GI 1 & 2 Pharm Notes PDF

GI 1 Gastric Rugae Folds Internal coiled sections of tissue in mucosal and submucosal layers of the stomach, where glands are Provide elasticity for stomach expansion via mechanoreceptors responding to increased pressure when bolus enters until we feel full Provides the stomach with increased surfac...

GI 1 Gastric Rugae Folds Internal coiled sections of tissue in mucosal and submucosal layers of the stomach, where glands are Provide elasticity for stomach expansion via mechanoreceptors responding to increased pressure when bolus enters until we feel full Provides the stomach with increased surface area for nutrient absorption (10-20%) Stomach glands have "dips" which are covered by an epithelium with different types of cells that each gives the stomach different functions Stomach lining has gastric glands An adequate environment must be created to digest food with acidity, but that does not irritate our stomach lining. Certain substrates in pre-epithelial liquid layer protect the lining. Pepsin (protein degradation), prostaglandins (protects epithelial), HCL (breaks down food) Stomach divides into corpus (body) and antrum (pylor) Gastric Pits are also called foveolous Isthmus = progenitor zone Neck Base A. Oxyntic / Corpus glands: Pit = surface mucous cells Isthmus = progenitor zone Neck = mucous neck cells, parietal cells, enterochromaffin-like (ECL), enterochromaffin cells (EC), D cell Base = chief cells B. Pyloric glands: Pit (very long pit)= surface mucous cells, mucous neck cells, G cells Progenitor zone Base = deep mucous, G cells, D cells, enterochromaffin (EC), ECL Mucous cells Foveolar, have microvilli Mucous producing cells which covers inside of stomach Protects from corrosive nature of gastric acid Lines gastric mucosa Found in necks of gastric pits and surface Large nucleus, endoplasmic ret for protein formation, many goblet cells with microvilli (where mucous is expelled) Parietal cell Acid secretion Responsible for gastric acid secretion, HCL Aids in digestion of food, absorption of minerals, control of harmful bacteria Ach (directly from vagus), Histamine (from ECL), Gastrin (from food presence) enter through one side of the cell to activate it. H2O + CO2 rx catalyzed by carbonic anhydrase forms carbonic acid, which dissociates into bicarbonate and H. H stays inside the cell, towards H/K ATPase pump. Bicarbonate leaves the cell into bloodstream so Cl can enter and travel to lumen. Proton pump on other side of cell permits H passage into lumen. Proton pump is on apical side, so HCl ends up un lumen (antacids work inside lumen to neutralize HCl) H2, G and Ach receptors are on basal side. Enterochromaffin-like cells / ECL Neuroendocrine cell found in gastric mucosa beneath epithelium, close to parietals. Aids (indirectly) in production of gastric acid by releasing histamine. Receives stimulus by: G cells : by secreting gastrin Vagus nerve : Gastrin-release peptide (to stimulate G cells to secrete gastrin) and PACAP (pituitary adenyl cyclase activating polypeptide) Chief cell Synthesis and production of pepsin Zymogenic, peptic cells Release pepsinogen and chymosin Pepsinogen is activated when in contact with HCL from parietals, and turns into pepsin (digestive enzyme) Breaks down proteins G cells Neuroendocrine cells responsible for synthesis and secretion of gastrin Mainly found in pyloric antrum Present in duodenum and pancreas Secrete gastrin when stimulated directly by direct vagus efferent neuron and GRP Food content also stimulates gastrin secretion Stimulates parietals to produce HCL Increases GI motility When we eat, gastrin stimulates by food presence. If gastrin levels are high, lab tests must be done FASTING. Delta cells Dispersed throughout the whole GI tract Produce somatostatin = GhIh growth hormone inhibiting hormone Activated by HCl, when excess H is in lumen Produced in many locations: GI, pancreas, hypothalamus Inhibiting effects on acid production in the stomach, motor activity of intestines and digestive enzymes release from pancreas Controls secretions, it's a modulator Enterochromaffin cells (EC) Neurogenic cells dispersed throughout the stomach Contain secretory granules that release serotonin, a key/main neurotransmitter of the stomach Released by many stimuli, mostly mucosal stroking (mechanical) Serotonin stimulates enteric nerves (myenteric plexus) to initiate