GI Pharm part 2

• Natural: Psyllium, methylcellulose
• Synthetic: Polycarbophil

• Ingestible, hydrophilic colloid that forms a gel, promoting peristalsis
• Side Effects: bloating, flatus (gas)

Don't be Psylly! It's natural!

• Docusate
• Glycerin suppository
• Mineral Oil

Soften fecal material, permitting water/lipids to enter

"Docu-self on the toilet"

• Increase stool liquidity
• Nonabsorbable sugars/salts: MgO, sorbitol, lactulose, Mg citrate, Na phosphate
• Use: Tx of acute constipation or prevention of chronic
• Side Effects: MgO -> hypermagnesemia, electrolyte fluctuation (no cardiac or renal disease pts), bloating & flatus w/sorbitol and lactulose

"if I point my Mag at you, you liquid flatulate (lactulose), and exclaim Mag?! Shitrate! spit sodium on my phosphace, then absorbital? ... or something"

• Osmotic Laxative
• Inert, nonabsorbable, osmotically active sugar (PEG) with Na2SO4, NaCl, NaHCO3, and KCl
• Use: complete colonic cleansing prior to GI endoscopy (exciting!)
• No side effects like other osmotic lax's

• Aloe, Senna, Cascara
• Stimulant Laxatives (Cathartics)
• MOA: Induce BM by stimulating enteric nervous system & colonic electrolye/fluid excretion
• Natural plant products, poorly absorbed
• Side Effect: Melanosis Coli with chronic use (brown pigmentation)

"Jenna likes wearing Cascara for Al, the superhero saving the world from anthrax planted by his nemesis Melanosis Coli... it's a bit cathartic for him and stimulates his nerves... and then he excretes fluid"

• Potent Stimulant Laxative
• acts in 2-6hrs
• Hydrolyzed in upper intestine to Ricinoleic Acid, a local irritant that stimulates motility

"Rick is a local uptown mechanic trying to get laid while changing your oil. It takes 2-6 hours, that's irritating, you just want him to move it along"

• Laxative
• Partial serotonin 5-HT4 receptor agonist
• enhances release of NT stimulating 2nd order neurons that promote peristaltic reflex
• Use: chronic constipation
• Does not cross BBB, relatively safe drug, avoid in pts with severe hepatic/renal disease
• "Take a rod and stick it... somewhere... to make you release serotonin. Don't go as high up as your kidneys and liver, but don't worry, it won't reach your brain"

• Antidiarrheal Agent
• Opioid receptor agonist: increase colonic phasic segmenting activity (via presynaptic cholinergic inhibition) = increased transit time and fecal water absorption. Decreases mass colonic movements and gastrocolic reflex.
• Does NOT cross BBB (no analgesic/addictive properties)

"When Dr. Lopes has the runs, it takes longer to get there and you have to drink more water, but it's worth it b/c you get runner's high (like opiates)"

• Antidiarrheal Agent
• Opioid receptor agonist: increase colonic phasic segmenting activity (via presynaptic cholinergic inhibition) = increased transit time and fecal water absorption. Decreases mass colonic movements and gastrocolic reflex.
• Dependence forming
• Atropine added to discourage overdosing

"Dr. Lopes encourages us to Dive In to material, however, you may become addicted to her lectures, OD, then need atropine shot into your heart. BAM!!"

• Antidiarrheal Agent
• Naturally occurring hydrated Mg Al silicate (clay mineral)
• MOA: Absorbs bacteria, toxins, fluid (may bind other drugs)
• Use: Acute diarrhea
• Side Effects: Constipation

• Antidiarrheal Agent
• Indigestible carbohydrate from apples
• MOA: Absorbs bacteria, toxins, fluid (may bind other drugs)
• Use: Acute diarrhea
• Side Effects: Constipation

• Antidiarrheal Agents
• Bile Salt binding resins
• Use: treat diarrhea caused by excess fecal bile acid
• Side Effects: bloating, flatulence, constipation (may bind other drugs)

• Antidiarrheal Agent
• Analog of somatostatin; inhibits hormone/NT secretion
• -decrease fluid secretion
• -slows motility
• -inhibit gallbladder contraction
• Use: Inhibition of endocrine tumor effects, treat other causes of diarrhea (hyperactive hormone/enzyme diarrhea)
• Side Effects: fat-soluble vitamin deficiency (impaired pancreatic secretion), gallstones, hyper or hypoglycemia, hypothyroidism, bradycardia

"Octopus in the tide says Don't go there!"

