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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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