Pharmacology
Gastrointestinal
Regarding the management of ulcerative colitis, acute mild to moderate proctosigmoiditis should be treated initially with:
Answer:
A topical aminosalicylate is recommended as first-line treatment for patients with a mild-to-moderate initial presentation or inflammatory exacerbation of proctosigmoiditis or left-sided ulcerative colitis. If remission is not achieved within 4 weeks, consider adding a high-dose oral aminosalicylate, or switching to a high-dose oral aminosalicylate and 4 to 8 weeks of a topical corticosteroid. If response remains inadequate, stop topical treatment and offer an oral aminosalicylate and 4 to 8 weeks of an oral corticosteroid.Management of Inflammatory Bowel Disease
Pharmacology / Gastrointestinal
Last Updated: 30th March 2023
Ulcerative colitis
Pathophysiology:
Ulcerative colitis is a chronic inflammatory condition, characterised by diffuse mucosal inflammation—it has a relapsing-remitting pattern. It is a life-long disease that is associated with significant morbidity. It most commonly presents between the ages of 15 and 25 years, although diagnosis can be made at any age. The pattern of inflammation is continuous, extending from the rectum upwards to a varying degree. Inflammation of the rectum is referred to as proctitis, and inflammation of the rectum and sigmoid colon as proctosigmoiditis. Left-sided colitis refers to disease involving the colon distal to the splenic flexure. Extensive colitis affects the colon proximal to the splenic flexure, and includes pancolitis, where the whole colon is involved. Common symptoms of active disease or relapse include bloody diarrhoea, an urgent need to defaecate, and abdominal pain. Complications associated with ulcerative colitis include an increased risk of colorectal cancer, secondary osteoporosis, venous thromboembolism, and toxic megacolon.
Treatment principles:
Treatment is focused on treating active disease to manage symptoms and to induce and maintain remission. Management of ulcerative colitis is dependent on factors such as clinical severity, extent of disease, and patient preference. Clinical and laboratory investigations are used to determine the extent and severity of disease and to guide treatment. Severity is classified as mild, moderate or severe by using the Truelove and Witts' Severity Index to assess bowel movements, heart rate, erythrocyte sedimentation rate and the presence of pyrexia, melaena or anaemia. The extent of disease should be considered when choosing the route of administration for aminosalicylates and corticosteroids; whether oral treatment, topical treatment or both are to be used. If the inflammation is distal, a rectal preparation is adequate but if the inflammation is extended, systemic medication is required.
Treatment of acute mild-to-moderate ulcerative colitis:
- Proctitis
- A topical aminosalicylate is recommended as first-line treatment for patients with a mild-to-moderate initial presentation or inflammatory exacerbation of proctitis. If remission is not achieved within 4 weeks, adding an oral aminosalicylate should be considered. If response remains inadequate, consider addition of a topical or an oral corticosteroid for 4 to 8 weeks.
- Monotherapy with an oral aminosalicylate can be considered for patients who prefer not to use enemas or suppositories, although this may not be as effective. If remission is not achieved within 4 weeks, adding a topical or an oral corticosteroid for 4 to 8 weeks should be considered.
- Proctosigmoiditis and left-sided ulcerative colitis
- A topical aminosalicylate is recommended as first-line treatment for patients with a mild-to-moderate initial presentation or inflammatory exacerbation of proctosigmoiditis or left-sided ulcerative colitis. If remission is not achieved within 4 weeks, consider adding a high-dose oral aminosalicylate, or switching to a high-dose oral aminosalicylate and 4 to 8 weeks of a topical corticosteroid. If response remains inadequate, stop topical treatment and offer an oral aminosalicylate and 4 to 8 weeks of an oral corticosteroid.
- Monotherapy with a high-dose oral aminosalicylate can be considered for patients who prefer not to use enemas or suppositories, although this may not be as effective. If remission is not achieved within 4 weeks, an oral corticosteroid for 4 to 8 weeks in addition to the high-dose aminosalicylate should be offered.
