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61 Cards in this Set
- Front
- Back
Ach regulation path for gastric acid secretion
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M3 receptor - PLC - Ca2+ influx - PKC
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Gastrin Regulation of gastric acid secretion
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G cells gastrin receptor PLC Ca2+ PKC
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Histamin Regulation of gastric acid secretion
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ECL cells H2 receptor adenylate cyclase cAMP PKA
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Histamin comes from what cell?
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ECL - activated at night - not post prandial
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Na bicarbonate, Ca carbonate,
Mg hydroxide, Al hydroxide |
antacids
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Cimetidine, ranitidine, famotidine, nizatidine
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H2 antagonists
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Omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole
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proton pump inhibitors
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Sucralfate Misoprostol (Prostaglandin Analogs) Bismuth subsalicylate
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Mucosal Protective Agents
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Antacids MOA, Clinical Uses
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dec intragastric acidity by reacting with gastric HCl to form a salt and water -
Dyspepsia, acid-peptic disorders |
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Antacids Side effects
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Belching & metabolic alkalosis (CO2)
Diarrhea (Mg) or constipation (Al) Fluid retention (Na bicarbonate produces NaCl) Hypercalcemia (milk-alkali syndrome) dec absorption of other medicines |
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H2-Recptor Antagonists MOA, clinical uses
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Competitive inhibition at the parietal cell H2 receptor
Effective at inhibiting nocturnal acid secretion (stimu. by histamine), but have a modest impact on meal-stimulated acid secretion (stimu. by gastrin, Ach, and histamine) GERD (longer duration than antacids), peptic ulcer disease (replaced by PPI), prevention of bleeding from stress-related gastritis |
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H-2 Receptor Antagonist Side Effects and Drug Interactions
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Safe (<3%: diarrhea, headache, fatigue, constipation) Cross placenta and secret in breast milk
Block cardiac H2 receptor (rapid IV- radycardia/hypotension) CNS (confusion, hallucination, agitation) Cimetidine- only Gynecomastia, impotence, galactorrhea Drug interactions Cimetidine & ranitidine inhibit p450 drug metabolism Inhibit gastric first-pass metabolism of alcohol, esp in women (except for famotidine) |
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Most potent H-2 R antagonist
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Femotidine = 20-50x compared to cimetidine
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PPI MOA
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Administered as inactive prodrugs Enteric-coated for delayed release (acid-labile)
MOA: Prodrugs are protonated & concentrated in parietal cell canaliculus; converted to the active thiophilic sulfonamide cations, which inactivate H+/K+ ATPase irreversibly Inhibit both fasting and meal-stimulated acid secretion |
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Clinical Uses for PPI
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GERD (most effective) Peptic ulcer disease H. pylori: ‘triple therapy’ (w/ larithromycin & amoxicillin or metronidazole) Prevention of stress-related mucosal bleeding Gastrinoma & other hypersecretory cond’ns
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PPI Side Effects and interactions
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Safe (1-5% diarrhea, headache, abdominal pain)
dec oral Vit B12 absorption Respiratory and enteric infections (gastric acid prevents colonization and infection of the GI) Increases serum gastrin (feedback mechanism) Drug interactions: All PPI are metabolized by hepatic p450 cytochromes Altered intragastric acidity affect other drug bioavailability |
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Sucralfate MOA, Clinical Use, SE
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(negatively charged)
A salt of sucrose complexed with sulfated Al hydroxide MOA: Forms a viscous paste that selectively binds to ulcers or erosions Clinical uses dec GI bleeding Side effects No systemic adverse effect (not absorbed) Constipation (<2%; due to aluminum salt) May bind to other medications |
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Misoprostol MOA, Clinical Use, SE
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(PGE1 analog) Short half-life (tid or qd)
MOA Noncompetitive inhibition of histamine- mediated cAMP production in parietal cells Clinical uses NSAID-induced peptic ulcer Side effects Diarrhea, cramping abdominal pain (10-20%) Stimulate uterine contractions (abortifacient) |
