Gastrointestinal drugs pharma
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The document discusses the anatomy and physiology of the gastrointestinal (GI) system and common GI diseases. It provides details on the structure and function of the oral cavity, esophagus, stomach, small intestine, large intestine, and accessory organs. It then focuses on peptic ulcer disease, describing its causes, types, symptoms, and treatment, including antimicrobials, gastric acid inhibitors, and mucosal protectants. The document also reviews drugs used to treat constipation and diarrhea.
Gastrointestinal drugs pharma
- 1. 07/07/14 1
- 2. 07/07/14 2 ANATOMY OF THE GI SYSTEM COMMON DISEASE OF THE GI SYSTEM ETIOLOGY DRUGS TO TREAT PEPTIC ULCER LAXATIVES ANTI DIARRHEALS ANTIMOTILITY EMETIC/ANTIEMETIC
- 3. 07/07/14 3 Anatomy of the GI System
- 4. 07/07/14 4 Two Major Functions 1. Digestion-mechanical and/ or chemical process :ingestion,mastication,deglutition,peristalsis,absorption and defecation. >Ingestion-taking of food into GI by mouth(M) >Mastication-chewing(M),salivary action-© >Deglutition-swallowing (M) >Peristalsis-rhythmic contraction-moves food through the GI
- 5. 07/07/14 5 >Absorption-passage of food molecules through the mucus membrane of the GI into the circulatory or the lymphatic system(M,C) 2. Elimination >defecation-discharge of indigestible wastes,called feces from the GI tract(M)
- 6. 07/07/14 6 Two Major Parts I. Alimentary Canal/bucal or oral cavity (mouth, pharynx, esophagus, stomach, small intestine, large intestine)
- 7. 07/07/14 7 1.Mouth-grinds food and mix with saliva(amylase),initial digestion of CHO, 2.Pharynx-receives bolus from oral cavity 3.Esophagus-transport bolus to stomach by peristalsis
- 8. 07/07/14 8 4. Stomach -temporary storage of food -breaks down food into chyme -moves gastric content into the small intestine -gastrin, hydrochloric acid, pepsinogen, mucus
- 9. 07/07/14 9 5. Small intestine : duodenum, jejunum, ileum -complete food digestion -absorbs food molecules -secretes hormones that help control bile (secretin) and pancreatic juice (cholecystokinin) secretion
- 10. 07/07/14 10 6. Large intestine -absorbs water, Na, CI -secretes alkaline mucus -eliminates digestive wastes
- 11. 07/07/14 11 Accessory Organs of Digestion Liver -carbohydrate metabolism, detoxifies endogenous & exogenous toxins in plasma -synthesizes plasma proteins, nonessential a.a., & vit., stores Vit. K, D, B12 & iron -removes ammonia from body fluids converting it t urea for excretion in urine, helps regulate blood glucose levels, secretes bile
- 12. 07/07/14 12 Bile -greenish liquid composed of water, cholesterol, bile salts, and phospholipids -emulsification of fats, promotes intestinal absorption of fatty acids, cholesterol, and other lipids, aids in the excretion of bilirubin from the liver
- 13. 07/07/14 13 Gallbladder -stores & concentrates bile produced by the liver -releases bile to the duodenum Pancreas -performs both endocrine & exocrine function GI Tract Innervations
- 14. 07/07/14 14 Parasympathetic stimulation -increase gut & sphincter tone -increase smooth muscle contraction & motor secretory activities Sympathetic stimulation -reduces peristalsis & inhibits GI activity
- 15. 07/07/14 15 Common Diseases of the GI System Peptic Ulcer Disease – A group of disorders characterized by circumscribed lesions of the mucosa of the upper GI tract (stomach & jejunum)
