GI Pharmacology. PHRM 203 Allison Beale
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1 GI Pharmacology PHRM 203 Allison Beale
2 Anatomy of the GIT In order of food transport Mouth Esophagus Esophogeal sphincter Stomach Pyloric sphincter Small intestine Duodenum, Jejunum, Ileum Large intestine (cecum, colon & rectum) Anus Accessory Glands Salivary glands Pancreas Liver/gall bladder A Beale PHRM GI Pharmacology 2
3 Anatomy of the GIT GIT in four layers Mucosa Inner lining = epithelium + connective tissue + smooth muscle Mucosa muscularis 2 muscle layers Circular, longitudinal Nerve plexus Meissner s (inner) - 1 o controls secretions and blood flow Auerbach s (outer)- 1 o controls motor functions Adventitia Outer supportive layer, holds guts in place Hormone/NTs ACh NE ATP 5-HT DA Cholecystokinin Substance P Vasoactive intestinal peptide (VIP) Somatostatin Leu-enkephalin Met-enkephalin Bombesin A Beale PHRM GI Pharmacology 3
4 GIT secretions Saliva Pepsin Gastrin Somatostatin HCl Intrinsic Factor Secretin Cholecystokinin Mucous Sodium bicarbonate Pancreatic enzymes Chymotrypsin and trypsin, lipase, amylases Bile A Beale PHRM GI Pharmacology 4
5 GIT Hormones Hormone Release trigger Function (Stimulates:) Gastrin Peptides, AA, FFA in stomach Gastric acid secretion Ghrelin grey-lyn Gastric emptiness? Appetite, GH secretion Motilin Fasting? Stomach, SI motility Cholecystokinin koh-leh-siss-toh- KYN-in HCl, Fatty acids, AA in small intestine (SI) Pancreas & gall bladder gastric emptying Secretin Acidic ph in SI Pancreas bicarb & H2O Gastric inhibitory polypeptide - GIP Fat, glucose in SI gastric secretion & motility, insulin release A Beale PHRM GI Pharmacology 5
6 GI reflexes: 3 basic types In gut wall enteric system Control GI secretions and motor functions From gut to autonomic ganglion and back E.g., Signal from stomach to colon to empty From gut to spinal cord or brain and back Other reflexes to control motor and secretory activities Pain reflexes Defecation reflexes A Beale PHRM GI Pharmacology 6
7 Gastroenteric reflex GI reflexes Stretching of stomach activity in small intestine Gastrocolic reflex Stretching of stomach activity in colon to empty colon to provide space for coming chyme Duodenal-colic reflex Stretching of duodenum activity in colon A Beale PHRM GI Pharmacology 7
8 Ileogastric reflex GI reflexes, continued Stretch of large intestine stomach activity Intestinal-intestinal reflex Irritation to one area of small intestine triggers a in activity above the irritation and activity below (think, Montezuma s revenge) Peritoneointestinal reflex Irritation of the peritoneum (injury or inflammation) of all movement in the GI tract A Beale PHRM GI Pharmacology 8
9 GI reflexes, continued Renointestinal reflex Irritation of the kidney (injury or inflammation to the capsule) of movement in the GI tract Vesicointestinal reflex Irritation or overstretching of the bladder of movement in the GI tract Somatointestinal reflex Taut stretching of the skin over the abdomen irritates the nerve plexus of movement in the GI tract (leading to constipation - tight clothes can have the same effect!) A Beale PHRM GI Pharmacology 9
10 GI reflexes, continued CNS mediated reflexes Swallowing Vomiting Food bolus shuts off nasal cavity with soft palate, which stops respirations, so the larynx and pharynx close off trachea, causing the pharyngeal muscles to move the food bolus into the esophagus where pairs of muscles contract to move the food to the stomach. A very complex reflex involving >25 pairs of muscles. Assist by: icing tongue. Emetic zone triggers projectile vomiting. Chemoreceptor trigger zone (CTZ) triggered by: touching the back of the throat, excessive stomach distention, intracranial pressure, stimulation of vestibular receptors in the inner ear, or of stretch receptors in uterus and bladder, intense pain, exposure to certain chemicals (including those from cell death, e.g., during chemotherapy). CTZ receptors: D2, 5HT3, opioid, ACh, sp A Beale PHRM GI Pharmacology 10
11 Diseases and s that can cause difficulty swallowing Diseases or conditions Spinal cord or head injury, Stroke Cerebral palsy, Myasthenia gravis, Acid reflux disease Head, neck or esophageal tumor Parkinson s Multiple sclerosis Huntington s Amyotrophic lateral sclerosis s Nitrates Anti-cholinergic antidepressants and anti-allergy medications Calcium and iron tablets Vitamin C Anti-psychotics Tetracycline (acne medication) Calcium channel blockers A Beale PHRM GI Pharmacology 11