secretion and propulsive motility (peristalsis) Rapidly destructed in the blood and liver Serotonin helps the glands produce secretions in submucosal plexus Stimuli comes from our normal flora, activates afferent cells to cause GI motility Nutrients go into circulation, serotonin helps metabolize some glucose and lipids Gastric mucosal barrier Thick, alkaline mucous secretion of mucosal cells in pyloric region Protects stomach and duodenum epithelium from harsh acid conditions Stimulated by mechanical and chemical irritation and parasympathetic innervation If gastrin excess happens, mucosal layers sense the excess of acids and wants to protect the lining In turn, produces an increase of mucous production from pyloric area to protect the rest of the stomach Susceptible to bacterial and viral infections, drugs, aspirin Every time we eat spoiled fool (milk, bread, cheese, mayo), the mucosal area gets disrupted by bacteria, it cant protect the stomach, so we get the symptoms (diarrhea, pain, etc). Mayo can cause gastroenteritis (board question). The purpose of all these cells is to produce good secretion to optimize food content degradation in our bodies/stomach. Somatostatin and Prostaglandin E2 decrease gastric acid production Gastrin and Ach increase intracellular Ca levels Conditions: 1. Gastroesophageal Reflux Disease (GERD) Backflow of stomach acid into esophagus Normally the LES relaxes to allow food and liquid into stomach, then it closes again If sphincter does not relax (stiff or flaccid) as it should or it weakens, stomach acid can flow back into esophagus Esophagus is not equipped to handle stomach acid, it will scar and heartburn. Usual symptom is heart burn, an uncomfortable burning sensation It is behind the sternum, MI often mistaken for GERD Older pt with acidity and stomach/epigastric pain = order EKG, Must rule out an infarct (MI) Young pt with same symptoms are most likely to have GERD Severe symptoms: dysphagia (difficulty swallowing) and chest pain Reflux can cause sore throat Complications: esophageal erosions, esophageal ulcers, narrowing of esophagus (stricture) Barrett's esophagus - happens in 10% of pts. Normal esophageal epithelium (SS) is replaced by abnormal stomach epithelium (glandular). Linked to cancer (adenocarcinoma), must be monitored Risk factors/ precipitants/ things that worsen it: Fatty food, alcohol, caffeine, smoking, obesity, pregnancy, sauces Chronic relapsing Once you get GERD, most likely its chronic. If diet is altered, might not need meds 2. Peptic Ulcer disease (PUD) Disruption of mucosa and submucosa Benign: normal gastric acid production, weak mucosal barrier Malignant: excessive gastric acid secretion, overwhelms mucosal barrier. Cause: 95% is H. pylori bacteria (biopsy to check) or NSAIDs (aspirin, arthritis meds). 5% is benign pancreatic tumor secretions or idiopathic Things that increase acidity = things that cause ulcers Tx for heartburn, GERD and PUD: Antacids, H2 receptor blockers, mucosal protective agents, PPI, anti-cholinergics, prostaglandin analogs, anti-microbial agents Antacids Mostly calcium based Systemically its sodium bicarbonate. Go into circulation and create alkalosis. Not for long term use, are last-line therapy option Non systemic: not absorbed into systemic circulation, does not produce alkalosis. May give diarrhea. Can affect kidney functions over time. Weak bases that react with gastric acid to form water and salt, diminishes acidity Symptomatic relief of PUD and GERD Reduces pepsin activity, which needs acidic environment to activate Maalox and Mylanta: Aluminum hydroxide + Magnesium hydroxide Tums: Calcium carbonate. Magnesium may cause diarrhea Calcium and Aluminum may cause constipation Do NOT use in impaired renal function pt Good for rheumatoid pts who need to use NSAIDs ANC = antacid neutralizing capacity 1N HCL = 36.5g HCl/liter meq (milliequivalent) 1N HCl (1 meq/dose) brings pH up to 3.5 by antacid in 15 mins FDA required minimum of 5 meq treated per dose ANC increases, neutralizing capacity increases Maalox = 28 Mylanta = 23 Tums = 15 Histamine H2 receptor blockers Inhibit secretion of gastric acid (HCl) though reversible, competitive inhibition of Histamine receptors at parietal cells ECL release histamine and parietals have the histamine receptors They block ECL and parietal receptors. Prevention and Tx of: GERD, PUD, esophagitis, GI