Inflammatory bowel disease therapy Flashcards
What are the aims of IBD therapy?
Control inflammation and heal mucosa Restore normal bowel habit Improve quality of life Balance the effects of the disease with the side effects of the treatment Avoid long-term complications Be a good advocate for the patient
What are the three therapeutic strategies?
Lifestyle advice
Drugs
Surgery
What lifestyle advice can be given in the treatment of IBD?
Smoking aggravates Crohn’s.
Diet is not implicated in pathogenesis but can influence symptoms
What drugs are used in the treatment of ulcerative colitis?
5ASA (mesalazine)
Steroids
Immunosuppressants
Anti-TNF therapy- not allowed to use these for UC in Britain
Step up treatment depening on severity of disease
What drugs are used in the treatment of Crohn’s disease?
Steroids
Immunosuppressnats
Anti-TNF therapy
Step up treatment depending on severity of disease
Why is mesalazine not used to treat Crohn’s disease?
It is not potent enough
What is the mechanism of action of 5ASA drugs?
It has a topical effect
It dissolves as it travels through the intestines and coats the lining of the colon
The medicine only releases the active ingredient when it hits the colon.
It has anti-inflammatory properties
It reduces the risk of colon cancer
What are the side effects of 5ASA drugs?
Diarrhoea
Idiosyncratic nephritis
What forms of administration do 5ASA drugs come in?
Oral:
pro drugs
pH dependent release
delayed release
Topical:
Suppositories
Enemas
Name some 5ASA conjugates
Sulphasalazine Balsalazide Mezavant Mesalazine Asacol (pH release) Pentasa (delayed release)
How safe is it to give big 5ASA drug doses?
Quite safe to give big doses
Want to avoid moving up to steroids as the side effects are greater
What properties do corticosteroids have?
Systemic anti-inflammatory properties
When and for how long should steroids be given?
To induce remission
For a short course
High dose initially, reducing over 6-8 weeks
Name two corticosteroids
Prednisolone
Beclametasone
What are side effects of steroids?
Musculoskeletal:
Avascular necrosis
Osteoporosis
Gastrointestinal
Cutaneous: Acne Thinning of skin Metabolic: Weight gain Diabetes hypertension
Neuropsychiatric
Cataracts
Growth failure
What should be co-prescribed along with steroids?
Vitamin D and calcium
When should immunosuppression treatment be used?
When more potent suppression of the inflammation is required.
If a patient is requiring repeated steroid treatments, may step up to immunosuppression to spare the use of steroids.
All Crohn’s patients should be on immunosuppression from the beginning, as maintenance therapy.
Give examples of immunosuppresive drugs
Azathioprine/mercaptopurine
methotrexate
What test should routinely be done before starting a patient on azathioprine?
A gene test.
The enzyme important in the metabolism of this drug is lacking in 0.3% of patients. If those patients kept taking the drug, they would have bone marrow problems within a week.
Which enzyme’s activity contributes to the toxicity of azathioprine?
TPMT
What should not be co-prescribed with azathioprine?
Allopurinol (xanthine oxidase inhibitor)
What are side effects of azathioprine?
pancreatitis
leucopaenia
Hepatitis
Small risk of lymphoma and skin cancer
How does anti-TNF therapy work?
The drugs attach to tumour necrosis factor alpha (a pro-inflammatory cytokine) and disable it.
What are the anti-TNF drugs?
They are antibodies to TNF
infliximab- part human part mouse. Give IV and must be given in hospital in case of anaphylaxis
Adalimumab- completely human. Give subcutaenously and can be given at home.
How long does it takae anti-TNF drugs to work?
They work within 24 hours
As well as disabling TNF alpha, what else to anti-TNF drugs to?
They promote apoptosis of activated T-lymphocytes
How long do the effects of anti-TNF drugs last for?
Several weeks.
The patients have to get regular therapy.
Which condition is anti-TNF therapy used to treat?
Crohn’s disease
What are patients tested for before being started on anti-TNF therapy?
TB
When should anti-TNF therapy be used?
as part of long term strategy, including immune suppression, surgery, supportive therapy
refractory / fistulising disease
exclude current infection / TB
When is surgery used in the treatment of IBD?
Emergency Failure to respond to medical therapy, small bowel obstruction, abscess, fistulae Elective Failure to respond to medical therapy Dysplasia of colon mucosa
Is surgery in Crohn’s curative?
No.
Why should the amount of bowel removed in Crohn’s disease be minimised?
Repeated resection of small intestine can result in ‘short gut syndrome’ and requirement of lifelong total parenteral nutrition (reduced life expectancy)
What is the surgical treatment for recurrent perianal abscesses?
Why is it damaging to have repeated abscess formation?
The insertion of a seton.
It is passed into the cavity and back out the other side, and acts like a wick, drawing fluid out.
Repeated abscess formation would lead to damage of external sphincter and incontinence.
What is the surgery for ulcerative colitis?
Is it curative or not?
It is curative. The options are Permanent ileostomy OR Restorative proctocoloectomy and pouch
What sort of pouch can be formed in a restorative proctocoleoctomy?
A J pouch.
This acts like a rectum to hold “faeces”- although it is not true faeces, and everything that comes out will be liquid.
How often to patients with J pouches go to the toilet?
What complications are there?
They go 4/5 times a day and in the night
Incontinence is common
There can be pouch failure after a number of years and inflammation can set in
What is the IBD therapy pyramid?
Smoking cessation 5-ASA (UC) Steroid if required Immunosuppression Anti-TNF therapy Surgery may be the best treatment in some
