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Pharmacology of Lower GIT (Aminosalicylates (Decreases the symptoms of…
Pharmacology of Lower GIT
Aminosalicylates
Decreases the symptoms of mild disease and prevents relapse in ulcerative colitis and Crohn's disease
Anti-inflammatory agents which inhibit LK/PG formation and blocks transcription of inflammatory cytokines sucha s TNF and IL-1 in colonic epithelial cells.
SULFASALAZINE
: Prodrug which gives mesalazine and sulfapyridine
MESALAZINE
and
OLSALAZINE
are less toxic
Oral and has SE such as GIT disturbance, thrombocytopenia and hypersensitivity reactions caused by sulfapyridine
Corticosteroids
Inhibition of cytokine production to induce remission. There is also a risk of relapse with withdrawal and dependancy.
S.E: long-term use can lead to osteoporosis
PREDNISLONE
(first line, oral),
HYDROCORTISONE
(i.v and topical) and
BUDESONIDE
(oral and has low bioavailability due to high first pass metabolism
Immunosuppressive agents
In the treatment of inflammatory bowel disease
Purine analogues inhibiting nucleic acid synthesis for long-term maintenance
AZATHIPRINE
- Prodrug which gives mercaptopurine as an active metabolite
MERCAPTOPURINE
- Bone marrow suppression
Antimicrobials
Used in secondary complications such as abscesses and fistualting Crohn's
It affects the bacterial action in inflammation
METRONIDAZOLE
TNF-alpha inhibitors
INFLIXIMAB
A response to the inflammatory effects of TNF-alpha. TNF stimulates the production of cytotoxic metabolites by macrophages to increase phagocytic activity
Used for refractory Crohn's disease and it is used in people who do not respond to other treatments
Other examples of anti-TNF therapy includes
GOLIMUMAB
and
ADALIMUMAB
Laxatives
Drugs which promote defaecation
Eliminates soft formed stool. It retains water and electrolytes in the lumen via hydrophilic and osmotic properties which will increase the transit by increasing the bulk. The mucosal absorption of water and electrolytes decrease but the intestinal motility increases.
Dietary fibre/bulk forming
Increases stool mass via polysaccharides so the transit is increased for 1-7 days.
BRAN, METHYCELLULOSE, ISPAGHULA
Adverse effects: Decreased absorption of drugs and it may also cause intestinal impaction/obstruction and oesophageal obstruction due to dry bulk and insufficient water.
Osmotic
MAGNESIUM SULPHATE, MAGNESIUM HYDROXIDE and SODIUM PHOSPHATE/BIPHOSPHATE
Holds water in the lumen due to the osmotic properties and increases the transit for 1-3 hours. Only a little is absorbed but could cause problems in children with renal impairment.
Contact/stimulant
Directly stimulates the myenteric plexus which reduces the permeability of the mucosal surface. There will be increase in mass movement and decrease in segmentation.
SENNA
- Prodrug for active anthracine derivatives,
BISACODYL
- Suppository which increases the transit for 15-30 mins
Anti-diarrhoea agents
Maintaining fluid and electrolyte balance by oral rehydration and NaCl and glucose for infants.
Anti-infective agents can be used for diarrhoea caused by anti-microbials. Used for the treatment of simple gastroenteritis
Constipating agents can also be used because diarrhoea can be caused due to Crohn's disease and ulcerative colitis
Absorbent compounds absorb fluids. These include
KAOLIN, PECTIN and ALUMINIUM HYDROXIDE
Opiates increase muscle tone and decreases the propulsive movements. The sensory stimulation for the defeacation reflex is also decreased. Examples include
MORPHINE
and
CODEINE
Opiate derivatives without CNS effects include
DIPHENOXYLATE
and
LOPERAMIDE- IMODIUM