bleeding, stress ulcers, Zollinger-Ellison Syndrome Zollinger-Ellison syndrome: gastrinoma in pancreas or duodenum causing hypersecreting of gastric acid, ulcers, diarrhea, heartburn. PM/HS administration Good for nocturnal acid secretion Decrease dose in renal or hepatic impaired pt Cimetidine (tagamet), Ranitidine (Zantac), Famotidine (pepcid) (best choice), Nizatidine (axid) (100% bioavailability) Very few SE. Expect Cimetidine, inhibits estrogen metabolism (P450) Suppresses gastric secretion by 70% during 24 hrs Ranitidine (Zantac) was removed by FDA due to potentially causing cancer PPI has given these meds a decreased use Proton Pump inhibitors (PPI) Strong inhibitors of gastric acid secretion through irreversible inhibition of proton pump (H/K ATPase) Prevents pumping / release of gastric acid during 24 hrs Towards apical side Preferred drug, take while fasting Pro-drugs with acid resistant enteric coating Tx for: GERD, PUD, gastritis and Zollinger-Ellison Faster relief and healing than H2 blockers Decreases acid secretion by 95% during 48 hrs 4-8 week tx course Omeprazole (prilosec), Pantoprazole (protonix), Lansoprazole (prevacid), Esomeprazole (nexium), Rabeprazole (aciphex) In combo with sodium bicarbonate gives faster absorption In combo with antimicrobials, eradicate H pylori Metabolites excreted in urine and feces SE: nausea, diarrhea, HA, GI disturbance, bone fracture (long term use) Misoprostol Also called Cytotec Synthetic prostaglandin E1 analog Stimulates prostaglandin E1 receptors on parietal cells in stomach to reduce gastric acid secretion Stimulates mucosal cells so mucous and bicarbonate secretion increased Thickens mucosal bilayer so mucosa can generate new cells Tx for: NSAID induced ulcers SE: diarrhea, pain, cramps (30%), uterine contractions Do NOT use in women in childbearing years, unless on reliable BC Can cause birth defects and premature birth. Not used much due to SE. Left for pt that need something else in addition to PPI or an H2 Pirenzepine Anticholinergic Muscarinic M1 Ach receptor antagonist/ blocker Blocks gastric acid secretion Reduces gastric motility Same effective as H2 blockers Rarely used, more as adjunct therapy SE: anorexia, blurry vision (dilates), constipation, dry mouth, sedation (all symptoms of sympathetic) Acid reducing tx: Antacids (neutralizes HCl), H2 blocker, PPI, Anticholinergic, Prostaglandin Mucosal Protective agents Cytoprotective compounds Enhance mucosal protection, reduce inflammation, heal ulcers A. Sucralfate (Carafate) Prevention and tx for PUD Most used (liquid form) Required acid pH to be activated Forms sticky polymer in acidic environment, adheres to ulcer to form a barrier and reduce discomfort 2 hrs before or after drugs Take on empty stomach, before meals Do NOT use with PPI, H2 blockers or antacids Does NOT heal B. Chelated Bismuth Pepto-bismol, Kaopectate Protects ulcer crater, allows healing Some activity against H. pylori Do NOT use repeatedly, or for more than 2 months Creates basic pH SE: black stool, constipation H pylori Passed from person to person through direct contact with saliva, vomit, or stool May also spread through contaminated food or water, unwashed utensils Are gram neg (-) bacteria able to attach to epithelial cells of stomach and duodenum, preventing from being washed out of system Once attach, they damage the cells by secreting degradative enzymes, toxins, and initiating a self-destructive immune response 85% of PUD is caused by H pylori Non-self pathogen that decreases mucosal production by increasing acidity, irritating the area. It also decreases the absorption of drugs. Urea test - a marker to check if H. pylori is completely irradiated after 2 weeks of treatment. Must be completely fasted. H pylori tx: Antibiotic Ulcer therapy (For PUD caused by H pylori) combinations of: Bismuth - disrupts bacterial cell wall Clarithromycin - inhibits protein synthesis Amoxicillin - disrupts cell wall Tetracycline - inhibits protein synthesis (least used, interfered when food is present) Metronidazole - used in case of bacterial resistance to amoxicillin or tetracycline, or intolerance Triple therapy: 80-85% effective, 14 days tx PPI + amoxicillin or tetracycline + metronidazole or clarithromycin Quadruple therapy: same effectivity, 10 days tx Add Bismuth to triple therapy Bismuth does NOT neutralize stomach acid, they inhibit pepsin and increase