Medications Used

in Inflammatory Bowel
Diseases
For Third Year Medical Undergraduates
Dr S. Bowatte
Learning objectives
• Recall Knowledge on UC and CD
• Outline the Diagnosis of UC and CD
• Outline the management of UC and CD:
• Induction of Remission & Maintenance of remission
• Symptomatic and Supportive care
• Emergency management
• Surgical management
• Describe the medication groups:
• Amino-salicylates, Immunomodulators, Steroids, Antibiotics
Diagnoses
Guidance

• British Society of Gastroenterology Guidelines (BSG) (2019)

• European Crohn's and Colitis Organization Guidelines on Medical &

Surgical Treatment (ECCO) (2019)

• American Gastroenterological Association Guidelines (AGA) (2020)

UC - Mild – moderate disease:

• Target:
• symptomatic remission combined with mucosal healing.

• Induction and maintenance:

• 5-aminosalicylic acid (5-ASA), oral +/- enaemas (Sulphasalazine / mesalazine)

• If 5-ASA therapy has failed or is not tolerated:

• prednisolone oral +/- topical (budesonide).
UC – moderate to severe disease
• Induction of remission:
• oral Corticosteroids.
• Maintenance:
• 5-ASA
• If 5-ASA fail:
• Azathioprine, Biologics (anti–TNF therapy, vedolizumab, or
tofacitinib)
• Surgical resection:
• patients refractory to optimal medical therapy.
Proctitis in ulcerative colitis

• Mild or moderately active ulcerative proctitis:

• 5-ASA suppository.

• Not responding / intolerant 5-ASA:

• switched to corticosteroid suppositories.

• Refractory proctitis:
• corticosteroids, immunomodulators, biological therapy.
Acute severe ulcerative colitis
• high-dose intravenous corticosteroids
• prophylactic low-molecular-weight heparin.
• If patients do not respond by day 3:
• rescue therapy with intravenous infliximab or cyclosporine

• Patients that do not respond /deteriorate / complications (severe

hemorrhage, perforation, toxic megacolon):
• colectomy and ileostomy

• IV antibiotics /supportive / ICU care

CD – mild to moderate
• Induction of remission:
• oral steroids
• 5-ASA is less effective
• Antibiotics to cover potential infections
• Maintenance with Azathioprine, Methotrexate
• Surgical treatment for localized ileocecal Crohn disease:
• Open surgery / laparoscopic surgery
• (1) in whom initial medical therapy failed
• (2) who relapsed after initial medical therapy,
• (3) who prefer surgery over continued medical treatment
CD – moderate to severe disease

• ileocolonic Crohn disease:

• systemic corticosteroids

• extensive disease or other poor prognostic features:

• early introduction of biological therapy.

• Patients responsive to prednisolone:

• maintenance therapy with thiopurines (Azathioprne) or methotrexate
Perianal Crohn disease
• Antibiotics
• Steroids / biologics
• Surgery
Supportive care
• Anti-diarrhoeals
• best avoided in active disease,
• Can be used in maintenance if necessary
• Nutrition:
• Fe, B12, Folate,
• Probiotic supplementation:
• reduce ulcerative colitis disease activity index
• Antibiotics:
• ulcerative colitis: limited treatment efficacy /increased risk of developing
antibiotic-associated pseudomembranous colitis
• Crohn’s disease, antibiotics are used for various indications: perianal
disease, fistulas, intra-abdominal inflammatory masses.
Homework….
• Draw 2 charts
Mild disease Mild disease Moderate Severe disease Severe disease
induction maintenance disease induction Maintenance
induction

UC
CD
Surgical Indications UC CD
Pharmacology of Medications
 1. Corticosteroids
• Structurally and Pharmacologically similar to endogenous cortisol

• Endogenous steroids Involved in:

1. Stress response
2. Immune response
3. Regulation of inflammation
4. Carbohydrate and protein metabolism
5. Blood electrolyte levels
6. Behaviour
• Pharmacologic steroids used to alter/modify above
 Mechanism of action of corticosteroids
• Fat soluble but not water soluble: Transported bound to protein
carriers.
• Crosses plasma membrane easily.
• Binds to receptor in Cytoplasm / nucleus / cell membrane
• Steroid-receptor complex binds DNA in the nucleus.
• Effects on transcription (m RNA) in synthesizing specific proteins.

• Metabolism
• By cytochrome P450 oxidase
• Excreted in urine and bile.
 Effects of Corticosteroids
Mineralocorticoid action –
• Increased retention of sodium by the renal tubule.
• Increased excretion of potassium in the urine.

Glucocorticoid action –
• Carbohydrate metabolism-Increased gluconeogenesis, Hyperglycaemia
• Protein metabolism-negative nitrogen balance with muscle wasting,
Osteoporosis, delayed wound healing.
• Fat storage
Effects of Treatment with Steroid

• Depresses inflammatory response –

• by inhibition of Neutrophil and macrophage function.
• Immunosuppressive-
• Inhibition of delayed hypersensitivity reactions.
• Suppress allergic response
• Inhibition of type 1 hypersensitivity
• Anti proliferative effects –
• inhibition of DNA synthesis and cell turnover
• Vasoconstrictive effects
 Examples and route of administration.
• Prednisolone – oral, IV, IM ( Methylprednisolone), per rectal
• Hydrocortisone – oral, IV, intra articular, IM, per rectal,
• Fludrocortisone - IV
• Beclamethasone inhaled (topical)
• Budesonide- oral, inhaled,
• Triamcinolone – topical, IM, IA
• Betamethasone – oral, IM, IV
• Dexamethasone – oral, IV
Comparison of Steroids According to its
Action.
 Pharamacokinetics of steroids

• Topical steroids (skin,lungs,joints) can cause enough

absorption to cause systemic side effects.