- 16. 07/07/14 16 Manifestation 1. Duodenal ulcer – 80% peptic ulcers are of this type > pain restricted to midepigastrict area and may radiate below the costal margins into the back or right shoulder > occurs between midnight and 2 am > relieved by food >patient gains weight
- 17. 07/07/14 17 2. Gastric ulcer – pain is referred to the left subcostal region > rarely produce noctumal pain > aggravated by food >patient loses weight
- 18. 07/07/14 18 3. GERD ( Gastroesophageal Reflux Disease) > retrograde movement of gastric contents from the stomach into the esophagus > heartburn, chest pain, belching, regurgitation, etc. 4. Hypersecretory state ( Zolliger – Ellison syndrome ) > hyper secretion of HCI due to gastrin-secreting tumor
- 19. 07/07/14 19 APUD ( Acid-Peptic Ulcer Disease ) -imbalance between aggressive and defensive factors Aggressive -HCI, Pepsin, H.pylori Defensive -Bicarbonate, Mucus, PG
- 20. 07/07/14 20 3 General Factors 1.infxn w/ H.pylori 2. Increase HCI secretion 3. Inadequate mucosal defense against gastric acid
- 21. 07/07/14 21 Treatment Plan 1. Eradicate H. pylori Antimicrobial Agents ROC: Triple therapy 1.Bismuth 2.Metronidazole 3. Tetracycline *duration: 2 weeks Antisecretory agent is usually added – PPI, antimuscarinic 2nd line: Metronidazole + Amoxicillin/Clarithromycin
- 22. 07/07/14 22 Etiology 1. Infection with H. pylori ( >90% DU; 60-90% GU) >able to survive in the acidic gastric environment by its ability to produce UREASE, w/c hydrolyzes urea into ammonia. 2. Genetic factors ( 20 – 50% ) >1st degree relative of ulcer patient: 3x >Blood type:O
- 23. 07/07/14 23 3. Use of NSAIDs 4. Cigarette smoking – delays ulcer healing >accelerates emptying of stomach acid into the duodenum >prevents pancreatic & billiary bicarbonate secretion
- 24. 07/07/14 24 5. Alcohol Intake – mucosal irritant 6. Coffee – contains peptides that stimulate release of Gastrin
- 25. 07/07/14 25 Drugs Used To Treat Peptic Ulcer Disease Antimicrobials > Helps heal ulcers and decreae recurrence > Two or more antibiotics in combination with other drugs such as PPIs for 2 weeks and PPIs fo 6 more weeks > Amoxicillin, Clarithromycin, Metronidazole, Tetracycline >>>Dairy products decrease absorption of tetracycline
- 26. 07/07/14 26 Gastric Acid Secretion
- 27. 07/07/14 27 Proton-pump Inhibitor MOA: Binds to the H+/K+-ATPase enzyme system (proton pump) suppressing secretion of gastric acid > more potent and rapidly effective than H2-blockers > enteric coated preparations > highly protein-bound and metabolized extensively in the liver > administer in the morning before eating
- 28. 07/07/14 28 Lansoprazole > prevention & healing of NSAID-induced GU Rabeprazole Pantoprazole > IV preparation used for Zollinger-Ellison syndrome
- 29. 07/07/14 29 >>Omeprazole & Lansoprazole Approved for used in infants & children for the short-term treatment of GERD & corrosive esophagitis S/E: headache, n&v, abdominal pain, diarrhea and flatulence
- 30. 07/07/14 30 Drug Interactions > Increase half-life of diazepam, phenytoin & warfarin > Interferes with the absorption of drugs that depend on gastric pH ( Ketoconazole, Digoxin, Ampicillin, & iron salts ) > Lansoprazole will increase clearance of theophylline > Esomeprazole, Lansoprazole & Pantoprazole’s biovailability are affected by food
