Gastrointestinal drugs pharma
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Gastrointestinal drugs pharma






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Gastrointestinal drugs pharma Gastrointestinal drugs pharma Presentation Transcript

  • 07/07/14 1
  • 07/07/14 3 Anatomy of the GI System
  • 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
  • 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)
  • 07/07/14 6 Two Major Parts I. Alimentary Canal/bucal or oral cavity (mouth, pharynx, esophagus, stomach, small intestine, large intestine)
  • 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
  • 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
  • 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
  • 07/07/14 10 6. Large intestine -absorbs water, Na, CI -secretes alkaline mucus -eliminates digestive wastes
  • 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
  • 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
  • 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
  • 07/07/14 14 Parasympathetic stimulation -increase gut & sphincter tone -increase smooth muscle contraction & motor secretory activities Sympathetic stimulation -reduces peristalsis & inhibits GI activity
  • 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)
  • 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
  • 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
  • 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
  • 07/07/14 19 APUD ( Acid-Peptic Ulcer Disease ) -imbalance between aggressive and defensive factors Aggressive -HCI, Pepsin, H.pylori Defensive -Bicarbonate, Mucus, PG
  • 07/07/14 20 3 General Factors 1.infxn w/ H.pylori 2. Increase HCI secretion 3. Inadequate mucosal defense against gastric acid
  • 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
  • 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
  • 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
  • 07/07/14 24 5. Alcohol Intake – mucosal irritant 6. Coffee – contains peptides that stimulate release of Gastrin
  • 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
  • 07/07/14 26 Gastric Acid Secretion
  • 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
  • 07/07/14 28 Lansoprazole > prevention & healing of NSAID-induced GU Rabeprazole Pantoprazole > IV preparation used for Zollinger-Ellison syndrome
  • 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
  • 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
  • 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
  • 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
  • 07/07/14 33 Famotidine – Oral, IV > most potent, 94% reduction Nizatidine – Oral > newest H2- receptor blocker
  • 07/07/14 34 S/E: headache & dizziness > Ranitidine – hepatotoxixity, bradychardia > Cimetidine - heoatotoxixity, bradychardia agranulocytosis, aplasti anemia, weak androgenic effect (male gynecomastaia & impotence)
  • 07/07/14 35 Drug Interactions > Cimetidine – enzyme inhibitor - reduce clearance of propranolol & lidocaine - inhibits excretion of procainamide - absorption is impaired by antacid (Ranitidine)
  • 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
  • 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
  • 07/07/14 38 Bismuth subsalicylate Colloifal Bismuth subcitrate S/E: dark stools and tongue salicylism at high dose
  • 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
  • 07/07/14 40 > Nonsytemic – Al or Mg > Systemic antacids – Sodium bicarbonate ( alkalosis ), CALCIUM CARBONATE > Antacid mixture – Aluminum OH & Magnesium OH
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 07/07/14 49 Muscarinic receptors: Inc.GI motility Inc.GI secretion Muscarinic Receptor Blocker/anticholinergic Dec.GI motility Dec.GI secretion
  • 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
  • 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
  • 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.
  • 07/07/14 53 Treatment >Nonpharmacologic -increase fluid and fiber intake -exercise regularly -bowel training ti increase regularity
  • 07/07/14 54 Pharmacologic Laxatives – stimulate defection, should not be taken if nausea, vomiting, or abdominal pain is present
  • 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
  • 07/07/14 56 > Natural bulk-forming laxatives Psyllium (Metamucil, Fiberall, Konsyl-D, Perdium Fiber Granules), Malt soup extract (Maltsupex)
  • 07/07/14 57 > Synthetic bulk-forming laxatives Methylcellulose, Polycarbophil (Ca Polycarbophil impairs Tetracycline absorption)
  • 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
  • 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 `
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 07/07/14 70 2. Adsorbent MOA: adsorb toxins, bacteria, gases & fluids Kaolin, Bismuth subsalicylate 3. Anti-infectives
  • 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
  • 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
  • 07/07/14 73 Crohn’s Disease – chronic, segmental inflammation of the GI tract (ileum) Sulfasalazine – 5-aminosalicylate (anti-inflammatory)
  • 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
  • 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
  • 07/07/14 76 > Ondansetron – antiemetic of choice in the US -serotonin receptor antagonist > Metoclopramide – effective against Cisplatin- induced vomiting > Butyrophenones- drromperodol, haleperidol, droperidol
  • 07/07/14 77 > Phenothiazines- prochlorperazine > Benzodiazepines – alprazolam, lorazepam > Marijuana > Corticosteroids- dexamethasone, methylpednisolone
  • 07/07/14 78