Lec 32-IBS and IBD Flashcards
Irritable bowel syndrome (what is the limit to class as having it)
Symptoms at least 3 days/month
1) abs pain or cramping
2) Diarrhoea or constipation often alternating
3) Flatulence
4) Bloated feeling
5) Feeling of incomplete bowel movement
6) Mucus in stool
4 IBS sub-types
1) IBS with constipation: Hard or lumpy poo at least 25% of time
- Loose still less than 25% of time
2) IBS with Diarrhoea: Loose stools at least 25% of time
- Hard stool less than 25% of time
3) Mixed: hard and loose stools at least 25% of time (for each one)
4) Unsubtyped IBS: Both hard and loose stools less than 25% of time
Diagnosis (rome ||| criteria 2006)
-Ab pain/discomfort for >3days a months for 3 months that has 2 of the following 3 features:
-Relieved by defecation and/or
-Onset associated with a change in frequency of stool and/or
-Onset associated with a change in appearance of stool
Diagnosis shouldn’t be by exclusion but must rule out other conditions including Coeliac disease (anti-cranslutaminase anti-bodies)
IBD (feacal elastase; blood in stool)
-Recommend simple blood tests: FBC, ESR, CRP< TTG< EMA- to exclude diagonsis
Treatment options: lifestyle advice
1) management of stress- checked and ensure hey have enough relaxation and leisure time
2) Encourage exercise
3) Diet: (1) general advice- alcohol, F&V, fizzy drinks, fibre (2) probiotics often to regulate bowels (3) FODMAP under specialist supervision
- For all these important to monitor symptoms. Make changes gradually so patients can monitor its affects
- For foods- important to keep a roof diary to monitor if something triggers symptoms or improves condition
Treatment options: Diet and motility control (foods to avoids as well as drugs that can be used)
Foods to avoid
- Excess fructose- fruit; sweetener; honey
- Lactose
- Fructans- veg (artichoke, broccoli, cabbage)
- Galactans- baked bean, chickpea, kidney bean
- Polyols- Fruit (apple, blackberry, cherry)
- For pain and cramps by hypermitulity, try anticholinergic drugs: meberverine, hyoscine
- Peppermint oil has antispasmodic effects (smooth muscle relaxation by Ca channel block)
Treatment options for IBS-C (and monitoring)
-Increased dietary fibre. Bran may make symptoms worse and bulking agent which contain fibre isohel and fybogel
-SSRI’s act both centrally and on GI-tract (Speed up transit time) and also help with chronic pain
-Ispaghula Husk
-Avoid laxatives (dependence)
Monitoring
-Adjust dose in Accord with patient response
-Check Bristol stool chart
Other treatment options for IBS-C new drugs
- Linaclotide- minimally absorbed peptide granulate cyclase C receptor agonist: 290mcg OD for 26 weeks, 34% reached primary endpoint with drug, 14% with placebo
- Lubiprostone- activator of intestinal chloride channel CIC-2 increases fluid secretion and thereby motility (stop after 2/52 if not working): 8mcg OD for 12/52
- Prucalopride- SS 5HT4 agonist increases motility (both if 2 laxatives not working): 2mg OD over 12 weeks
Treatment options for IBS-D
- For diarrhoea: loperamide (opiate agonist which doesn’t cross the blood brain barrier) 2-4mg QDS
- 2nd line: Tricyclic anti-depressants like imipramine (slow down transit) also help with pain
- 3rd line: SSRI
IBD: inflammatory bowel disease (typical symptoms)
-Chronic GI disease- inflammation of the gut either Crohns or ulcerative colitis Symptoms 1) ab pain or cramping 2) bloody diarrhoea 3) weight loss 4) Extreme tiredness
Crohns disease
Manifestation
-Episodic bloody diarrhoea and abdominal pain
Location
-Any part of the GI tract but especially the ileum
Pathology
-Inflammation of whole wall but localised
-Granulomas common
-Goblet cells and surface mucus present
Epidemiology
-71 genetic loci identified associated with increased risk including gene for NOD2 which recognises intracellular muramyl dipeptide
-Associated with smoking
-Typical onset- white 15-25
-50-100 per 100k
Ulcerative colitis
Manifestation -Episodic bloody diarrhoea and abdominal pain Location -Large bowel (rectum and colon) Pathology -Continuous inflammation of mucosa -Granulomas rare -Goblet cells depleted, mucus layer thin or absent Epidemiology -47 genetic loci identified which increase risk of disease -Associated with non-smoking -Typical onset white aged 15-25 -240 per 100k
Investigation of inflammatory bowel disease uses sigmoidoscopy and colonoscopy
- Colonoscopy examines the entire length of the colon; sigmoidoscopy examines only the lower 1/3rd
- High faecal lactoferrin and calprotectin are indicative of inflammation and distinguish from IBS
Aetiology of IBD
-Inappropriate response of the mucosal immune system to the normal enteric flora (also possible dietary antigens in crohns disease) in a genetically susceptible individual
Severity of Crohns disease and ulcerative colitis are assessed by scoring systems
ULCERITIVE COLITIS- Truelove and witts system
- Bowel movements (No. per day): Mild= <4; Moderate=4-6; Severe= <6
- Blood in stools: Mild= small amount; Moderate between mild+ severe; Severe visible blood
- Pyrexia (more than 37.8’C): Mild and moderate= NO; Severe = Yes
- Pulse >90 BPM: Mild+moderate= No; Severe= Yes
- Anaemia: Mild & moderate= No; Severe= yes
- Erythrocyte sedimentation rate: Mild&Moderate= <30; Severe= >30
Step 1: gain control of inflammation
- Severe: IV hydrocortisone up to 100mg 6hourly
- Moderate: oral prednisolone 30-60mg daily