12 Histamine-2 Antagonists Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Cimetidine (Tagamet) Famotidine (Pepcid) Nizaridine Ranitidine (Zantac) Indication/use All are PO, IM/IV Duodenal ulcer, benign gastric ulcer, pathological hyper-secretion syndrome, gastro esophageal reflux disease (GERD), prophylaxis of stress ulcers, relief of heartburn symptoms, acid indigestion, sour stomach. These drugs are generally not recommended for use in kids. Best taken just before bed Ranitidine may the absorption of Glipizide by >30% and Midazolam by >60% A Beale PHRM GI Pharmacology 12
13 Histamine-2 Antagonists Cimetidine (Tagamet) Interactions Cimetidine decreases the metabolism of (and therefore increases the circulating levels of): - Warfarin, phenytoin, propranolol, nifedipine, diazepam, TCAs, lidocaine, theophylline and metronidazole - Cimetidine affects the absorption of ketoconazole ( ). Because of all it s adverse interactions, cimetidine is not used nearly as much as ranitidine (Zantac) and famotidine (Pepsid). s that stomach acidity ( ph) - H2 antagonists, antacids, proton pump inhibitors, etc. diarrhea The Vestibulocochlear nerve (CN VIII) has lots of machr and H1 receptors, so H2 antagonists have no effect on emesis and as anti-emetics, H1 antagonists are really best at treating nausea caused by motion sickness! A Beale PHRM GI Pharmacology 13
14 Taking antacids too often leads to acid rebound - the neutral ph stimulates gastrin secretion which triggers gastric acid secretion! Antacids Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Aluminum salts Calcium salts Magaldrate (Riopan) Magnesium salts Sodium bicarbonate Indication/Use GI hyperacidity, hyperphosphatemia, prevention of phosphate urinary stones GI hyperacidity, calcium deficiency, prevention of hypocalcemia GI hyperacidity (ulcers) GI hyperacidity, prophylaxis of gastric ulcers, constipation, tetany, dialysis, etc. GI hyperacidity, uric acid crystalluria, adjunct to treatment for severe diarrhea A Beale PHRM GI Pharmacology 14
15 OTC & Proton Pump Inhibitors Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Esomeprazole (Nexium) Lansoprazole (Prevacid) Omeprazole (Prilosec) Rabeprazole (Aciphex) Pantoprazole (Protonix) Indication/Use GERD, severe erosive esophagitis, duodenal ulcers, pathological hypersecretory conditions Gastric ulcer, GERD, pathological hypersecretory conditions, healing duodenal ulcers or esophagitis, combo therapy to eradicate Helicobacter pylor infection, heartburn, erosive esophagitis GERD A Beale PHRM GI Pharmacology 15
16 Proton Pump Inhibitors Interactions Omeprazole (Prilosec, Zegerid) Delayed elimination: phenytoin, warfarin and diazepam Interference with the absorption of drugs where gastric ph is a determinant: ketoconazole, ampicillin esters, iron salts plasma levels: atazanavir (protease inhibitor) plasma levels: tacrolimus (Prograf, immunosuppressant) Amoxicillin/Clarithromycin/lansoprazole (or omeprazole) = triple therapy for Heliobacter pylori caused duodenal ulcers. Zegerid OTC approved Dec 2009 PO, IV A Beale PHRM GI Pharmacology 16
17 Antipeptic Agent Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Indication PO Sucralfate (Carafate) Short-term (up to 2 months) treatment of duodenal ulcers, healing ulcers, and oral or esophageal ulcers caused by radiation or chemotherapy Contraindications: None known! Mechanism: Unknown - it does form a proteinaceous glob over the ulcer and reduces pepsin activity in gastric juices by 1/3. A Beale PHRM GI Pharmacology 17
18 Prostaglandin Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, Indication PO Misoprostol (Cytotec) Prevention of NSAID-induced ulcers in adults at high risk It is a prostaglandin E analog, used off label as a medical aborticant and to induce labor May cause abortion, not for pregnant women Contraindications: X, allergy to prostaglandins ADRs: GI - diarrhea; Gynecological - pain and bleeding A Beale PHRM GI Pharmacology 18
19 Digestive enzymes Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Indication PO Pancrelipase (Ultrase) Saliva substitute Digestion and absorption aid for fats, proteins and carbohydrates in conditions resulting in a loss of this enzyme. An aid in conditions that result in dry mouth: stroke, radiation therapy, chemotherapy, various medications (especially anti cholinergics) and diseases A Beale PHRM GI Pharmacology 19
