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GIT DISORDERS

• Peptic Ulcer Disease

• Constipation & Diarrhea

• IBS, IBD

• Emesis

Stomach wall

• The mucosal layer protects the stomach from acid.

• If damaged, it exposes the underlying tissue to gastric acid.

• This can lead to open sores in the stomach lining → Peptic Ulcer Disease (PUD).

Physiology of gastric acid secretion

• Gastric acid is secreted by the PROTON PUMP in the PARIETAL cells
• H⁺/K⁺-ATPase
• Stimulated by:

1. ACETYLCHOLINE

2. HISTAMINE (H2)

3. GASTRIN

• Gastric acid secretion is inhibited by PG/PROSTAGLANDIN, which stimulate HCO3- and MUCUS by epithelial cells

PEPTIC ULCER DISEASE

Damage to the MUCOUS MEMBRANE normally protects the esophagus, stomach, and duodenum from GASTRIC ACID and PEPSIN

PEPTIC ULCER DISEASE

Causes

• Microbe: H. Pylori

• NSAIDs

• Alcohol

• Stress

Gastric Ulcer

An ulcer in the stomach is called

Duodenal ulcer

Damage in the first part of the small intestine, the duodenum is called

Aggressive factors

1. Acid (HCl)

2. Pepsin

3. Bile acid

4. NSAIDs

5. H. Pylori

Defensive factors

1. Prostaglandin/PG

2. HCO3-

3. Mucus

Goal of Therapy for PUD

• Decrease acid secretion

• Increase cytorotection (defensive factors)

• Eradicate H. Pylori (monotherapy is not allowed)

Eradicate H. pylori

Triple Therapy

1. PPIs (pantoprazole)

2. Clarithromycin

3. Amoxicillin; Metronidazole

Eradicate H. pylori

Quadruple Therapy:

• Non-Bismuth therapy

  • PPI (+ 3 antimicrobials)

  • → Rabeprazole plus amoxicillin, clarithromycin, and metronidazole

• Bismuth-based therapy

  • PPIs

  • Metronidazole

  • Tetracycline

  • Bismuth subsalicylate

Reduce Gastric Secretion

• H₂-blockers

• Proton Pump Inhibitors (PPIs)

• Antacids

H₂-blockers

MOA

• Inhibition of Histamine 2 receptor = decrease cAMP = decrease gastric acid secretion

• -tidine

Drugs

• Cimetidine

  • weak anti-androgen (can cause gynecomastia), enzyme inhibitor

• Ranitidine

• Famotidine

  • most Fotent

• Nizatidine

  • nicely absorbed → most bioavailable H2 Blocker

Proton Pump Inhibitors (PPIs)

MOST IMPORTANT DRUGS FOR ULCER; DOC

MOA

• Reduce stomach acid production by irreversibly blocking the H+/K+-ATPase enzyme (also known as the proton pump) in the parietal cells of the stomach.

  • This enzyme is the final step in the acid secretion process.

  • By blocking, ↓ acid secretion

Drugs

• Omeprazole

  • 1st PPI

• Rabeprazole

• Pantoprazole

• Esomeprazole

***NOTE THAT ARIPIPRAZOLE IS AN ATYPICAL ANTIPSYCHOTIC DRUG

Proton Pump Inhibitors (PPIs)

Preferred drugs for:

• PUD (NSAIDs, stress, H. Pylori

• Zollinger - Ellison (pancreatic tumor - gastrinoma)

• GERD

• Dyspepsia (indigestion)

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Advantage:

• Increase efficacy as compared to others

• Shorter course of therapy

Antacids

MOA

• Act as CHEMICAL ANTAGONIST (neutralizers of HCl)

• Remember: they do not act on receptors, they act as neutralizers

Drugs

• NaHCO₃ - systemic antacid

  • Can cause rebound hyperacidity, metabolic alkalosis, edema ⭐

• Al(OH)₃ - non systemic antacid

  • Constipation

• Mg(OH)₂ - non systemic antacid

  • Diarrhea

• CaCO₃ - non systemic antacid

  • Constipation

Remember:

• Ala Ca Tae - Constipation

• Mg Tae - Diarrhea

Enhance cytoprotection

Enhance protection of the gastric mucosa from becoming inflammed and necrotic on being exposed to noxious agents.