- Mild: 5-aminosalicyclic acid (not recommended for Crohn’s for UC; see later
- Steroid cause: adrenal suppression, diabetes, increased BP
- Steroid dosage must be tapered off (over 8 weeks) with maintenance of control
Other steroid: budesonide and beclometasone dipropionate
Budesonide (2nd line after prednisolone not for Ulcerative colitis)
- High topical activity (200x the potency of prednisolone) but rapidly and extensively metabolised in 1st pass through the liver to compounds with much lower activity
- Causes less suppression of plasma cortisol levels when administered rectally or orally and gives fewer GC related adverse effects than prednisolone
- Available as controlled ideal release capsule for treatment of mild to moderate Crohns disease
- Beclometasone may be used in conjunction with 5-aminosalicyclic acid in UC
Other therapeutic agents |
Cyclosporine
- Immunosuppressive therapy
- Patients with severe steroid refractory ulcerative colitis who would otherwise face surgery
- Major complications are renal impairment, increased BP, K and Mg electrolyte disturbances, infections and neurotoxicity
Other therapeutic agents || thiopurines: azathioprine and mercaptopurine
- Azathioprine is metabolised to mercaptopurine
- 1 in 300 individuals will be highly deficient in thiopurine methyltransferase, one of the 2 enzyme which breaks down mercaptopurine- altered metabolism causes neutrapaenia (neutrophil count drops low)
- Immunosuppressive induce T cell Apoptosis
- Useful for inducing remission in relapsing or steroid deponent crowns disease and for maintenance of crohns disease and ulcerative colitis
- Slow onset of action (3 months) means mainly used as adjunct to other treatment
- Methotrexate may be used as an immunosuppressant in those refractory to or intolerant of azathioprine and mercaptopurine
Infliximab (Remicade)
- A chimeric monoclonal IgG1 antibody directed against TNF-a
- Neutralises TNF-a and maybe by reacting with cell-associated TNF-a causes cell apoptosis
- Single dose (infusion 5mg/kg) decrease Crohn’s disease activity index 4 weeks later
- Licensed for use in severe active Crohn’s disease where non-response or intolerance to other therapies
- Planned course of treatment over 12 months
- Patients can develop antibodies and infectious events are quite common (>5% side effects)
- Also beneficial in ulcerative colitis and licensed if no response or intolerance to there therapies
Inflixamab promotes healing of fistula’s in Crohn’s disease
- Fistula’s are when liquid stool penetrates through anorectal ulcers and then comes into contact with tissue
- This causes infection and immune-response with greatly worsens the Crohn’s disease e
- Infliximab can be used when: antibiotics (metronidazole, ciprofloxacin); Surgery; and immunosuppression have all failed
Other therapeutic agents |||
- Adalimumab (licensed for Crohn’s disease and UC) and golimumab (for UC) are humanised monoclonal antibodies that form stable complexes with transmembrane and soluble for of TNF-a
- Adalimumab can be administered by SC injection, infliximab and golimumab require infusion. Widely used in practise
Surgery when things go bad: colostomy and iileostomy
Ostomy: surgury create an opening (stomach) in the ab wall for the elimination of dietary waste- maybe permanent or temporary
- Colostomy: section of the colon
- Ileostomy: section of the ileum
Step 2 (after step 1): maintenance of remission use of derivatives of 5-aminosalicyclic acids
-Good evidence for effectiveness in UC less for Chrons
-Sulfasalazine was the 1st drug for maintenance of remission in UC
-Prevents absorption of 5-aminoslaicyclic acid to early in the GI tract
-Upto 30% of patients on sulfasalazine get side effects including nausea, vomiting, rash, anaemia, hepatic dysfunction
NB- if side effects check for blood dyscrasia (abnormal cellular elements shown by WBC over 1 million)
Therapies for UC: MILD
- Mesalazine in appropriate formulation and delivered route (if this is unsuccessful move onto moderate treatment)
- Mesalazine maintenance
- If the maintenance if unsuccessful than add infliximab or thiopurine in
Therapies for UC: Moderate
- Oral prednisolone maybe with thiopurines (if this is unsuccessful then move to severe treatment)
- Move to mesalazine maintenance
- If this is unsuccessful add infliximab or thiopurines
Therapies for UC: Severe
- Admission to hospital, fluid and electrolyte replacement blood transfusion if necessary
- If that is unsuccessful move to IV hydrocortisone (if successful move to Mesalazine maintenance like other steps)
- If unsuccessful place on either infliximab or give IV cyclosporin (if these are successful move to mesalasine and infliximab or thiopurine maintenance)
- If IV cyclosporin is unsuccessful give surgery
Therapies for Chrons disease: MILD
- Mesalazine
- If successful elemental diets e.g. vivonex high nitrogen, low fat
Therapies for Chrons disease: Moderate
- Oral prednisolone probably with thiopurine; Budesonide for ileal disease
- If successful elemental diets e.g. vivonex high nitrogen, low fat
Therapies for Chrons disease: Severe
- Admission to hospita , fluid and electrolytes, blood transfusion is necessary
- If unsuccessful add IV hydrocortisone (if this is successful add maintenance thiopurine -> if that is unsuccessful add infliximab plus thiopurine)
- if this is unsuccessful add infliximab (if this is successful same pathway as before)
- If unsuccessful surgery
