IBD Therapy Flashcards
Use of 5-ASA (Aminosalicylic acid) in UC?
Anti-inflammatory properties
Reduces risk of colon cancer
Side effects of 5-ASA?
Diarrhoea
Idiosyncratic nephritis
Caution with 5-ASA use?
Must check renal function before commencement
Oral version of 5-ASA and examples?
Pro-drugs
pH dependent release
Delayed release
Topical versions of 5-ASA?
Suppositories
Enemas
Examples of 5-ASA conjugate drugs?
Sulphasalazine - produces metabolites of sulphapyridine and 5-ASA
Balsalazide (inert carrier of 5-ASA)
Mezavant
Mesalazine
Asacol (pH release)
Pentasa (delayed release)
Where does pentasa release 5-ASA?
Entirety of small and large intestine
Where does asacol release 5-ASA?
Ileum and colon
Where does balsalazide release 5-ASA?
Colon
Where does salazopyrin release 5-ASA?
Colon
When and why are suppositories used in treatment of UC?
Coat
How is the suppository spread in the bowel?
Reflex contraction aids proximal spread of the foam or liquid enema
Why is foam enema preferred?
There is less of a need to go to the bathroom after and so patients can hold the drug for longer
Why are steroids used in treatment of UC and Crohn’s?
Systemic anti-inflammatory properties
How are steroids used to induce remission?
Begin with a high dose but reduce it over a 6-8 week period; they are used as a “bridge” to maintenance therapy
What is steroid dependence?
Sometimes, people will be removed from steroids and have a subsequent flare in there symptoms
What are the side effects of steroids?
Musculoskeletal - avascular necrosis, osteoporosois
GI - nausea, vomiting, GI bleeding and gastritis (begin patient on a PPI)
Cutaneous - acne, thin skin
Metabolic - weight gain, diabetes, hypertension
Neuropsychiatric (manic and then, when removed from steroids, depression)
Cataracts
Growth failure, in children
Mechanism of action of azathioprine?
Azathioprine (AKA 6-MP) is a purine analogue and interferes with DNA synthesis of T and B lymphocytes
Metabolism of azathioprine?
TPMT (thiopurine methyltransferase) - metabolises 6-MP to 6-MMP
Xanthine oxidase - metabolises 6-MP to 6-TU
HPRT (hypoxanthine phosphoribyl transferase) - metabolises 6-MP to 6-TGN, which is active and has a therapeutic effect
Why are changes in TPMT levels important/dangerous?
There are different forms that can be low, moderate or high metabolisers
Somebody who is homo/heterozygous for the low metaboliser should not use azathioprine, as these people are at great risk of developing life-threatening bone marrow toxicity with normal doses of azathioprine or mercaptopurine
Onset of action of azathioprine?
Slow onset of action (16 weeks)
Cautions with azathioprine use?
Avoid co-prescription of allopurinol (xanthine oxidase inhibitor)
Regular blood monitoring required
Side effects of azathioprine use?
Pancreatitis
Leucopaenia
Hepatitis
Small risk of lymphoma and skin cancer
How do T cells exit the circulation?
MadCAM-1 on endothelium
What is anti-TNF therapy and mechanism of action?
Antibodies that have been generated to prevent effects of TNF-alpha (pro-inflammatory cytokine) by promoting apoptosis of activated T-cells
Types of anti-TNF therapy?
Chimeric (part mouse and part human antibodies)
Humanised (fully human antibodies)
Onset of action of anti-TNF therapy?
Rapid
Duration of remission with anti-TNF therapy?
8-12 weeks but this is maintained with re-treatment
Side effects of anti-TNF therapy?
Lymphoma
Solid tumours
Demyelinating disease
Development of antibodies against anti-TNF antibodies
How is anti-TNF therapy used in IBD?
As part of a long-term strategy, inc. immune suppression, surgery (in Crohn’s) and supportive therapy
In refractory/fistulating disease
Cautions with anti-TNF therapy?
Exclude current infections by looking for abscesses
Ensure there has been no exposure to TB, as TNF (gIFN and IL-12 network) is important in preventing reactivation of latent TB
Different versions of anti-TNFs?
Inflectra and Remsima