- 31. 07/07/14 31 H2-Receptor Blockers MOA: Inhibits the action of histamine at parietal cell receptors sites, reducing the volume of hydrogen ion concentration & gastric acid secretion >used to treat GERD, duodenal ulcer, & erosive esophagitis
- 32. 07/07/14 32 Cimetidine – Oral, IV, 1st H2 blocker approved, 50% reduction in gastric secretion Ranitidine – Oral, IV, IM > more potent, 70% reduction in gastric acid secretion Ranitidine Bismuth Citrate + Clarithromycin: H. pylori eradication
- 33. 07/07/14 33 Famotidine – Oral, IV > most potent, 94% reduction Nizatidine – Oral > newest H2- receptor blocker
- 34. 07/07/14 34 S/E: headache & dizziness > Ranitidine – hepatotoxixity, bradychardia > Cimetidine - heoatotoxixity, bradychardia agranulocytosis, aplasti anemia, weak androgenic effect (male gynecomastaia & impotence)
- 35. 07/07/14 35 Drug Interactions > Cimetidine – enzyme inhibitor - reduce clearance of propranolol & lidocaine - inhibits excretion of procainamide - absorption is impaired by antacid (Ranitidine)
- 36. 07/07/14 36 Mucosal Protective Sucralfate – nonadsorbable dissacharide containing sucrose MOA: adheres to the base of the ulcer crater forming a protective barrier A: 1g, 4x a day ( 1hr before meals & at bedtime ) S/E: constipation
- 37. 07/07/14 37 Bismuth compounds MOA: Prevents adhesions of H. pylori to mucosa & suppresses its growth & inhibits release of proteolytic enzymes >CBS – inhibits pepsin activity, stimulates PG synthesis > highly effective when combined with PPIs
- 38. 07/07/14 38 Bismuth subsalicylate Colloifal Bismuth subcitrate S/E: dark stools and tongue salicylism at high dose
- 39. 07/07/14 39 Antacids MOA: neutralize gastric acid, inhibit pepsin activity & strengthen mucosal barrier > equally effective as H2 blockers > heal peptic ulcers and control ulcer pain > liquid forms provider greater buffering action
- 40. 07/07/14 40 > Nonsytemic – Al or Mg > Systemic antacids – Sodium bicarbonate ( alkalosis ), CALCIUM CARBONATE > Antacid mixture – Aluminum OH & Magnesium OH
- 41. 07/07/14 41 A: 1 hour and 3 hrs after meals and bedtime S/E: Aluminum – constipation Magnesium – diarrhea Calcium carbonate – constipation, acid rebound, milk-alkali syndrom Sodium bicarbonate – alkalosis, C/l in patients with HTN, CHF, severe renal desease
- 42. 07/07/14 42 D/l: > Antacids bind to tetracycline & fluoroquinolones inhibiting their absorption > Antacids may destroy enteric-coating of drugs leading to premature dissolution in the stomach >>>administer drugs 30-60 minutes before antacids
- 43. 07/07/14 43 Choice of Agents Nonsystemic antacids – Mg or Al substances preferred than Na bicarbonate to avoid risk of alkalosis Liquid Antacid forms – greater buffering capacity than tablets Antacid Mixtures – more sustained action, permits a lower dosage of each compound and negate each other untoward effects.
- 44. 07/07/14 44 Ca Carbonate – usually avoided because it causes Acid Rebound, may delay pain relief and ulcer healing and induce constipation -Ca Carbonate + milk or other alkali subs results to Milk-Alkali Syndrome
- 45. 07/07/14 45 *Al(OH)3 -adsorbs pepsin and removes it from solution at pH>3 -delays GET (constipation) by relaxing small muscles of the stomach -stimulate mucus secretion -hypophosphatemia
- 46. 07/07/14 46 *Mg(OH)2 -keeps pH sufficiently high to keep pepsin absorbed to it -lessens relaxant effect (diarrhea) *CaCO3 -can caused rebound acidosis that is prolonged and prominent *Absorption of cations from antacids may be an important consideration in HPN/CHF Px.