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Bismuth subsalicylate
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OTC (Pepto-Bismol)
MOA Bismuth coats ulcer and erosions Salicylate inhibits intestinal prostaglandin & Cl secretion Clinical uses Dyspepsia, acute diarrhea Side effects Safe Black stool (bismuth), dark tongue (liq. formulations) Salicylate toxicity: nausea, vomiting, sweating, rapid breathing, ringing in the ears, and fever |
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Bethanechol MOA
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Increase GI Motility
Stimulate M3 receptors on muscle cells & myenteric plexus synapses Long duration (resistant to cetylcholinesterase) |
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Neostigmine MOA, Clinical, SE
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Increase GI Motility
Acetylcholinesterase inhibitor Enhances gastric, intestinal & colonic emptying Useful in acute colonic pseudo-obstruction (aka Ogilvie syndrome) Side effects: cholinergic effects (salivation, nausea,vomiting, diarrhea, bradycardia) = give with atropine |
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Metoclopramide & Domperidone MOA
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Stimulate GI Motility
Block the activation of dopamine receptor (activation of dopamine receptors in GI inhibits cholinergic smooth muscle stimulation) Anti-nausea/anti-emetic (act on D2 receptors in medulla) |
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Metoclopramide & Domperidone Clinical uses and SE
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Clinical uses
GERD, impaired gastric emptying, nonulcer dyspepsia, prevention of vomiting, Side effects Galactorrhea, gynecomastia, impotence (increases prolactin) Metoclopramide:CNS syndromes (restlessness, drowsiness, insomnia, anxiety, agitation) Extrapyramidal effects (dystonia, parkinsonian) AVOID LT Use **Domperidone does not cross BBB** |
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Erythromycin MOA, Clinical use
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Stimulates GI Motility
Stimulate motilin receptors on GI smooth muscle Used in p’ts with acute upper GI hemorrhage to promote gastric emptying of blood prior to endoscopy |
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Lubiprostone MOA, Clinical use, SE
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(PGE1 derivative)
increase secretion of chloride-rich fluid which promotes bowel movement Treat idiopathic chronic constipation Side effects: nausea (30%), diarrhea, headache |
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Psyllium, methylcellulose MOA, Clinical Use, SE
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Bulk-forming laxatives
Natural Plant Products Indigestible, hydrophilic colloid that absorb water,forming a bulky gel that promotes peristalsis Side effects: bloating, flatus |
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Polycarbophil
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Bulk-forming laxatives
Synthetic Product Indigestible, hydrophilic colloid that absorb water,forming a bulky gel that promotes peristalsis Side effects: bloating, flatus |
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Docusate, Glycerin suppository, Mineral oil - Use, MOA
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Stool surfactant agents (softeners)
Soften fecal material, permitting water/lipids to penetrate |
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MgO, sorbitol, lactulose, Mg-Citrate, Na phosphate - MOA, Use, SE
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Osmotic Laxatives
Nonabsorbable Sugars or Salts Increase Stool Liquidity Used for the treatment of acute constipation or the prevention of chronic constipation Side effects MgO: hypermagnesemia Electrolyte fluctuation (avoid use in p’ts with renal failure or cardiac diseases) Sorbitol, lactulose: bloating, flatus |
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Balanced Polyethylene Glycol
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Osmotic Laxatives
Increase Stool Liquidity Contain an inert, nonabsorbable, osmotically active sugar (PEG), with Na2SO4, NaCl, NaHCO3, and KCl Used for complete colonic cleansing prior to GI endoscopy (no electrolyte fluctuation, no bloating) |
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Aloe, senna, cascara: drug class, clinical use, SE
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Anthraquinone derivatives
Stimulant Laxatives (Cathartics) MOA Induce bowel movement Stimulate enteric nervous system & colonic electrolyte & fluid secretion Poorly absorbed; hydrolyzed in colon, producing bowel movement Chronic use leads to a characteristic brown pigmentation of the colon (melanosis coli) |
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Castor oil drug class, clinical use, SE
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Stimulant Laxatives (Cathartics)
MOA Induce bowel movement Stimulate enteric nervous system & colonic electrolyte & fluid secretion A potent stimulant laxative (acts in 2-6 hrs) Hydrolyzed in the upper intestine to ricinoleic acid, a local irritant that stimulate intestinal motility |
