lower GI pharmacology Flashcards
Constipation
Multiple causes- lack of dietary fiber, drugs, hormonal , neurogenic or emotional disorders, illness
Laxatives- enhance the retention of intraluminal fluid in stool, decrease absorption or increase secretion of fluid by gut wall, increase propulsive motility
increases fluid–> increased stretch–> increased propulsions
dietary fiber- laxatives
food that resists enzymatic digestion- unfermented fiber attracts water (lignin)- Bran, fruits and veggies are more easily fermented and draw less water
Synthetic celluloses - Psyllium (metamucil), Methylcellulose (citrucel)
Effects– bloating
laxatives- osmotic agents
Saline laxatives- Magnesium citrate, magesium hydroxide
MOA: Osmotic water retention, increased volume promotes peristalsis
SE: caution with renal insufficiency, cardiac disease, diuretics or electrolyte abnormalities
Non digestable sugars-osmotic laxatives
Lactulose
Hydrolyzed to short chain fatty acids in the colon biota, osmotically drawing water into the lumin
Use for opiod induced constipation, old constipation, idiopathic, portal system encephalopathy (increased excretion of ammonia), acidifies
sE: gas and cramping
osmotic agents other
polyethylene glycol- poorly absorbed, retain water due to osmosis Colonic cleansing (w/ electrolytes-- pre surgery), occasional constipation
Docusate salts- surfactan that increases the water content of stool, Therapeutic use, mild constipation
Stimulant laxatives
Stimulant/irritant laxatives
MOA: induce giant migrating colonic contractions, water and electrolyte secretion
Bisacodyl- prodrug, requires hydrolysis by endogenous esterases in the bowel – 6 hours
Senna- plant- prodrug, activated in the colon, SE- diarrhea, abdominal pain, hypokalemia (chronic use), dependency
Abuse for losing wt, atonic colon
Laxatives- prostaglandin analog
Lubiprostane-
Chronic idiopathic constipation, opiod-constipation, IBS
MOS: prostaglandin analog, activates CL channels, increased water in lumen
Side effects- nausea, diarrhea, headache
opiod constipation
Mu receptor activation–>
Inhibit peristalsis
Increase sphincter
Increase fluid absorption
Opiod receptor antagonist- laxative
MEthylnaltrexone- blocks mu opiod receptor, prevents suppression of peristalsis
Therapeutic use- after conventional laxatives, opiod induced constipation
SE: contraindicated with GI obstruction, abdominal pain
Does not cross BBB
Diarrhea
Causes of diarrhea-
Osmotic load, retention of water in the lumen
Excessive secretion of electrolytes and water
Exudation of protein and fluid from the mucosa
Dehydration and electrolyte imbalance are the main risk in severe cases of diarrhea
A balanced mixture of glucose and salts can prevent dehydration because sodium and chloride absorption is linked to glucose uptake followed by movement of water
Pharm therapy is best reserved for pts with significat and/or persistant symptoms, anitdiarrheal agents provide symptomatic relief but do not treat the underlying cause
Bismuth subsalicylate
Travelers diarrhea, episodic diarrhea and acute gastroenteritis, infection
MOA: antisecretory, anti-inflammatory, and antimicrobial, bismuth passes unabsorbed into the feces, salicylate is absorbed in the stomach and small intestine
SE: dark stool, black hairy tongue, warning regarding REye’s syndrome
Anti diarrheal agen
Probiotics/ fecal transplant
MOA: gut recolonization with non-pathogenic bacteria
Acute diarrheal conditions, antibiotic associated diarrhea, and infectious diarrhea
Opiod derivatives
Loperamide (imodium)- over the counter, mu receptor agonis, poor CNS penetration
Diphenoxylate- mu receptor agonist, CNS penetration, may combine with atropine
