Despite limited understanding of therapeutic aetiopathogenesis of
ulcerative colitis and
Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and
biological therapies. It is equally important to recognise toxicity of the medical armamentarium for
inflammatory bowel disease (IBD).
Sulfasalazine consists of
sulfapyridine linked to
5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to
sulfapyridine 'intolerance' include
headache,
nausea,
anorexia, and malaise. Other allergic or toxic adverse effects include
fever,
rash,
haemolytic anaemia,
hepatitis,
pancreatitis, paradoxical worsening of
colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of
sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include
nausea,
dyspepsia and
headache.
Olsalazine may cause a secretory diarrhoea. Uncommon
hypersensitivity reactions, including worsening of
colitis,
pancreatitis,
pericarditis and
nephritis, have also been reported.
Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy,
corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include
acne, fluid retention, fat redistribution,
hypertension, hyperglycaemia, psycho-neurological disturbances,
cataracts, adrenal suppression, growth failure in children, and
osteonecrosis. Newer
corticosteroid preparations offer potential for targeted
therapy and less
corticosteroid-related adverse effects.
Azathioprine and
mercaptopurine are associated with
pancreatitis in 3 to 15% of patients that resolves upon
drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of
methotrexate include
nausea, leucopenia and, rarely,
hypersensitivity pneumonia or hepatic
fibrosis. Common adverse effects of
cyclosporin include nephrotoxicity,
hypertension,
headache,
gingival hyperplasia, hyperkalaemia,
paresthesias, and
tremors. These adverse effects usually abate with
dose reduction or cessation of
therapy.
Seizures and
opportunistic infections have also been reported. Antibacterials are commonly employed as primary
therapy for
Crohn's disease. Common adverse effects of
metronidazole include
nausea and a
metallic taste.
Peripheral neuropathy can occur with prolonged administration.
Ciprofloxacin and other antibacterials may be beneficial in those intolerant to
metronidazole. Newer
immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD.
Tacrolimus has an adverse effect profile similar to
cyclosporin, and may cause
renal insufficiency.
Mycophenolate mofetil, a
purine synthesis inhibitor, has primarily gastrointestinal adverse effects.
Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD.
Infliximab, a chimeric antibody targeting tumour
necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess
long term adverse effects.