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Tegaserod
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partial serotonin 5-HT4 receptor agonist = promotes the parastaltic reflex
Low bioavailability (taken before meals) Avoid in p’ts with severe hepatic or renal impairment Used in chronic constipation Does not cross BBB (no effect on central serotonin R) Safe (9% diarrhea) |
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Loperamide
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Antidiarrheal
Opioid receptor agonists MOA Inc colonic phasic segmenting activity through inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses and lead to increased colonic transit time and fecal water absorption dec mass colonic movements and the gastrocolic reflex does not cross BBB; no analgesic/addiction |
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Diphenoxylate
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Antidiarrheal
Opioid receptor agonists MOA Inc colonic phasic segmenting activity through inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses and lead to increased colonic transit time and fecal water absorption dec mass colonic movements and the gastrocolic reflex dependence (high doses & long term use) Atropine is usually added to discourage overdosage |
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Kaolin & Pectin
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Antidiarrheal Agents
Kaolin: a naturally occurring hydrated Mg Al silicate Pectin: an indigestible carbohydrate from apples MOA: Absorbents of bacteria, toxins and fluid Used in acute diarrhea Not absorbed (no significant side effect except constipation) May bind other drugs |
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Cholestyramine, colestipol
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Antidiarrheal Agents
Bile salt-binding resins Used to treat diarrhea caused by excess fecal bile acid Side effects: bloating, flatulence, constipation May bind other drugs |
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Octreotide MOA, Clinical use
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Antidiarrheal Agents
analog of somatostatin Inhibits the secretion of hormones and transmitters decreases intestinal fluid secretion Slows GI motility and inhibits gallbladder contraction Clinical uses (poor GI absorption-SC administered) Inhibition of endocrine tumor effects Other causes of diarrhea (e.g., vagotomy, dumping syndrome) |
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Octreotide Side Effects
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Antidiarrheal Agents
analog of somatostatin Side effects fat-soluble Vit deficiency (impaired pancreatic secretion) gallstones hyperglycemia or hypoglycemia hypothyroidism bradycardia Somatostatin is an inhibitory hormone released from GI tract, pancreatic D cells, hypothalamus, and enteric nerves |
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Dicyclomine, hyoscyamine
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Tx IBS
Inhibit muscarinic cholinergic receptors (MR) in the enteric plexus and on smooth muscle Side effects: Anti-cholinergic effects (high doses) |
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Alosetron
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Serotonin 5-HT3-Receptor Antagonists
Tx IBS Inhibition of afferent GI 5-HT3-receptor (hence inhibits nausea, bloating, and pain) Blockade on the terminals of enteric cholinergic neurons inhibits colonic motility Long duration Used for women with diarrhea-predominant IBS’ Side effects: GI toxicity Constipation, ischemic colitis) |
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Drug induced emesis effects this area of the brain
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Chemoreceptor Trigger Zone using NK1 - signals the vomiting center in the lower medula
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Motion sickness induced emesis effects this area of the brain
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Vestibular apparatus
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Ondansetron, granisetron, dolasetron, palonosetron
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Serotonin 5-HT3 receptor antagonists
Antiemetics Palonosetron has a long half-life (40 hrs) No effect on dopamine or muscarinic receptors No effect on esophageal or gastric motility Clinical uses: Chemotherapy-induced nausea/vomiting Postoperative and postradiation nausea/vomiting Side effects: Well-tolerated Headache, dizziness, and constipation Prolongation of QT interval (esp dolasetron) |
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Aprepitant
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Neurokinin Receptor Antagonists
substance P antagonist Antiemetic Agent Mediated through central blockade in the area postrema Highly selective NK1 receptor antagonist that cross BBB and occupies brain NK1 receptor Used in combination with 5-HT3 receptor antagonists and dexamethasone for the prevention of acute and delayed nausea/vomiting from chemotherapeutic regimens Side effects: fatigue, dizziness, diarrhea Metabolized by CYP3A4 and may inhibit other drug metabolism by the CYP3A4 pathway |
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Prochlorperazine, promethazine, thiethylperazine