20 Prolonged laxative use leads to atonic, dilated colon! Chemical stimulant laxatives Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Indication PO Bisacodyl (Dulcolax) Casara Castor oil (Neoloid) Senna (Senokot) Bowel preparation, prevention of constipation after surgery, MI, or obstetrical delivery; acute constipation Short term constipation therapy, evacuation of bowel for Dx exam Short term constipation therapy, treatment of encopresis (inability to retain stools) Constipation worsened by: Ca ++, anti-cholinergics and CCBs, opioids etc. A Beale PHRM GI Pharmacology 20
21 Bulk laxatives Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Lactulose Magnesium citrate Magnesium hydroxide (Milk of Magnesia) Polycarbophil Psyllium Indication PO Short term constipation therapy, especially in patients with CV disorders Evacuation of bowel for Dx exam Short term constipation therapy, prevention of straining after surgery, delivery, MI Mild laxative; short-term constipation therapy A Beale PHRM GI Pharmacology 21
22 Lubricant laxatives Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Docusate Glycerin Mineral oil Indication PO Prevention of straining post-op, post-mi, and post-partum Short-term treatment of constipation A Beale PHRM GI Pharmacology 22
23 GI Stimulants Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Dexpanthenol Metoclopramide (Reglan, Octamide, Maxolon, etc.) PO, IV, IM Indication Prevention of intestinal atony post-op GERD, chemotherapy or PONV, diabetic gastroparesis, promotion of GI movement during small bowel intubation or promotion of barium movement. Stimulates lactation. Muscarinic receptors in sm. muscle and 5-HT 3&4 DA receptors in CTZ Not for >12 wks use risk of tardive dyskinesia A Beale PHRM GI Pharmacology 23
24 Antidiarrheals Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Indications PO Bismuth subsalicylate (Peptobismol, Keopectate) Loperamide (Imodium) Diphenoxylate (+atropine) (Lomotil) C-V Traveler s diarrhea, irritable bowel syndrome, prevention of cramping and distention associated with dietary excess and some viral infections Short-term treatment of cramping and diarrhea A Beale PHRM GI Pharmacology 24
25 Antidiarrheals Loperamide (Imodium) Interactions Loperamide is a P-glycoprotein substate; quinidine and ritonavir are both P-glycoprotein inhibitors. Coadministration with either inhibitor can double or triple the plasma levels of loperamide. Remember: P-GP important in the BBB, liver, kidney and GIT. A Beale PHRM GI Pharmacology 25
26 Antiemetics Anticholinergics Antihistamines (H 1 receptor antagonists) Benzodiazepines Cannabinoids DA antagonists 5-HT 3 antagonists NK 1 antagonists Steroids Others All anti-emetics may mask the symptoms of ADRs or OD on other drugs, including antineoplastics, and may interfere with Dx of other conditions including GI obstruction, brain tumors & Reye s syndrome. NOTE: post-op nausea & vomiting = PONV. It s a common acronym A Beale PHRM GI Pharmacology 26
27 Anti-cholinergic anti-emetics Note: s like Droperidol, Diphenhydramine & Prochlorperazine work as anti-emetics because of their anti-cholinergic side effects Scopolamine hydrobromide (Scopace, Transderm Scop) AKA Hyoscine hydrobromide Uses Nausea and vomiting associated with motion sickness. Anesthesia adjunct, anti-arrhythmic, anticholinergic, anti-dysmenorrheal, anti-emetic, antivertigo, antispasmodic for GI and urinary tract. Precautions Don t combine with CNS depressants Avoid overheating (reduced ability to sweat) Blurred vision, dry mouth, drowsiness, dizziness & hypotension are possible (anti-muscarinic effects) A Beale PHRM GI Pharmacology 27
28 Antihistaminic antiemetics Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Diphenhydramine (Benadryl, Sominex) Dimenhydrinate (Dramamine) Hydroxyzine ( hydralazine!) Meclizine (Bonine, Antivert) Indication Used for severe morning sickness, too Nausea associated with motion sickness; sleeplessness; mild Parkinson s symptoms & EPS; allergic reactions; cough Nausea and vomiting associated with motion sickness. Off label: Post-op & pregnancy related nausea/vomiting Anxiolytic and sedative with weak antiemetic effects. Prepartum, postpartum and PONV Nausea and vomiting associated with motion sickness 12 years old. Antivert Axert (almotriptan for migraines) AKA Dramamine Less Drowsy!! All may mask symptoms of ototoxicity, brain tumors or intestinal obstructions A Beale PHRM GI Pharmacology 28