• In the blood 5% of the steroids are carried free(active

form).The rest is bound to transcortin and other proteins.

• Hence steroid dose should be reduced in low albumin

states and liver disease.
 Indications for the use of Steroids
1. RS: Acute severe asthma
2. Skin: Exfoliative dermatitis and pemphigus
3. Joints & Collagenous tissues:
• SLE, Rheumatoid arthritis, Polymyalgia rheumatica, giant cell arteritis,
dermatomyositis, acute Gout
4. Haematology: Acquired haemolytic anaemia
5. Immunology:
• Severe allergic (hypersensitivity) reactions
• Organ transplant rejection
6. GIT: IBD
7. Renal: Nephrotic syndrome
 Special Precautions in using corticosteroids.
• Give a single daily dose –early morning.

• Use for the shortest possible courses.

• If continued for >3 months – needs bone protection

• Gut mucosal protection

• Check for hyperglycaemia

• Tail off on discontinuation over an adequate time

• Pregnancy: no contraindication
 Adverse Effects of
Corticosteroids
Usually following prolonged administration
1. Cushing’s syndrome
2. Diabetes mellitus
3. Proximal myopathy
4. Osteoporosis/ Avascular necrosis of bone
5. Peptic ulcer and haemorrhage
6. Pancreatitis
7. Depression, psychosis, insomnia
8. Posterior subcapsular lens cataract,
glaucoma
9. Growth retardation in children-esp. if
treatment exceeds 6 months.
 2. Methotrexate

• Folic acid antagonist.

• Competitive inhibition of enzyme dihydrofolate reductase.
• Protein synthesis effected.
• Has anti- inflammatory effects and Cytokine modulating effects.
• Used in maintainance therapy in IBD.
• Best tolerated DMARD
• Teratogenic – avoid in pregnancy
• ROUTES OF ADMINISTRATION – oral, IM, IV, intrathecal
Folate metabolism

• MTX Interferes with DNA

synthesis
• Target Lymphocytes
• Other rapidly proliferating
cells get affected.
Methotrexate uses

• Solid organ malignancies (breast, uterus, head & neck, sarcoma)

• Haematological malignancies (leukaemia / lymphoma)

• Rheumatoid arthritis
• Juvenile rheumatoid arthritis
• Psoriasis
• Psoriatic arthritis

• (in non-neoplastic use, it is given once a week and is combined with folic
acid or folinic acid)
• ADVERSE EFFECTS
• Pancytopenia
• Hepatitis
• Acute and chronic interstitial pneumonitis
• Nausea, vomiting, diarrhoea
• Painful mouth ulcers,
Pharmacology

• Orally well absorbed – 60%

• Protein bound 50%
• Pregancy: contraindicated
• Mertabolised by liver
• Eliminated in urine 80%
 3. 5 - Amino Salicylic Acid (5-ASA) compounds
• act by activating gamma
form of peroxisome
proliferator-activated
receptors.
• Controls:
• inflammation
• cell proliferation
• apoptosis
• metabolic function
5 - ASA

• Sulphasalazine, Mesalamine, Balsaraside

• Used in induction and maintainance therapy in UC

• Cautious in hepatic and renal impairment.

• Safe in pregnancy and breast feeding

• ROUTES OF ADMINISTRATION – Oral, per rectal

• ADVERSE EFFECTS
• Hepatotoxicity
• Renal toxicity
• Skin reactions (SJS/TEN)
• Gastrointestinal disturbances

• OTHER INDICATIONS
• RA
• Spondyloarthropathy with peripheral joint involvement
• Psoriatic arthritis.
Pharmacology

• Orally well absorbed

• Pregnancy: no risk observed
• Protein binding 80%
• Metabolism: colon and liver
• Excretion: faeces > urine
 4. Azathioprine
• Metabolized to 6-mercaptopurine; Inhibitor of purine synthesis , Cellular
response is impaired.
• TPMT(thiopurine methyltransferase) metabolizes 6 mercaptopurine.
• Low levels of TPMT leads to toxicity
• Used in maintainance therapy of both UC and CD
• Treatment should not be initiated during pregnancy. Can use under specialist
supervision.
• Dose adjustment is required in hepatic and renal impairment
• ROUTES OF ADMINISTRATION – oral, IV
• ADVERSE EFFECTS
• Marrow suppression
• Liver toxicity
• Hypersensitivity
• Nausea, vomiting, Diarrhoea
• Rash

• OTHER INDICATIONS
• RA, SLE, other Auto immune diseases
• Psoriatic arthritis
• Immuno suppressant in post organ transplant.
 6. Biologics

•Agents derived from natural substances and chemically altered.

•Used when there is poor response to DMARDS and sometimes as
primary therapy.
•Expensive.
1. Infliximab
2. Daclizumab
3. Adalimumab
4. Rituximab
5. Golimumab
Monoclonal antibodies
Other Biologics..

• Fusion proteins – Etanercept

• Immune pathway inhibitors - Imitinib
 Infliximab

•Widely used biologic agent.

•Used for remission induction in IBD.
•Contraindicated in moderate to severe heart failure
and severe infection

•Better to avoid in pregnancy , safe in breast feeding.

•ROUTES OF ADMINISTRATION - IV
• ADVERSE EFFECTS
• Secondary Infections
• Hypertension
• Skin reactions
• Fatigue
• Worsening congestive cardiac failure

•OTHER INDICATIONS
•Resistant RA
•Ankylosing spondylitis
•Psoriasis
Questions??
Thank you.