mucous secretion. For whichever therapy, wait 2 weeks before testing again. GI 2 Inflammatory Bowel Disease (IBD) Ulcerative colitis: Diffused mucosal and submucosal inflammation limited to colon Continuous, uniform inflammation Bloody diarrhea, colicky acute pain, urgency, tenesmus (desire to evacuate even with empty bowels, nerve ending inflammation) Crohn's disease: Patchy transmural inflammation May affect any part of the GI with ulcers Abdominal pain, diarrhea, weight loss, intestinal obstruction Harder to tx Tx: resolve acute episodes and prolong remission Exacerbations are inevitable. Therapeutics to reduce inflammation Aminosalicylates - for mild symptoms Corticosteroids - for moderate symptoms Thiopurines - for active and chronic symptoms Methotrexate - for active and chronic symptoms Cyclosporin - for active and chronic symptoms refractory to corticosteroids (significant SE) Infliximab - antibody infusion Aminosalicylate Aspirin derivative in combination with another med Called 5-amino salicylic acid (5-ASA) Sulfasalazine: 5-ASA + sulphapyridine as carrier) Mesalamine Balsalazide: pro-drug. Given in a lower dose. Changes into active ingredient. More bioavailability than first 2 Olsalazine: dimer cleaves in colon to release active ingredient Oral or rectal preparation Used for maintaining remission, active disease, to reduce colorectal cancer risk SE: nausea, HA, epigastric pain, diarrhea, hypersensitivity, pancreatitis, blood disorders, lung disorders, myo/pericarditis Caution in renal impaired, pregnant, or breastfeeding pt Do NOT take if allergic to aspirin NSAIDs inhibit prostaglandins which cause vasodilation. So it vasoconstricts, which makes kidneys not able to function. Elevates bp. Corticosteroids Anti-inflammatory agent for moderate to severe relapses Inhibit inflammatory pathways: decrease IL transcription, suppresses arachidonic acid metabolism, lymphocyte apoptosis Expresses anti-inflammatory proteins They get into the inflamed cell, links to a receptor that transports them to the nucleus. In nucleus, they activate another receptor called GRE. GRE can do: Trans - repression: inhibition of trans-activation, gives anti-inflammatory response. Decreases interleukins. Cis-repression : Inhibition of trans activation. Steroids cause side effects Trans-activation: of anti-inflammatory components/proteins which produce inflammatory response. Decreases interleukins (a cytokine - inflammatory mediator) overexpressed in inflammation. Arachidonic acid decreased. Inhibition of phospholipase 2 Lymphocyte apoptosis - proteins that go into surface antigen of lymphocytes (inflammatory cells) to destroy them IV administration of their derivatives can also be given SE: acne, moon face, sleep or mood disturbance, dyspepsia, glucose intolerance, cataracts, increases IOP, osteoporosis, myopathy Ej. Prednisone (oral), Hydrocortisone (topical) Thiopurines Purine derivatives, antimetabolites immunosuppressants Deactivate key processes in T lymphocytes that lead to inflammation Good for long term maintenance, NOT for acute attacks Attacks DNA formation of inflammatory cells. Also of other cells (disadvantage) MOA - inhibit ribonucleotide synthesis, inducing T cell apoptosis by modulating cell signaling Ej. Azathioprine, Mercaptopurine (Active metabolites) Azathioprine is metabolized to mercaptopurine and 6-thioguanine nucleotides Used for active and chronic disease, steroid sparing SE: leucopoenia, monitor for signs of infection, sore throat, flu like symptoms after 2-3 weeks, liver and pancreas toxicity Methotrexate Inhibits dihydrofolate reductase Inhibits T cell proliferation and cytokine and eicosanoid synthesis (PG, LT) Use for relapsed or active crohn;s disease refractory or intolerance to ASA or thiopurine SE: GI disturbance, hepatotoxicity, pneumonitis Inhibits event of folic acid. Conversion of folate to tetrahydrofolate is blocked. Reduces amount of inflammatory cells, decreased inflammation Oral Reduces intermediary metabolism of folic acid to reduce amount of nitrogenous base that forms DNA of inflammatory cells. Must be given with B9 which is folic acid, daily. Cyclosporin Inhibition of cytokine production, involved in T cell activation of IL2 transcription IL-2 transcription inhibition. Nuclear factor of activated T cells (NFAT) proteins are a family of transcription factors whose activation is controlled by