Effective against travelers diarrhea, and chronic diarrheal disesase,
MOA: inhibit peristalsis and prolong transit time, increases visocosity
SE: Abdominal pain, constipation, overdose–> CNS depression, and paralytic ileus, risk for toxic megacolon
Octreotide
Somatostatin analog
MOA: Inhibits hormone secretion from tumors, including 5HT, gastrin, VIP
USe: hormone secreting carcinoid tumors of the pancreas and GIT, dumping syndrome, following gastric surgery
SE: nausea, gallstone formation, hypo/hyperglycemia
IBS
Chronic disorder of the characterized by abdominal pain and altered bowel habits in the absence of an organic disease
Etiology of IBS is poorly understood- motility, visceral hypersensitivity
Treatment- dietary modifications
Constipation IBS- Lubiprostone
Diarrhea-hypscyamine, alosetron
Hyoscyamine
MOA: muscarinic antagonist, decrease smooth muscle contractions
USE- adjuvant thearpy IBS-D, divertivulitis, colic
SE: dry mouth, urinary retention, palpitations
Alosetron
5ht3 antagonist, decreases GI contractility, increase colontic transit time
Improvements in abdominal pain, stool frequency and consistency, may also blunt visceral sensation
Use- Women with IBS-d who have not responded to convetional therapy, (concern for ischemic colitis)
Pathogenesis of IBD
disruption of epithelial barrier, bacteria go to DCs, Dcs–activate helper T cells– TNF a release– activation of macrophage–> postitive feedback
IL12 also releasede
IBD goals of therapy
Relief of symptoms (acute attacks), induction of remission , precention of relapse, treats the complications (fistulas)
5 aminosalicylates, corticosteroids, Immunosuppressive agents, biologics, Jak kinase inhibitor
5 aminosalicylates
Sulfasalaine- prodrug activated by colonic bacteria, SE- headache, nausea, dizziness (5 ASA thrp, sulfapyridine)
Mesalamine- delayed release formulation, pH sensitive coating, SE- infrequent, headache and rash
Osalazine- dimer of 2 mesalamines, bacteria cleave in distal portion of gut
MOA- unclear, inhibitionof IL1, TNFa and lipoxygenase pathway, no COx inhibition
USe for mild to moderate ulcerative colitis
Corticosteroids
Prednisone- most common
Budesonide- enteric release synthetic steroid use for mild to moderate crohns disease, low F delivers therapy to bowel while minimizing side effects
Therapy- Induce remission in all type of UC or Crohns
MOA- dampen the inflammatory response, decrease ILs and TNFa
SE- systemic effects, wt gain, emothional and sleep disturbances glaucoma
Immunosuppressive agents
AKA Thipurine derivatives
6- MC
Azathioprine
MOA- impair purine biosynthesis and inhibit cell proliferation
Theraputic use- Crohns and UC (maintain remission), Crohns releated fistulas
SE- bone marrow supression, vomiting, jaundice, pancreatitis
Methotrexate
MOA- irreversibly inhibits DHF reductase, blocking DNA synthesis, repair, proliferation and causing cell death
Anti inflammatory
USe- steroid resistant or steroid dependent IBD (Crohns- induces and maintains remission
X preg
Infliximab
IV Ig, Neutralizes TNF a
Use- UC and Crohns, closes fistulas, deceases acute flates, maintains remission
SE- respiratory tract infection, reactivation of TB
Contraindicated in pts with severe congestive HF
Ab against infliximab, combined with azathioprine
Adalimumab and Certolizumab also TNFa against , mod to severe crohns
natalizumab and vedolizumab
Ab inhibits Alpha 4 integrins
MOA: reduces extravasion of lymphocytes to sites of inflammation
USe- mod to severe crohns
SE- upper respiratory infection, hypersensitivity reaction, hepatotoxivity
ContInd with immune modulating drugs, multifocal leukoencephalopathy
ustekinumab
IL12 andIL 23 antagonist
prevents activation of lymphocytes
SE- infectionarthralgia
