L25: Lower GI Pharmacology Flashcards
What is TNF Alpha and what diseases is it present in?
TNF Alpha = inflammatory cytokine
- stimualtes macrophages to produce cytotoxic metabolites and increase phagocytic activity
a/w Crohn’s Disease and IBS
List 5 drugs that may be used in the treatment of IBD
- 5-Aminosalicylates
- Corticosteroids
- Immunosuppressive Agents
- Antimicrobials
- TNF Alpha Inhibitors (Anti-TNF Alpha Therapy)
What are 5-ASAs used for and what is their MOA?
Uses:
- prevents relapse in UC
- widely used in Crohn’s
MOA:
- inhibits leukotriene/prostaglandin formation
- blocks transcription of inflammatory cytokines
Give an example of a 5-ASA
Sulfasalazine (prodrug)
Mesalazine (active metabolite)
Sulfasalazine = Mesalazine + Sulfapyridine
List the adverse effects of 5-ASAs
- GIT disturbance due to hypersensitivity rxns by sulfapyridine
- thrombocytopenia
What GIT condition may corticosteroids be used for and what is their MOA?
- used for IBD
- inhibits cytokine production (stops inflammation)
List 3 corticosteroids that may be used to treat IBD - which one is first line treatment?
- Prednisolone - first line
- Hydrocortisone
- Budesonide
What is a side effect of long term use of corticosteroids?
osteoporosis
What are immunosuppressive agents and what is their MOA in treating IBD?
- purine analogues
- inhibit nucleic acid synthesis for long-term maintenance
Give an example of an immunosuppressive agent used in the treatment of IBD
Azathioprine (prodrug)
Mercaptopurine (active metabolite)
Azathioprine = Mercaptopurine
Why may mercaptopurine, an immunosuppressive agent used to treat IBD, NOT be used during pregnancy?
causes bone marrow suppression
Why may antimicrobials be used when treating IBD?
- treats secondary complications (abscesses, fistulas)
e. g. Metronidazole
What antimicrobial may be used to treat complications of IBD?
Metronidazole
What are TNF Alpha Inhibitor drugs used for? (GIT)
- refractory Crohn’s disease
- severe UC/Crohn’s disease
List 3 anti-TNF alpha therapies that may be used to treat IBD
- Infliximab
- Adalimumab
- Golimumab
What are the MOAs of the 3 anti-TNF alpha therapies that may be used to treat IBD
- Infliximab
- chimeric immunoglobulin
- binds to soluble TNF & prevents it from binding to its receptor - Adalimumab
- humanized immunoglobulin
- binds to TNF & blocks its interaction w/ p55 and P75 TNFRs - Golimumab
- humanized anti-TNF antibody
- lyse (all) cells involved in inflammatory process
What are laxatives?
- drugs promoting defecatin
- eliminate soft, formed stool
List the 4 main types of laxatives
- Bulk-Forming
- Osmotic
- Contact/Stimulant
- Lubricants (not mentioned)
What is the MOA of dietary fibre/bulk forming laxatives?
- increases stool mass
- insoluble + nonabsorbable carbs causes them to take up water and expand in lumen
- e.g. bran, methycellulose, ispaghula extracts
How long does it take for dietary fibre/bulk forming laxatives to take effect?
1-7 days
Give 3 examples of dietary fibre/bulk forming laxatives
- bran extracts
- methycellulose extracts
- ispaghula extracts
List the adverse effects of dietary fibre/bulk forming laxatives
- decreased absorption of drugs
- intestinal impaction + obstruction [dry bulk]
- oesophageal obstruction [dry bulk]
What is the MOA of osmotic laxatives?
hold water in the lumen via osmotic properties (increased ions)
- this increases transit
Give 4 examples of osmotic laxatives
- magenesium sulphate
- magnesium hydroxide
- sodium phosphate/biphosphate
- lactulose
Which osmotic laxatives have a fast transit time of 1-3 hours?
- magenesium sulphate
- magnesium hydroxide
- sodium phosphate/biphosphate
What is the transit time for lactulose, an osmotic laxative?
2-3 days
What is an adverse effect/precaution that one should mind when administering osmotic laxatives?
need to take care in children + those w/ renal impairment
What is the MOA of contact/stimulant laxatives?
- direct stimulation of myenteric plexus/mucosa
- increases peristalsis/mass movements
Contact/stimulant laxatives increase transit for how long normally?
increase transit over 6-8 hours
Give 2 examples of contact/stimulant laxatives
- Senna
2. Bisacodyl
Bisacodyl is a contact/stimulant laxative. How is it administered and what is its transit time?
- suppository (usually rectally)
- increases transit over 15-30 mins
Which laxative will most likely be administered in patients that cannot swallow or have trouble swallowing?
Bisacodyl - given suppository
Give an example of a lubricant laxative
Docusate
Anti-diarrheal agents are essentially…
constipating agents
List the 3 types of anti-diarrheal agents/constipating agents
- Absorbent Compounds
- Opiates
- Opiate Derivatives
How do “absorbent compound” anti-diarrheal agents/constipating agents work? Give 3 examples
- absorb fluids/toxins
- increase mass
- Kaolin
- Pectin
- Aluminum Hydroxide
What is the MOA of opiates as anti-diarrheal agents? Give examples
MOA:
- increase muscle tone
- decrease propulsive movements
- decrease sensory stimulation for defecation reflex
e.g. morphine + codeine
Give examples of opiate derivatives that may be used as an anti-diarrheal agent
Diphenoxylate
Loperamide (Imodium)
What is the benefit of using opiate derivatives as an anti-diarrheal agent over opiates?
- without CNS effects
- less dependence liability