calcineurin, a calcium-dependent phosphatase Inside the cell, changes occur in nuclear factor of deactivated cells/proteins (de-phosphorylates it). Calcineurin inhibition (a phosphatase). Use for active and chronic disease, steroid sparing, bridging therapy SE: tremor, paranesthesia (numb sensation), malaise, HA, abnormal LFT; gingival hyperplasia, hirsutism, renal impairment, infections, neurotoxicity Monitor bp and renal function. CMP regularly. Used in ocular form: Dry eye tx Infliximab Anti TNF-a A potent paracrine and endocrine mediator of inflammatory and immune functions Monoclonal antibody that attacks tumor necrosis factor alpha (cytokine that causes signaling of inflammation from cell to cell) Potent anti-inflammatory effects Use for fistulizing Crohn's pt ( from one area of the colon to another, or from colon to urethra, etc. Defecating material in the urine) , severe active chronic disease refractory, intolerance of steroids or immunosuppression Done by IV infusion SE: infusion reaction, sepsis, reactivation of TB Monoclonal antibodies - Biological agents, multiple availability to treat diverse diseases. Not too specific, pretty general, leading to diverse SE +PPD pt (purified protein derivative to check tuberculosis) should NOT use these. Constipation Treated effectively with dietary modification If this fails, then use laxatives #1 cause of constipation is laxative abuse One of the most common type of GI disorder Modification of diet can treat it. High fiber, lots of fluid Todays lifestyle eating out creates it more of a problem Pt tend to auto-medicate themselves Tx: Bulking agents - fibers increases stool bulk Osmotic laxatives - increases fluid content of stool Stimulant drugs - increase peristalsis Stool softeners - lubricate stool Bulk agents Increase bowel content and volume, triggering stretch receptors of intestinal wall. Expands colon by volume increase. Stretch receptor stimulation causes reflex contraction (peristalsis) that propels bowel content forward Soluble, insoluble, non absorbable, non digestible Must be taken with LOTS of water, or constipation will worsen due to calcium accumulation Bran, fiber Metamucil - psyllium based Methylcellulose - synthetic fibers (Citrucel) Calcium polycarbophil - complex, non-absorbable starch (Fibercon) Does not work immediately, must use for several days, then stop to see how it responds. If nothing happens, start a new cycle all over again. Salts and Osmotic Laxative Effective in 1-3 hours Used to purge intestine (sx, poisoning) Fluid drawn into bowel by osmotic force, increasing volume and triggering peristalsis magnesium citrate, magnesium hydroxide, and sodium phosphate are nonabsorbable salts (anions and cations) that hold water in the intestine by osmosis. Nondigestible sugars and alcohol : Lactulose - broken down by bacteria into acetic and lactic acid, causing osmotic effect Can mix with milk of magnesia and mineral oil. Salts: Milk of magnesia, Epsom salt, glaubers salt, sodium phosphate (enema), sodium citrate (enema) Polyethylene glycol PEG (Miralax) for procedures or otc. Also seen in car coolant. 1 time a day for 7 days. Stop. Wait 3 days to see how bowel movement is. If nothing helped, start cycle again. Fluid accumulation, soft stool defecation Magnesium should be taken daily Stool softener Emollients or surfactants Emulsify; prophylactic Lubricates and softens consistency of stool Activates peristalsis Docusate sodium - surfactant and stimulant Glycerin suppositories Stimulant/ irritant laxatives Increases intestinal motility Irritates GI mucosa, pulls water into lumen For severe constipation where a rapid effect is required (6-8 hours) Produces a bit of pain Senna - plant derivative Lubiprostone - PGE1 derivative that stimulates Cl channels, producing Cl rich secretions (mucosal hydration, watery stool due to increasing fluid secretion in intestine) Bisacodyl - suppositories or enteric coating tablets Laxative abuse or dependence Most common cause of constipation Becomes vicious cycle Longer time needed to fill colon is misinterpreted as constipation, resulting in repeated use Enteral loss of water and salts causes release of aldosterone. Stimulates intestinal reabsorption, but increases renal secretion of K. Double loss of K causes hypokalemia, reducing peristalsis (bowel inertia). Misinterpreted as constipation, resulting in repeated use Diarrhea