IBD and peptic ulcers Flashcards
What are the two types of peptic ulcer disease?
What are the differences?
- Gastric - deep penetrating lesion extending beyond the mucosa (less common). Less symtpomatic, is aggravated by food and associated with weight loss. Burning epigastric pain
- Duodenal - usually multiple lesions occurring near pylorus (more common)
Relieved by food as there is a dull ache on empty stomach. Associated with weight gain
Causes of peptic ulcer disease?
Crohn's H.pylori Chronic illness (CKD) NSAID use Zollinger- Ellison syndrom
What are alarm signals of dyspepsia that would initiate a referral?
GI bleed Weight loss Coffee ground vomit Abdo swelling Difficulty swallowing OTC meds don't work
What are the NICE guidelines for unvestigated dyspepsia?
- H.pylori testing
- If no response to lifestyle, full dose PPI for 1 month
- If no response to PPI, h2 receptor antagonist for 1 month or prokinetic (domperidone)
1st choice PPI = omeprazole 20mg OD
What is H.pylori?
- Gram -ve, rod shaped
- Unipolar flagella gives it motility
- Resides between gastric epithelium and mucous gel layer of stomach
- Found in most patients with PUD
How do you test for H.pylori?
13C-urea test as h.pylori breaks down urea and release carbon dioxide after ingestion of 13-C urea
Shouldn’t be performed within 4 weeks of anti-bacterial or within 2 weeks of anti-secretory
What is 1st line for H.pylori?
7 day triple therapy:
PPI + 2 ABX
(amoxicillin/metronidazole/clarithromycin)
What is 2nd line for H.pylori?
Quadruple therapy for 2 weeks:
Tetracycline 500mg QDS
Metronidazole 400mg TDS
Full dose PPI
And another ABX that was different to the last course of treatment
How do you reduce the risk of NSAID related GI bleeds?
- PPI
- Paracetamol as baseline analgesic
- Use lower risk NSAID (ibuprofen)
- Review need for NSAID
- Switch to COX-2 selective inhibitor (long term risks such as cardio)
- Lowest effective dose for shortest time
What are the risks of PPIs?
- C.difficile
- Masks other symptoms
- Fracture risks
What is Crohn’s disease?
- Affects any part of the GI tract
- Patchy inflammation- cobble stone/granular appearance
- Defined by local pattern
- Inflammatory, fistulating structures
- CARD gene
- Has a small bowel obstruction risk
- Life expectancy is reduced
- Redness and oedema in mucosal lining
What is ulcerative colitis?
- Mucosal inflammation
- Limied to the colon
- Distal (rectum) or extensive disease
- Not associated with fistulae
- HCA gene
- Severe diarrhoea with blood and mucous (fluid/electrolyte imbalance risk)
- Anaemia
- Better outcome with surgery than CD
- Most cases are left sides
Found that smoking is protective
IBD patients and their pharmacology
- Enhanced production of cytokines and chemokines IL-12 IL-18 and TNFa
- Have activated and acquired T and B cells and loss of tolerance to commensal bacteria
Surgery can be used to help with CD. What procedures are they?
- Using balloon to open up the tract
- Can cut open the narrowing part of the tract and sew it the other way
What are fistulae?
Abnormal pathways to organs
Can be enterenteric (between the colon) which is not a massive problem, however it can be from colon to vagina resulting in an infection
- Can also have extra passages from colon to anus which are painful
What are the respective disease activity scores for CD and UC?
CD - Harvey Bradshaw Index
UC - Simple colitis activity index
What investigations are needed for UC and CD?
- Disease activity score
- BP, temperature, abdo tenderness
- Stools to rule out cultures such as C.difficile
- History (FH, travel, medication)
- Electrolytes, iron, FBC
What extraintestinal diseases can cause IBD?
- Osteoporosis
- Anklyosing Spondylitis
What is the treatment for mild-moderate CD to induce remission?
- Oral steroids
(prednisolone) - Budesonide/5-ASA if
prednisolone not tolerated
May need add on therapy: 1. Azathioprine/ Mercaptopurine 2. Methotrexate If>2 exacerbations in 12 months OR steroids cannot be weaned
What is the treatment for severe CD to induce remission?
- Glucocorticosteroids
(PO/IV) - Infliximab Adalimumab
- Vedolizumab
(Biologicals can take 1-2 weeks to work)
May need add on therapy:
- Azathioprine/
Mercaptopurine - Methotrexate
What is the treatment for fistulating disease to induce remission?
- Antibiotics/ drainage
- Infliximab
May need add on therapy:
- Azathioprine/6MP
- Infliximab
What is 1st and 2nd line maintenance therapy for all stages of CD?
- Azathiopurine/mercaptopurine
2. Metotrexate
Other than 1st and 2nd line therapy, what can be used as maintenance therapy for CD?
-Infliximab for severe and fistulating disease
Vedolizumab can also be used in severe CD
What is the treatment for mild UC to induce remission?
1. Oral mesalazine (topical 5- ASA either alone or in combination if L-sided disease). Up to 4.8grams per day
- Oral steroids if 5-ASA
ineffective (Prednisolone or
beclomethasone) - Immunosuppressants (AZA,
6-MP) add-on if steroid
therapy often required - Tacrolimus
What is the treatment for moderate UC to induce remission?