• Sucralfate

• Misoprostol

Sucralfate

Polymer of sulfated sucrose and aluminum hydroxide

A/E: Constipation

Misoprostol

MOA: “dual action”

a. Parietal cells

• (+) Activate Prostaglandin receptor → ↓ decrease cAMP → ↓ Decrease Acid secretion

b. Epithelial cells

• ↑ Increase Bicarbonate (HCO₃⁻) & mucus secretion → ↑ Increase Mucosal protection

Use:

• NSAID-induced ulcers (especially in high-risk patients)

Adverse Effects (A/E):

• Diarrhea

• Intestinal cramping

• Uterine contraction → May lead to abortion (contraindicated in pregnancy)

CONSTIPATION

• Difficult passage of stool

• Infrequent bowel movement

Cause:

• LOW PERISTALSIS MOVEMENT

• INADEQUATE FIBER INTAKE

• DRUG INDUCED (morphine, antacid)

• DEHYDRATION

• LACK OF PHYSICAL ACTIVITY

Laxatives

increase bowel movements/peristalsis and facilitate defecation

True

Laxatives and cathartics both promote bowel movements, but cathartics have a stronger, more forceful effect, causing more rapid and watery evacuation of the colon, while laxatives generally produce a milder effect.

Laxatives

Classification (based on MOA)

• Bulk-Forming Laxatives

• Emollient Laxatives

• Osmotic Laxatives

• Stimulant (Secretory) Laxatives

• Lubricant laxatives

Bulk-Forming Laxatives

• Increase the size of fecal matter

• Recommendation

• 1 glass of water to ensure adequate hydration and to avoid intestinal obstruction

• SAFEST and MOST FUNCTIONAL type of laxative

• Preferred in CHRONIC CONSTIPATION

• Examples:

• Fibers

• Psyllium

• Polycarbophil

Emollient Laxatives

• AKA STOOL SOFTENERS

• because they facilitate the incorporation of water into fatty intestinal material (ACT AS SURFACTANTS)

• Examples:

• Docusate (Na, K, Ca)

Osmotic Laxatives

Help relieve constipation by drawing water into the colon through osmosis, softening the stool and making it easier to pass

Osmotic Laxatives

Salts

• Short-term use only

a. MgSO₄

b. MgO

c. Na₃PO₄

Osmotic Laxatives

Sugars (nonelectrolytes)

• Long-term use

a. Lactulose

b. PEG

Lactulose

• Hydrolysis:

• Lactulose → Gal + Fru

• Fermentation:

• Lactulose → Acetic Acid + Lactic Acid

• Use:

• Cathartic, portal-systemic encephalopathy

Stimulant (Secretory) Laxatives

• AKA secretory laxatives

• Act directly on the intestinal mucosa to alter fluid secretion and stimulate peristalsis

• Examples:

• Castor oil (Ricinoleic acid)

• Anthraquinone glycosides

  • Cascara sagrada

  • Senna

• Synthetic: bisacodyl

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A/E

• Abdominal cramping

• Electrolyte imbalance

• Chronic:

  • Dependence

  • Melanosis coli (blackening of colon)

  • Cathartic colon

Lubricant laxatives

• Lubricate the stool surface resulting in smooth passage of fecal contents

• Example: Mineral oil

• A/Es and DI:

• Lipid pneumonitis

• Aspiration pneumonia

• Mineral oil + Fat Soluble Vit (ADEK) = deceeased absorption of ADEK

Prescription medications for Constipation

• Methylnaltrexone

• Lubiprostone

• Lactulose

Methylnaltrexone

• Approved for the management of opioid induced constipation

Lubiprostone

• Chloride channel activator

• For irritable bowel syndrome - constipation, chronic idiopathic constipation, for opioid induced constipation

Lactulose

For hepatic encephalopathy

Mechanism of Action:

• Lactulose is a non-absorbable disaccharide

• Reaches the colon → fermented by bacteria → produces lactic acid & acetic acid

• This acidifies the colon, converting ammonia (NH₃) to ammonium (NH₄⁺)

  • NH₄⁺ is non-absorbable and excreted in stool

  • ↓ ammonia levels in the blood

DIARRHEA

• Increase frequency and liquidity of bowel movements

• Increase peristalsis

• LBM - loose, watery stool

• Factors:

• Food poisoning (infections)

• Food intolerance

• Drug - MgSO4, Mg(OH)2

• Goal: Decrease peristalsis movement

ANTIDIARRHEAL DRUGS

• Opioid Drugs

• Eluxadoline

• Locally Acting Drugs

• Bismuth subsalicylate

• Anti-microbials

Opioid Drugs

• Most efficacious antidiarrheal drugs

• MOA: (+) Activate mu (μ) receptors in smooth muscle → decrease peristalsis

• Examples:

