic acid
Tacrolimus
Oral Tacrolimus can be used to induce remission in mild-moderate UC if not responsive to other treatments
Ciclosporin
IV Ciclosporin – induce remission in severe acute UC refractory to steroids
What are the two biologic medicines used to treat IBD
Infliximab and Adalimumab
How do Infliximab and Adalimumab work
They are monoclonal antibodies which bind to the cytokine - Tumour Necrosis Factor-α (TNF- α)
Inhibit inflammatory effects in gut
(TNF- α) has multiple actions
TNF:
Naturally occurring cytokine with multiple actions
Mediates inflammatory responses and modulates the immune system
TNF alpha – central role in Crohn’s
When do we use biologics
In moderate-severe active IBD and if the patient has not responded to/intolerant of anti-inflammatory and immuno-modulating therapies
Therapeutic drug monitoring can be performed
If no response to one biologic options include:
Increasing dose
Decreasing time interval between administration
Switching to alternative agents
What is infliximab and how does it work
First TNF blocker (biologic) approved for IBD
Given by intravenous (IV) infusion
Murine and human amino-acid sequences
What precautions must be taken before administeing infliximab
Infusion related reaction can occur – flu-like symptoms so pre-medication is given
Pre-treatment screening to ensure the effects it has on the immune system wont cause damage. These include: Tuberculosis (TB) Hepatitis B Hepatitis C HIV
What is adalimumab and what precautions must be taken when a patient is put on it
Fully humanised
Given by subcutaneous (SC) injection
Risk of reactivation of infections and malignancy as with Infliximab
Pre-treatment screening must be performed as per Infliximab
Biosimilar available
Ustekinumab
and Vedolizumab
are also biologics. Give details on how they work and why we might use these instead of the first line biologics
Other monoclonal antibodies which can be used in refractory cases e.g. lost response or intolerant to TNF- α treatment
Ustekinumab
Anti-interleukin – blocks interleukin-12 (IL-12) and interleukin-23 (IL-23)
Inhibit inflammatory effects in gut
Initial IV infusion then SC injection
Risk of reactivation of infections and malignancy
Vedolizumab
Leucocyte adhesion inhibitor – inhibits leucocyte migration to parenchymal tissue in the gut and reduces inflammation
IV infusion
Risk of reactivation of infections and malignancy
How do Faecal Microbiota Transplants (FMT) work
It is thought the composition of gut microbes in IBD is different and possibly abnormal
We can transfer healthy gut micro-organisms into the intestinal tract of recipient
Routes range from colonoscopy to enteric coated capsules
Clinical trials ongoing
What other ‘future therapies’ are used in IBD
Probiotics
New biologics
Small molecule inhibitors of RNA and intracellular cytokine pathways
Why might we resort to surgery to treat IBD
Some IBD complications will require immediate surgery: Intestinal blockage Bleeding Perforation Fistula Abscess Toxic megacolon
Can surgery cure IBD
Yes, but only in UC (not in CD - surgery can only help treat certain areas of disease and manage symptoms and complications)
What is the pharmacists general role in the treatment of IBD
Recommendations on choice of therapy and treatment options
Ensure appropriate formulations used
Practical administration advice to patient’s and other healthcare professionals
Safe and appropriate use of biologics
Plan how to stop medicines for patient’s in remission
“Rescue strategies” if relapse
Support adherence and health literacy
Therapeutic drug monitoring
Number of more specialist roles have developed with advent biologics – prescribing clinics
Input into IBD standards, NICE guidelines etc.
Use of biosimilars
What must the pharmacist ensure they are aware of with particular reference to corticosteroids and aminosalicylates
Patients on corticosteroids:
Ensure appropriate dose and reduction regimen
Co-prescription of calcium and vitamin d to prevent osteoporosis
Adverse effect monitoring
Patients on aminosalicylates:
Adjustment dose during flares/remission
Side-effect counselling – blood dyscrasias