- Extensive ulcerative colitis
- A topical aminosalicylate and a high-dose oral aminosalicylate are recommended as first-line treatment for patients with a mild-to-moderate initial presentation or inflammatory exacerbation of extensive ulcerative colitis. If remission is not achieved within 4 weeks, stop topical aminosalicylate treatment and offer a high-dose oral aminosalicylate and 4 to 8 weeks of an oral corticosteroid. An oral corticosteroid for 4 to 8 weeks should be considered for patients in whom aminosalicylates are unsuitable.
Treatment of acute moderate-to-severe ulcerative colitis:
- Under specialist care, Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators, and biological drugs (such as anti-lymphocyte monoclonal antibodies, interleukin inhibitors, and tumor necrosis factor alpha (TNF-a) inhibitors) may be used for the treatment of moderate-to-severe active ulcerative colitis.
Treatment of acute severe ulcerative colitis
- Acute severe ulcerative colitis of any extent can be life-threatening and is regarded as a medical emergency. Immediate hospital admission is required for treatment.
- Intravenous corticosteroids (such as hydrocortisone or methylprednisolone) should be given to induce remission in patients with acute severe ulcerative colitis (at first presentation or an exacerbation) while assessing the need for surgery. If intravenous corticosteroids are contraindicated, declined or cannot be tolerated, then intravenous ciclosporin [unlicensed indication] or surgery should be considered. A combination of intravenous ciclosporin with intravenous corticosteroids, or surgery is second line therapy for patients who have little or no improvement within 72 hours of starting intravenous corticosteroids or whose symptoms worsen despite treatment.
Crohn's disease
Pathophysiology:
Crohn's disease is a chronic, inflammatory bowel disease that mainly affects the gastrointestinal tract. It is characterised by thickened areas of the gastrointestinal wall with inflammation extending through all layers, deep ulceration and fissuring of the mucosa, and the presence of granulomas; affected areas may occur in any part of the gastrointestinal tract, interspersed with areas of relatively normal tissue. Crohn's disease may present as recurrent attacks, with acute exacerbations combined with periods of remission or less active disease. Symptoms depend on the site of disease but may include abdominal pain, diarrhoea, fever, weight loss and rectal bleeding. Complications of Crohn's disease include intestinal strictures, abscesses in the wall of the intestine or adjacent structures, fistulae, anaemia, malnutrition, colorectal and small bowel cancers, and growth failure and delayed puberty in children. Crohn's disease may also be associated with extra-intestinal manifestation: the most common are arthritis and abnormalities of the joints, eyes, liver and skin. Crohn's disease is also a cause of secondary osteoporosis and those at greatest risk should be monitored for osteopenia and assessed for the risk of fractures. Fistulating Crohn's disease is a complication that involves the formation of a fistula between the intestine and adjacent structures, such as perianal skin, bladder, and vagina. It occurs in about one quarter of patients, mostly when the disease involves the ileocolonic area.
Treatment principles:
Treatment is largely directed at the induction and maintenance of remission and the relief of symptoms. Active treatment of acute Crohn's disease should be distinguished from preventing relapse. The aims of drug treatment are to reduce symptoms and maintain or improve quality of life, while minimising toxicity related to drugs over both the short and long term. In fistulating Crohn's disease, surgery and medical treatment aim to close and maintain closure of the fistula.
Treatment of acute disease:
- A corticosteroid (either prednisolone or methylprednisolone or intravenous hydrocortisone), is used to induce remission in patients with a first presentation or a single inflammatory exacerbation of Crohn's disease in a 12-month period.
- In patients with distal ileal, ileocaecal or right-sided colonic disease, in whom a conventional corticosteroid is unsuitable or contraindicated, budesonide may be considered. Budesonide is less effective but may cause fewer side-effects than other corticosteroids, as systemic exposure is limited. Aminosalicylates (such as sulfasalazine and mesalazine) are an alternative option in these patients. They are less effective than a corticosteroid or budesonide, but may be preferred because they have fewer side-effects. Aminosalicylates and budesonide are not appropriate for severe presentations or exacerbations.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
