Lower GI Pharm - Gauthier Flashcards
What is the go-to treatment for diarrhea?
Oral rehydration–medication is reserved for significant or persistent diarrhea! Anti-diarrheals treat only symptoms, and may worsen outcomes in infectious etiologies.
What is the mechanism of action of Loperamide?
How is Diphenoxylate different from Loperamide?
µ receptor agonist, reduces GI motility.
Diphenoxylate firstly is a prodrug (de-esterified to difenoxin). It also has CNS effects (and so is coadministered with atropine)
What role do bulk increasers and absorbents play in treating diarrhea?
(eg Kaopectate, fiber)
Increasing bulk may slow motility and absorb water. Infectious toxins may also be sequestered and removed.
Describe the mechanism of action and side effect profile of the drug indicated for traveler’s diarrhea.
Bismuth Subsalicylate; the metal is thought to be anti-secretory, anti-inflammatory, and antimicrobial. Side effects: Black tongue and black stool (product of bismuth + bacterial sulfides)
How would you treat someone with carcinoid-induced diarrhea?
What are some other uses for this drug?
Octreotide (somatostatin analog; reduces hormone secretion).
Also for “post-operative dumping syndrome” and stopping active variceal bleeds.
By what 3 mechanisms is constipation treated?
- Increase retention of intralumenal fluid
- Decrease absorption of intralumenal fluid
- Increase motility (propulsive, not segmenting)
By what mechanisms does fiber treat constipation?
Side effects?
Fermentable (water-soluble) fibers are fermented by colonic bacteria, producing SCFAs which facilitate motility. SE: Gas, bloating.
Nonfermented fiber retains water and increases bulk. SE: (Contraindicated in obstructive constipations)
Milk of magnesia belongs to what class of laxatives?
Describe how this class treats constipation.
“Saline cathartics”, a subset of osmotic laxatives.
Mostly consists of inorganic ions that are not absorbed (eg Magnesium, not phosphate)
What is lactulose’s mechanism of action? Side effects?
Lactulose is a carbohydrate that reaches the colon undigested. Metabolism by bacteria there generates SCFAs (pro-motility) as well as acidifying and trapping ammonia.
Side effects: Gas, cramping.
How is PEG administered?
Contrast its mechanism of action with that of ducosate salts.
As a powder, generally mixed with isotonic Na and K salts.
PEG relies on osmotic effect to reduce constipation. Ducosate salts are anionic surfactants which lower stool surface tension.
Compare and contrast the mechanisms and kinetics of bisacodyl and senna
Both are stimulant laxatives which promote diarrhea by irritating the mucosal lining of the colon.
Bisacodyl is a diphenylmethane prodrug, activated by bowel esterases.
Senna is a plant-derived anthraquinone prodrug, activated by colonic bacteria.
Lubiprostone is a ___ analog that activates ____. It is used to treat ____, and has the side effects of nausea, headache, and diarrhea.
PGE1 analog, activates chloride channels, to treat chronic constipation and constipation-dominant IBS (not IBD!).
Describe the structure of linaclotide.
What is its mechanism of action?
Side effects?
14-amino acid peptide.
Activates GC to increase cGMP both intracellularly (increases chloride/bicarbonate secretion) and extracellularly (decreases visceral pain).
Diarrhea, abdominal pain.
Name two µ opioid receptor ANTagonists.
Methylnaltrexone and alvimopan.
What role might a 5-HT3 receptor antagonist play in irritable bowel disease? Can you name such a drug and its side effects?
5-HT may underlie the bowel wall sensitivity and motility. Inhibition with a drug like alosetron may improve symptoms at the risk of ischemic colitis (not bolded…)
When are steroids indicated in the treatment of IBD?
How do patients generally respond to them?
For moderate to severe attacks.
Response stratified into responsive & non-dependent (40%), responsive & dependent (40%), and unresponsive (20%).
Distinguish between budesonide and prednisone.
Both are corticosteroids for the treatment of IBD. Budesonide is enteric-coated and is directed more towards Crohn’s.
What is the mechanism of action of 5-ASAs?
Can you name 3 such drugs? Which are azo drugs?
5_ASAs have an unclear mechanism; they may inihibit IL-1/TNF/LPO, and may scavenge free radicals.
Mesalamine, Olsalazine (*azo prodrug), Sulfasalazine (*azo prodrug)
Compare and contrast the kinetics and side effect profile of Mesalamine, Olsalazine, and Sulfasalazine.
Mesalamine: Available delayed or pH-dependent release. SEs: Headache, dyspepsia, skin rash.
Olsalazine: Prodrug converted to mesalamine. SEs: Diarrhea
Sulfasalazine: Prodrug converted to mesalamine. SEs: Fever, malaise, vomiting, headache.
What role do immunosuppressors (not steroids) play in treating IBD?
Name three. What is each one used for?
Reduce the inflammatory response.
Azathioprine (+6MP; both), Methotrexate (Crohn’s), Cyclosporine (UC).
Name 3 immunoglobulins against TNFa.
What is the mechanism of the fourth remaining immunotherapy?
Infliximab, Adalimumab, Certolizumab (actually a Fab fragment)
Natalizumab, binds 4-integrin to reduce leukocyte extravasation.
What side effects are seen in biological TNFa inhibitors such as Infliximab?
Lupus-lke symptoms, delayed hypersensitivity, increased infections (URIs), non-hodgkin lymphomas.
What extremely bizarre method is being researched as a potential therapy for IBD?
Helminths and helminth-associated molecules, which may reduce disease activity.
They’re not only for victorian women anymore!
