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ANATOMY OF THE GI SYSTEM
COMMON DISEASE OF THE GI SYSTEM
ETIOLOGY
DRUGS TO TREAT PEPTIC ULCER
LAXATIVES
ANTI DIARRHEALS
ANTIMOTILITY
EMETIC/ANTIEMETIC
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Anatomy of the GI System
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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
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>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)
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Two Major Parts
I. Alimentary Canal/bucal or oral cavity (mouth, pharynx, esophagus, stomach, small intestine, large intestine)
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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
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4. Stomach
-temporary storage of food
-breaks down food into chyme
-moves gastric content into the small intestine
-gastrin, hydrochloric acid, pepsinogen, mucus
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5. Small intestine : duodenum, jejunum, ileum
-complete food digestion
-absorbs food molecules
-secretes hormones that help control bile (secretin) and pancreatic juice (cholecystokinin) secretion
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6. Large intestine
-absorbs water, Na, CI
-secretes alkaline mucus
-eliminates digestive wastes
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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
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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
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Gallbladder
-stores & concentrates bile produced by the liver
-releases bile to the duodenum
Pancreas
-performs both endocrine & exocrine function GI Tract Innervations
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Parasympathetic stimulation
-increase gut & sphincter tone
-increase smooth muscle contraction & motor secretory activities
Sympathetic stimulation
-reduces peristalsis & inhibits GI activity
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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)
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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
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2. Gastric ulcer – pain is referred to the left subcostal region
> rarely produce noctumal pain
> aggravated by food
>patient loses weight
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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
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APUD ( Acid-Peptic Ulcer Disease )
-imbalance between aggressive and defensive factors
Aggressive
-HCI, Pepsin, H.pylori
Defensive
-Bicarbonate, Mucus, PG
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3 General Factors
1.infxn w/ H.pylori
2. Increase HCI secretion
3. Inadequate mucosal defense against gastric acid
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Treatment Plan
1. Eradicate H. pyloriAntimicrobial AgentsROC: Triple therapy
1. Bismuth2. Metronidazole3. Tetracycline
*duration: 2 weeksAntisecretory agent is usually added – PPI, antimuscarinic 2nd line: Metronidazole + Amoxicillin/Clarithromycin
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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
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3. Use of NSAIDs
4. Cigarette smoking – delays ulcer healing
>accelerates emptying of stomach acid into the duodenum
>prevents pancreatic & billiary bicarbonate secretion
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5. Alcohol Intake – mucosal irritant
6. Coffee – contains peptides that stimulate release of Gastrin
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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
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Gastric Acid Secretion
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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
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Lansoprazole> prevention & healing of NSAID-induced GU
RabeprazolePantoprazole
> IV preparation used for Zollinger-Ellison syndrome
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>>Omeprazole & LansoprazoleApproved for used in infants & children for
the short-term treatment of GERD & corrosive esophagitis
S/E: headache, n&v, abdominal pain, diarrhea and flatulence
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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
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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
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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
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Famotidine – Oral, IV
> most potent, 94% reduction
Nizatidine – Oral
> newest H2- receptor blocker
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S/E: headache & dizziness
> Ranitidine – hepatotoxixity, bradychardia
> Cimetidine
- heoatotoxixity, bradychardia agranulocytosis, aplastic anemia, weak androgenic effect (male gynecomastaia & impotence)
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Drug Interactions
> Cimetidine – enzyme inhibitor
- reduce clearance of propranolol & lidocaine
- inhibits excretion of procainamide
- absorption is impaired by antacid (Ranitidine)
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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
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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
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Bismuth subsalicylate
Colloifal Bismuth subcitrate
S/E: dark stools and tongue
salicylism at high dose
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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
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> Nonsytemic – Al or Mg
> Systemic antacids – Sodium bicarbonate ( alkalosis ), CALCIUM CARBONATE
> Antacid mixture – Aluminum OH & Magnesium OH
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A: 1 hour and 3 hrs after meals and bedtimeS/E:Aluminum – constipationMagnesium – diarrheaCalcium carbonate – constipation, acid rebound,
milk-alkali syndromSodium bicarbonate – alkalosis, C/l in patients with
HTN, CHF, severe renal desease
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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
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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.
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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
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*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
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*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.
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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
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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
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Muscarinic receptors:
Inc.GI motility
Inc.GI secretion
Muscarinic Receptor Blocker/anticholinergic
Dec.GI motility
Dec.GI secretion
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e.g. PIRENZEPINE
-specific M1 receptor antagonist
-currently investigated as an antisecretory agent
**suppresses gastric secretion at doses having minimal effect on other organs
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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
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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.
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Treatment
>Nonpharmacologic
-increase fluid and fiber intake
-exercise regularly
-bowel training ti increase regularity
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Pharmacologic
Laxatives – stimulate defection, should not be taken if nausea, vomiting, or abdominal pain is present
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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
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> Natural bulk-forming laxatives
Psyllium (Metamucil, Fiberall, Konsyl-D, Perdium Fiber Granules), Malt soup extract (Maltsupex)
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> Synthetic bulk-forming laxatives
Methylcellulose, Polycarbophil (Ca Polycarbophil impairs Tetracycline absorption)
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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
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> Saline laxatives – sodium and magnesium salts
> Should not be used in patients with HPN, CHF, & renal impairment
> Magnesium citrate, Magnesium hydroxide, Magnesium sulfate, Sodium `
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> Osmotis laxatives
> Glycerin – rectal burning
> Lactulose – decrease blood ammonia levels in hepatic encephalopathy, S/E flatulence & cramping
> Sorbitol – nonabsorbable sugar
> Polyethylene glycol
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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
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> Anthraquinone glycoside – melanoma coliSennosides – most potentCascara sagradaCasanthranol – 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
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4. Emollient laxativesMOA: 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 sodiumDocusate calciumDocusate potassium
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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
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* 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
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Causes:
1. Infection – virus, bacteria,protozoa
2. Diet – induced ( high fiber, fatty or spicy food, large amounts caffeine, milk intolerance)
3. Drug – induced
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Treatment
> Antidiarrheal may prevent an attack or relieve existing symptoms
Non-pharmacological approach
Food – BRAT diet (Banana, Rice, Applesauce, Toast) not advised anymore
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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
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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
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2. Adsorbent
MOA: adsorb toxins, bacteria, gases & fluids
Kaolin, Bismuth subsalicylate
3. Anti-infectives
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Irritable Bowel Syndrome
> pain, cramping, gassiness, constipation and/or diarrhea
> symptoms appear after eating or during stress and result from abnormal motility
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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
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Crohn’s Disease – chronic, segmental inflammation of the GI tract (ileum)
Sulfasalazine – 5-aminosalicylate (anti-inflammatory)
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Pseudomembranous colitis – inflammation of the colon resulting from the use of antibiotics
> Clostridium difficile
> Mild to bloody diarrhea, abdominal pain, fever
> Metronidazole or Vancomycin
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*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
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> Ondansetron – antiemetic of choice in the US
-serotonin receptor antagonist
> Metoclopramide – effective against Cisplatin-induced vomiting
> Butyrophenones- drromperodol, haleperidol, droperidol
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> Phenothiazines- prochlorperazine
> Benzodiazepines – alprazolam, lorazepam
> Marijuana
> Corticosteroids- dexamethasone, methylpednisolone
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