Treating IBD Flashcards
What are the 4 main groups of pharmacotherapies for the treatment of IBD?
Aminosalicylates
Corticosteroids
Immunosuppressants
Biological therapy
What are the 3 key principles behind treating IBD?
1) induce remission
2) maintain remission
3) prevent secondary effects
What is the main therapeutic quality of corticosteroids and aminosalicylates?
They are anti-inflammatories
What is considered the first line treatment for Ulcerative Colitis?
Aminosalicylates
What 3 therapeutic effects do aminosalicylates have in the treatment of UC?
Induce remission
Maintain remission
Prevent colonic cancer
What is currently the first line aminosalicylate prescribed in UC?
Mesalazine
What two methods of administration are used for mesalazine?
Oral and PR (pr can be more effective in rectal limited UC)
What are the 3 main brand names for mesalazine?
Asacol
Pentasa
Mezavant
Why might Pentasa be selected for prescription in UC over Asacol?
It has a pH independent coating and so is released more slowly, working throughout the GI tract and not just in ileum and proximal colon
How do aminosalicylates (Asacol and Pentasa) have their anti-inflammatory impact?
By inhibiting the synthesis of inflammatory mediators:
- prostaglandins
- thromboxane
- platelet-activating factor
What was the first aminosalicylate on the market?
Sulfasalazine
What side effects does sulfasalazine have?
Allergic reactions - rash, fever, leukopenia, agranulocytosis
Male infertility
Orange bodily fluid secretions
(Hence not first line - mesalazine is far better tolerated)
If aminosalicylates alone are found to be ineffective what might you add to them?
Corticosteroids
What is the main aim of treating IBD with corticosteroids?
To induce remission (NOT used for maintenance as significant side effects if used long term)
What is the mechanism of action behind corticosteroids?
Potent anti-inflammatory agent
Inhibit inflammatory processes (immunosuppressant)
How do steroids immunosuppress?
Inactivate pro-inflammatory transcription factors: NF-KB and AP-1
What inflammatory mediators do steroids suppress?
Prostaglandins
Leukotrienes
Cytokines
Platelet activating factor
What is the main steroid we produce naturally in our adrenal cortex which contributes to the immune response?
Cortisol (a glucocorticoid - a natural anti-inflam and immunosuppressant)
(Aldosterone is the principle mineralcorticoid produced in the adrenal cortex; androgens are anabolic steroids both of which are not involved in immunity)
List some steroid side effects.
- Cushing’s-like symptoms: thinning skin, easy bruising, moon face with red cheeks, poor wound healing, increased abdominal fat /obesity
- HTN; Euphoria; Cataracts; increased appetite
- Osteoporosis (inc. osteoclastic activity, dec. osteoblastic activity)
- Increased susceptibility to infection
What would you prescribe alongside steroids as prophylactic treatment for osteoporosis?
Bisphosphonates
Calcium / Vit D
Why must you NOT withdraw corticosteroids suddenly after several weeks use?
Your body stops releasing ACTH in response to the additional steroids so you need to give it time to being production again - risk ‘cortisone crisis’
What are the 3 main oral corticosteroids?
Prednisolone (at moment most commonly used)
Budesonide (CD, mucosal anti-inflam. Not as well absorbed)
Beclometasone (beginning to be used more in UC now)
What 2 forms does hydrocortisone come in?
IV and topical (suppository)
What group of drug would be recommended if aminosalicylates are ineffective or not tolerated or if a patients UC was becoming steroid dependent (requiring 2 or more courses in 12 month period) - despite not being licensed for use in IBD?
Thiopurines (Azathioprine or 6-mercaptopurine
Used in CD remission maintenance as 1st line also
What MUST be measured before treatment with Thiopurine begin?
TPMT (Thiopurine methyltransferase) as deficiency puts people more at risk of bone marrow suppression (a more serious side effect of Thiopurines)
If IV steroid therapy is unaffective in treatment of active UC after 7 days what rescue therapy would you use?
Cyclosporin
How do cyclosporine act?
They immunosuppress by preventing expansion of T cell subsets - in so doing they induce remission in Ulcerative Colitis
If you are giving an infusion of a ciclosporin for longer than a period of 6 hrs what sort of ‘giving set’ should you use?
A non PVC one as it interacts with PVC
Why should cyclosporin not be given alongside macrolides (the -mycin antibiotics)?
Because they (macrolides) are enzyme inhibitors and so would inhibit the metabolism of cyclosporin thereby increasing the dose that the patient was getting
What are Azathioprine and Methotrexate used for in the treatment of Crohn’s?
1st and 2nd line treatment (respectively) for maintenance of remission
What is methotrexate classed as pharmacologically?
An anti-inflammatory; inhibiting cytokine & eicosanoid synthesis
When is it used in the Tx of Crohn’s?
When Azathioprine is not tolerated or resistance to it is evident
Why is Folate generally prescribed weekly alongside methotrexate?
Because its GI side effects (vomiting and diarrhoea) mean a patient is likely to poorly absorb folate
What is the MOST important thing to remember when prescribing methotrexate?
To always prescribe a weekly dose no matter what it is treating. On a drugs chart ensure you cross through any days they are not supposed to have the drug.
What two things should you monitor when someone is on methotrexate?
FBC
Liver function tests
(Report any signs of liver toxicity and blood disorders early!)
What are Infliximab and Adalimumab?
Humanised monoclonal antibodies
Ectopically produced anti-TNF (anti-immune stimulating) antibody
How do Infliximab and Adalimumab act?
Target membrane-bound TNF and kill host cell by complement-induced lysis (anti-inflammatory action)
How must Infliximab be administered?
In hospital, IV, combined with paracetamol and antihistamines as has a delayed hypersensitivity reaction (must have anaphylaxis at hand)
Why should patients be screened for TB before being administered Infliximab?
It is known to relapse latent TB
Subcutaneous Adalimumab is used for what?
Severe active Crohn’s
At what stage of therapy are monoclonal antibodies (Infliximab and Adalimumab) used in the Tx of Crohn’s?
As a last resort in either severe active Crohn’s or remission maintenance before opting for a surgical approach
What is first line treatment for active Crohn’s?
Corticosteroids (Prednisolone, Budesonide or IV hydrocortisone)