• Loperamide

• Diphenoxylate

• Eluxadoline

Eluxadoline

IBS-diarrhea (IBS-D)

Locally Acting Drugs

• Psyllium hydrophilic mucilloid

• Calcium polycarbophil

• Both are adsorbents

Bismuth subsalicylate

• Appears to produce its antidiarrheal effect by inhibiting intestinal secretions

• Most effective in treating infectious diarrhea

Bacteria causing diarrhea

• Traveler’s diarrhea (E. coli)

• Clostridium difficile colitis

• Amebiasis (E. histolytica)

• Rice-watery diarrhea (V. cholerae)

Traveler’s diarrhea (E. coli)

“ETEC”

• Co-Trimoxazole

• Quinolones (Fluoroquinolones - Ciprofloxacin)

Clostridium difficile colitis

Px will suffer from bloody diarrhea

• Metronidazole

• Oral Vancomycin

• Fidaxomicin

Amebiasis (E. histolytica)

• Metronidazole

Rice-watery diarrhea (V. cholerae)

• Tetracycline

IRRITABLE BOWEL SYNDROME

• Common problem in the large intestine

• Chronic abdominal pain intestinal spasms altered bowel habits

IRRITABLE BOWEL SYNDROME

Symptoms

• Cramping

• Abdominal pain

• Diarrhea and/or constipation

Anti-spasmodic agents

Refers to drugs designed to relieve or prevent spasms of the gastrointestinal tract, primarily used in patients with symptoms consistent with irritable bowel syndrome (IBS)

1. Dicyclomine (Dicycloverine)

2. Hyoscyamine

3. Hyoscine = Scopolamine

4. Natural: Peppermint Oil

Loperamide

Tx for Mild IBS-D:

Polyethylene glycol (PEG)

Tx for Mild IBS-C:

IBS-CONSTIPATION

• Tegaserod

• Lubiprostone

• Linaclotide

Tegaserod

• 5-HT4 agonist = ↑ peristalsis

• Reserved drug due to CVD

Lubiprostone

• (+) Chloride channel activator = ↑Cl = ↑ peristalsis

• A/E:

• Nausea

• Mx: take with meal

• Use:

• IBS-C

• Chronic idiopathic condition

• Opioid-induced constipation

Linaclotide

• (+) Activate guanylate cyclase → ↑ Increase cGMP levels → ↑ Increase secretion of Cl⁻ and HCO₃⁻

• Use: CIC & IBS-C

IBS-DIARRHEA

• Eluxadoline

• Rifaximin

• Alosetron

• Crofelemer

Eluxadoline

• (+) Activates mu (μ) receptors = lead to decreased peristalsis

Rifaximin

Antibiotic with minimal systemic absorption - reduce overgrowth of bacteria

Alosetron

• 5-HT 3 receptor blocker = decrease bowel tone = decrease peristalsis movement

• A/E: GI effects including ischemic colitis

• Use: IBS-D in females

Crofelemer

• MOA:

• ↓ Decrease chloride secretion = ↓ Decrease sodium and water excretion

• Helps maintain fluid balance and reduce diarrhea

• Use: Chronic Diarrhea in HIV/AIDS

• Can cause Hypovolemia (may be fatal)

Inflammatory Bowel Diseases

• Ulcerative colitis

• Crohn’s Disease

Ulcerative colitis

• Inflammation of GI mucosa

• Limited to the colon and rectum

Crohn’s Disease

• Inflammation is transmural

• Occurs in any part of the GIT

Drugs for Inflammatory Bowel Diseases

• GLUCOCORTICOIDS

• AMINOSALICYLATES

• IMMUNOSUPPRESSIVE AGENTS

GLUCOCORTICOIDS

• Hydrocortisone

• Budesonide (Uceris)

Hydrocortisone

Treatment of both ulcerative colitis and Crohn’s disease

Budesonide (Uceris)

Specifically indicated for the treatment of ulcerative colitis (rectal aerosol foam)

AMINOSALICYLATES

• Sulfasalazine (sulfonamide compound)

• Olsalazine (salicylate compound)

Sulfasalazine (sulfonamide compound)

• Sulfonamide compound converted to:

a. 5-ASA (mesalamine/mesalazine) - anti-inflammatory

b. Sulfapyridine - antibacterial

Olsalazine (salicylate compound)

• Salicylate compound

• Contains mesalamine