Caused by toxins, antibiotic associated colitis, microorganisms (E coli, salmonella, shigella, campylobacter, clostridium difficile Increased GI motility and decreased absorption of fluid Tx: more than 2-3 days, chronic inflammatory disease, severe diarrhea in elderly or children, when specific cause is determined Treat generally if cause is unknown Anti-diarrheal agents Anti-motility, stops peristalsis Reduce peristalsis by stimulating opioid receptors of the bowels (morphine, codeine) Allows more time for water to be absorbed Do NOT use if caused by toxic material, microorganisms, AAD (toxic colitis/ megacolon) A. Diphenoxylate / Atropine Anti-motility agents Centrally active opioid drugs Used in combo with atropine Dipheno Slows intestinal contractions and Atropine prevents drugs abuse Schedule V, Rx SE: drowsy, dizziness, abd cramps B. Loperamide Binds to opiate receptor in intestinal wall Reduces peristalsis by Inhibit Ach release, and increases intestinal transit time Increases tone of anal sphincter, reducing incontinence and urgency Poor CNS penetration Schedule V (no potential for abuse), OTC Clostridium Difficile Spore forming, gram + anaerobic bacili that produces 2 exotoxins: Toxin A and Toxin B Part of our rectal system microbiotics. It proliferates if flora imbalance is provoked by antibiotic use. Major cause of AAD and colitis (20%) Distal aspect of colon Steps to infection: alteration of normal fecal flora > colonic colonization of the bacteria > growth and toxin production > infection leads to colitis formation and toxic megacolon Tx: discontinue offending antibiotic, Metronidazole (tx h pylori, do not use if liver or renal impaired), Vancomycin (do not use if renal impaired) Anti-flatulence drugs Used to relieve painful symptoms associated with gas Simethicone (detergent) Alters elasticity of mucous coated bubbles, causing them to rupture and release the gas causing pressure on our abdominal wall. Large bubbles turn into smaller bubbles, less gas, less pain. Adsorbents: Aluminum hydroxide and Methylcellulose control diarrhea by adsorbing intestinal toxins or microorganisms. Also provide coating. Bismuth: decrease fluid secretion. NOT neutralize stomach acid, they inhibit pepsin and increase mucous secretion. Disrupts cell wall. Emesis Vomiting Can be provoked by seeing something repulsive, ingesting a toxin or motion sickness Two brainstem sites have key roles in the vomiting reflex pathway. The chemoreceptor trigger zone is located in the area postrema It is out-side the blood-brain barrier, thus, it can respond directly to chemical stimuli in the blood or cerebrospinal fluid. Area postrema = chemoreceptor trigger zone (CTZ). Located on dorsal surface of medulla oblongata Stimulated directly or indirectly via: stomach/ GI tract, vestibular system, sensory cortex/thalamus Antiemetics A. Scopolamine M1 receptor antagonist / blocker Anti cholinergic Vestibular affection: motion sickness, BPPV SE: dry mouth, dizziness, restlessness, dilated pupils, allergic reaction (sympathetic symptoms) Contraindications/ do NOT use: kidney or liver disease, enlarged prostate, difficulty urinating (bladder problems), heart disease, glaucoma B. Phenothiazine Promethazine (Phenergan), Prochlorperazine (Compazine) Dopamine D2 receptor blocker, Neuroleptics = typical antipsychotics SE: blurred vision, dry mouth, dizziness, restlessness, seizures, hypotension, extrapyramidal effect (long term tx) of tardive dyskinesia (uncontrolled movement) Contraindications: Glaucoma, livre disease, prostate or bladder problems Act directly in CTZ C. Meclizine First-gen antihistamine (non selective H1 blocker) Central anti cholinergic actions BPPV (go to vestibular apparatus) D. Metoclopramide Antiemetic action due to its antagonist activity of D2 receptors in CTZ of CNS SE: extrapyramidal effects Contraindications: Parkinsons Substituted benzamide E. Ondansetron (Zofran), Granisetron Serotonin 5-HT3 receptor antagonist/ blocker NOT for BPPV Long duration of action Excellent for chemotherapy induced nausea and vomiting SE: very few, usually well tolerated. HA and constipation. Trigger the CTZ IV or oral Work better in low doses if following a good nutritional plan Absorption in stomach as well CTZ: Chemo/serotonin drugs (Ondansetron, Graniseton), Dopamine antagonists (Phenothiazine, Metoclopramide) Vestibular: Scopolamine, Antihistamines (Meclizine)