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Antipsychotic agents (antiemetic/sedative)
Inhibit dopamine & muscarinic receptors (antiemetic) Antihistamine activity (sedative) Side effects: Extrapyramidal effects & hypotension |
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Droperidol
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Antipsychotic agents (antiemetic/sedative)
Central dopaminergic blockade (antiemetic/sedative) Side effects: Extrapyramidal effects & hypotension Droperidol may prolong QT interval |
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Metoclopramide
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Dopamine Receptor antagonists
MOA: dopamine-receptor blockade Metoclopramide is used as an antiemetic & prokinetic Side effects: extrapyramidal effects |
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diphenhydramine, dimenhydrinate, meclizine
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Histamine H1 antagonists
Useful for the prevention/treatment of motion sickness Side effects: dizziness, sedation, confusion, dry mouth, cycloplegia, urinary retention Meclizine has less anticholinergic side effect than dimenhydrinate or diphenhydramine |
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hyoscine
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Anticholinergics
Muscarinic receptor antagonist Prevention of motion sickness Side effects: high anticholinergic effects (transdermal patches are better tolerated) |
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Lorazepam, diazepam
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Benzodiazepines
(anti-anxiety) Antiemetic Agents Bind to GABA receptor Used prior to chemotherapy to dec anxiety-induced vomiting |
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Dronabinol, nabilone
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Cannabinoids
Antiemetics The major psychoactive chemical (THC) in marijuana Used as an appetite stimulant and as an antiemetic (MOA?) Side effects: euphoria, dysphoria, sedation, hallucination, dry mouth, increased appetite, autonomic effects tachycardia, orthostatic hypotension |
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Sulfasalazine, balsalazine, olsalazine
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Aminosalicylates (5-ASA)
Azo compounds Used to Tx IBD (UC/Crohn's) Modulate inflammatory mediators derived from both COX and LOX pathways Act ‘topically’ on diseased GI mucosa Azo structures dec absorption of the parental drugs from the small intestine |
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Mesalamine,
pentasa (time-release), rowasa (enema), canasa (suppository) |
Aminosalicylates (5-ASA)
Mesalamine compounds Used to Tx IBD (UC/Crohn's) Modulate inflammatory mediators derived from both COX and LOX pathways Act ‘topically’ on diseased GI mucosa |
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Sulfasalazine Side Effects
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Azole - Tx IBD (UC/Crohn's)
Dose-related nausea, GI upset, headaches, arthralgias, myalgias, bone marrow suppression, malaise hypersensitivity to sulfapyridine (fever, hepatitis, hemolytic anemia) Impaired folate absorption/processing Take Folate! |
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Prednisone, prednisolone, hydrocortisone, budesonide
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Glucocorticoids Tx IBD (UC/Crohn's)
Treat moderate to severe active IBD |
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Azathioprine, 6-mercaptopurine
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Purine Analogs
Immunosuppressive activities Tx IBD (UC/Crohn's) Clinical uses: induction/maintenance of remission of ulcerative colitis and Crohn’s disease Side effects: nausea/vomiting, bone marrow depression, & hepatic toxicity (monitor blood count/liver function) Low TPMT inc. production of active metabolites and Inc. risk of bone marrow suppression |
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Methotrexate
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Inhibits DHFR (high doses inhibit cell proliferation)
Treat Crohn’s disease Side effects: rarely bone marrow suppression (high doses) Take Folate! |
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Infliximab
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Anti-TNF Therapy
Used to treat moderate to severe Crohn’s disease & ulcerative colitis Side effects: infection (immunosuppression), reactivation of TB, hepatic failure (monitor liver enzymes) |
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Pancreatin, Pancrelipase
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Pancreatic Enzyme Supplements
Treat exocrine pancreatic insufficiency (fat/protein maldigestion) Pancreatin: extract of hog pancreas (low enzyme activities) Pancrelipase: Mixtures of amylase, peptidase, lipase (rapidly inactivated by gastric acid: enteric coating or taken with PPI) |
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Ursodiol
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Bile Acid Therapy For Gallstones
only FDA approved drug to treat primary biliary cirrhosis Dissolve gallstones works only when stones are made of cholesterol and the opening of the gallbladder is not blocked |