- 47. 07/07/14 47 Dl: Aviod concurrent use with other dx impair absorption of Cimetidine and Ranitidine (give 1 hr apart), Digoxin, INH, Anticholinergics, Iron products and Phenothiazine *also interfere absorption of some drugs and enteric-coated tablets -can form insoluble complexes (e.g. AI and levodopa), bind with Tetracycline and Fluoroquinolones
- 48. 07/07/14 48 Antimuscarinic >MOA: delays or prolongs gastric emptying > used with antacids > has no use in ulcer healing > Belladona leaf, atropine, propantheline > S/E: CBUD > C/I: glaucoma, gastric ulcer
- 49. 07/07/14 49 Muscarinic receptors: Inc.GI motility Inc.GI secretion Muscarinic Receptor Blocker/anticholinergic Dec.GI motility Dec.GI secretion
- 50. 07/07/14 50 e.g. PIRENZEPINE -specific M1 receptor antagonist -currently investigated as an antisecretory agent **suppresses gastric secretion at doses having minimal effect on other organs
- 51. 07/07/14 51 Prostagladin >Moa: Suppress gastric acid secretion and guards the mucosa form NSAD-induces ulcers >Misoprostol – a prostagladin analogue with antisecretory & mucosal protective activity by increasing bicarbonate and mucuc secretions -indicated for NSAID-induces gastric ulcers >S/E:diarrhea and abdominal pain >C/I: pregnant, women with child-bearing potential
- 52. 07/07/14 52 CONSTIPATION – difficult or infrequent passage of stool S/S: abdominal bloating, headaches, sense of rectal fullness Causes: >Insufficient dietary fiber >lack of exercise >Medications (anticholinergic, antacids, narcotics) >Organic problems- intestinal obstruction, IBS, tumor etc.
- 53. 07/07/14 53 Treatment >Nonpharmacologic -increase fluid and fiber intake -exercise regularly -bowel training ti increase regularity
- 54. 07/07/14 54 Pharmacologic Laxatives – stimulate defection, should not be taken if nausea, vomiting, or abdominal pain is present
- 55. 07/07/14 55 1. Bulk-forming laxatives MOA: natural or synthetic polysaccharide that absorb water to soften stool and increase bulk, which stimulates peristalsis > slow onset of action (12-24 hrs, 72 hrs) thus preventive > take with 8 oz of water > C/I obstruction bowel lesion, intestinal strictures, Crohn’s disease
- 56. 07/07/14 56 > Natural bulk-forming laxatives Psyllium (Metamucil, Fiberall, Konsyl-D, Perdium Fiber Granules), Malt soup extract (Maltsupex)
- 57. 07/07/14 57 > Synthetic bulk-forming laxatives Methylcellulose, Polycarbophil (Ca Polycarbophil impairs Tetracycline absorption)
- 58. 07/07/14 58 2. Saline & Osmotic Laxatives MOA: creates an osmotic gradient pulling water into the small and large intestines, stimulates the activity of cholecystokinin-pancreozymin which increases the secretion of fluids into the GI tract >Onset of oral: 3-6 hrs: rectal – 5-30 minutes
- 59. 07/07/14 59 > Saline laxatives – sodium and magnesium salts > Should not be used in patients with HPN, CHF, & renal impairment > Magnesium citrate, Magnesium hydroxide, Magnesium sulfate, Sodium `
- 60. 07/07/14 60 > Osmotis laxatives > Glycerin – rectal burning > Lactulose – decrease blood ammonia levels in hepatic encephalopathy, S/E flatulence & cramping > Sorbitol – nonabsorbable sugar > Polyethylene glycol
- 61. 07/07/14 61 3. Stimulant laxatives MOA: stimulate intestinal motility and increase secretion of fluid into the bowel > Onset of action of oral: 6-10 hrs; rectal 30-60 minutes > Chronic use can lead to cathartic colon (should not be used for more than 1 week) S/E: abdominal cramping