- Oral/ Intravenous steroids (5 days)
- ciclosporin
- IFX, Adalimumab,
Golimumab, Vedolizumab
What is the treatment for fulimant in UC?
Life threatening and needs surgery as it impacts entire colon and causes very severe pain
What is the maintenance therapy in mild UC?
1. Oral or topical 5-ASA Minimum or daily dose: mesalazine 2.4grams sulphasalazine 2000mg olsalazine 1000mg
- Azathioprine,Mercaptopurine
- Tacrolimus
What is the maintenance therapy in moderate severe UC?
- Azathioprine, 6MP,
- Infliximab, Golimumab,
Adalimumab,
Vedolizumab
What is the role of corticosteroids in IBD?
- Used only to induce remission in acute flares
- Has no role in maintenance
- ADRs if used for more than 12 weeks
- Reduce dose over 8 weeks to avoid relapse
When would you escalate therapy of IBD and consider immunsuppressant therapy?
- No response to steroids
- > 2 steroid courses in 12 months
- Relapse if corticosteroid has been weaned (especially within 12 months)
What is budesonide?
- Used mainly in CD
- Alternative to prednisolone
- Extensive 1st pass metabolism
What are aminosalicylates (5-ASA)?
- Usually topically acting rather than systemically which for UC that is a disease in colon and rectum. Foams, enemas, suppositories
- Mesalazine
- Sulphasalazine (5-ASA + sulphapyridine linked by azo bond)
-
What are the s/e of 5-ASA?
- Headaches
- Dry skin
- Many are dose related and dose just needs reducing
REVERSIBLE MALE INFERTILITY WITH SULPHASALAZINE
What is azathioprine and 6-mercaptopurine?
- Immunosuppressant therapy used in steroid dependent/resistant patients
- Has a slow onset so use steroids for 8-12 weeks as well so cannot be used for monotherapy in active disease
- Can lead to mucosal healing
- Inhibits ribonucleotide synthesis
- Metabolised to active thioguanine molecules
- Azathiopurine is a prodrug of mercaptopurine as the presence of imidazole ring increases bioavailiability
What is important when deciding a dose for azathioprine and 6-mercaptopurine?
TMPT levels (Thiopurine methyltransferase) which helps to metabolise these drugs
What are adverse effects of immunosuppressants?
- Flu-like symptoms
- Fatique, nausea
- Bone marrow suppression
- Monitor FBC, LFT
- Liver toxicity
What is the role of methotrexate in IBD therapy?
- Once a week
- Folic acid to counteract ADRs
- Remission is 25mg/week
- Maintenance is 15mg/week
- Important to measure methotrexate polyglutamate levels as it takes 8 weeks to reach steady state
- Monitor FBC, LFTs and lung function
What are the side effects of methotrexate?
- Mouth ulcers
- Bone marrow suppression
- Teratogenic
What is ciclosporin?
- Only used in UC
- Immunosuppressant
- Given as IV infusion inititially, then oral
- Minitor BP, FBC, LFT
What is tacrolimus?
- Moderate-severe UC
- Oral
- Immunosuppressant
- Not well tolerated so is a hospital medication only
- Nephrotoxicity risk
What is infliximab?
- Genetically engineered murine-human chimeric monocloncal antibody
- Review after 2nd or 3rd dose
- Infusion over 2 hours , given every 8 weeks
- Escalate doses if no response or switch to adalimumab
- Anti-TNFa activity
- expensive
- Eventually, patient will develop antibodies for it
- Reactivation of latent infections
What is adalimumab?
- Fully humanised anti-TNF monoclonal antibody so has less s/e and less risk of developing antibodies
- Can be self-administered at home (s/c injection)
- Weekly
- Immunsuppressive therapy should be given as well if possible
How often is vedolizumab?
8 weekly infusion
Biologics are c/i when?
- Active infections
- Heart failure
- Known hypersensitivity to drug
Pre-screening is needed (TB, blood counts) .
Reassess patient every 12 months
How often is golimumab?
- 4 weekly s/c injection
Only for UC
What ABX are used in IBD?
- Metronidazole to prevent relapse after surgery. It isn’t used regularly due to peripheral neuropathy
- Rifampicin
What adjunctive treatment is used in IBD?
Smoking cessation - CD
Diet (elemental, low FODMAP)
Antimotility and antispasmodic drugs eg. codeine, loperamide – limited use (short-term symptomatic use in nmild exacerbations), may induce toxic megacolon in UC
Diarrhoea - cholestyramine if due to bile salt
malabsorption, esp after small bowel surgery
Iron and vitamins
Stress management
What are the indications for surgery in IBD?
UC:
- unresponsive to medical therapy
- toxic megacolon
- colorectal cancer
CD:
- unresponsive to medical therapy
- Disease is treatable by surgery
- severe perianal infection, cancer, obstruction, fistula, abscess, strictures
What are the risks of IBD surgery?
- faecal incontinence, - prolapse - anastomotic stricture/leak, - - stoma - short bowel syndrome
What are the surgery options in UC?
UC:
Colectomy (total or partial)
Ileal pouch-anal anastomosis as
an alternative to a stoma (to allow patients to have some anal function)
UC is a surgically curable
disease if the entire colorectal mucosa is removed
However, risk of infection (pouchitis)