29 Benzodiazapines Use as anti-emetic PO, IV, IM Midazolam (Versed) C-IV Lorazepam (Ativan) C-IV Off label - Adjuvant for Post-op nausea and vomiting (PONV) Inadvertent intraarterial injection causes arteriospasm that can lead to gangarene and amputation! Remember the basic uses of BZDs: sedation, hypnosis, anxiolysis, muscle relaxation, anticonvulsant, amnesiac and some anesthesia. PONV = post op- CINV = chemo- RINV = radiation- Induced nausea and vomiting A Beale PHRM GI Pharmacology 29
30 Used for cachexia, cytotoxic nausea and or vomiting that is unresponsive to other drugs Cannabinoids Cannabis Dronabinol (Marinol) Nabilone (Cesamet) Indication C-I - anti-emetic for CINV and AIDs patients C-III - anti-emetic for CINV and AIDs patients, anorexia in Alzheimer s patients Has sympathomimetic effects on HR C-II - synthetic used to treat severe CINV PO Use with caution in CV, substance abuse, psych, elderly, pregnant patients A Beale PHRM GI Pharmacology 30
31 Phenothiazine antiemetics (DA antagonists) Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Chlorpromazine Perphenazine Prochlorperazine (Compazine) PO, PR, IM, IV Promethazine (antihistamine) Indication Nausea and vomiting, including that associated with anesthesia. Severe vomiting, intractable hiccoughs Severe nausea and vomiting, including that associated with anesthesia and chemotherapy. OTC & I Nausea, vomiting & pain associated with motion sickness and surgery, allergies, used to induce a light sleep EPS, NMS, sedation & other ADRs limit usefulness, but DA antagonists are used for radiation sickness, drug-induced nausea/vomiting & neoplasms. A Beale PHRM GI Pharmacology 31
32 Nonphenothiazine DA antagonist antiemetics Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Metoclopramide (Reglan, etc.) ( like moclobemide an MAOI) Indication Nausea and vomiting, especially if due to CTZ stimulation Not for >12 wks use risk of tardive dyskinesia Droperidol (Inapsine) A butyrophenone, antipsychotic, sedative, tranquilizer, anti emetic for PONV. Metoclopramide ADRs: suicidal ideation, EPS, NMS, seizures, arrhythmias, neutropenia, prolactin. May trigger catecholamine release, hypertensive crisis may be controlled with phentolamine. Adults only; use for <12 weeks. A Beale PHRM GI Pharmacology 32
33 5-HT 3 Receptor Blockers Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Dolasetron Granisetron Ondansetron (Zofran) PO, IV, IM Palonosetron Indication May mask ileus &/or gastric distension CINV, RINV, PONV Ondansetron = 1 st choice for PONV Acute and delayed CINV 5-HT 3 receptors on vagal nerve terminals in GIT mucosa and in the CTZ (medulla) sense irritants (chemical, radioactive and bacterial/viral (etc.) A Beale PHRM GI Pharmacology 33
34 Substance P/Neurokinin 1 Receptor Antagonist antiemetic Adapted from: Focus on Nursing Pharmacology, 4th Ed., by AM Karch. Lippincott, Williams & Wilkins, 2008 Aprepitant (Emend) Indication CYP3A4 CYP2C9 Acute and delayed CINV or PONV PO, IV Aprepitant antagonizes Substance P and neurokinin-1 receptors in the CNS (including CTZ). It is not used alone and shouldn t be taken with grapefruit in the diet. Use in combination with 5-HT 3 antagonist and a corticosteroid. Serious ADRs include constipation and hiccups. Rarely neutropenia, bradycardia A Beale PHRM GI Pharmacology 34
35 Steroids Indication/use as anti-emetic Dexamethasone PONV PO, IM, IV, Topical Dexamethasone = 1 st choice for PONV due to low cost and few ADRs Dexamethasone has an EXTENSIVE list of indications including allergic, dermatologic, endocrine, GI, hematologic, neoplastic, neurologic (e.g., MS), eye, kidney, lung and rheumatic conditions or disorders. To see a full listing, go to or Google dexamethasone dailymed As with other corticosteroids, it is contraindicated in fungal infections. A Beale PHRM GI Pharmacology 35
36 Miscellaneous antiemetics Trimethobenzamide Ginger Propofol (Diprivan) Peppermint Indication Nonsedating antiemetic Herbal used to prevent/treat motion-related, PONV, pregnancy (morning sickness), and CINV IV rescue for severe emesis (Ultra-short acting anesthetic) Herbal used to treat nausea (usually as a tea) A Beale PHRM GI Pharmacology 36
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