- 62. 07/07/14 62 > Anthraquinone glycoside – melanoma coli Sennosides – most potent Cascara sagrada Casanthranol – mild stimulant laxative > Bisacodyl (Dulcolax) – diphenylmethane derivative, enteric-coated > Castor oil – onset: 2-6 hrs; works in the small intestine which C/I in pregnant women
- 63. 07/07/14 63 4. Emollient laxatives MOA: act as surfactants by allowing absorption of water into stool > Slow onset of action: 24-72 hrs > Should not be used with mineral oil because it facilitates systemic absorption of mineral oil leading to hepatotoxicity > Docusate sodium Docusate calcium Docusate potassium
- 64. 07/07/14 64 5. Lubricant laxative (Mineral oil) MOA: works at the colon to increase water retention in the stool > onset of action: 6-8 hrs > May cause anal seepage, lipid pneumonotis, decrease vit. A,D,E,K absorption
- 65. 07/07/14 65 * ANTIDIARRHEA DIARRHEA > Abnormal increase in the frequency and looseness of stools > Happens when some factors impair the ability of the intestines to absorb water from the stool
- 66. 07/07/14 66 Causes: 1. Infection – virus, bacteria,protozoa 2. Diet – induced ( high fiber, fatty or spicy food, large amounts caffeine, milk intolerance) 3. Drug – induced
- 67. 07/07/14 67 Treatment > Antidiarrheal may prevent an attack or relieve existing symptoms Non-pharmacological approach Food – BRAT diet (Banana, Rice, Applesauce, Toast) not advised anymore
- 68. 07/07/14 68 Fluids – ORS (NaCI, KCI, Na bicar, Glucose, Water) -Fluids to be avoided: Hypertonic fruit juice, apple juice, powdered drink mixes, gelatin water, carbonated and caffeine-containing beverages -Gatorade diluted in Water (1:1)provided necessary combination of glucose, Na and K
- 69. 07/07/14 69 1. Antimotility/Antiperistaltic MOA: stimulate mu opioid receptor slowing motility of the small and large intestines Loreramide, Diphenoxylate/atropine S/E: abdominal pain, distension, dizziness, drowsiness, dry mouth
- 70. 07/07/14 70 2. Adsorbent MOA: adsorb toxins, bacteria, gases & fluids Kaolin, Bismuth subsalicylate 3. Anti-infectives
- 71. 07/07/14 71 Irritable Bowel Syndrome > pain, cramping, gassiness, constipation and/or diarrhea > symptoms appear after eating or during stress and result from abnormal motility
- 72. 07/07/14 72 Treatment Alosetron – a serotonin antagonist which blocks serotonin in the GI tract thereby reducing the abdominal cramping, urgency, and diarrhea associated with IBS Antispasmodic – hyoscyamine, dicyclomine Bulk – forming agents –psyllium Antiflatulent – simethicone Loperamide
- 73. 07/07/14 73 Crohn’s Disease – chronic, segmental inflammation of the GI tract (ileum) Sulfasalazine – 5-aminosalicylate (anti-inflammatory)
- 74. 07/07/14 74 Pseudomembranous colitis – inflammation of the colon resulting from the use of antibiotics > Clostridium difficile > Mild to bloody diarrhea, abdominal pain, fever > Metronidazole or Vancomycin
- 75. 07/07/14 75 *Emetic/Antiemetics Emetic > Used to induce vomiting in cases of poisoning > Ipecac syrup is used to induce vomiting in the early management of oral poisoning or drug overdose MOA: Stimulates the chemoreceptor trigger zone in the medulla Antimetic – Agents that decrease the nausea, reducing the urge to vomit
- 76. 07/07/14 76 > Ondansetron – antiemetic of choice in the US -serotonin receptor antagonist > Metoclopramide – effective against Cisplatin- induced vomiting > Butyrophenones- drromperodol, haleperidol, droperidol
- 77. 07/07/14 77 > Phenothiazines- prochlorperazine > Benzodiazepines – alprazolam, lorazepam > Marijuana > Corticosteroids- dexamethasone, methylpednisolone
- 78. 07/07/14 78