• Anticholinergics
• Inhibit muscarinic receptors in enteric plexus/smooth muscle
• Use: antispasmodics used to treat IBS
• Side Effects: "red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare" anticholinergic effects (high doses)

• Serotonin 5HT3 Receptor Antagonist
• Use: Inhibits nausea, bloating, and pain associated with IBS- specifically women with diarrhea predominant IBS
• Blockade terminals of enteric cholinergic neurons inhibits colonic motility
• Long duration
• Side Effects: GI toxicity (constipation, ischemic colitis)

• granisetron, dolasetron, palonosetron
• Antiemetics
• Serotonin 5HT3 Receptor antagonists
• Palonesetron has long half life (40hrs)
• Use: Treat chemotherapy induced, postoperative, and postradiation N/V
• Side Effects: Well tolerated, HA, dizzy, constipation, prolongation of QT interval (esp dolasetron)

• Antiemetic Agent
• Neurokinin Receptor Antagonist (Substance P antagonist)
• Crosses BBB to occupy NK1 Receptor in postrema (vomiting center)
• Use: in combination with 5HT3 receptor antagonists + dexamethasone to prevent acute and delayed N/V from chemotherapy
• Side Effects: fatigue, dizzy, diarrhea
• CYP3A4 metobolism (may inhibit other drugs in this metabolism pathway)

• Antiemetic
• Dopamine (2) receptor antagonist (in CNS)
• Also used as a prokinetic agent (enhances motility)
• Side Effects: extrapyramidal effects

• Promethazine, Thiethylperazine, Droperidol
• Antipsychotic agents used as antiemetics
• Inhibit dopamine, muscarinic receptors
• antihistamine activity
• Side Effects: extrapyramidal effects, hypotension, (droperidol = prolonged QT)

• Dimenhydrinate, meclizine
• Antihistamine used for prevention/treatment of motion sickness
• Side Effects: dizzy, sedation, confusion, dry mouth, cycloplegia (paralysis of ciliary eye muscle), urinary retention (all effects less so in meclizine)

• Anticholinergic used as antiemetic
• Muscarinic receptor antagonist
• use: prevent motion sickness
• Side Effects: red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare
• Transdermal patch is better tolerated

• Diazepam
• Benzos used as antiemetics prior to chemotherapy to decrease anxiety induced vomiting
• (Reminder: benzos increase opening frequency of chloride channel at GABA receptor, increasing potency of GABA)

• Nabilone
• Cannabinoids, THC
• MOA is uknown, used as appetite stimulant and antiemetic
• Side Effects: euphoria, dysphoria, sedation, hallucination, dry mouth, munchies, autonomic effects, tachycardia, orthostatic hypotension

• Sulfasalazine, balsalazine, olsalazine
• Modulate inflammatory mediators from COX/LOX pathways
• Act topically on GI mucosa to treat IBD (UC and Crohn's)
• Side Effects: dose related, caused by the metabolite Sulfapyridine = HA, nausea, arthralgias, myalgias, bone marrow suppression, malaise, impaired folate absorption, hypersensitivity (fever, hepatitis, rash, hymolytic anemia)
• Take folate supplements

• Modulate inflammatory mediators from COX/LOX pathways
• Act topically to treat GI mucosa in IBD (UC & Crohn's)
• Mesalamine
• Pentasa (time release)
• Rowasa (enema)
• Canasa (suppository)

• Prednisolone, Hydrocortisone, Budesonide
• Glucocorticoids
• Treat moderate to severe IBD (UC & Crohn's)

• Azathioprine, 6-mercaptopurine
• Immunosuppressive
• Use: induction/maintenance of remission of UC & Chrohn's
• Side Effects: N/V, bone marrow depression (due to low thiopurine-S-methyltransferase [TPMT] causing excess metabolites), hepatic tox

• dihydrofolate reductase inhibitor
• Use: treat Crohn's disease
• Side Effects: bone marrow suppression at high doses
• Take folate supplements

• IBD Drug
• chimeric anti-TNF monoclonal antibody
• Use: treat moderate to severe Crohn's & UC
• Side Effects: Infection (immunosuppressive), reactivation of TB, hepatic failure

• Pancreatin = essence of hog pancreas... really
• Pancrelipase = mixture of amylase, lipase, peptidase
• -rapidly inactivated by gastric acid, take with PPI
• Use: Treat exocrine pancreatic insufficiency

• Bile Acid therapy for Gallstones
• Dissolves them, alternative to surgery only if there's no blockage and only if they're cholesterol based
• the only FDA approved drug for primary biliary cirrhosis

• Chemoreceptor trigger zone: Neurokinin 1, D2, 5HT3
• Vomiting Center: H1 and Ach
• Vestibular Apparatus: H1 and Ach
• Vagus nerve and GI tract: 5HT3
• (I like knowing this b/c it helps me remember why which types of drugs work best in certain cases of nausea)

• Ulcer: licorice, ginger
• Constipation: flaxseed, psyllium, rhubarb
• Diarrhea: pomegranate, apple, blueberry, tea
• IBD: Tea, onion skin, peppermint