IBD and IBS Flashcards
What is IBD (Irritable Bowel Disease)?
- A severe anti-inflammatory disorder affecting the lower GI tract. Inflammation is destructive and very painful.
- ->Perforation can occur, which can be fatal.
2 Main Types of IBD:
-Crohns Disease
-Ulcerative Colitis
(Treatment addressing both inflammation and activating the immune response)
What are Aminosalicylates?
- Discovered in the 1930’s (originally used to treat rheumatoid arthritis)
- Mechanism isn’t fully understood (causes anti- inflammation)
Mesalamine:
5-aminosalicyclic acid (5-ASA)
- ->Anti-inflammatory activity
- Inhibits inflammatory mediators including TNFalpha and MAY inhibit COX (there are likely other mechanisms that contribute)
*Acts locally, and therefore targets the colon.
Strategies: Prodrug cleaved in the colon, enteric coating dissolved in the colon, microspheres release drug slowly, as well as rectal administration.
Sulfasalzine
5-ASA + Sulfapyridine
- 2 molecules separated in the colon by bacteria.
- Efficacy largely due t 5-ASA, and the adverse effects are largely due to Sulfapyridine (acts as the drugs escort)
Asacol and Saloflak (5-ASA EC):
Delayed release of 5-ASA (released based on pH)
- -The drug can’t be released in the stomach due to it’s low pH
- Begins releasing drug in the terminal ileum (Small Intestine) and continues through the the rectum.
5- ASA ER (Pentasa):
Extended Release (ER) Microsphere -->Release 5-ASA all the way throughout the small intestine to the rectum.
Suppositories:
Effects may extend to the upper rectum.
Enema:
Enema’s reach much further than suppositories- up to the distal colon
Side Effects of Rectal’s (Suppositories and Enema)
- Gastrointestinal (worse with Sulfasalazine)
- Headache
TNF-alpha Inhibitors:
TNFalpha plays a major role in mediating inflammation.
- ->Appears to be very important in IBD
- Different types in drugs, including Monoclonal Antibodies & Corticosteroids
Infliximab:
Monoclonal antibodies bind to TNF-alpha and prevent it from interacting with it’s receptor..
Side Effects:
- Opportunistic Infections and Immunosuppressive effects may increase risk of infection.
- Reactivation of TB can occur (should be screened)
- Hypersensitivity reactions (Acute or Delayed)
- Infliximab is chimeric (animal/ human) while others are human mabs.
- -In theory, there may be a higher risk of reactions with infliximab
- Malignancies- due to reduced immune surveillance (TNF-alpha lyses tumour cells)
- Extent of risk is still unclear.
Prednisone, Budesonide
Oral corticosteroids
- Budesonide has low bioavailability, therefore tends to act locally in the GI tract.
- -Has a lower efficacy than Prednisone
Adverse Effects:
-Numerous serious side effects with systemic agents like Prednisone (fewer with Budesonide)
Azathioprine:
-Converted to a structural analogue of guanine.
“False Nucleotides” halts DNA/ RNA synthesis.
-Lymphocytes rely on de novo purine synthesis (synthesis of complex molecules from simple sugars or amino acids, as opposed to recycling after partial degradation.
-Is more susceptible to actions of anti- metabolites.
Adverse Effects: Related to effects on the immune system (Infection, Cancer), as well as related to rapidly dividing cells (Bone Marrow Suppression and Gastrointestinal)
Methotrexate:
Folate antagonist
–Significant adverse effects
Antibiotics/ Probiotics to treat IBD:
Acute Complications:
–>Antibiotics for the management of acute complications (infections)
–>Chronic management: Theory is that an imbalance of pro and anti inflammatory bacteria contribute to IBD
What is Irritable Bowel Syndrome (IBS)?
Very common & challenging to treat
- -Occurs in 3 forms:
1. IBS-C (Constipation)
2. IBS-D (Diarrhea)
3. Mixed - -Abdominal pain is significant & is affected by physiological & dietary components.
-Treated with laxatives and anti- diarrheals
Hyoscine:
- Anti- cholinergic (anti-spamics)
- Muscarinic Receptor Antagonist (decreases peristalsis & decreases contractions of the colon)
Side Effects: Dry Mouth, Urinary Retention & Constipation
Pinaverium:
Ca2+ Antagonist
- Blocks entry of calcium into smooth muscle cells of the GI tract.
- Blocking calcium inhibits smooth muscle contraction
Side Effects include constipation and abdominal distention
SERIOUS side effects include Esophageal Irritation
-Patients should take Pinaverium with a full glass of water/ small snack to make sure it clears the esophagus.
Linaclotide:
cGMP Agonist
- Increases intestinal secretions
- Reduces transmission of pain signals
- Anti-depressants are also used to treat IBS
- ->Particularly, if there is co-morbid depression and anxiety.
TCA’s and SSRI’s:
Common anti-depressant drugs with anti- cholinergic effects.
- TCA is better suited for people with IBS-D
- TCA’s are more reliable than SSRI’s on the GI tract.
Amitriptyline:
TCA which exhibits anti cholinergic effects.
- Off target effects
- Normally, constipation is considered an adverse effect of TCA’s but in this case, it can be used to treat IBS-D
-Can also be prescribed to treat chronic pain.
Citalopram:
SSRI
-Typically used to treat IBS-C, but effects on the GI Tract are not as reliable as TCA’s
